Intellectual Property India

IN THE MATTER OF:

THE PATENTS ACT 1970, THE PATENTS (Amendment) RULES 2016

IN THE MATTER of a Pre-grant Opposition under Section 25(1)

IN THE MATTER OF:

IN201717025098 filed on 14/07/2017, by EMORY UNIVERSITY

In the matter of:

Entrepreneurship Development Center …OPPONENT VS.

EMORY UNIVERSITY,

…………. RESPONDENT/APPLICANT

STATEMENT OF CASE OF THE OPPONENT

1. The Opponent herein is on behalf of Entrepreneurship Development Center, a not for

profit registered company, having it’s Registered office at Pune, having place of business

at 100, NCL Innovation Park, Dr Homi Bhabha Rd, Pune, Maharashtra 411008.

Entrepreneurship Development Center (aka Venture Center) is a DSIR

approved Scientific and Industrial Research Organization that aims to nurture science

based innovation and entrepreneurship. It also hosts projects related to National Missions

including the National Biopharma mission.

2. Entrepreneurship Development Center serves as the Nerve Center supporting the

activities of the Task Force for Repurposing of Drugs for COVID19 created by the Office

of PSA, Govt of India under the aegis of the S&T Core Group on COVID19. Thus, the

Petitioner has real and substantial interest in the matter at hand.

3. The Petitioner has learnt that the Applicant has filed Indian Application No.

201717025098 on July 14, 2007 which is currently pending before the Patent Office.

The said application has been filed in respect of an invention for “N4

HYDROXYCYTIDINE AND DERIVATIVES AND ANTI VIRAL USES RELATED

THERETO” filed by Emory University (hereinafter referred to as “Applicant”).

4. The Petitioner has learnt, the application has been published on November 03, 2017 with

publication number 44/2017. First examination report has been issued on Dec 20, 2019

and replied on Sept 18, 2020. FER and reply to the FER attached as Annexure 1.

5. The claims on record as in response to FER filed on Sept 18, 2020 as per the IPO website

attached as Annexure 2.

For sake of convenience the claims on records which Opponent has contests are as following: CLAIM 1: A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound having Formula I

Formula I, or salt thereof, wherein Q is O, -O(C=O)-, -O(C=O)V-, or NR7; V is O, NH, NR7, CH2, or CHR7; W is O; X is CH2,CHMe, CMe2, CHF, CF2, or CD2; Y is CR”; Z is CR”; each R” is independently selected from is H, D, F, Cl, Br, I, CH3, CD3, CF3, C1-22alkyl, acyl, C2- 22alkenyl, C2-22alkynyl, hydroxyl, formyl or SCH3; R1 is

Monophosphate ester, diphosphate ester

C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R10 is optionally substituted with one or more, the same or different, R20; R11 is hydrogen, deuterium, (C1-C22)alkyl, methyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R11 is optionally substituted with one or more, the same or different, R20; R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl, 1-naphthyl, 2-naphthyl,aromatic, heteroaromatic, 4-substituted phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, naphthyl, or heterocyclyl, wherein R12 is optionally substituted with one or more, the same or different, R20; R13 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl, or heterocyclyl, wherein R13 is optionally substituted with one or more, the same or different, R20; R14 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C12-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R14 is optionally substituted with one or more, the same or different, R20; R20 is deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; and wherein the lipid comprises a C6-22 alkyl, (C1-C22)alkoxy, polyethylene glycol, or (C6- C12)aryl substituted with an (C1-C22)alkyl group, heterocyclylis acarbocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur, and heteroaromatic is an aromatic heterocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur and at least 1 carbon atom.

CLAIM 2: The pharmaceutical composition of claim 1, wherein Q-R7 is OH. CLAIM 3: The pharmaceutical composition of claim 1, wherein R1 is

R8 is hydrogen, hydroxy, or benzyloxy, and R9 is (C6-C22)alkyl. CLAIM 4. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula IB,

Formula IB, or salts thereof, wherein V is absent, O, NH, NR15, S, CH2, or CHR15; X is CH2,CHMe, CMe2, CHF, CF2, or CD2; Y is H, D, F, Cl, Br, I, CH3, CD3, CF3, (C1-C6)alkyl, acyl, (C2-C6)alkenyl, (C2-C6)alkynyl, hydroxyl, formyl or SCH3; R1

Monophosphate ester, diphosphate ester alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, carbanoyl, esteryl, alkoxy, (C1C22)alkylthio, (C1-C22)alkylamino, ((C1- C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl, or heterocyclyl, or phosphoramidyl,wherein R1 is optionally substituted with one or more, the same or different, R20; Y1 is O or S; Y2 is OH, OR12, OAlkyl, or BH3-M+; Y3 is OH or BH3-M+; R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxymethyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, , (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, , (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; R5 is hydrogen, hydroxy, or halogen; R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, benzyloxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl,orheterocyclyl, wherein R8 is optionally substituted with one or more, the same or different, R20; R9 is hydrogen, methyl, ethyl, tert-butyl, (C1-C22)alkyl, halogen, nitro, cyano, hydroxy, amino,mercapto, formyl, carboxy, carbamoyl, cycloalkyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino,((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl,(C6-C12)aryl,orheterocyclyl, wherein R9 is optionally substituted with one or more, the same or different, R20; R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, methyl, ethyl, isopropyl, cyclopentyl, cyclohexyl, butyl, pentyl, hexyl, neopentyl, benzyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy,carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R10 isoptionally substituted with one or more, the same or different, R20; R11 is hydrogen, deuterium, (C1-C22)alkyl, methyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R11 is optionally substituted with one or more, the same or different, R20; 5

R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl, 1-naphthyl, 2-naphthyl,aromatic, heteroaromatic, 4-substituted phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, naphthyl, or heterocyclyl, wherein R12 is optionally substituted with one or more, the same or different, R20; R13 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl,(C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R13 is optionally substituted with one or more, the same or different, R20; R14 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C12-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R14 is optionally substituted with one or more, thesame or different, R20; R15 is hydrogen, Lipid, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1-C22), -(C=O)NHalkyl(C1-C22), - (C=O)N-dialkyl(C1-C22), -(C=O)Salkyl(C1-C22), hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl, halogen, nitro, cyano,amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R15 is optionally substituted with one or more, the same or different, R20; R20 is deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; and wherein the lipid comprises a C6-22 alkyl, (C6-C22)alkoxy, polyethylene glycol, or (C6- C12)aryl substituted with an alkyl group,heterocyclylis acarbocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur, and heteroaromatic is an aromatic heterocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur and at least 1 carbon atom. CLAIM 5 The composition of claim 3, wherein the compound is selected from: 1-(3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-4((nonanoyloxy)amino)pyrimidin- 2-one, 1-(3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-4- ((((heptyloxy)carbonyl)oxy)amino)pyrimidin-2-one, and isopropyl(((3,4-dihydroxy-5-(4-(hydroxyamino)-2-oxopyrimidin-1(2H)-yl)tetrahydrofuran-2- yl)methoxy)(phenoxy)phosphoryl)alaninate. CLAIM 6 A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of Formula IC,

6 or salts thereof, wherein X is CH2,CHMe, CMe2, CHF, CF2, or CD2; Y is H, D, F, Cl, Br, I, CH3, CD3, CF3, alkyl, acyl, alkenyl, alkynyl, hydroxyl, formyl or SCH3; R1 is hydrogen, monophosphate, diphosphate, triphosphate,

C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R10 isoptionally substituted with one or more, the same or different, R20; R11 is hydrogen, deuterium, (C1-C22)alkyl, methyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino,(C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, orheterocyclyl, wherein R11 is optionally substituted with one or more, the same or different, R20; R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl, 1-naphthyl, 2- naphthyl,aromatic,heteroaromatic, 4-substituted phenyl, 4-fluorophenyl, 4-chlorophenyl, 4- bromophenyl, naphthyl, or heterocyclyl, wherein R12 is optionally substituted with one or more, the same or different, R20; R13 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R13 is optionally substituted with one or more, the same or different, R20; R14 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C12-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R14 is optionally substituted with one or more, the same or different, R20; R15 is hydrogen, Lipid, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1-C22), -(C=O)NHalkyl(C1-C22), - (C=O)N-dialkyl(C1-C22), -(C=O)Salkyl(C1-C22), hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl, halogen, nitro, cyano,amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino,(C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R15 is optionally substituted with one or more, the same or different, R20; R20 is deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; and wherein the lipid comprises a C6-22 alkyl, (C6-C22)alkoxy, polyethylene glycol, or (C6- C12)aryl substituted with an alkyl group,heterocyclylis acarbocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur, and heteroaromatic is an aromatic heterocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur and at least 1 carbon atom. CLAIM 7 7. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of Formula ID,

Formula ID, 8 or salt thereof, wherein W is CH2, NH, S or O; X is CH2,CHMe, CMe2, CHF, CF2, or CD2; Y is N or CR”; Z is N or CR”; each R” is independently selected from is H, D, F, Cl, Br, I, CH3, CD3, CF3, alkyl, acyl, alkenyl, alkynyl, hydroxyl, formyl or SCH3; R1 is hydrogen, monophosphate, diphosphate, triphosphate, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, carbanoyl, esteryl, alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, or phosphoramidyl, or wherein R1 is optionally substituted with one or more, the same or different, R20; Y1 is O or S; Y2 is OH, OR12, OAlkyl, or BH3-M+; Y3 is OH or BH3-M+; R2 is hydrogenor hydroxy; R3 is hydrogen, hydroxy, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl,carbocyclyl, aryl, or heterocyclyl; R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxymethyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1- C22)alkoxy, (C1- C22)alkylthio,(C1-C22)alkylamino, ((C1-C22)alkyl)2amino,(C1-C22)alkylsulfinyl,(C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; R5 is hydrogen, hydroxy, or halogen; R6 is hydrogen, hydroxy, alkoxy, alkyl, ethynyl, allenyl, halogen, nitro, cyano, amino, mercapto,formyl, carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl; R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, benzyloxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl,orheterocyclyl, wherein R8 is optionally substituted with one or more, the same or different, R20; R9 is hydrogen, methyl, ethyl, tert-butyl, (C1-C22)alkyl, halogen, nitro, cyano, hydroxy, amino,mercapto, formyl, carboxy, carbamoyl, cycloalkyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino,((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R9 is optionally substituted with one or more, the same or different, R20; R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, methyl, ethyl, isopropyl, cyclopentyl, cyclohexyl,butyl, pentyl, hexyl, neopentyl, benzyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy,carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R10 is optionally substituted with one or more, the same or different, R20; R11 is hydrogen, deuterium, (C1-C22)alkyl, methyl, halogen, nitro, cyano, hydroxy, amino, 9 mercapto,formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino,(C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R11 is optionally substituted with one or more, the same or different, R20; R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl, 1-naphthyl, 2- naphthyl,aromatic,heteroaromatic, 4-substituted phenyl, 4-fluorophenyl, 4-chlorophenyl, 4- bromophenyl, naphthyl, or heterocyclyl, wherein R12 is optionally substituted with one or more, the same or different, R20; R13 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1- C22)alkoxy, (C1-C22)alkylthio,(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl,(C3-C6)carbocyclyl, (C6- C12)aryl, or heterocyclyl, wherein R13 is optionally substituted with one or more, the same or different, R20; R14 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C12-C22)alkynyl, halogen, nitro, cyano,hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1- C22)alkoxy, (C1-C22)alkylthio,(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R14 is optionally substituted with one or more, the same or different, R20; R15 is hydrogen, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1-C22), -(C=O)NHalkyl(C1-C22), - (C=O)Ndialkyl(C1-C22), -(C=O)Salkyl(C1-C22), hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl, halogen, nitro, cyano, amino,mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl,wherein R15 is optionally substituted with one or more, the same or different, R20; R15’ is hydrogen, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1-C22), -(C=O)NHalkyl(C1-C22), - (C=O)Ndialkyl(C1-C22), -(C=O)Salkyl(C1-C22), hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl, halogen, nitro, cyano, amino,mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; R15 and R15’ can form a ring that is optionally substituted with one or more, the same or different, R20; R20 is deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; and wherein the lipid comprises a C6-22 alkyl, (C6-C22)alkoxy, polyethylene glycol, or (C6- C12)aryl substituted with an (C1-C22)alkyl group heterocyclylis acarbocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur, and heteroaromatic is an aromatic heterocyclylcomprising 1-4 heteroatoms selected from nitrogen,oxygen, or sulfur and at least 1 carbon atom. CLAIM 8 8. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of Formula IE,

Formula IE, or salt thereof, wherein Q is O, -O(C=O)-, -O(C=O)Lipid, -O(C=O)V-, NH, or NR7; V is O, NH, NR7, S, CH2, or CHR7; W is CH2, NH, S or O; X is CH2,CHMe, CMe2, CHF, CF2, or CD2; Y is N or CR”; Z is N or CR”; each R” is independently selected from is H, D, F, Cl, Br, I, CH3, CD3, CF3, alkyl, acyl, alkenyl, alkynyl, hydroxyl, formyl or SCH3; R2 is hydrogen, alkyl, alkenyl, alkynyl, ethynyl, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, hydroxymethyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, azido, or heterocyclyl; R3 is hydrogen, hydroxy, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio, alkylamino, alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl; R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxymethyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio,(C1-22)alkylamino, ((C1-C22)alkyl)2amino,(C1- C22)alkylsulfinyl,(C1-22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; R5 is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, alkynyl, ethynyl, fluoromethyl, difluoromethyl,trifluoromethyl, hydroxymethyl, allenyl, halogen, nitro, cyano, amino, mercapto, formyl, carboxy, carbamoyl,alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl,or heterocyclyl; R6 is hydrogen, hydroxy, alkoxy, alkyl, ethynyl, allenyl, halogen, nitro, cyano, amino, mercapto,formyl, carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio, lkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl,arylsulfonyl, carbocyclyl, aryl, or heterocyclyl; each R7 is independently selected from absent, hydrogen, -(C=O)Oalkyl, -(C=O)alkyl, - (C=O)NHalkyl, -(C=O)N-dialkyl, -(C=O)Salkyl, hydroxy, alkoxy, alkyl, higher alkyl, (C6- C16)alkyl, (C6-C22)alkyl, halogen, nitro, cyano, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio,alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, whereineach R7 is optionally substituted with one or more, the same or different, R20; R15 is hydrogen, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1-C22), -C=O)NHalkyl(C1-C22), - (C=O)Ndialkyl(C1-C22), -(C=O)Salkyl(C1-C22), hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl, halogen, nitro, cyano, amino,mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- 12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl,wherein R15 is optionally substituted with one or more, the same or different, R20; R15’ is hydrogen, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1-C22), -C=O)NHalkyl(C1-C22), - (C=O)Ndialkyl(C1-C22), -(C=O)Salkyl(C1-C22), hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl,

11 halogen, nitro, cyano, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1- C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; R15 and R15’ can form a ring that is optionally substituted with one or more, the same or different,R20; If Q = -O(C=O)V- and V = NR7 then the R7s can together form a ring that is optionally substitutedwith one or more, the same or different, R20; R20 is deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy,amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1-22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; and wherein lipid comprises a C6-22 alkyl, (C6-C22)alkoxy, polyethylene glycol, or (C6-C12)aryl substituted with an (C1-C22)alkyl group, heterocyclylis carbocyclyl comprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur, and heteroaromatic is an aromatic heterocyclylcomprising 1-4 heteroatoms selected from nitrogen,oxygen, or sulfur and at least 1 carbon atom. CLAIM 9 A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of Formula II,

or salt thereof, wherein Q is O, -O(C=O)-, -O(C=O)Lipid, -O(C=O)V-, NH, or NR7; V is O, NH, NR7, S, CH2, or CHR7; W is CH2, NH, S or O; X is CH2 or O; Y is N or CR”; Z is N or CR”; each R” is independently selected from is H, D, F, Cl, Br, I, CH3, CD3, CF3, alkyl, acyl, alkenyl, alkynyl, hydroxyl, formyl or SCH3; R1 is monophosphate, diphosphate, triphosphate,

Y1 is O or S; Y2 is OH, OR12, OAlkyl, or BH3-M+; Y3 is OH or BH3-M+; R2 is hydrogen, alkyl, alkenyl, alkynyl, ethynyl, fluoromethyl, difluoromethyl, trifluoromethyl,chloromethyl, hydroxymethyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl,azido, or heterocyclyl; R3 is hydrogen, hydroxy, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio, alkylamino, alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl; R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, difluoromethyl, rifluoromethyl, hydroxymethyl,halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio,(C1-C22)alkylamino, ((C1- C22)alkyl)2amino,(C1-C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; R5 is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, alkynyl, ethynyl, fluoromethyl, difluoromethyl,trifluoromethyl, hydroxymethyl, allenyl, halogen, nitro, cyano, amino, mercapto, formyl, carboxy, carbamoyl,alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl,or heterocyclyl; R6 is hydrogen, hydroxy, alkoxy, alkyl, ethynyl, allenyl, halogen, nitro, cyano, amino, mercapto,formyl, carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl,arylsulfonyl, carbocyclyl, aryl, or heterocyclyl; each R7 is independently selected from absent, hydrogen, -(C=O)Oalkyl, -(C=O)alkyl, - (C=O)NHalkyl, -(C=O)N-dialkyl, -(C=O)Salkyl, hydroxy, alkoxy, alkyl, higher alkyl, (C6- C16)alkyl, (C6-C22)alkyl, halogen, nitro, cyano, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio,alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein each R7 is optionally substituted with one or more, the same or different, R20; R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano,hydroxy, benzyloxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- 12)aryl,orheterocyclyl, wherein R8 is optionally substituted with one or more, the same or different, R20; R9 is hydrogen, methyl, ethyl, tert-butyl, (C1-C22)alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, cycloalkyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino,((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl,(C6-C12)aryl,orheterocyclyl, wherein R9 is optionally substituted with one or more, the same or different, R20; R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, methyl, ethyl, isopropyl, cyclopentyl, cyclohexyl,butyl, pentyl, hexyl, neopentyl, benzyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy,carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R10 is optionally substituted with one or more, the same or different, R20; R11 is hydrogen, deuterium, (C1-C22)alkyl, methyl, halogen, nitro, cyano, hydroxy, amino, 13 mercapto,formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino,(C1-22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R11 is optionally substituted with one or more, the same or different, R20; R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl, 1-naphthyl, 2- naphthyl,aromatic,heteroaromatic, 4-substituted phenyl, 4-fluorophenyl, 4-chlorophenyl, 4- bromophenyl, naphthyl, or heterocyclyl, wherein R12 is optionally substituted with one or more, the same or different, R20; R13 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano,hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1- C22)alkoxy, (C1-C22)alkylthio,(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl,(C3-C6)carbocyclyl, (C6- C12)aryl, or heterocyclyl, wherein R13 is optionally substituted with one or more, the same or different, R20; R14 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C12-C22)alkynyl, halogen, nitro, cyano,hydroxy, amino, amido, mercapto, formyl, carboxy, arbamoyl, lipid, azido, (C1- C22)alkoxy, (C1-C22)alkylthio,(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R14 is optionally substituted with one or more, the same or different, R20; If Q = -O(C=O)V- and V = NR7 then the R7s can together form a ring that is optionally substituted with one or more, the same or different, R20; R20 is deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy,amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1-22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; and wherein lipid comprises a C6-22 alkyl, (C6- C22)alkoxy, polyethylene glycol, or (C6-C12)aryl substituted with an (C1-C22)alkyl group, heterocyclylis acarbocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur, and heteroaromatic is an aromatic heterocyclylcomprising 1-4 heteroatoms selected from nitrogen,oxygen, or sulfur and at least 1 carbon atom.

CLAIM 10 The pharmaceutical composition of claim 1,further comprising a propellant.

CLAIM 11 The pharmaceutical composition of claim 10, wherein the propellant is compressed air, ethanol, nitrogen, carbon dioxide, nitrous oxide, hydrofluoroalkanes (HFA), 1,1,1,2,-tetrafluoroethane, 1,1,1,2,3,3,3-heptafluoropropane or combinations thereof.

CLAIM 12 The composition of claim 1, wherein the compound has a structure according to Formula IA

or salt thereof, wherein R7 is H, X is CH2, CHMe, CMe2, CHF, CF2, or CD2; Y is independently selected from is H, D, F, Cl, Br, I, CH3, CD3, CF3, alkyl, acyl, alkenyl, alkynyl, hydroxyl, formyl or SCH3;

R1 is

monophosphate ester, diphosphate ester

amino, mercapto, formyl, carboxy, carbanoyl, esteryl, alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, or phosphoramidyl, wherein R1 is optionally substituted with one or more, the same or different, R20, Y1 is O or S; Y2 is OH, OR12, OAlkyl, or BH3-M+; Y3 is OH or BH3-M+; R4 is hydrogen, hydroxy, (C1-C22)alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxymethyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl, or heterocyclyl, wherein R4 is optionally substituted with one or more, the same or different, R20; R5 is hydrogen, hydroxy, or halogen; R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, benzyloxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl,orheterocyclyl, wherein R8 is optionally substituted with one or more, the same or different, R20; R9 is hydrogen, methyl, ethyl, tert-butyl, (C1-C22)alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, cycloalkyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino,((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl,(C6-C12)aryl,orheterocyclyl, wherein R9 is optionally substituted with one or more, the same or different, R20; R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, methyl, ethyl, isopropyl, cyclopentyl, cyclohexyl,butyl, pentyl, hexyl, neopentyl, benzyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy,carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R10 is optionally substituted with one or more, the same or different, R20; R11 is hydrogen, deuterium, (C1-C22)alkyl, methyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino,(C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R11 is optionally substituted with one or more, the same or different, R20; R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl, 1-naphthyl, 2-naphthyl, aromatic,

15 heteroaromatic, 4-substituted phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, naphthyl, or heterocyclyl, wherein R12 is optionally substituted with one or more, the same or different, R20; R13 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R13 is optionally substituted with one or more, the same or different, R20; R14 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C12-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R14 is optionally substituted with one or more, the same or different, R20;

CLAIM 13 The composition of claim 1, wherein R4 is hydrogen, hydroxy, alkyl, halogen, or fluoro. CLAIM 14 The composition of claim 1, wherein R5 is hydrogen, hydroxy, alkoxy, alkyl, methyl, ethynyl, or allenyl.

6. Background of the prior art: Molnupiravir (development codes MK-4482 and EIDD- 2801) is an experimental antiviral drug which is orally active and was developed for the treatment of influenza. It is a prodrug of the synthetic nucleoside derivative N4- hydroxycytidine, and exerts its antiviral action through introduction of copying errors during viral RNA replication. Activity has also been demonstrated against corona viruses including SARS, MERS and SARS-CoV-2. Molnupiravir is chemically is ((2R,3S,4R,5R)-3,4-dihydroxy-5-(hydroxyimino)-2-oxo-3,4 dihydropyrimidin-1(2H)-yl) tetrahydro furan-2-yl)methyl isobutyrate having the chemical structure.

The drug was developed at Emory University by the university's drug innovation company, Drug Innovation Ventures at Emory (DRIVE). First patent application WO2002032920 covering the molecule was filed on Oct 18, 2001 by Pharmasset Limited. Pharmasset was founded in 1998 by Raymond Schinazi and Dennis Liotta, scientists at Emory University. The company's research and development concentrated 16

on nucleoside analogs. This information is freely available on https://en.wikipedia.org/wiki/Molnupiravir .

This patent seems to be the foundation prior art for all further developments on antivirals involving core N4-hydroxycytidine nucleoside moiety until now including IN20717025098. The reasons to support the understanding shall be discussed in detail further. WO2002032920 is included as D1 in this opposition representation.

7. Accordingly, the Opponent submits their opposition by way of representation under Section 25(1) in respect of the said Indian Application No. 201717025098 on the following amongst other grounds listed below, which are without prejudice and in the alternative to each other:

a. 25(1)(b): that the invention so far as claimed in any claim of the complete

specification has been published before the priority date of the claim.

b. 25(1)(c): that the invention so far as claimed in any claim of the complete

specification is claimed in a claim of a complete specification published on

or after priority date of the applicant's claim and filed in pursuance of an

application for a patent in India, being a claim of which the priority date is

earlier than that of the applicant's claim;

c. 25(1)(e): that the invention so far as claimed in any claim of the complete

specification is obvious and clearly does not involve any inventive step,

having regard to the matter published as mentioned in clause (b) or having

regard to what was used in India before the priority date of the Applicant

’s claim;

d. 25(1)(f): that the subject of any claim of the complete specification is not

an invention within the meaning of this Act, or is not patentable under this

Act;

e. 25(1)(g): that the complete specification does not sufficiently and clearly

describe the invention or the method by which it is to be performed.

f. 25(1)(j): that the complete specification does not disclose or wrongly

mentions the source or geographical origin of biological material used for

the invention;

To oppose the application, Opponent relies on following documents:

D1: US 2003/0087873 D2: US20140235566A1 D3: WO2013142525A1 D4: EP2615101B1

GROUND I:

I) Section 25(1) (b)/(c): Lack of novelty:

CLAIMS 1-14: The invention as claimed in claims 1-14 lack novelty under Section 25(1) (b)/(c) of the Patents Act, 1970 (as amended in 2005; hereinafter referred to as “The Act”). i) Lack of novelty in view of US 2003/0087873 to Lieven Stuyver (D1)

A. US 2003/0087873 filed on Oct 18, 2001 having a priority date Oct 18, 2000 & April 6, 2001 is an admissible prior art for IN20717025098 having priority date of Dec 26, 2014.

US 2003/0087873 discloses a composition for and a method of treating a Flaviviridae (including BVDV and HCV), Orthomyxoviridae (including Influenza A and B) or Paramyxoviridae (including RSV) infection, or conditions related to abnormal cellular proliferation, in a host, including animals, and especially humans, using a nucleoside of general formula (I)-(XXIII) or its pharmaceutically acceptable salt or prodrug. This invention also provides an effective process to quantify the viral load, and in particular BVDV, HCV or West Nile Virus load, in a host, using real-time polymerase chain reaction ('TR-PCR'). Additionally, the invention discloses probe molecules that can fluoresce proportionally to the amount of virus present in a sample.

We shall discuss in further detail as to how the disclosure of US 2003/0087873 anticipates each claim of impugned patent application

Claim 1: IN201717025098 D1: US 2003/0087873 A1 CLAIM 1: A pharmaceutical composition [0124] comprising a pharmaceutically acceptable In another embodiment of the invention, anti- virally or anti proliferatively effective nucleoside is a B-L excipient and a compound having Formula I nucleoside of the general formula (III)

[0114] each D is hydrogen, alkyl, acyl, monophosphate, diphosphate, triphosphate, Formula I, or salt thereof, wherein monophosphate ester, diphosphate ester, Q is O, -O(C=O)-, -O(C=O)V-, or NR7; triphosphate ester, phospholipid or amino acid; [0116] each X1 and X2 is independently hydrogen, halogen (F, Cl, Br or I), NH, NHR4', NR4'R4'',NHOR4, NR4'NR4’’R4", OH, OR, SH or SR'; V is O, NH, NR7, CH2, or CHR7; [0117] each Y is O, S or Se; [0119] each R1 and R1' is independently hydrogen, W is O; lower alkyl, lower alkenyl, lower alkynyl, aryl, X is CH2,CHMe, CMe2, CHF, CF2, or CD2; alkylaryl, halogen (F, Cl, Br or I), NH, NHR, NRR, Y is CR”; NHOR, NRNHR, NRNRR", OH, OR, SH, SR5, NO, Z is CR”; NO, CH-OH, CHOR, COH, COR, CONH, CONHR, CONRR or CN: each R” is independently selected from is H, D, [0120] each R2 and R2’ independently is hydrogen or F, Cl, Br, I, CH3, CD3, CF3, C1-22alkyl, acyl, C2- halogen (F, Cl, Br or I), OH, SH, OCH3, SCH3, 22alkenyl, C2-22alkynyl, hydroxyl, formyl or NH2, NH2CH3, CH2=CH2, CN, CH2-NH, CH2-OH, CO2H. SCH3; Monophosphate ester, diphosphate [0121] each R3 and R3’ independently is hydrogen or R1 is ester halogen (F, Cl, Br or I), OH, SH, OCH3, SCH3, NH, NHCH3, CH3, C2H3, CH=CH, CN, CH-NH2, CH2OH, CO2H. [0122] each R4, R4', R4", R5, R5’ and R5" independently is hydrogen, lower alkyl, lower alkenyl, aryl, or arylalkyl Such as unsubstituted or Substituted phenyl or benzyl, [0123] such that for each nucleoside of the general formula (1) or (II), at least one of R2 and R2’ is alkyl, halogen, nitro, cyano, hydroxy, amino, hydrogen and at least one of R3 and R3’ is mercapto, formyl, carboxy, carbamoyl, hydrogen. carbanoyl, esteryl, alkoxy, (C1-C22)alkylthio, Compound of impugned application also mentioned (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- in [0260] as compound IIIa C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- [0341] In a preferred embodiment, the B-D and B-L C12)aryl, or heterocyclyl, or nucleosides of general formula (I-a) and (III-a) are represented by the non-limiting examples provided in phosphoramidylwherein R1 is optionally Table 1. substituted with one or more, the same or different, R20; Y1 is O or S; Y2 is OH, OR12, OAlkyl, or BH3 - M+; Y3 is OH or BH3 - M+; R2 is hydrogen or hydroxy; R3 is hydrogen, hydroxy, (C1-C22)alkyl, X1 Y1 R1 R1 R2 R2’ R3 R3’

19 halogen, nitro, cyano, hydroxy, amino, BS NH- O H H H - H - mercapto, formyl, carboxy, carbamoyl, , (C1- OH OH OH BT NH- O F H H - H - C22)alkoxy, (C1-C22)alkylthio, , (C1- OH OH OH C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- BU NH- O BR H H - H - C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- OH OH OH C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- BV NH- O I H H - H - OH OH OH C12)aryl, or heterocyclyl; BW NH- O H H OH -H H - R4 is hydrogen, hydroxy,(C1-C22)alkyl, OH OH fluoromethyl, difluoromethyl, trifluoromethyl, hydroxymethyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino,(C1- C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl, or heterocyclyl; R5 is hydrogen, hydroxy, or halogen; R6 is hydrogen, hydroxy, (C1-C22)alkoxy, (C1- C22)alkyl, ethynyl, allenyl, halogen, nitro, cyano, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl,orheterocyclyl; each R7 is independently selected from absent, hydrogen, -(C=O)Oalkyl(C1-C22), - (C=O)alkyl(C1- C22), -(C=O)NHalkyl(C1-C22), - (C=O)N-dialkyl(C1-C22), -(C=O)Salkyl(C1-C22), hydroxy, (C1-C22)alkoxy, (C1- C22)alkyl, halogen, nitro, cyano, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1- 127 C22)alkylthio, (C1-C22)alkylamino, ((C1- C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein each R7 is optionally substituted with one or more, the same or different, R20; R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, benzyloxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl,orheterocyclyl, wherein R8 is optionally substituted with one or more, the same or different, R20; R9 is hydrogen, methyl, ethyl, tert-butyl, (C1- 20

C22)alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, cycloalkyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl,orheterocyclyl, wherein R9 is optionally substituted with one or more, the same or different, R20; R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, methyl, ethyl, isopropyl, cyclopentyl, cyclohexyl, butyl, pentyl, hexyl, neopentyl, benzyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl,orheterocyclyl, wherein R10 is optionally substituted with one or more, the same or different, R20; R11 is hydrogen, deuterium, (C1-C22)alkyl, methyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl, or heterocyclyl, wherein R11 is optionally substituted with one or more, the same or different, R20; R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl, 1-naphthyl, 2-naphthyl,aromatic, heteroaromatic, 4-substituted phenyl, 4- fluorophenyl, 4-chlorophenyl, 4-bromophenyl, naphthyl, or heterocyclyl, wherein R12 is optionally substituted with one or more, the same or different, R20; R13 is hydrogen, deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl, or heterocyclyl, wherein R13 is optionally substituted with one or more, the same or different, R20; R14 is hydrogen, deuterium, (C1-C22)alkyl, (C2- 21

C22)alkenyl, (C12-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6- C12)aryl, or heterocyclyl, wherein R14 is optionally substituted with one or more, the same or different, R20; R20 is deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6- C12)aryl, or heterocyclyl; and wherein the lipid comprises a C6-22 alkyl, (C1-C22)alkoxy, polyethylene glycol, or (C6-C12)aryl substituted with an (C1-C22)alkyl group, heterocyclylis acarbocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur, and heteroaromatic is an aromatic heterocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur and at least 1 carbon atom.

Thus, it is clear that all elements of claim 1 of IN201717025098 are covered in D1. The features completely overlap with portions of D1 as detailed above. Therefore claim 1 and all dependent claims 2, 3, 10, 12, 13 & 14 are not novel wrt to disclosure of D1 alone totally. Other compounds claimed in claims 4, 6, 7, 9 framed as independent claims are carrying the same chain skeleton and are covered under the markush of claim 1 so they are also novel for the reasons for claim 1.

Therefore, claim 1 and all claims dependent on claim 1 lack novelty in view of D1.

Claim 2: IN201717025098 D1: US 2003/0087873 A1 CLAIM 2: The pharmaceutical composition of claim 1, [0124] wherein Q-R7 is OH. In another embodiment of the invention, anti- virally or anti proliferatively effective nucleoside is a B-L nucleoside of the general formula (III)

[0116] each X1 and X2 is independently hydrogen, halogen (F, Cl, Br or I), NH, NHR4', NR4'R4'',NHOR4, NR4'NR4’’R4", OH, OR, SH or SR'; [0122] each R4, R4', R4", R5, R5’ and R5" independently is hydrogen, lower alkyl, lower alkenyl, aryl, or arylalkyl Such as unsubstituted or Substituted phenyl or benzyl,

Claim 3:

IN201717025098 D1: US 2003/0087873 A1 CLAIM 3: The pharmaceutical composition of claim 1, [0124] wherein R1 is In another embodiment of the invention, anti- virally or anti proliferatively effective nucleoside is a B-L nucleoside of the general formula (III)

R8 is hydrogen, hydroxy, or benzyloxy, and R9 is (C6-C22)alkyl.

[0114] each D is hydrogen, alkyl, acyl, monophosphate, diphosphate, triphosphate, monophosphate ester, diphosphate ester, triphosphate ester, phospholipid or amino acid;

Claim 4:

IN201717025098 D1: US 2003/0087873 A1 CLAIM 4. Compound of Formula I b is covered broadly under markush of A pharmaceutical composition comprising a claim 1. Therefore, the compound is not novel for the arguments pharmaceutically acceptable excipient and a compound of applicable for claim 1. formula IB, Further, the overlap is shown in following excerpts from D1.

[0124] In another embodiment of the invention, anti- virally or anti proliferatively effective nucleoside is a B-L nucleoside of the general formula (III)

[0114] each D is hydrogen, alkyl, acyl, monophosphate, 23

diphosphate, triphosphate, monophosphate ester, diphosphate ester, triphosphate ester, phospholipid or amino acid;

[0116] each X1 and X2 is independently hydrogen, halogen (F, Cl, Br or I), NH, NHR4', NR4'R4'',NHOR4, NR4'NR4’’R4", OH, OR, SH or SR';

[0117] each Y is O, S or Se;

[0121] each R3 and R3’ independently is hydrogen or halogen alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, (F, Cl, Br or I), OH, SH, OCH3, SCH3, NH, NHCH3, CH3, formyl, C2H3, CH=CH, CN, CH-NH2, CH2OH, CO2H. carboxy, carbamoyl, carbanoyl, esteryl, alkoxy, [0122] each R4, R4', R4", R5, R5’ and R5" indepenently is (C1C22)alkylthio, (C1-C22)alkylamino, ((C1- hydrogen, lower alkyl, lower alkenyl, aryl, or arylalkyl Such as C22)alkyl)2amino, unsubstituted or Substituted phenyl or benzyl, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- [0123] such that for each nucleoside of the general formula (1) C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or or (II), at least one of R2 and R2’ is hydrogen and at least one of heterocyclyl, or phosphoramidyl,wherein R1 is optionally R3 and R3’ is hydrogen. substituted with one or more, the same or different, R20; Y1 is O or S; Y2 is OH, OR12, OAlkyl, or BH3-M+; Y3 is OH or BH3-M+; R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxymethyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, , (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1- C22)alkyl)2amino, (C1-C22)alkylsulfinyl, , (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; R5 is hydrogen, hydroxy, or halogen; R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, benzyloxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1- C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R8 is optionally substituted with one or more, the same or different, R20; R9 is hydrogen, methyl, ethyl, tert-butyl, (C1-C22)alkyl, halogen, nitro, cyano, hydroxy, amino,mercapto, formyl, carboxy, carbamoyl, cycloalkyl, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino,((C1- C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl,(C6-C12)aryl,orheterocyclyl, wherein R9 is optionally substituted with one or more, the same or different, R20; R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, methyl, ethyl, isopropyl, cyclopentyl, cyclohexyl, butyl, pentyl, hexyl, neopentyl, benzyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy,carbamoyl, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl,(C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R10 isoptionally substituted with one or more, the same or different, R20; R11 is hydrogen, deuterium, (C1-C22)alkyl, methyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, 24 carboxy, carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R11 is optionally substituted with one or more, the same or different, R20; R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl, 1- naphthyl, 2-naphthyl,aromatic, heteroaromatic, 4- substituted phenyl, 4-fluorophenyl, 4-chlorophenyl, 4- bromophenyl, naphthyl, or heterocyclyl, wherein R12 is optionally substituted with one or more, the same or different, R20; R13 is hydrogen, deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl,(C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R13 is optionally substituted with one or more, the same or different, R20; R14 is hydrogen, deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C12-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R14 is optionally substituted with one or more, thesame or different, R20; R15 is hydrogen, Lipid, -(C=O)Oalkyl(C1-C22), - (C=O)alkyl(C1-C22), -(C=O)NHalkyl(C1-C22), -(C=O)N- dialkyl(C1-C22), -(C=O)Salkyl(C1-C22), hydroxy, (C1- C22)alkoxy, (C1-C22)alkyl, halogen, nitro, cyano,amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R15 is optionally substituted with one or more, the same or different, R20; R20 is deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2- C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; and wherein the lipid comprises a C6-22 alkyl, (C6- C22)alkoxy, polyethylene glycol, or (C6-C12)aryl substituted with an alkyl group,heterocyclyl is a carbocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur, and heteroaromatic is an aromatic heterocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur and at least 1 carbon atom.

Claim 5: IN201717025098 D1: US 2003/0087873 A1 CLAIM 5 Claim 5 depends on claim 1, therefore the arguments The composition of claim 3, wherein the compound is applicable for claim 1 are applicable here as well selected from: 1-(3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2- yl)4((nonanoyloxy)amino)pyrimidin- 2-one,1-(3,4- dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-4 ((((heptyloxy)carbonyl)oxy)amino)pyrimidin-2-one, and 25 isopropyl(((3,4-dihydroxy-5-(4-(hydroxyamino)-2- oxopyrimidin-1(2H)-yl)tetrahydrofuran-2- yl)methoxy)(phenoxy)phosphoryl)alaninate.

Claim 6:

IN201717025098 D1: US 2003/0087873 A1 CLAIM 6 [0124] A pharmaceutical composition comprising a In another embodiment of the invention, anti- virally or anti pharmaceutically acceptable excipient and a compound proliferatively effective nucleoside is a B-L nucleoside of the of Formula IC, general formula (III)

or salts thereof, wherein X is CH2,CHMe, CMe2, CHF, CF2, or CD2; [0114] each D is hydrogen, alkyl, acyl, monophosphate, Y is H, D, F, Cl, Br, I, CH3, CD3, CF3, alkyl, acyl, diphosphate, triphosphate, monophosphate ester, diphosphate alkenyl, alkynyl, hydroxyl, formyl or SCH3; ester, triphosphate ester, phospholipid or amino acid; R1 is hydrogen, monophosphate, diphosphate, triphosphate, [0116] each X1 and X2 is independently hydrogen, halogen (F, Cl, Br or I), NH, NHR4', NR4'R4'',NHOR4, NR4'NR4’’R4", OH, OR, SH or SR';

[0117] each Y is O, S or Se;

[0119] each R1 and R1' is independently hydrogen, lower alkyl, lower alkenyl, lower alkynyl, aryl, alkylaryl, halogen (F, Cl, Br or I), NH, NHR, NRR, NHOR, NRNHR, NRNRR", OH, OR, SH, SR5, NO, NO, CH-OH, CHOR, COH, COR, CONH, CONHR, CONRR or CN: [0120] each R2 and R2’ independently is hydrogen or halogen (F, Cl, Br or I), OH, SH, OCH3, SCH3, NH2, NH2CH3, CH2=CH2, CN, CH2-NH, CH2-OH, CO2H. [0121] each R3 and R3’ independently is hydrogen or halogen (F, Cl, Br or I), OH, SH, OCH3, SCH3, NH, NHCH3, CH3, C2H3, CH=CH, CN, CH-NH2, CH2OH, CO2H. [0122] each R4, R4', R4", R5, R5’ and R5" indepenently is hydrogen, lower alkyl, lower alkenyl, aryl, or arylalkyl Such as unsubstituted or Substituted phenyl or benzyl, [0123] such that for each nucleoside of the general formula (1) or (II), at least one of R2 and R2’ is hydrogen and at least one of R3 and R3’ is hydrogen. alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, carbanoyl, esteryl, alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1- C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, or phosphoramidyl, or wherein R1 is optionally substituted with one or more, the same or different, R20; Y1 is O or S; Y2 is OH, OR12, OAlkyl, or BH3-M+; Y3 is OH or BH3-M+; R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxymethyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1- C22)alkylthio,(C1-C22)alkylamino, ((C1- C22)alkyl)2amino,(C1-C22)alkylsulfinyl,(C1- 26

C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; R5 is hydrogen, hydroxy, or halogen; R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, benzyloxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1- C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R8 is optionally substituted with one or more, the same or different, R20; R9 is hydrogen, methyl, ethyl, tert-butyl, (C1-C22)alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, cycloalkyl, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino,((C1- C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl,(C6-C12)aryl,orheterocyclyl, wherein R9 is optionally substituted with one or more, the same or different, R20; R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, methyl, ethyl, isopropyl, cyclopentyl, cyclohexyl,butyl, pentyl, hexyl, neopentyl, benzyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy,carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl,orheterocyclyl, wherein R10 isoptionally substituted with one or more, the same or different, R20; R11 is hydrogen, deuterium, (C1-C22)alkyl, methyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1- C22)alkyl)2amino,(C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, orheterocyclyl, wherein R11 is optionally substituted with one or more, the same or different, R20; R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl, 1-naphthyl, 2-naphthyl,aromatic,heteroaromatic, 4- substituted phenyl, 4-fluorophenyl, 4-chlorophenyl, 4- bromophenyl, naphthyl, or heterocyclyl, wherein R12 is optionally substituted with one or more, the same or different, R20; R13 is hydrogen, deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R13 is optionally substituted with one or more, the same or different, R20; R14 is hydrogen, deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C12-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R14 is optionally substituted with one or more, the same or different, R20; R15 is hydrogen, Lipid, -(C=O)Oalkyl(C1-C22), - (C=O)alkyl(C1-C22), -(C=O)NHalkyl(C1-C22), - (C=O)N-dialkyl(C1-C22), -(C=O)Salkyl(C1-C22), hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl, halogen, 27 nitro, cyano,amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino,(C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R15 is optionally substituted with one or more, the same or different, R20; R20 is deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2- C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; and wherein the lipid comprises a C6-22 alkyl, (C6- C22)alkoxy, polyethylene glycol, or (C6-C12)aryl substituted with an alkyl group,heterocyclylis acarbocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur, and heteroaromatic is an aromatic heterocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur and at least 1 carbon atom.

Thus, clearly D1 anticipates the claimed subject matter.

Claim 7:

IN201717025098 D1: US 2003/0087873 A1

7. A pharmaceutical composition comprising a [0124] pharmaceutically acceptable excipient and a compound In another embodiment of the invention, anti- virally or anti of Formula ID, proliferatively effective nucleoside is a B-L nucleoside of the general formula (III)

Formula ID, or salt thereof, wherein W is CH2, NH, S or O; [0114] each D is hydrogen, alkyl, acyl, monophosphate, X is CH2,CHMe, CMe2, CHF, CF2, or CD2; diphosphate, triphosphate, monophosphate ester, diphosphate Y is N or CR”; ester, triphosphate ester, phospholipid or amino acid; Z is N or CR”; [0116] each X1 and X2 is independently hydrogen, halogen (F, each R” is independently selected from is H, D, F, Cl, Cl, Br or I), NH, NHR4', NR4'R4'',NHOR4, NR4'NR4’’R4", OH, Br, I, CH3, CD3, CF3, alkyl, acyl, alkenyl, alkynyl, OR, SH or SR'; hydroxyl, formyl or SCH3; [0117] each Y is O, S or Se; R1 is hydrogen, monophosphate, diphosphate, [0119] each R1 and R1' is independently hydrogen, lower alkyl, triphosphate, lower alkenyl, lower alkynyl, aryl, alkylaryl, halogen (F, Cl, Br or alkyl, halogen, nitro, I), NH, NHR, NRR, NHOR, NRNHR, NRNRR", OH, OR, SH, cyano, hydroxy, amino, mercapto, formyl, carboxy, SR5, NO, NO, CH-OH, CHOR, COH, COR, CONH, CONHR, carbamoyl, carbanoyl, esteryl, alkoxy, (C1- CONRR or CN: C22)alkylthio, (C1-C22)alkylamino, ((C1- [0120] each R2 and R2’ independently is hydrogen or halogen C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- (F, Cl, Br or I), OH, SH, OCH3, SCH3, NH2, NH2CH3, C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- CH2=CH2, CN, CH2-NH, CH2-OH, CO2H. C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, or [0121] each R3 and R3’ independently is hydrogen or halogen phosphoramidyl, or wherein R1 is optionally substituted (F, Cl, Br or I), OH, SH, OCH3, SCH3, NH, NHCH3, CH3, with one or more, the same or different, R20; C2H3, CH=CH, CN, CH-NH2, CH2OH, CO2H. Y1 is O or S; [0122] each R4, R4', R4", R5, R5’ and R5" indepenently is Y2 is OH, OR12, OAlkyl, or BH3-M+; hydrogen, lower alkyl, lower alkenyl, aryl, or arylalkyl Such as Y3 is OH or BH3-M+; unsubstituted or Substituted phenyl or benzyl, R2 is hydrogenor hydroxy; [0123] such that for each nucleoside of the general formula (1) or 28

R3 is hydrogen, hydroxy, alkyl, halogen, nitro, cyano, (II), at least one of R2 and R2’ is hydrogen and at least one of R3 hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, and R3’ is hydrogen. alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl,carbocyclyl, aryl, or heterocyclyl; R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxymethyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1- C22)alkylthio,(C1-C22)alkylamino, ((C1- C22)alkyl)2amino,(C1-C22)alkylsulfinyl,(C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; R5 is hydrogen, hydroxy, or halogen; R6 is hydrogen, hydroxy, alkoxy, alkyl, ethynyl, allenyl, halogen, nitro, cyano, amino, mercapto,formyl, carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl; R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, benzyloxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1- C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R8 is optionally substituted with one or more, the same or different, R20; R9 is hydrogen, methyl, ethyl, tert-butyl, (C1-C22)alkyl, halogen, nitro, cyano, hydroxy, amino,mercapto, formyl, carboxy, carbamoyl, cycloalkyl, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino,((C1- C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R9 is optionally substituted with one or more, the same or different, R20; R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, methyl, ethyl, isopropyl, cyclopentyl, cyclohexyl,butyl, pentyl, hexyl, neopentyl, benzyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy,carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl,orheterocyclyl, wherein R10 is optionally substituted with one or more, the same or different, R20; R11 is hydrogen, deuterium, (C1-C22)alkyl, methyl, halogen, nitro, cyano, hydroxy, amino, mercapto,formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1- C22)alkyl)2amino,(C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R11 is optionally substituted with one or more, the same or different, R20; R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl, 1-naphthyl, 2-naphthyl,aromatic,heteroaromatic, 4- substituted phenyl, 4-fluorophenyl, 4-chlorophenyl, 4- bromophenyl, naphthyl, or heterocyclyl, wherein R12 is optionally substituted with one or more, the same or different, R20; R13 is hydrogen, deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1- C22)alkylthio,(C1-C22)alkylamino, ((C1- C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl,(C3- 29

C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R13 is optionally substituted with one or more, the same or different, R20; R14 is hydrogen, deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C12-C22)alkynyl, halogen, nitro, cyano,hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1- C22)alkylthio,(C1-C22)alkylamino, ((C1- C22)alkyl)2amino, alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl, or heterocyclyl, wherein R14 is optionally substituted with one or more, the same or different, R20; R15 is hydrogen, -(C=O)Oalkyl(C1-C22), - (C=O)alkyl(C1-C22), -(C=O)NHalkyl(C1-C22), - (C=O)Ndialkyl(C1-C22), -(C=O)Salkyl(C1-C22), hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl, halogen, nitro, cyano, amino,mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl,wherein R15 is optionally substituted with one or more, the same or different, R20; R15’ is hydrogen, -(C=O)Oalkyl(C1-C22), - (C=O)alkyl(C1-C22), -(C=O)NHalkyl(C1-C22), - (C=O)Ndialkyl(C1-C22), -(C=O)Salkyl(C1-C22), hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl, halogen, nitro, cyano, amino,mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; R15 and R15’ can form a ring that is optionally substituted with one or more, the same or different, R20; R20 is deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2- C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; and wherein the lipid comprises a C6-22 alkyl, (C6- C22)alkoxy, polyethylene glycol, or (C6-C12)aryl substituted with an (C1-C22)alkyl group heterocyclylis acarbocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur, and heteroaromatic is an aromatic heterocyclylcomprising 1-4 heteroatoms selected from nitrogen,oxygen, or sulfur and at least 1 carbon atom.

Claim 8:

IN201717025098 D1: US 2003/0087873 A1

CLAIM 8 8. A pharmaceutical composition comprising a [0124] pharmaceutically acceptable excipient and a compound In another embodiment of the invention, anti- virally or anti of Formula IE, proliferatively effective nucleoside is a B-L nucleoside of the general formula (III)

Formula IE, [0114] each D is hydrogen, alkyl, acyl, monophosphate, or salt thereof, wherein diphosphate, triphosphate, monophosphate ester, diphosphate ester, Q is O, -O(C=O)-, -O(C=O)Lipid, -O(C=O)V-, NH, or triphosphate ester, phospholipid or amino acid; NR7; [0116] each X1 and X2 is independently hydrogen, halogen (F, Cl, V is O, NH, NR7, S, CH2, or CHR7; Br or I), NH, NHR4', NR4'R4'',NHOR4, NR4'NR4’’R4", OH, OR, W is CH2, NH, S or O; SH or SR'; X is CH2,CHMe, CMe2, CHF, CF2, or CD2; [0117] each Y is O, S or Se; Y is N or CR”; [0119] each R1 and R1' is independently hydrogen, lower alkyl, Z is N or CR”; lower alkenyl, lower alkynyl, aryl, alkylaryl, halogen (F, Cl, Br or each R” is independently selected from is H, D, F, Cl, I), NH, NHR, NRR, NHOR, NRNHR, NRNRR", OH, OR, SH, Br, I, CH3, CD3, CF3, alkyl, acyl, alkenyl, alkynyl, SR5, NO, NO, CH-OH, CHOR, COH, COR, CONH, CONHR, hydroxyl, formyl or SCH3; CONRR or CN: R2 is hydrogen, alkyl, alkenyl, alkynyl, ethynyl, [0120] each R2 and R2’ independently is hydrogen or halogen (F, fluoromethyl, difluoromethyl, trifluoromethyl, Cl, Br or I), OH, SH, OCH3, SCH3, NH2, NH2CH3, CH2=CH2, chloromethyl, hydroxymethyl, halogen, nitro, cyano, CN, CH2-NH, CH2-OH, CO2H. hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, [0121] each R3 and R3’ independently is hydrogen or halogen alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino, (F, Cl, Br or I), OH, SH, OCH3, SCH3, NH, NHCH3, CH3, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, C2H3, CH=CH, CN, CH-NH2, CH2OH, CO2H. aryl, azido, or heterocyclyl; [0122] each R4, R4', R4", R5, R5’ and R5" indepenently is R3 is hydrogen, hydroxy, alkyl, halogen, nitro, cyano, hydrogen, lower alkyl, lower alkenyl, aryl, or arylalkyl Such as hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, unsubstituted or Substituted phenyl or benzyl, alkoxy, (C1-C22)alkylthio, alkylamino, alkyl)2amino, [0123] such that for each nucleoside of the general formula (1) or alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, (II), at least one of R2 and R2’ is hydrogen and at least one of R3 aryl, or heterocyclyl; and R3’ is hydrogen. R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxymethyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1- C22)alkylthio,(C1-22)alkylamino, ((C1- C22)alkyl)2amino,(C1-C22)alkylsulfinyl,(C1- 22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; R5 is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, alkynyl, ethynyl, fluoromethyl, difluoromethyl,trifluoromethyl, hydroxymethyl, allenyl, halogen, nitro, cyano, amino, mercapto, formyl, carboxy, carbamoyl,alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl,or heterocyclyl; R6 is hydrogen, hydroxy, alkoxy, alkyl, ethynyl, allenyl, halogen, nitro, cyano, amino, mercapto,formyl, carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio, lkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl,arylsulfonyl, carbocyclyl, aryl, or heterocyclyl; each R7 is independently selected from absent, hydrogen, -(C=O)Oalkyl, -(C=O)alkyl, -(C=O)NHalkyl, -(C=O)N-dialkyl, -(C=O)Salkyl, hydroxy, alkoxy, alkyl, higher alkyl, (C6-C16)alkyl, (C6-C22)alkyl, halogen, nitro, cyano, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio,alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, whereineach R7 is optionally substituted with one or more, the same or different, R20; R15 is hydrogen, -(C=O)Oalkyl(C1-C22), - (C=O)alkyl(C1-C22), -C=O)NHalkyl(C1-C22), - (C=O)Ndialkyl(C1-C22), -(C=O)Salkyl(C1-C22), hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl, halogen, nitro, cyano, amino,mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- 31

C22)alkylsulfonyl, (C6-12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl,wherein R15 is optionally substituted with one or more, the same or different, R20; R15’ is hydrogen, -(C=O)Oalkyl(C1-C22), - (C=O)alkyl(C1-C22), -C=O)NHalkyl(C1-C22), - (C=O)Ndialkyl(C1-C22), -(C=O)Salkyl(C1-C22), hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl, halogen, nitro, cyano, amino, mercapto, formyl, carboxy, carbamoyl, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1- C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; R15 and R15’ can form a ring that is optionally substituted with one or more, the same or different,R20; If Q = -O(C=O)V- and V = NR7 then the R7s can together form a ring that is optionally substitutedwith one or more, the same or different, R20; R20 is deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy,amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; and wherein lipid comprises a C6-22 alkyl, (C6-C22)alkoxy, polyethylene glycol, or (C6-C12)aryl substituted with an (C1-C22)alkyl group, heterocyclylis carbocyclyl comprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur, and heteroaromatic is an aromatic heterocyclylcomprising 1-4 heteroatoms selected from nitrogen,oxygen, or sulfur and at least 1 carbon atom.

Claim 9:

IN201717025098 D1: US 2003/0087873 A1 CLAIM 9 A pharmaceutical composition [0124] comprising a pharmaceutically acceptable In another embodiment of the invention, anti- virally or anti proliferatively excipient and a compound of Formula II, effective nucleoside is a B-L nucleoside of the general formula (III)

[0114] each D is hydrogen, alkyl, acyl, monophosphate, diphosphate, or salt thereof, wherein triphosphate, monophosphate ester, diphosphate ester, triphosphate ester, Q is O, -O(C=O)-, -O(C=O)Lipid, -O(C=O)V-, phospholipid or amino acid; NH, or NR7; [0116] each X1 and X2 is independently hydrogen, halogen (F, Cl, Br or V is O, NH, NR7, S, CH2, or CHR7; I), NH, NHR4', NR4'R4'',NHOR4, NR4'NR4’’R4", OH, OR, SH or SR'; W is CH2, NH, S or O; [0117] each Y is O, S or Se; X is CH2 or O; [0119] each R1 and R1' is independently hydrogen, lower alkyl, lower Y is N or CR”; alkenyl, lower alkynyl, aryl, alkylaryl, halogen (F, Cl, Br or I), NH, Z is N or CR”; NHR, NRR, NHOR, NRNHR, NRNRR", OH, OR, SH, SR5, NO, NO, each R” is independently selected from is H, D, CH-OH, CHOR, COH, COR, CONH, CONHR, CONRR or CN: F, Cl, Br, I, CH3, CD3, CF3, alkyl, acyl, alkenyl, [0120] each R2 and R2’ independently is hydrogen or halogen (F, Cl, Br alkynyl, hydroxyl, formyl or SCH3; or I), OH, SH, OCH3, SCH3, NH2, NH2CH3, CH2=CH2, CN, CH2-NH, R1 is monophosphate, diphosphate, triphosphate, CH2-OH, CO2H. [0121] each R3 and R3’ independently is hydrogen or halogen (F, Cl, Br or I), OH, SH, OCH3, SCH3, NH, NHCH3, CH3, C2H3, CH=CH, CN, CH-NH2, CH2OH, CO2H. 32

[0122] each R4, R4', R4", R5, R5’ and R5" indepenently is hydrogen, lower alkyl, lower alkenyl, aryl, or arylalkyl Such as unsubstituted or Substituted phenyl or benzyl, [0123] such that for each nucleoside of the general formula (1) or (II), at least one of R2 and R2’ is hydrogen and at least one of R3 and R3’ is hydrogen.

Y1 is O or S; Y2 is OH, OR12, OAlkyl, or BH3-M+; Y3 is OH or BH3-M+; R2 is hydrogen, alkyl, alkenyl, alkynyl, ethynyl, fluoromethyl, difluoromethyl, trifluoromethyl,chloromethyl, hydroxymethyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, (C1- C22)alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl,azido, or heterocyclyl; R3 is hydrogen, hydroxy, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio, alkylamino, alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl; R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, difluoromethyl, rifluoromethyl, hydroxymethyl,halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio,(C1- C22)alkylamino, ((C1-C22)alkyl)2amino,(C1- C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl, or heterocyclyl; R5 is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, alkynyl, ethynyl, fluoromethyl, difluoromethyl,trifluoromethyl, hydroxymethyl, allenyl, halogen, nitro, cyano, amino, mercapto, formyl, carboxy, carbamoyl,alkoxy, (C1- C22)alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl,or heterocyclyl; R6 is hydrogen, hydroxy, alkoxy, alkyl, ethynyl, allenyl, halogen, nitro, cyano, amino, mercapto,formyl, carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl,arylsulfonyl, carbocyclyl, aryl, or heterocyclyl; each R7 is independently selected from absent, hydrogen, -(C=O)Oalkyl, -(C=O)alkyl, - (C=O)NHalkyl, -(C=O)N-dialkyl, -(C=O)Salkyl, hydroxy, alkoxy, alkyl, higher alkyl, (C6- C16)alkyl, (C6-C22)alkyl, halogen, nitro, cyano, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio,alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, 33 wherein each R7 is optionally substituted with one or more, the same or different, R20; R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano,hydroxy, benzyloxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- 12)aryl,orheterocyclyl, wherein R8 is optionally substituted with one or more, the same or different, R20; R9 is hydrogen, methyl, ethyl, tert-butyl, (C1- C22)alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, cycloalkyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino,((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl,(C6- C12)aryl,orheterocyclyl, wherein R9 is optionally substituted with one or more, the same or different, R20; R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, methyl, ethyl, isopropyl, cyclopentyl, cyclohexyl,butyl, pentyl, hexyl, neopentyl, benzyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy,carbamoyl, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- 22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl,orheterocyclyl, wherein R10 is optionally substituted with one or more, the same or different, R20; R11 is hydrogen, deuterium, (C1-C22)alkyl, methyl, halogen, nitro, cyano, hydroxy, amino, mercapto,formyl, carboxy, carbamoyl, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino,(C1- 22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl, or heterocyclyl, wherein R11 is optionally substituted with one or more, the same or different, R20; R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl, 1-naphthyl, 2- naphthyl,aromatic,heteroaromatic, 4-substituted phenyl, 4-fluorophenyl, 4-chlorophenyl, 4- bromophenyl, naphthyl, or heterocyclyl, wherein R12 is optionally substituted with one or more, the same or different, R20; R13 is hydrogen, deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano,hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1- C22)alkoxy, (C1-C22)alkylthio,(C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl,(C3-C6)carbocyclyl, (C6- C12)aryl, or heterocyclyl, wherein R13 is optionally substituted with one or more, the same or different, R20; R14 is hydrogen, deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C12-C22)alkynyl, halogen, nitro, cyano,hydroxy, amino, amido, mercapto, formyl, carboxy, arbamoyl, lipid, azido, (C1-C22)alkoxy, (C1-C22)alkylthio,(C1-C22)alkylamino, ((C1- C22)alkyl)2amino, alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, 34 wherein R14 is optionally substituted with one or more, the same or different, R20; If Q = -O(C=O)V- and V = NR7 then the R7s can together form a ring that is optionally substituted with one or more, the same or different, R20; R20 is deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy,amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1- 22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; and wherein lipid comprises a C6-22 alkyl, (C6- C22)alkoxy, polyethylene glycol, or (C6- C12)aryl substituted with an (C1-C22)alkyl group, heterocyclylis acarbocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur, and heteroaromatic is an aromatic heterocyclylcomprising 1-4 heteroatoms selected from nitrogen,oxygen, or sulfur and at least 1 carbon atom.

Claim 10:

IN201717025098 D1: US 2003/0087873 A1 CLAIM 10 The pharmaceutical composition of Claim 10 is dependent on claim 1. Argument for claim 1 claim 1,further comprising a propellant. applies as such here making claim 10 not novel. Propellant itself is no invention.

Claim 11:

IN201717025098 D1: US 2003/0087873 A1 CLAIM 11 The pharmaceutical composition of Claim 10 is dependent on claim 1. Argument for claim 1 claim 10, wherein the propellant is compressed air, applies as such here making claim 10 not novel. Propellant ethanol, nitrogen, carbon dioxide, nitrous oxide, hydrofluoroalkanes (HFA), 1,1,1,2,- itself is no invention. tetrafluoroethane, 1,1,1,2,3,3,3-heptafluoropropane or combinations thereof.

Claim 12:

IN201717025098 D1: US 2003/0087873 A1 CLAIM 12 The composition of claim 1, wherein [175] In a sub-embodiment of the present invention, the the compound has a structure according to anti-virally or anti-proliferatively effective E-D or B-L Formula IA nucleoside is of the formula (XX):

or salt thereof, wherein R7 is H, X is CH2, CHMe, CMe2, CHF, CF2, or CD2;

Y is independently selected from is H, D, F, Cl, Br, I, CH3, CD3, CF3, alkyl, acyl, alkenyl, [0185] or its pharmaceutically acceptable salt or prodrug 35 alkynyl, hydroxyl, formyl or SCH3; thereof, wherein: R1 is [0186 ] each D, P1, P2, P3, R1, R4, R4’ and R9 is the Same as defined monophosphate previously. ester, diphosphate [0114] each D is hydrogen, alkyl, acyl, monophosphate, diphosphate, ester triphosphate, monophosphate ester, diphosphate ester, triphosphate ester, phospholipid or amino acid; [0119] each R1 and R1' is independently hydrogen, lower alkyl, lower alkenyl, lower alkynyl, aryl, alkylaryl, halogen (F, Cl, Br or I), NH, NHR, NRR, NHOR, NRNHR, NRNRR", OH, OR, SH, SR5, NO, NO, CH-OH, CHOR, COH, COR, CONH, CONHR, CONRR or CN:

[0122] each R4, R4', R4", R5, R5’ and R5" indepenently is hydrogen, lower alkyl, lower alkenyl, aryl, or arylalkyl Such as unsubstituted or Substituted phenyl or benzyl,

[0178] each R9 is hydrogen, halogen (F, Cl, Br or I) or OP3; [0179] each P1 is hydrogen, lower alkyl, lower alkenyl, aryl, arylalkyl (such as an unsubstituted or substituted phenyl or benzyl), OH, OR, NH, NHR' or NR'R'; and [0180] each P2 and P3 is independently hydrogen, alkyl, acyl, -MS, -Ts, monophosphate, diphosphate, triphosphate, mono-phosphate ester, diphosphate ester, triphosphate ester, phospholipid or amino acid, though preferably hydrogen

[0319] In another sub-embodiment of the present invention, the anti- amino, mercapto, formyl, carboxy, carbanoyl, virally or anti-proliferatively effective ᵝ-D or ᵝ-L nucleoside is of the esteryl, alkoxy, (C1- formula (XX): C22)alkylthio, (C1-C22)alkylamino, ((C1- C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, or phosphoramidyl, wherein R1 is optionally substituted with one or more, the same or different, R20, Y1 is O or S; Y2 is OH, OR12, OAlkyl, or BH3-M+; Y3 is OH or BH3-M+; R4 is hydrogen, hydroxy, (C1-C22)alkyl, [0320] or its pharmaceutically acceptable salt or prodrug fluoromethyl, difluoromethyl, trifluoromethyl, thereof, wherein: hydroxymethyl, halogen, nitro, cyano, hydroxy, [0321] each D, P', P, P, R, R', R"and R is the Same as defined previously. amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1- [0341] In a preferred embodiment, the B-D and B-L nucleosides of C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- general formula (I-a) and (III-a) are represented by the non-limiting C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- examples provided in Table 1. C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl, or heterocyclyl, wherein R4 is optionally substituted with one or more, the same or different, R20; R5 is hydrogen, hydroxy, or halogen; R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, benzyloxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, X1 Y1 R1 R1 R2 R2’ R3 (C1-C22)alkoxy, (C1-C22)alkylthio, (C1- BS NH-OH O H H H -OH H C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- BT NH-OH O F H H -OH H C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- BU NH-OH O BR H H -OH H C12)aryl,orheterocyclyl, wherein R8 is optionally BV NH-OH O I H H -OH H substituted with one or more, the same or BW NH-OH O H H OH -H H different, R20; R9 is hydrogen, methyl, ethyl, tert-butyl, (C1- Claim 32 C22)alkyl, halogen, nitro, cyano, hydroxy, A method for the treatment or prophylaxis of host exhibiting a amino, mercapto, formyl, carboxy, carbamoyl, Flaviviridae, Orthomyxoviridae or Paramyxoviridae viral infection or cycloalkyl, (C1-C22)alkoxy, (C1-C22)alkylthio, abnormal cellular proliferation comprising administering an effective (C1-C22)alkylamino,((C1-C22)alkyl)2amino, amount of a compound of the general formula (XX): (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl,(C6- C12)aryl,orheterocyclyl, wherein R9 is optionally substituted with one or more, the same or different, R20; R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, methyl, ethyl, isopropyl, cyclopentyl, 36 cyclohexyl,butyl, pentyl, hexyl, neopentyl, benzyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy,carbamoyl, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl,orheterocyclyl, wherein R10 is optionally substituted with one or more, the same or different, R20; R11 is hydrogen, deuterium, (C1-C22)alkyl, methyl, halogen, nitro, cyano, hydroxy, amino, its β-L enantiomer or its pharmaceutically acceptable salt thereof, mercapto, formyl, carboxy, carbamoyl, (C1- wherein: C22)alkoxy, (C1-C22)alkylthio, (C1- each D, P1, P2, P3, R1, R4, R4′ and R9 is the same as defined previously. C22)alkylamino, ((C1-C22)alkyl)2amino,(C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- Claim 33. A method for the treatment or prophylaxis of host exhibiting a C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- Flaviviridae, Orthomyxoviridae or Paramyxoviridae viral infection or C12)aryl, or heterocyclyl, wherein R11 is abnormal cellular proliferation comprising administering an effective optionally substituted with one or more, the same amount of a compound of the general formula (XXI): or different, R20; R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl, 1-naphthyl, 2-naphthyl, aromatic, heteroaromatic, 4-substituted phenyl, 4- fluorophenyl, 4-chlorophenyl, 4-bromophenyl, naphthyl, or heterocyclyl, wherein R12 is optionally substituted with one or more, the same or different, R20; R13 is hydrogen, deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1- its β-L enantiomer or its pharmaceutically acceptable salt thereof, C22)alkoxy, (C1-C22)alkylthio, wherein: each D, P1, P2, P3, R1, R4 and R4′ is the same as defined (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, previously. (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, Claim 34. A method for the treatment or prophylaxis of host exhibiting a (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- Flaviviridae, Orthomyxoviridae or Paramyxoviridae viral infection or C12)aryl, or heterocyclyl, wherein R13 is abnormal cellular proliferation comprising administering an effective optionally substituted with one or more, the same amount of a compound of the general formula: or different, R20; R14 is hydrogen, deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C12-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- its β-L enantiomer or its pharmaceutically acceptable salt thereof, C12)aryl, or heterocyclyl, wherein R14 is wherein: optionally substituted with one or more, the same each D, P2 and P3 is the same as defined previously. or different, R20; Claim 37. A method for the treatment or prophylaxis of host exhibiting a Flaviviridae, Orthomyxoviridae or Paramyxoviridae viral infection or abnormal cellular proliferation comprising administering an effective amount of a compound of the general formula (XXIII):

its β-L enantiomer or its pharmaceutically acceptable salt thereof, wherein: each D, P1, P2, P3, R1, R4 and R4′ is the same as defined previously. 44. A method for the treatment or prophylaxis of a hepatitis C virus infection in a host comprising administering an effective treatment amount of a compound according to any one of claims 1-29.

Claim 45. A method for the treatment or prophylaxis of a hepatitis C virus infection in a host comprising administering an effective treatment amount of a β-D nucleoside of the formula (XIX):

its β-L enantiomer or its pharmaceutically acceptable salt thereof, wherein: each D, R1, R4 and R4′ is the same as defined previously; each R9 is hydrogen, halogen (F, Cl, Br or I) or OP3; each P1 is hydrogen, lower alkyl, lower alkenyl, aryl, arylalkyl (such as an 4 4 unsubstituted or substituted phenyl or benzyl), OH, OR , NH2, NHR or NR4R4′; and each P2 and P3 is independently hydrogen, alkyl, acyl, -Ms, -Ts, monophosphate, diphosphate, triphosphate, mono-phosphate ester, diphosphate ester, triphosphate ester, phospholipid or amino acid; optionally in a pharmaceutically acceptable carrier.

Claim 47. A method for the treatment or prophylaxis of a hepatitis C virus infection in a host comprising administering an effective treatment amount of a 1-D nucleoside of the formula (XX):

its β-L enantiomer or its pharmaceutically acceptable salt thereof, wherein: each D, P1, P2, P3, R1, R4, R4′ and R9 is the same as defined previously; optionally in a pharmaceutically acceptable carrier. Claim 48. A method for the treatment or prophylaxis of a hepatitis C virus infection in a host comprising administering an effective treatment amount of a β-D nucleoside of the formula (XXI):

its 1-L enantiomer or its pharmaceutically acceptable salt thereof, wherein: each D, P1, P2, P3, R1, R4 and R4′ is the same as defined previously; optionally in a pharmaceutically acceptable carrier. Claim 49. A method for the treatment or prophylaxis of a hepatitis C virus infection in a host comprising administering an effective treatment amount of a β-D nucleoside of the formula:

its β-L enantiomer or its pharmaceutically acceptable salt thereof, wherein: each D, P2 and P3 is the same as defined previously; optionally in a pharmaceutically acceptable carrier.

Claim 55 A method for the treatment or prophylaxis of a hepatitis C virus infection in a host comprising administering an effective treatment amount of a nucleoside of the formula:

or its pharmaceutically acceptable salt thereof; optionally in a pharmaceutically acceptable carrier.

Claim 13:

IN201717025098 D1: US 2003/0087873 A1 CLAIM 13 [0124] The composition of claim 1, wherein R4 is In another embodiment of the invention, anti- virally or anti proliferatively hydrogen, hydroxy, alkyl, halogen, or fluoro. effective nucleoside is a B-L nucleoside of the general formula (III)

[0114] each D is hydrogen, alkyl, acyl, monophosphate, diphosphate, triphosphate, monophosphate ester, diphosphate ester, triphosphate ester, phospholipid or amino acid; [0116] each X1 and X2 is independently hydrogen, halogen (F, Cl, Br or I), NH, NHR4', NR4'R4'',NHOR4, NR4'NR4’’R4", OH, OR, SH or SR'; [0117] each Y is O, S or Se; [0119] each R1 and R1' is independently hydrogen, lower alkyl, lower alkenyl, lower alkynyl, aryl, alkylaryl, halogen (F, Cl, Br or I), NH, NHR, NRR, NHOR, NRNHR, NRNRR", OH, OR, SH, SR5, NO, NO, CH-OH, CHOR, COH, COR, CONH, CONHR, CONRR or CN: [0120] each R2 and R2’ independently is hydrogen or halogen (F, Cl, Br or I), OH, SH, OCH3, SCH3, NH2, NH2CH3, CH2=CH2, CN, CH2-NH, CH2-OH, CO2H. [0121] each R3 and R3’ independently is hydrogen or halogen (F, Cl, Br or I), OH, SH, OCH3, SCH3, NH, NHCH3, CH3, C2H3, CH=CH, CN, CH-NH2, CH2OH, CO2H. 39

Also mentioned in [0260] as compound IIIa

[0341] In a preferred embodiment, the B-D and B-L nucleosides of general formula (I-a) and (III-a) are represented by the non-limiting examples provided in Table 1.

Claim 14:

IN201717025098 D1: US 2003/0087873 A1 CLAIM 14 [0124] The composition of claim 1, wherein R5 is In another embodiment of the invention, anti- virally or anti proliferatively hydrogen, hydroxy, alkoxy, alkyl, methyl, effective nucleoside is a B-L nucleoside of the general formula (III) ethynyl, or allenyl.

Also mentioned in [0260] as compound IIIa

Without prejudice and in the alternative it is submitted that all the claims of the impugned application are anticipated by the disclosure of D1.

Thus all claims of IN201717025098 lack novelty as per section 2(1)(l) of the Act. For this reason alone the opposed application should not be granted a patent as per section 25(1)(b).

B. Opponent further introduces prior art US20140235566A1 (D2) to Franck Amblard contest the novelty of the invention. US20140235566A1 to Franck Amblard of Emory University, was filed on Oct 29, 2013 having priority dates of Oct 29, 2012 & Feb 12, 2013 is a permissible prior art for IN20717025098 having priority date of Dec 26, 2014.

ii) Lack of novelty in view of US20140235566A1 (D2) to Franck Amblard

D2 discloses compounds, compositions and methods for treating or preventing cancer and viral infections, in particular, HIV, HCV, Norovirus, Saporovirus, cytomegalovirus (CMV), herpes viruses (HSV-1, HSV-2), Dengue virus, Yellow fever, or HBV in human patients or other animal hosts. The compounds are certain A-hydroxycytidine nucleosides derivatives, modified monophosphate and phosphonates prodrugs analogs, and pharmaceutically acceptable, salts, prodrugs, and other derivatives thereof. In particular, the compounds show potent antiviral activity against HIV-1, HIV-2, HCV, Norovirus, Saporovirus, cytomegalovirus (CMV), herpes viruses (HSV-1, HSV-2), Dengue virus, Yellow fever, and HBV.

Petitioner discusses the reasons of anticipation of claims wrt to disclosure of D2.

Claim 1:

IN201717025098 D2: US20140235566A1 CLAIM 1: A pharmaceutical composition [0040] In one embodiment, the compound is a compound of Formula (I): comprising a pharmaceutically acceptable excipient and a compound having Formula I

[0041] or a pharmaceutically acceptable salt or prodrug thereof, wherein:

[0042] i) X1 is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6, alkoxy, C1-C6

alkenyl, C1-C6 alkynyl, COR', or COOR'; Formula I, or salt thereof, wherein [0043] ii) X2 is hydrogen, COR', or COOR' wherein each R' is, Q is O, -O(C=O)-, -O(C=O)V-, or NR7; independently, CH2-O(CO)- X5, CH2- O(CO)O X5C1-20 alkyl, the V is O, NH, NR7, CH2, or CHR7; carbon chain derived from a fatty alcohol or C1-20 alkyl substituted with 41

W is O; a C1-C6, alkyl, alkoxy, di(C1-C6 alkyl)-amino, fluoro, C3-10 cycloalkyl, X is CH2,CHMe, CMe2, CHF, CF2, or CD2; cycloalkyl alkyl, cycloheteroalkyl, aryl, heteroaryl, substituted aryl, or Y is CR”; substituted heteroaryl; wherein the Substituents are C1-6 alkyl, or C1-6 Z is CR”; alkyl Substituted with a C1-C6 alkyl, C1—C6 alkoxy, di(C1-C6 alkyl)- each R” is independently selected from is H, D, amino, fluoro, or C3-10 cycloalkyl F, Cl, Br, I, CH3, CD3, CF3, C1-22alkyl, acyl, [0045] iii) Each X3 and X4 is independently H, C1-6, alkyl, C2-6alkenyl, C2- 22alkenyl, C2-22alkynyl, hydroxyl, formyl C-alkynyl, aryl, alkylaryl, halogen (F, Cl,Br, I), NH2, OH, SH, CN, or or SCH3; NO2. R1 is [0046] In one embodiment, Sugar is ribose or a modified ribose of the general Formula (II):

Monophosphate ester, diphosphate ester

[0047] wherein: [048] D is H, C(O)R1, C(O)OR1, diphosphate ester, or triphosphate ester; [0049] R' is as defined above: [0050] W is CL2 or CL2CL2, wherein L independently is selected from the group consisting of H, C1-6 alkyl, C2-6 alkenyl, and C2-6alkynyl, wherein C1-6 alkyl, C2-6alkenyl, and C2-6 alkynyl can each optionally contain one or more heteroatoms; alkyl, halogen, nitro, cyano, hydroxy, amino, [0051] A is O, S, CH, CHF, CF, C=CH, C=CHF, or C—CF; mercapto, formyl, carboxy, carbamoyl, [0052] R4, R5, R5’ R6, R6’, and R7 are independently selected from the carbanoyl, esteryl, alkoxy, (C1-C22)alkylthio, group consisting of H, F, Cl, Br, I, OH, SH, NH, NHOH, NHNH, N, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, C(O)CH, CN, CHOH, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, C(O)NH, C(S)NH, C(O)OR, R, OR, SR, SSR, NHR,and NR2; (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- [0173] C12)aryl, or heterocyclyl, or phosphoramidylwherein R1 is optionally substituted with one or more, the same or different, R20; Y1 is O or S; Y2 is OH, OR12, OAlkyl, or BH3 - M+; Y3 is OH or BH3 - M+; R2 is hydrogen or hydroxy; R3 is hydrogen, hydroxy, (C1-C22)alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1- C22)alkoxy, (C1-C22)alkylthio, , (C1-

C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl, or heterocyclyl; R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxymethyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino,(C1- [174] In one embodiment, at least one of R5 or R5’ is F, Cl, or Me. C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6- [0177] In another embodiment, L is methyl. C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- [0178] In another embodiment, the base is a pyrimidine, and one of R5 C12)aryl, or heterocyclyl; and R 5’ is OH, Cl, or F. R5 is hydrogen, hydroxy, or halogen; [0179] The compounds described herein can be in the form of the ᵝL- or R6 is hydrogen, hydroxy, (C1-C22)alkoxy, (C1- ᵝD-configuration, or a mixture thereof, including a racemic mixture C22)alkyl, ethynyl, allenyl, halogen, nitro, thereof. cyano, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1- 1-((2R,3R,4R,5R)-3-fluoro-4-hydroxy-5-(hydroxymethyl)-3- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- methyltetrahydrofuran-2-yl)-4-((octanoyloxy)amino)pyrimidin-2(1H)-one C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- 40 C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- 0465. C12)aryl,orheterocyclyl; To a precooled (-20°C.) solution of 39 (0.06g, 0.23mmol) in 2 mL of each R7 is independently selected from absent, anhydrous pyridine was added octanoyl chloride (44 uL, 0.26 mmol). hydrogen, -(C=O)Oalkyl(C1-C22), - After stirring the mixture at 4C. for 16 h, the reaction was quenched with (C=O)alkyl(C1- C22), -(C=O)NHalkyl(C1-C22), MeOH (2 mL) and the Solution was concentrated under reduced pressure. -(C=O)N-dialkyl(C1-C22), -(C=O)Salkyl(C1- AcOEt (10 mL) was then added and the mixture was washed with water C22), hydroxy, (C1-C22)alkoxy, (C1- C22)alkyl, (3x5 mL). The organic layer was dried overn NaSO filtered and 42 halogen, nitro, cyano, amino, mercapto, formyl, concentrated under reduced pressure. The residue was purified by silica carboxy, carbamoyl, (C1-C22)alkoxy, (C1- 127 gel column chromatogra C22)alkylthio, (C1-C22)alkylamino, ((C1- phy (CH.Cl:MeOH=95:5 to 85:15 v/v) to give 40 (0.04 g, 0.09 mmol) in C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- 37% yield. LCMS (ESI) Calcd for C.H.FNO. 401.4, observed (M+1) C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3- 402.3 C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, Example 4 wherein each R7 is optionally substituted with one or more, the same or different, R20; R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, benzyloxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl,orheterocyclyl, wherein R8 is optionally substituted with one or more, the same or different, R20; R9 is hydrogen, methyl, ethyl, tert-butyl, (C1- C22)alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, cycloalkyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl,orheterocyclyl, wherein R9 is optionally substituted with one or more, the same or different, R20; R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, methyl, ethyl, isopropyl, cyclopentyl, cyclohexyl, butyl, pentyl, hexyl, neopentyl, benzyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl,orheterocyclyl, wherein R10 is optionally substituted with one or more, the same or different, R20; R11 is hydrogen, deuterium, (C1-C22)alkyl, [0474] methyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl, or heterocyclyl, wherein R11 is optionally substituted with one or more, the same or different, R20; R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl, 1-naphthyl, 2-naphthyl,aromatic, heteroaromatic, 4-substituted phenyl, 4- fluorophenyl, 4-chlorophenyl, 4-bromophenyl, naphthyl, or heterocyclyl, wherein R12 is optionally substituted with one or more, the same or different, R20; R13 is hydrogen, deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl, or heterocyclyl, wherein R13 is optionally substituted with one or more, the same or different, R20; R14 is hydrogen, deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C12-C22)alkynyl, halogen, nitro, 43 cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6- C12)aryl, or heterocyclyl, wherein R14 is optionally substituted with one or more, the same or different, R20; R20 is deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1- C22)alkylamino, ((C1- C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; and wherein the lipid comprises a C6-22 alkyl, (C1-C22)alkoxy, polyethylene glycol, or (C6- C12)aryl substituted with an (C1-C22)alkyl group, heterocyclylis acarbocyclylcomprising 1-4 [0487] HCV and toxicity data for MP prodrug 39 and the parent heteroatoms selected from nitrogen, oxygen, or nucleoside 51 is shown below in Table 3. sulfur, and heteroaromatic is an aromatic heterocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur and at least 1 carbon atom.

[0534] The data on Vero, human PBM, and CEM (human lymphoblastoid) cells is shown below in Table 5:

[0545]

Claim 1 1. A compound of Formula (I):

or a pharmaceutically acceptable salt or prodrug thereof, wherein: X1 is H, C1-C6 alkyl, C1-C6haloalkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, COR', or COOR'; X2 is hydrogen, COR1, or COOR1 wherein each R1 is, independently, CH2-O(CO)-X5, CH2-O(CO)O-X5, C1-10 alkyl, the carbon chain derived from a fatty alcohol or C1-20 alkyl substituted with a C1-C6 alkyl, alkoxy, di(C-C alkyl)-amino, fluoro, Co cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aryl, heteroaryl, substituted aryl, or substituted heteroaryl; wherein the Substituents are C1-6 alkyl, or C1-6 alkyl substituted with a C-C alkyl, C1-C6 alkoxy, di(C-C alkyl)- amino, fluoro, or C3-10 cycloalkyl X5 is independently, C1-20 alkyl, the carbon chain derived from a fatty alcohol or C1-20 alkyl Substituted with a C1-C6 alkyl, alkoxy, C1-6 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aryl, heteroaryl, substituted aryl, or substituted heteroaryl; wherein the substituents are C1-6alkyl, or C1-6alkyl substituted with a C1-C6 alkyl, C1-C6,alkoxy, di(C-C alkyl)- amino, fluoro, or C3-10 cycloalkyl eachX3 and X4 is independently H, C1-6 alkyl, C2-6alkenyl, C2- 6alkynyl, aryl, alkylaryl, halogen, NH2, OH, SH, CN, or NO2. Claim 2 The compound of claim 1, wherein each R' is, independently, Co alkyl, the carbon chain derived from a fatty alcohol or C1-20 alkyl substituted with a C1-C20 alkyl, alkoxy, di (C1-C6 alkyl)-amino, fluoro, C1-6 cycloalkyl, cycloalkyl, alkyl, cycloheteroalkyl, aryl, heteroaryl, Substituted aryl, or substituted heteroaryl; wherein the substituents are Calkyl, or C. alkyl Substituted with a C1-C6 alkyl, C1-C6 alkoxy, di (C1- C6 alkyl)-amino, fluoro, or C3-10 cycloalkyl. 3. The compound of claim 1, wherein Sugar is ribose or a modified ribose of the general Formula (II):

wherein: [D is H, C(O)R1, C(O)OR1, diphosphate ester, or triphosphate ester; R' is as defined above: W is CL2 or CL2CL2, wherein L independently is selected from the group consisting of H, C1-6 alkyl, C2-6 alkenyl, and C2-6alkynyl, wherein C1-6 alkyl, C2-6alkenyl, and C2-6 alkynyl can each optionally contain one or more heteroatoms; A is O, S, CH, CHF, CF, C=CH, C=CHF, or C—CF; R4, R5, R5’ R6, R6’, and R7 are independently selected from the group consisting of H, F, Cl, Br, I, OH, SH, NH, NHOH, NHNH, N, C(O)CH, CN, CHOH, C(O)NH, C(S)NH, C(O)OR, R, OR, SR, SSR, NHR,and NR2; 5. The compound of claim3, wherein R7’ is independently selected from the group consisting of H, F, Cl, Br, I, N,C(O)OH, CN, CH-OH, C(O)NH, C(S)NH, C(O)OR, and R, and wherein R is independently a C-C alkyl, C2-alkenyl, C-alkynyl, C. cycloalkyl, (C-C cycloalkyl) aryl, alkylaryl, or arylalkyl, wherein the groups can be substituted with one or more substituents as defined above in claim 1.

Thus, it is clear that all elements of claim 1of IN201717025098 are covered in D2.

Therefore, claim 1 and all dependent claims lacks novelty in view of D2 also.

Claim 2:

IN201717025098 D2: US20140235566A1 CLAIM 2: The pharmaceutical composition of [0040] In one embodiment, the compound is a compound of Formula claim 1, wherein Q-R7 is OH. (I):

[0041] or a pharmaceutically acceptable salt or prodrug thereof, wherein: [0043] ii) X2 is hydrogen, COR', or COOR' Claim 1 1. A compound of Formula (I):

or a pharmaceutically acceptable salt or prodrug thereof, wherein: X2 is hydrogen, COR1, or COOR1

Thus, all referred claims of IN201717025098 are anticipated by D2. Claim 3

IN201717025098 D2: US20140235566A1 CLAIM 3: The pharmaceutical composition of 6. The compound of claim 1, wherein Sugar is ribose or modified ribose claim 1, wherein R1 is of the general Formulas (III) or (IV):

R8 is hydrogen, hydroxy, or benzyloxy, and

wherein: Y is O or S; R9 is (C6-C22)alkyl. Z is selected from the group consisting of CL2, CL2CL2, CL2OCL2, CL2SCL2, CL2O, OCL2 and CL2NHCL2, wherein L independently is selected from the group consisting of H, F, C1-6 alkyl, C2-6 alkenyl, and C2- 6alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6alkynyl can each optionally contain one or more heteroatoms; A is O, S, CH2, CHF, CF2, C═CH2, C═CHF, or C═CF2; R4′, R5, R5′, R6, R6′, and R7′ are independently selected from the group consisting of H, F, Cl, Br, I, OH, SH, NH2, NHOH, NHNH2, N3, C(O)OH, CN, CH2OH, C(O)NH2, C(S)NH2, C(O)OR, R, OR, SR, SSR, NHR, and NR2; R5′ and R6′ can come together to form a ring

7′ wherein when A is O or S, R cannot be OH, SH, NH2, NHOH, NHNH2, OR, SR, SSR, NHR, or NR2, and R is independently a C1-6 alkyl, C2-6 alkenyl, and C2-6alkynyl, C3- C6 cycloalkyl, aryl, alkylaryl, or arylalkyl, wherein the groups can be substituted with one or more substituents as defined above in claim 1, R24 is selected from the group consisting of OR15,

and fatty alcohols, R15 is selected from the group consisting of H, Li, Na, K, phenyl and pyridinyl; wherein phenyl and pyridinyl are optionally substituted with one to three substituents independently selected from the group consisting 16 16 of (CH2)0-6CO2R and (CH2)0-6CON(R )2; 17 R is selected from those groups occurring in natural L-amino acids, C1- 6 alkyl, C2-6 alkenyl, C2-6alkynyl, C3-C6 cycloalkyl, aryl, alkylaryl, or arylalkyl, wherein the groups can be substituted with one or more substituents as defined above in claim 1, 18 R is H, C1-20 alkyl, the carbon chain derived from a fatty alcohol or C1- 20 alkyl substituted with a C1-C6 alkyl, C1-C6 alkoxy, di(C1-C6 alkyl)- amino, fluoro, C3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aryl, heteroaryl, substituted aryl, or substituted heteroaryl; wherein the substituents are C1-5 alkyl, or C1-5 alkyl substituted with a C1-C6 alkyl, C1- 47

C6 alkoxy, di(C1-C6 alkyl)-amino, fluoro, C3-10 cycloalkyl, or cycloalkyl; R2 and R3 are independently selected from the group consisting of: 8 8 (a) OR where R is H, Li, Na, K, C1-20 alkyl, C3-6 cycloalkyl, C1- 6 haloalkyl, aryl, or heteroaryl, optionally substituted with one to three substituents independently selected from the group consisting of C1- 9a 6 alkyl, C2-6 alkenyl, C2-6alkynyl, C1-6 alkoxy, (CH2)0-6CO2R , halogen, 9a C1-6 haloalkyl, —N(R )2, C1-6 acylamino, —NHSO2C1-6 alkyl, — 9a 9b SO2N(R )2, —SO2C1-6 alkyl, COR , nitro, cyano

Claim 4:

IN201717025098 D2: US20140235566A1 CLAIM 4. [0040] In one embodiment, the compound is a compound of Formula (I): A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of formula IB,

Formula IB, or salts thereof, wherein [0041] or a pharmaceutically acceptable salt or prodrug thereof, wherein: V is absent, O, NH, NR15, S, CH2, or CHR15; [0042] i) X1 is H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6, alkoxy, C1-C6 X is CH2,CHMe, CMe2, CHF, CF2, or CD2; alkenyl, C1-C6 alkynyl, COR', or COOR'; Y is H, D, F, Cl, Br, I, CH3, CD3, CF3, (C1- [0043] ii) X2 is hydrogen, COR', or COOR' wherein each R' is, C6)alkyl, acyl, (C2-C6)alkenyl, (C2- independently, CH2-O(CO)- X5, CH2- O(CO)O X5C1-20 alkyl, the C6)alkynyl, hydroxyl, formyl or SCH3; carbon chain derived from a fatty alcohol or C1-20 alkyl substituted with R1 a C1-C6, alkyl, alkoxy, di(C1-C6 alkyl)-amino, fluoro, C3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aryl, heteroaryl, substituted aryl, or substituted heteroaryl; wherein the Substituents are C1-6 alkyl, or C1-6 alkyl Substituted with a C1-C6 alkyl, C1—C6 alkoxy, di(C1-C6 alkyl)- amino, fluoro, or C3-10 cycloalkyl [0045] iii) Each X3 and X4 is independently H, C1-6, alkyl, C2-6alkenyl, C-alkynyl, aryl, alkylaryl, halogen (F, Cl,Br, I), NH2, OH, SH, CN, or NO2. [0046] In one embodiment, Sugar is ribose or a modified ribose of the general Formula (II):

Monophosphate ester, diphosphate ester [0047] wherein: [048] D is H, C(O)R1, C(O)OR1, diphosphate ester, or triphosphate ester; alkyl, halogen, nitro, cyano, hydroxy, amino, [0049] R' is as defined above: mercapto, formyl, [0050] W is CL2 or CL2CL2, wherein L independently is selected from carboxy, carbamoyl, carbanoyl, esteryl, alkoxy, the group consisting of H, C1-6 alkyl, C2-6 alkenyl, and C2-6alkynyl, (C1C22)alkylthio, (C1-C22)alkylamino, ((C1- wherein C1-6 alkyl, C2-6alkenyl, and C2-6 alkynyl can each optionally C22)alkyl)2amino, contain one or more heteroatoms; (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, [0051] A is O, S, CH, CHF, CF, C=CH, C=CHF, or C—CF; (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- [0052] R4, R5, R5’ R6, R6’, and R7 are independently selected from the C12)aryl, or heterocyclyl, or group consisting of H, F, Cl, Br, I, OH, SH, NH, NHOH, NHNH, N, phosphoramidyl,wherein R1 is optionally C(O)CH, CN, CHOH, substituted with one or more, the same or C(O)NH, C(S)NH, C(O)OR, R, OR, SR, SSR, NHR,and NR2; different, R20; Y1 is O or S; Claim 1 Y2 is OH, OR12, OAlkyl, or BH3-M+; 1. A compound of Formula (I): Y3 is OH or BH3-M+; R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, 48 hydroxymethyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, , (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1- C22)alkyl)2amino, (C1-C22)alkylsulfinyl, , (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; R5 is hydrogen, hydroxy, or halogen; R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, benzyloxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-

C12)aryl,orheterocyclyl, wherein R8 is optionally or a pharmaceutically acceptable salt or prodrug thereof, substituted with one or more, the same or wherein: different, R20; X1 is H, C1-C6 alkyl, C1-C6haloalkyl, C1-C6 alkoxy, C2-C6 alkenyl, R9 is hydrogen, methyl, ethyl, tert-butyl, (C1- C2-C6 alkynyl, COR', or COOR'; C22)alkyl, halogen, nitro, cyano, hydroxy, X2 is hydrogen, COR1, or COOR1 amino,mercapto, formyl, carboxy, carbamoyl, wherein each R1 is, independently, CH2-O(CO)-X5, CH2-O(CO)O-X5, cycloalkyl, (C1-C22)alkoxy, (C1-C22)alkylthio, C1-10 alkyl, the carbon chain derived from a fatty alcohol or C1-20 alkyl (C1-C22)alkylamino,((C1-C22)alkyl)2amino, substituted with a C1-C6 alkyl, alkoxy, di(C-C alkyl)-amino, fluoro, Co (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aryl, heteroaryl, substituted (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl,(C6- aryl, or substituted heteroaryl; wherein the Substituents are C1-6 alkyl, or C12)aryl,orheterocyclyl, wherein R9 is optionally C1-6 alkyl substituted with a C-C alkyl, C1-C6 alkoxy, di(C-C alkyl)- substituted with one or more, the same or amino, fluoro, or C3-10 cycloalkyl different, R20; X5 is independently, C1-20 alkyl, the carbon chain derived from a fatty R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, alcohol or C1-20 alkyl Substituted with a C1-C6 alkyl, alkoxy, C1-6 lipid, methyl, ethyl, isopropyl, cyclopentyl, cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aryl, heteroaryl, substituted cyclohexyl, butyl, pentyl, hexyl, neopentyl, aryl, or substituted heteroaryl; wherein the substituents are C1-6alkyl, or benzyl, halogen, nitro, cyano, hydroxy, amino, C1-6alkyl substituted with a C1-C6 alkyl, C1-C6,alkoxy, di(C-C alkyl)- mercapto, formyl, carboxy,carbamoyl, (C1- amino, fluoro, or C3-10 cycloalkyl C22)alkoxy, (C1-C22)alkylthio, (C1- eachX3 and X4 is independently H, C1-6 alkyl, C2-6alkenyl, C2- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- 6alkynyl, aryl, alkylaryl, halogen, NH2, OH, SH, CN, or NO2. C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6- Claim 2 C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- The compound of claim 1, wherein each R' is, independently, Co alkyl, C12)aryl,orheterocyclyl, wherein R10 the carbon chain derived from a fatty alcohol or C1-20 alkyl substituted isoptionally substituted with one or more, the with a C1-C20 alkyl, alkoxy, di (C1-C6 alkyl)-amino, fluoro, C1-6 same or different, R20; cycloalkyl, cycloalkyl, alkyl, cycloheteroalkyl, aryl, heteroaryl, R11 is hydrogen, deuterium, (C1-C22)alkyl, Substituted aryl, or substituted heteroaryl; wherein the substituents are methyl, halogen, nitro, cyano, hydroxy, amino, Calkyl, or C. alkyl Substituted with a C1-C6 alkyl, C1-C6 alkoxy, di (C1- mercapto, formyl, carboxy, carbamoyl, (C1- C6 alkyl)-amino, fluoro, or C3-10 cycloalkyl. C22)alkoxy, (C1-C22)alkylthio, (C1- 3. The compound of claim 1, wherein Sugar is ribose or a modified ribose C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- of the general Formula (II): C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl, or heterocyclyl, wherein R11 is optionally substituted with one or more, the same or different, R20;

R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, wherein: phenyl, 1-naphthyl, 2-naphthyl,aromatic, [D is H, C(O)R1, C(O)OR1, diphosphate ester, or triphosphate ester; heteroaromatic, 4-substituted phenyl, 4- R' is as defined above: fluorophenyl, 4-chlorophenyl, 4-bromophenyl, W is CL2 or CL2CL2, wherein L independently is selected from the naphthyl, or heterocyclyl, wherein R12 is group consisting of H, C1-6 alkyl, C2-6 alkenyl, and C2-6alkynyl, optionally substituted with one or more, the same wherein C1-6 alkyl, C2-6alkenyl, and C2-6 alkynyl can each optionally or different, R20; contain one or more heteroatoms; R13 is hydrogen, deuterium, (C1-C22)alkyl, (C2- A is O, S, CH, CHF, CF, C=CH, C=CHF, or C—CF; C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, R4, R5, R5’ R6, R6’, and R7 are independently selected from the group cyano, hydroxy, amino, amido, mercapto, formyl, consisting of H, F, Cl, Br, I, OH, SH, NH, NHOH, NHNH, N, C(O)CH, carboxy, carbamoyl, lipid, azido, (C1- CN, CHOH, C22)alkoxy, (C1-C22)alkylthio, C(O)NH, C(S)NH, C(O)OR, R, OR, SR, SSR, NHR,and NR2; (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, 5. The compound of claim3, wherein R7’ is independently selected from (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, the group consisting of H, F, Cl, Br, I, N,C(O)OH, CN, CH-OH, C(O)NH, (C6-C12)arylsulfonyl,(C3-C6)carbocyclyl, (C6- C(S)NH, C(O)OR, and R, and wherein R is independently a C-C alkyl, C12)aryl, or heterocyclyl, wherein R13 is C2-alkenyl, C-alkynyl, C. cycloalkyl, (C-C cycloalkyl) aryl, alkylaryl, or optionally substituted with one or more, the arylalkyl, wherein the groups can be substituted with one or more same or different, R20; substituents as defined above in claim 1. R14 is hydrogen, deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C12-C22)alkynyl, halogen, nitro, 49 cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl, or heterocyclyl, wherein R14 is optionally substituted with one or more, thesame or different, R20; R15 is hydrogen, Lipid, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1-C22), -(C=O)NHalkyl(C1-C22), -(C=O)N-dialkyl(C1-C22), -(C=O)Salkyl(C1- C22), hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl, halogen, nitro, cyano,amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl, or heterocyclyl, wherein R15 is optionally substituted with one or more, the same or different, R20; R20 is deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1- C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; and wherein the lipid comprises a C6-22 alkyl, (C6- C22)alkoxy, polyethylene glycol, or (C6- C12)aryl substituted with an alkyl group,heterocyclylis acarbocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur, and heteroaromatic is an aromatic heterocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur and at least 1 carbon atom.

Claim 5

IN201717025098 D2: US20140235566A1 CLAIM 5 Claim 5 is dependent on on claim 3 which is dependent on claim1. The composition of claim 3, wherein the compound is selected from: Arguments applicable for Claim 1 is applicable here as well 1-(3,4-dihydroxy-5- (hydroxymethyl)tetrahydrofuran-2-yl)- 4((nonanoyloxy)amino)pyrimidin- 2-one, 1-(3,4-dihydroxy-5- (hydroxymethyl)tetrahydrofuran-2-yl)-4- ((((heptyloxy)carbonyl)oxy)amino)pyrimidin-2- one, and isopropyl(((3,4-dihydroxy-5-(4-(hydroxyamino)-

2-oxopyrimidin-1(2H)-yl)tetrahydrofuran-2-

yl)methoxy)(phenoxy)phosphoryl)alaninate.

Claim 6

IN201717025098 D2: US20140235566A1 CLAIM 6 [0040] A pharmaceutical composition comprising a In one embodiment, the compound is a compound of pharmaceutically acceptable excipient and a compound Formula (I): of Formula IC,

[0041] or a pharmaceutically acceptable salt or prodrug thereof, wherein: or salts thereof, wherein i) X1 is H, C1-C6alkyl, C1-C6haloalkyl, C1-C6 alkoxy, X is CH2,CHMe, CMe2, CHF, CF2, or CD2; C2-C6 alkenyl, C2-C6 alkynyl, COR1, or COOR1; Y is H, D, F, Cl, Br, I, CH3, CD3, CF3, alkyl, acyl, alkenyl, ii) X2 is hydrogen, COR1, or COOR1 alkynyl, hydroxyl, formyl or SCH3; wherein each R1 is, independently, CH2—O(CO)—X5; R1 is hydrogen, monophosphate, diphosphate, CH2—O(CO)O—X5C1-20 alkyl, the carbon chain derived from a fatty alcohol or C1-20 alkyl substituted triphosphate, with a C1-C6 alkyl, alkoxy, di(C1-C6 alkyl)-amino, fluoro, C3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aryl, heteroaryl, substituted aryl, or substituted heteroaryl; wherein the substituents are C1-6 alkyl, or C1-6 alkyl substituted with a C1-C6 alkyl, C1- C6 alkoxy, di(C1-C6 alkyl)-amino, fluoro, or C3-10 cycloalkyl [0044] X5 is independently, C1-20 alkyl, the carbon chain derived from a fatty alcohol or C1-20 alkyl substituted with a C1-C6 alkyl, alkoxy, C3-10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aryl, heteroaryl, substituted aryl, or substituted heteroaryl; wherein the substituents are C1- 6 alkyl, or C1-6 alkyl substituted with a C1-C6 alkyl, C1- C6 alkoxy, di(C1-C6 alkyl)-amino, fluoro, or C3-10 cycloalkyl iii) Each X3 and X4 is independently H, C1-6 alkyl, C2- 6 alkenyl, C2-6 alkynyl, aryl, alkylaryl, halogen (F, Cl,

Br, I), NH2, OH, SH, CN, or NO2.

C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, benzyloxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1- C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R8 is optionally substituted with one or more, the same or different, R20; R9 is hydrogen, methyl, ethyl, tert-butyl, (C1-C22)alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, cycloalkyl, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino,((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl,(C6- C12)aryl,orheterocyclyl, wherein R9 is optionally substituted with one or more, the same or different, R20; R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, methyl, ethyl, isopropyl, cyclopentyl, cyclohexyl,butyl, pentyl, hexyl, neopentyl, benzyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy,carbamoyl, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1- C22)alkyl)2amino, (C1-C22)alkylsulfinyl,(C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R10 isoptionally substituted with one or more, the same or different, R20; R11 is hydrogen, deuterium, (C1-C22)alkyl, methyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino,(C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, orheterocyclyl, wherein R11 is optionally substituted with one or more, the same or different, R20; R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl, 1- naphthyl, 2-naphthyl,aromatic,heteroaromatic, 4- substituted phenyl, 4-fluorophenyl, 4-chlorophenyl, 4- bromophenyl, naphthyl, or heterocyclyl, wherein R12 is optionally substituted with one or more, the same or different, R20; R13 is hydrogen, deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R13 is optionally substituted with one or more, the same or different, R20; R14 is hydrogen, deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C12-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R14 is optionally substituted with one or more, the same or different, R20; R15 is hydrogen, Lipid, -(C=O)Oalkyl(C1-C22), - (C=O)alkyl(C1-C22), -(C=O)NHalkyl(C1-C22), - (C=O)N- dialkyl(C1-C22), -(C=O)Salkyl(C1-C22), hydroxy, (C1- C22)alkoxy, (C1-C22)alkyl, halogen, nitro, cyano,amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino,(C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or 52 heterocyclyl, wherein R15 is optionally substituted with one or more, the same or different, R20; R20 is deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2- C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1- C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; and wherein the lipid comprises a C6-22 alkyl, (C6- C22)alkoxy, polyethylene glycol, or (C6-C12)aryl substituted with an alkyl group,heterocyclylis acarbocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur, and heteroaromatic is an aromatic heterocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur and at least 1 carbon atom.

Claim 7

IN201717025098 D2: US20140235566A1 CLAIM 7 1. A compound of Formula (I): 7. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of Formula ID,

or a pharmaceutically acceptable salt or prodrug thereof,

wherein: Formula ID, 1 X is H, C1-C6 alkyl, C1-C6haloalkyl, C1-C6 alkoxy, C2- or salt thereof, wherein 1 1 W is CH2, NH, S or O; C6 alkenyl, C2-C6 alkynyl, COR , or COOR ; X2 is hydrogen, COR1, or COOR1 X is CH2,CHMe, CMe2, CHF, CF2, or CD2; 1 5 wherein each R is, independently, CH2—O(CO)—X ; Y is N or CR”; 5 Z is N or CR”; CH2—O(CO)O—X , C1-20 alkyl, the carbon chain derived each R” is independently selected from is H, D, F, Cl, Br, I, from a fatty alcohol or C1-20 alkyl substituted with a C1- CH3, CD3, CF3, alkyl, acyl, alkenyl, alkynyl, hydroxyl, C6 alkyl, alkoxy, di(C1-C6 alkyl)-amino, fluoro, C3- formyl or SCH3; 10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aryl, R1 is hydrogen, monophosphate, diphosphate, heteroaryl, substituted aryl, or substituted heteroaryl; triphosphate, wherein the substituents are C1-6 alkyl, or C1-6 alkyl alkyl, halogen, nitro, substituted with a C1-C6 alkyl, C1-C6 alkoxy, di(C1-C6 alkyl)- amino, fluoro, or C3-10 cycloalkyl cyano, hydroxy, amino, mercapto, formyl, carboxy, 5 carbamoyl, carbanoyl, esteryl, alkoxy, (C1-C22)alkylthio, X is independently, C1-20 alkyl, the carbon chain derived (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- from a fatty alcohol or C1-20 alkyl substituted with a C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C6 alkyl, alkoxy, C3-10 cycloalkyl, cycloalkyl alkyl, C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or cycloheteroalkyl, aryl, heteroaryl, substituted aryl, or heterocyclyl, or phosphoramidyl, or wherein R1 is substituted heteroaryl; wherein the substituents are C1- optionally substituted with one or more, the same or 6 alkyl, or C1-6 alkyl substituted with a C1-C6 alkyl, C1- C6 alkoxy, di(C1-C6 alkyl)-amino, fluoro, or C3-10 cycloalkyl different, R20; 3 4 Y1 is O or S; each X and X is independently H, C1-6 alkyl, C2-6 alkenyl, Y2 is OH, OR12, OAlkyl, or BH3-M+; C2-6alkynyl, aryl, alkylaryl, halogen, NH2, OH, SH, CN, or NO2. Y3 is OH or BH3-M+; 1 R2 is hydrogenor hydroxy; 2. The compound of claim 1, wherein each R is, R3 is hydrogen, hydroxy, alkyl, halogen, nitro, cyano, independently, C1-20 alkyl, the carbon chain derived from hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, a fatty alcohol or C1-20 alkyl substituted with a C1-C6 alkyl, alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino, alkoxy, di(C1-C6 alkyl)-amino, fluoro, C3-10 cycloalkyl, alkylsulfinyl, alkylsulfonyl, arylsulfonyl,carbocyclyl, aryl, cycloalkyl alkyl, cycloheteroalkyl, aryl, heteroaryl, or heterocyclyl; substituted aryl, or substituted heteroaryl; wherein the R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, substituents are C1-6 alkyl, or C1-6 alkyl substituted with a difluoromethyl, trifluoromethyl, hydroxymethyl, C1-C6 alkyl, C1-C6 alkoxy, di(C1-C6 alkyl)-amino, fluoro, or C3-10 cycloalkyl. 53 halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, 3. The compound of claim 1, wherein Sugar is ribose or a carboxy, carbamoyl, (C1-C22)alkoxy, (C1- modified ribose of the general Formula (II): C22)alkylthio,(C1-C22)alkylamino, ((C1- C22)alkyl)2amino,(C1-C22)alkylsulfinyl,(C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; R5 is hydrogen, hydroxy, or halogen; R6 is hydrogen, hydroxy, alkoxy, alkyl, ethynyl, allenyl, halogen, nitro, cyano, amino, mercapto,formyl, carboxy, wherein: carbamoyl, alkoxy, (C1-C22)alkylthio, alkylamino, D is H, C(O)R1, C(O)OR1, diphosphate ester, or (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, triphosphate ester; carbocyclyl, aryl, or heterocyclyl; R1 is as defined above; R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2- W is CL2 or CL2CL2, wherein L independently is selected C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, from the group consisting of H, C1-6 alkyl, C2-6 alkenyl, and hydroxy, benzyloxy, amino, amido, mercapto, formyl, C2-6alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6alkynyl carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1- can each optionally contain one or more heteroatoms; C22)alkylthio, (C1-C22)alkylamino, ((C1- A is O, S, CH2, CHF, CF2, C═CH2, C═CHF, or C═CF2; C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- R4′, R5, R5′, R6, R6′, and R7′ are independently selected C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- from the group consisting of H, F, Cl, Br, I, OH, SH, NH2, C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R8 is NHOH, NHNH2, N3, C(O)OH, CN, CH2OH, C(O)NH2, optionally substituted with one or more, the same or C(S)NH2, C(O)OR, R, OR, SR, SSR, NHR, and NR2; different, R20; R5′ and R6′ can come together to form a ring R9 is hydrogen, methyl, ethyl, tert-butyl, (C1-C22)alkyl, halogen, nitro, cyano, hydroxy, amino,mercapto, formyl, carboxy, carbamoyl, cycloalkyl, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino,((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl,

(C6-C12)aryl,orheterocyclyl, wherein R9 is optionally wherein: substituted with one or more, the same or different, R20; 4′ 7′ when A is O or CH2, D is H or acyl, W is CH2, R and R are R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, methyl, H then, R5, R5′, R6, R6′ can not be H, halogen, OH, SH, ethyl, isopropyl, cyclopentyl, cyclohexyl,butyl, pentyl, OCH3, SCH3, NH2, NHCH3, CH3, CH═CH2, CN, CH2NH2, hexyl, neopentyl, benzyl, halogen, nitro, cyano, hydroxy, CH2OH, COOH amino, mercapto, formyl, carboxy,carbamoyl, (C1- 7′ when A is O or S, R cannot be OH, SH, NH2, NHOH, C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1- NHNH2, OR, SR, SSR, NHR, or NR2, and C22)alkyl)2amino, (C1-C22)alkylsulfinyl,(C1- R is independently a C1-C6 alkyl, C2-6 alkenyl, C2-6alkynyl, C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C3-6 cycloalkyl, (C3-C6 cycloalkyl) aryl, alkylaryl, or arylalkyl, C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R10 wherein the groups can be substituted with one or more is substituents as defined above in claim 1. optionally substituted with one or more, the same or different, R20; R11 is hydrogen, deuterium, (C1-C22)alkyl, methyl, halogen, nitro, cyano, hydroxy, amino, mercapto,formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino,(C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R11 is optionally substituted with one or more, the same or different, R20; R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl, 1- naphthyl, 2-naphthyl,aromatic,heteroaromatic, 4- substituted phenyl, 4-fluorophenyl, 4-chlorophenyl, 4- bromophenyl, naphthyl, or heterocyclyl, wherein R12 is optionally substituted with one or more, the same or different, R20; R13 is hydrogen, deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1- C22)alkylthio,(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl,(C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R13 is optionally substituted with one or more, the same or different, R20; R14 is hydrogen, deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C12-C22)alkynyl, halogen, nitro, cyano,hydroxy, amino, amido, mercapto, formyl, 54 carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1- C22)alkylthio,(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R14 is optionally substituted with one or more, the same or different, R20; R15 is hydrogen, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1- C22), -(C=O)NHalkyl(C1-C22), -(C=O)Ndialkyl(C1-C22), - (C=O)Salkyl(C1-C22), hydroxy, (C1-C22)alkoxy, (C1- C22)alkyl, halogen, nitro, cyano, amino,mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl,wherein R15 is optionally substituted with one or more, the same or different, R20; R15’ is hydrogen, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1- C22), -(C=O)NHalkyl(C1-C22), -(C=O)Ndialkyl(C1-C22), - (C=O)Salkyl(C1-C22), hydroxy, (C1-C22)alkoxy, (C1- C22)alkyl, halogen, nitro, cyano, amino,mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; R15 and R15’ can form a ring that is optionally substituted with one or more, the same or different, R20; R20 is deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2- C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; and wherein the lipid comprises a C6-22 alkyl, (C6- C22)alkoxy, polyethylene glycol, or (C6-C12)aryl substituted with an (C1-C22)alkyl group heterocyclylis acarbocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur, and heteroaromatic is an aromatic heterocyclylcomprising 1-4 heteroatoms selected from nitrogen,oxygen, or sulfur and at least 1 carbon atom.

Claim 8

IN201717025098 D2: US20140235566A1 CLAIM 8 1. A compound of Formula (I): 8. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of Formula IE,

or a pharmaceutically acceptable salt or prodrug thereof, wherein: 1 Formula IE, X is H, C1-C6 alkyl, C1-C6haloalkyl, C1-C6 alkoxy, C2- 1 1 or salt thereof, wherein C6 alkenyl, C2-C6 alkynyl, COR , or COOR ; 2 1 1 Q is O, -O(C=O)-, -O(C=O)Lipid, -O(C=O)V-, NH, or NR7; X is hydrogen, COR , or COOR 1 5 V is O, NH, NR7, S, CH2, or CHR7; wherein each R is, independently, CH2—O(CO)—X ; 5 CH2—O(CO)O—X , C1-20 alkyl, the carbon chain derived 55

W is CH2, NH, S or O; from a fatty alcohol or C1-20 alkyl substituted with a C1- X is CH2,CHMe, CMe2, CHF, CF2, or CD2; C6 alkyl, alkoxy, di(C1-C6 alkyl)-amino, fluoro, C3- Y is N or CR”; 10 cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aryl, Z is N or CR”; heteroaryl, substituted aryl, or substituted heteroaryl; each R” is independently selected from is H, D, F, Cl, Br, I, wherein the substituents are C1-6 alkyl, or C1-6 alkyl CH3, CD3, CF3, alkyl, acyl, alkenyl, alkynyl, hydroxyl, substituted with a C1-C6 alkyl, C1-C6 alkoxy, di(C1-C6 alkyl)- formyl or SCH3; amino, fluoro, or C3-10 cycloalkyl 5 R2 is hydrogen, alkyl, alkenyl, alkynyl, ethynyl, X is independently, C1-20 alkyl, the carbon chain derived fluoromethyl, difluoromethyl, trifluoromethyl, from a fatty alcohol or C1-20 alkyl substituted with a C1- chloromethyl, hydroxymethyl, halogen, nitro, cyano, C6 alkyl, alkoxy, C3-10 cycloalkyl, cycloalkyl alkyl, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, cycloheteroalkyl, aryl, heteroaryl, substituted aryl, or alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino, substituted heteroaryl; wherein the substituents are C1- alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, 6 alkyl, or C1-6 alkyl substituted with a C1-C6 alkyl, C1- azido, or heterocyclyl; C6 alkoxy, di(C1-C6 alkyl)-amino, fluoro, or C3-10 cycloalkyl 3 4 R3 is hydrogen, hydroxy, alkyl, halogen, nitro, cyano, each X and X is independently H, C1-6 alkyl, C2-6 alkenyl, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, C2-6alkynyl, aryl, alkylaryl, halogen, NH2, OH, SH, CN, or alkoxy, (C1-C22)alkylthio, alkylamino, alkyl)2amino, NO2. alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, 2. The compound of claim 1, wherein each R1 is, or heterocyclyl; independently, C1-20 alkyl, the carbon chain derived from R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, a fatty alcohol or C1-20 alkyl substituted with a C1-C6 alkyl, difluoromethyl, trifluoromethyl, hydroxymethyl, halogen, alkoxy, di(C1-C6 alkyl)-amino, fluoro, C3-10 cycloalkyl, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, cycloalkyl alkyl, cycloheteroalkyl, aryl, heteroaryl, carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio,(C1- substituted aryl, or substituted heteroaryl; wherein the 22)alkylamino, ((C1-C22)alkyl)2amino,(C1- substituents are C1-6 alkyl, or C1-6 alkyl substituted with a C22)alkylsulfinyl,(C1-22)alkylsulfonyl, (C6- C1-C6 alkyl, C1-C6 alkoxy, di(C1-C6 alkyl)-amino, fluoro, or C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or C3-10 cycloalkyl. heterocyclyl; 3. The compound of claim 1, wherein Sugar is ribose or a R5 is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, alkynyl, modified ribose of the general Formula (II): ethynyl, fluoromethyl, difluoromethyl,trifluoromethyl, hydroxymethyl, allenyl, halogen, nitro, cyano, amino, mercapto, formyl, carboxy, carbamoyl,alkoxy, (C1- C22)alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl,or heterocyclyl; R6 is hydrogen, hydroxy, alkoxy, alkyl, ethynyl, allenyl, wherein: halogen, nitro, cyano, amino, mercapto,formyl, carboxy, D is H, C(O)R1, C(O)OR1, diphosphate ester, or carbamoyl, alkoxy, (C1-C22)alkylthio, lkylamino, triphosphate ester; (alkyl)2amino, alkylsulfinyl, alkylsulfonyl,arylsulfonyl, R1 is as defined above; carbocyclyl, aryl, or heterocyclyl; W is CL2 or CL2CL2, wherein L independently is selected each R7 is independently selected from absent, from the group consisting of H, C1-6 alkyl, C2-6 alkenyl, and hydrogen, -(C=O)Oalkyl, -(C=O)alkyl, -(C=O)NHalkyl, - C2-6alkynyl, wherein C1-6 alkyl, C2-6 alkenyl, and C2-6alkynyl (C=O)N-dialkyl, -(C=O)Salkyl, hydroxy, alkoxy, alkyl, can each optionally contain one or more heteroatoms; higher alkyl, (C6-C16)alkyl, (C6-C22)alkyl, halogen, nitro, A is O, S, CH2, CHF, CF2, C═CH2, C═CHF, or C═CF2; cyano, amino, mercapto, formyl, carboxy, carbamoyl, R4′, R5, R5′, R6, R6′, and R7′ are independently selected alkoxy, (C1-C22)alkylthio,alkylamino, (alkyl)2amino, from the group consisting of H, F, Cl, Br, I, OH, SH, NH2, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, NHOH, NHNH2, N3, C(O)OH, CN, CH2OH, C(O)NH2, or heterocyclyl, whereineach R7 is optionally substituted C(S)NH2, C(O)OR, R, OR, SR, SSR, NHR, and NR2; with one or more, the same or different, R20; R5′ and R6′ can come together to form a ring R15 is hydrogen, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1- C22), -C=O)NHalkyl(C1-C22), -(C=O)Ndialkyl(C1-C22), - (C=O)Salkyl(C1-C22), hydroxy, (C1-C22)alkoxy, (C1- C22)alkyl, halogen, nitro, cyano, amino,mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-

C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- wherein: 12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or 4′ 7′ when A is O or CH2, D is H or acyl, W is CH2, R and R are heterocyclyl,wherein R15 is optionally substituted with H then, R5, R5′, R6, R6′ can not be H, halogen, OH, SH, one or more, the same or different, R20; OCH3, SCH3, NH2, NHCH3, CH3, CH═CH2, CN, CH2NH2, R15’ is hydrogen, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1- CH2OH, COOH C22), -C=O)NHalkyl(C1-C22), -(C=O)Ndialkyl(C1-C22), - 7′ when A is O or S, R cannot be OH, SH, NH2, NHOH, (C=O)Salkyl(C1-C22), hydroxy, (C1-C22)alkoxy, (C1- NHNH2, OR, SR, SSR, NHR, or NR2, and C22)alkyl, halogen, nitro, cyano, amino, R is independently a C1-C6 alkyl, C2-6 alkenyl, C2-6alkynyl, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, C3-6 cycloalkyl, (C3-C6 cycloalkyl) aryl, alkylaryl, or arylalkyl, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- wherein the groups can be substituted with one or more C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- substituents as defined above in claim 1. C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; 56

R15 and R15’ can form a ring that is optionally substituted with one or more, the same or different,R20; If Q = -O(C=O)V- and V = NR7 then the R7s can together form a ring that is optionally substitutedwith one or more, the same or different, R20; R20 is deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2- C22)alkynyl, halogen, nitro, cyano, hydroxy,amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1- 22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; and wherein lipid comprises a C6-22 alkyl, (C6-C22)alkoxy, polyethylene glycol, or (C6-C12)aryl substituted with an (C1-C22)alkyl group, heterocyclylis carbocyclyl comprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur, and heteroaromatic is an aromatic heterocyclylcomprising 1-4 heteroatoms selected from nitrogen,oxygen, or sulfur and at least 1 carbon atom.

Claim 9

IN201717025098 D2: US20140235566A1 CLAIM 9 A pharmaceutical composition Claim 1 comprising a pharmaceutically acceptable Use of an effective amount of a compound selected from Formula (I), excipient and a compound of Formula II, Formula (II), and Formula (III), or a pharmaceutically acceptable salt of the foregoing, for amelioring or treating a viral infection caused by a virus selected from a henipavirus, a morbilli virus, a respirovirus, a rubulavirus and a metapneumovirus, wherein the compound is selected from Formula (I), Formula II), and Formula (III) has one of the following structures:

or salt thereof, wherein (I) (Π) Q is O, -O(C=O)-, -O(C=O)Lipid, -O(C=O)V-, NH, or NR7; V is O, NH, NR7, S, CH2, or CHR7; W is CH2, NH, S or O; X is CH2 or O;

Y is N or CR”; (HI) Z is N or CR”; wherein: each R” is independently selected from is H, D, B1A, B1B, and B1C are independently an optionally substituted F, Cl, Br, I, CH3, CD3, CF3, alkyl, acyl, alkenyl, heterocyclic base or an optionally substituted heterocyclic base with a alkynyl, hydroxyl, formyl or SCH3; protected amino group; R1 is monophosphate, diphosphate, triphosphate, R1A is selected from the group consisting of hydrogen, an optionally substituted

N-linked amino acid and an optionally substituted N-linked amino acid ester derivative; Y1 is O or S; R1C and R2C are independently selected from the group consisting of Y2 is OH, OR12, OAlkyl, or BH3-M+; O-, OH, an Y3 is OH or BH3-M+; R2 is hydrogen, alkyl, alkenyl, alkynyl, ethynyl, fluoromethyl, difluoromethyl, trifluoromethyl,chloromethyl, hydroxymethyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, (C1- C22)alkylthio, alkylamino, (alkyl)2amino, , an optionally substituted N-linked amino acid and an optionally alkylsulfinyl, alkylsulfonyl, arylsulfonyl, substituted N-linked amino acid ester derivative; or optionally carbocyclyl, aryl,azido, or heterocyclyl; substituted C1-6 alkoxy R3 is hydrogen, hydroxy, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio, alkylamino, alkyl)2amino, alkylsulfinyl, 2B 3c alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or R and R are independently selected from the group consisting of an heterocyclyl; optionally substituted Ci_6 alkyl, an optionally substituted C2-6 alkenyl, R4 is hydrogen, hydroxy,(C1-C22)alkyl, an optionally substituted C2-6 alkynyl, an optionally substituted C3-6 fluoromethyl, difluoromethyl, rifluoromethyl, cycloalkyl, an optionally substituted -0-C1-6 alkyl, an optionally hydroxymethyl,halogen, nitro, cyano, hydroxy, substituted -O-C3-6 alkenyl, an optionally substituted -0-C3-6 alkynyl and amino, mercapto, formyl, carboxy, carbamoyl, cyano; 4C c (C1-C22)alkoxy, (C1-C22)alkylthio,(C1- R is selected from the group consisting of OH, -OC(=0)R" and an C22)alkylamino, ((C1-C22)alkyl)2amino,(C1- optionally substituted O-linked amino acid; 4A 3B 5C C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6- R , R and R are independently a halogen; 5A 4B 6C C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- R , R and R are independently hydrogen or halogen; 6A 7A 8A C12)aryl, or heterocyclyl; R , R and R are independently selected from the group consisting of R5 is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, absent, hydrogen, an optionally substituted Ci_24 alkyl, an optionally alkynyl, ethynyl, fluoromethyl, substituted C2-24 alkenyl, an optionally substituted C2-24 alkynyl, an difluoromethyl,trifluoromethyl, hydroxymethyl, optionally substituted C3-6 cycloalkyl, an optionally substituted C3-6 allenyl, halogen, nitro, cyano, amino, mercapto, cycloalkenyl, an optionally substituted aryl, an optionally substituted formyl, carboxy, carbamoyl,alkoxy, (C1- heteroaryl, an optionally substituted aryl(Ci_6 alkyl), an optionally 15A 16A C22)alkylthio, alkylamino, (alkyl)2amino, substituted *-(CR R )p-0-Ci_24 alkyl, an optionally substituted *- 17A 18A alkylsulfinyl, alkylsulfonyl, arylsulfonyl, (CR R )q-0-Ci_24 carbocyclyl, aryl,or heterocyclyl; R6 is hydrogen, hydroxy, alkoxy, alkyl, ethynyl, allenyl, halogen, nitro, cyano, amino, mercapto,formyl, carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl,arylsulfonyl, carbocyclyl, aryl, or heterocyclyl; R6A is and R7 is absent or hydrogen; or each R7 is independently selected from absent, R and R , 7/AA are taken together to form a moiety selected from the hydrogen, -(C=O)Oalkyl, -(C=O)alkyl, - group (C=O)NHalkyl, -(C=O)N-dialkyl, -(C=O)Salkyl, consisting of an optionally substituted hydroxy, alkoxy, alkyl, higher alkyl, (C6- C16)alkyl, (C6-C22)alkyl, halogen, nitro, cyano, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio,alkylamino, and an optionally substituted (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein each R7 is optionally substituted with one or more, the same or different, R20; wherein the oxygens connected to R6A and R7A, the phosphorus and the R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2- moiety form a six-membered to ten-membered ring system;. C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, R9A is independently selected from the group consisting of an optionally cyano,hydroxy, benzyloxy, amino, amido, substituted Ci_24 alkyl, an optionally substituted C2-24 alkenyl, an mercapto, formyl, carboxy, carbamoyl, azido, optionally substituted C2-24 alkynyl, an optionally substituted 30A 31A (C1-C22)alkoxy, (C1-C22)alkylthio, (C1- C3_6 cycloalkyl, an optionally substituted C3_6 cycloalkenyl, NR R , C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- an optionally substituted N-linked amino acid and an optionally C22)alkylsulfinyl, (C1-22)alkylsulfonyl, (C6- substituted N-linked amino acid ester derivative; C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- R10A and R11A are independently an optionally substituted N-linked 12)aryl,orheterocyclyl, wherein R8 is optionally amino acid or an optionally substituted N-linked amino acid ester substituted with one or more, the same or derivative; different, R20; R12A, R13A and R14A are independently absent or hydrogen; R9 is hydrogen, methyl, ethyl, tert-butyl, (C1- each R15A, each R16A, each R17A and each R18A are independently 19A 20A C22)alkyl, halogen, nitro, cyano, hydroxy, hydrogen, an optionally substituted Ci_24 alkyl or alkoxy; R , R , amino, mercapto, formyl, carboxy, carbamoyl, R22A, R23A, R5B, R6B, R8B, R9B, R9C, R10C, R12C and R13C are 58 cycloalkyl, (C1-C22)alkoxy, (C1-C22)alkylthio, independently selected from the group consisting of hydrogen, an (C1-C22)alkylamino,((C1-C22)alkyl)2amino, optionally substituted Ci_24 alkyl and an optionally substituted aryl; (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, R2iA R24A R7B^ Ri

C22)alkoxy, polyethylene glycol, or (C6- C12)aryl substituted wherein: with an (C1-C22)alkyl group, heterocyclylis R is selected from the group consisting of hydrogen, halogen and NHR' acarbocyclylcomprising 1-4 heteroatoms KC2 wherein R is selected from the group consisting of hydrogen, - selected from nitrogen, oxygen, or sulfur, and C(=0)R U and heteroaromatic is an aromatic C(=0)OR^ ; heterocyclylcomprising 1-4 heteroatoms selected R is halogen or NHR , wherein R is selected from the group consisting of from nitrogen,oxygen, or sulfur and at least 1 hydrogen, an optionally substituted Ci_6 alkyl, an optionally substituted MC2 carbon atom. C2-6 alkenyl, an optionally substituted C3_8 cycloalkyl, -C(=0)R and - C(=0)ORNC2; RDC2 is hydrogen or NHR , wherein R is selected from the group consisting of hydrogen, -C(=0)RPC2 and -C(=0)ORQC2; R is selected from the group consisting of hydrogen, halogen, an optionally substituted Ci_6 alkyl, an optionally substituted C2_6 alkenyl and an optionally substituted C2_6 alkynyl; R EC2 is selected from the group consisting of hydrogen, hydroxy, an optionally substituted Ci_6 alkyl, an optionally substituted C3-8 cycloalkyl, -C(=0)R and - C(=0)ORSC2; R is selected from the group consisting of hydrogen, halogen, an optionally substituted Ci_6alkyl, an optionally substituted C2_6 alkenyl and an optionally substituted C2_6 alkynyl; Y2C and Y3C are independently N or CRIC2, wherein RIC2 is selected from the group consisting of hydrogen, halogen, an optionally substituted Ci_6-alkyl, an optionally substituted C2_6-alkenyl and an optionally substituted C2_6-alkynyl; R is an optionally substituted Ci_6 alkyl; R is hydrogen or NHR , wherein R is independently selected from the group consisting of hydrogen, -C(=0)RUC2 and -C(=0)ORVC2; and RKC2, RLC2, RMC2, RNC2, RPC2, RQC2 RRC2, RSC2 RUC2 and RVC2 are independently selected from the group consisting of Ci_6 alkyl, C2_6 alkenyl, C2_6 alkynyl, C3-6 cycloalkyl, C3-6 cycloalkenyl, C6-1o aryl, heteroaryl, heteroalicyclyl, aryl(Ci_6 alkyl), heteroaryl(Ci_6 alkyl) and heteroalicyclyl(Ci_6 alkyl).

Claim 10

IN201717025098 D2: US20140235566A1 CLAIM 10 The pharmaceutical composition of claim Claim 10 is dependent on 1. Arguments applicable for Claim 1

1,further comprising a propellant. are applicable here as well. Including a propellant in

composition is no invention.

Claim 11

IN201717025098 D2: US20140235566A1 CLAIM 11 The pharmaceutical composition of claim 10, Claim 11 is dependent on 1o which depends on claim 1. wherein the propellant is compressed air, ethanol, Arguments applicable for Claim 1 are applicable here as well. nitrogen, carbon dioxide, nitrous oxide, Including a propellant in composition is no invention. hydrofluoroalkanes (HFA), 1,1,1,2,-tetrafluoroethane,

1,1,1,2,3,3,3-heptafluoropropane or combinations thereof.

Claim 12

IN201717025098 D2: US20140235566A1 CLAIM 12 The composition of claim 1, wherein the Claim 25. A compound of the formula: compound has a structure according to Formula IA

or salt thereof, wherein R7 is H, X is CH2, CHMe, CMe2, CHF, CF2, or CD2;

Y is independently selected from is H, D, F, Cl, Br, pharmaceutically acceptable salts thereof. I, CH3, CD3, CF3, alkyl, acyl, alkenyl, alkynyl, hydroxyl, formyl or SCH3; R1 is monophosphate ester, diphosphate ester

C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl,orheterocyclyl, wherein R8 is optionally substituted with one or more, the same or different, R20; R9 is hydrogen, methyl, ethyl, tert-butyl, (C1- C22)alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, cycloalkyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino,((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl,(C6- C12)aryl,orheterocyclyl, wherein R9 is optionally substituted with one or more, the same or different, R20; R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, methyl, ethyl, isopropyl, cyclopentyl, cyclohexyl,butyl, pentyl, hexyl, neopentyl, benzyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy,carbamoyl, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1- C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R10 is optionally substituted with one or more, the same or different, R20; R11 is hydrogen, deuterium, (C1-C22)alkyl, methyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1- C22)alkyl)2amino,(C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R11 is optionally substituted with one or more, the same or different, R20; R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl, 1-naphthyl, 2-naphthyl, aromatic, heteroaromatic, 4-substituted phenyl, 4- fluorophenyl, 4-chlorophenyl, 4-bromophenyl, naphthyl, or heterocyclyl, wherein R12 is optionally substituted with one or more, the same or different, R20; R13 is hydrogen, deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl, or heterocyclyl, wherein R13 is optionally substituted with one or more, the same or different, R20; R14 is hydrogen, deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C12-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl, or heterocyclyl, wherein R14 is optionally substituted with one or more, the same or different, R20;

Claim 13

IN201717025098 D2: US20140235566A1 CLAIM 13 3. The compound of claim 1, wherein Sugar is ribose or a The composition of claim 1, wherein R4 is hydrogen, modified ribose of the general Formula (II): hydroxy, alkyl, halogen, or fluoro.

Claim 14

IN201717025098 D2: US20140235566A1 CLAIM 14 3. The compound of claim 1, wherein Sugar is ribose or a The composition of claim 1, wherein R5 is hydrogen, modified ribose of the general Formula (II): hydroxy, alkoxy, alkyl, methyl, ethynyl, or allenyl.

Therefore, it can be concluded that all claims of IN20717025098 lack novelty over D2 and the patent to opposed application should be rejected on that ground alone as per section

25(1)(b) & (c).

C. Opponent further introduces prior art WO/2013/142525 (D3) to Wang, Guangi to

contest the novelty of the invention. WO/2013/142525 has priority dates of Dec 20, 2012 &

March 21, 2012 is a permissible prior art for IN20717025098 having priority date of Dec 26,

2014.

iii) Lack of novelty in view of WO/2013/142525 (D3) to Wang, Guangi

WO/2013/142525 (D3) discloses nucleosides, nucleotides and analogs thereof,

pharmaceutical compositions that include one or more of nucleosides, nucleotides and

analogs thereof, and methods of synthesizing the same. Also disclosed herein are methods of

ameliorating and/or treating a disease and/or a condition, including an infection from a

paramyxovirus and/or an orthomyxovirus, with a nucleoside, a nucleotide and an analog

thereof.

Lack of novelty in claims of 201717025098 is disussed in following tables

Claim 1:

IN201717025098 D3: WO2013142525A1 CLAIM 1: A pharmaceutical composition comprising a Claim 1 pharmaceutically acceptable excipient and a compound Use of an effective amount of a compound selected from Formula having Formula I (I), Formula (II), and Formula (III), or a pharmaceutically acceptable salt of the foregoing, for amelioring or treating a viral infection caused by a virus selected from a henipavirus, a morbilli virus, a respirovirus, a rubulavirus and a metapneumovirus, wherein the compound is selected from Formula (I), Formula II), and Formula (III) has one of the following structures:

(I) (Π) Formula I, or salt thereof, wherein Q is O, -O(C=O)-, -O(C=O)V-, or NR7; V is O, NH, NR7, CH2, or CHR7; W is O; X is CH2,CHMe, CMe2, CHF, CF2, or CD2; Y is CR”; Z is CR”; (HI) each R” is independently selected from is H, D, F, Cl, wherein: Br, I, CH3, CD3, CF3, C1-22alkyl, acyl, C2- B1A, B1B, and B1C are independently an optionally substituted 22alkenyl, C2-22alkynyl, hydroxyl, formyl or SCH3; heterocyclic base or an optionally substituted heterocyclic base R1 is with a protected amino group; R1A is selected from the group consisting of hydrogen, an optionally substituted

A when the dashed line ( ) of Formula (I) is a single bond, R is CH2, Monophosphate and R is O (oxygen); ester, diphosphate when the dashed line ( ) of Formula (I) is absent, RZA is selected ester from the group consisting of an optionally substituted Ci_6 alkyl, an optionally substituted C2_6 alkenyl, an optionally substituted C2_6 alkynyl, an optionally substituted C3 cycloalkyl, an optionally substituted -O-C1-6 alkyl, an optionally substituted -0-C3_6 alkenyl, 3A an optionally substituted -O-C3-6 alkynyl and cyano, and R is selected from the group consistin of OH, -OC(=0)R"A and an optionally substituted O-linked amino acid;

alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, carbanoyl, esteryl, alkoxy,

(C1-C22)alkylthio, (C1-C22)alkylamino, ((C1- N-linked amino acid and an optionally substituted N-linked amino C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- acid ester derivative; C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- R1C and R2C are independently selected from the group C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, or consisting of O-, OH, an phosphoramidylwherein R1 is optionally substituted with one or more, the same or different, R20; Y1 is O or S; Y2 is OH, OR12, OAlkyl, or BH3 - M+; Y3 is OH or BH3 - M+; R2 is hydrogen or hydroxy; , an optionally substituted N-linked amino acid and an optionally R3 is hydrogen, hydroxy, (C1-C22)alkyl, halogen, substituted N-linked amino acid ester derivative; or optionally nitro, cyano, hydroxy, amino, mercapto, formyl, substituted C1-6 alkoxy carboxy, carbamoyl, (C1-C22)alkoxy, (C1- C22)alkylthio, , (C1-C22)alkylamino, ((C1- C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-

C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; 2B R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, R and R are independently selected from the group consisting of difluoromethyl, trifluoromethyl, hydroxymethyl, an optionally substituted Ci_6 alkyl, an optionally substituted C2-6 halogen, nitro, cyano, hydroxy, amino, mercapto, alkenyl, an optionally substituted C2-6 alkynyl, an optionally formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1- substituted C3-6 cycloalkyl, an optionally substituted -0-C1-6 alkyl, C22)alkylthio, (C1-C22)alkylamino, ((C1- an optionally substituted -O-C3-6 alkenyl, an optionally substituted -0-C3-6 alkynyl and cyano; C22)alkyl)2amino,(C1-C22)alkylsulfinyl,(C1- 4C c C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3- R is selected from the group consisting of OH, -OC(=0)R" and an optionally substituted O-linked amino acid; C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; 4A 3B 5C R5 is hydrogen, hydroxy, or halogen; R , R and R are independently a halogen; R5A, R4B and R6C are independently hydrogen or halogen; R6 is hydrogen, hydroxy, (C1-C22)alkoxy, (C1- 6A 7A 8A C22)alkyl, ethynyl, allenyl, halogen, nitro, cyano, R , R and R are independently selected from the group amino, mercapto, formyl, carboxy, carbamoyl, (C1- consisting of absent, hydrogen, an optionally substituted Ci_24 C22)alkylthio, (C1-C22)alkylamino, ((C1- alkyl, an optionally substituted C2-24 alkenyl, an optionally C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- substituted C2-24 alkynyl, an optionally substituted C3-6 C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- cycloalkyl, an optionally substituted C3-6 cycloalkenyl, an C6)carbocyclyl, (C6- C12)aryl,orheterocyclyl; optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aryl(Ci_6 alkyl), an optionally substituted *- each R7 is independently selected from absent, 15A 16A (CR R )p-0-Ci_24 alkyl, an optionally substituted *- hydrogen, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1- 17A 18A C22), -(C=O)NHalkyl(C1-C22), -(C=O)N-dialkyl(C1- (CR R )q-0-Ci_24 C22), -(C=O)Salkyl(C1-C22), hydroxy, (C1- C22)alkoxy, (C1- C22)alkyl, halogen, nitro, cyano, amino, mercapto, formyl, carboxy, carbamoyl, (C1- C22)alkoxy, (C1- 127 C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-

C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- R6A is and R7 is absent or hydrogen; or C12)aryl,orheterocyclyl, wherein each R7 is optionally R and R , 7/AA are taken together to form a moiety selected from substituted with one or more, the same or different, R20; the group R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2- consisting of an optionally substituted C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, benzyloxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1- and an optionally substituted C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-

C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein wherein the oxygens connected to R6A and R7A, the phosphorus and R8 is optionally substituted with one or more, the same the moiety form a six-membered to ten-membered ring system;. or different, R20; R9A is independently selected from the group consisting of an R9 is hydrogen, methyl, ethyl, tert-butyl, (C1-C22)alkyl, optionally substituted Ci_24 alkyl, an optionally substituted C2- halogen, nitro, cyano, hydroxy, amino, mercapto, 24 alkenyl, an optionally substituted C2-24 alkynyl, an optionally formyl, carboxy, carbamoyl, cycloalkyl, (C1- substituted C3_6 cycloalkyl, an optionally substituted 30A 31A C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, C3_6 cycloalkenyl, NR R , an optionally substituted N-linked ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- amino acid and an optionally substituted N-linked amino acid ester C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- derivative; C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R10A and R11A are independently an optionally substituted N-linked R9 is optionally substituted with one or more, the same amino acid or an optionally substituted N-linked amino acid ester or different, R20; derivative; R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, R12A, R13A and R14A are independently absent or hydrogen; methyl, ethyl, isopropyl, cyclopentyl, cyclohexyl, butyl, each R15A, each R16A, each R17A and each R18A are independently 19A pentyl, hexyl, neopentyl, benzyl, halogen, nitro, cyano, hydrogen, an optionally substituted Ci_24 alkyl or alkoxy; R , hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, R20A, R22A, R23A, R5B, R6B, R8B, R9B, R9C, R10C, R12C and R13C are (C1-C22)alkoxy, (C1-C22)alkylthio, (C1- independently selected from the group consisting of hydrogen, an C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- optionally substituted Ci_24 alkyl and an optionally substituted C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- aryl; C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- R2iA R24A R7B^ Ri

(I) (Π)

(HI) wherein: B1A B1B and B1C are independently an optionally substituted heterocyclic base or an optionally substituted heterocyclic base with a protected amino group; R , ΙΑ is selected from the group consisting of hydrogen, an optionally substituted acyl, an optionally substituted O-linked amino acid,

2A when the dashed line ( ) of Formula (I) is a single bond, R is CH2, and R3A is O (oxygen); when the dashed line ( ) of Formula (I) is absent, R2A is selected from the group consisting of an optionally substituted Ci_6 alkyl, an optionally substituted C2_6 alkenyl, an optionally substituted C2_6 alkynyl, an optionally substituted C3_6 cycloalkyl, an optionally substituted -0-Ci_6 alkyl, an optionally substituted -0- C3_6 alkenyl, an optionally substituted -0-C3_6 alkynyl and cyano, and R3A is selected from the group consisting of OH, - OC(=O)R"A and an optionally substituted O-linked amino acid; R2Cselected from the group consisting of O", OH,

, an optionally substituted N-linked amino acid and an optionally substituted N-linked amino acid ester derivative; R^ and R^ are independently selected from the group consisting of O", OH, an optionally substituted Ci_, alkoxy,

, an optionally substituted N-linked amino acid and an optionally substituted N-linked amino acid ester derivative; or

RZB and RJ are independently selected from the group consisting of an optionally substituted Ci_6 alkyl, an optionally substituted C2_6 alkenyl, an optionally substituted C2_6 alkynyl, an optionally substituted C3-6 cycloalkyl, an optionally substituted -0-C1-6 alkyl, an optionally substituted -0-C3-6 alkenyl, an optionally substituted - 0-C3-6 alkynyl and cyano; R is selected from the group consisting of OH, -OC(=0)R" and an optionally substituted 0-linked amino acid; R4A, R3B and R5C are independently a halogen; R , R and R , R6C are independently hydrogen or halogen; R6A, R7A and R8A are independently selected from the group consisting of absent, hydrogen, an optionally substituted Ci_24 alkyl, an optionally substituted C2_24 alkenyl, an optionally substituted C2_24 alkynyl, an optionally substituted C3-6 cycloalkyl, an optionally substituted C3-6 cycloalkenyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aryl(Ci_6 alkyl), an optionally substituted 15A 16A *- R )p-0-Ci_24 alkyl, an optionally substituted *- 17A 18A (CR R )q-0-Ci. 24

R6A is and R is absent or hydrogen; or R6A and R7A are taken together to form a moiety selected from the group consisting of an optionally substituted

and an optionally substituted

, wherein the oxygens connected to R6A and R7A, the phosphorus and the moiety form a six-membered to ten-membered ring system;. R9A is independently selected from the group consisting of an 68 optionally substituted Ci_24 alkyl, an optionally substituted C2_24 alkenyl, an optionally substituted C2-24 alkynyl, an optionally substituted C3-6 cycloalkyl, an optionally substituted C3-6 cycloalkenyl, NR30AR31A, an optionally substituted N-linked amino acid and an optionally substituted N-linked amino acid ester derivative; R10A and R11A are independently an optionally substituted N-linked amino acid or an optionally substituted N-linked amino acid ester derivative; R12A, R13A and R14A are independently absent or hydrogen; each R15A, each R16A, each R17A and each R18A are independently hydrogen, an optionally substituted Ci_24 alkyl or alkoxy; R19A, R20A, R22A, R23A, R5B, R6B, R8B, R9B, R9C, R10C, R12C and R13C are independently selected from the group consisting of hydrogen, an optionally substituted Ci_24 alkyl and an optionally substituted aryl; i R2IA R24A r7B^ R

5A wherein R is an unsubstituted Ci_4 alkyl or phenyl optionally para- substituted with a halogen or methyl and R9A is methyl ester, ethyl ester, isopropyl ester, n-butyl ester, benzyl ester or phenyl ester of an amino acid selected from the group consisting of glycine, alanine, valine, leucine, phenylalanine, tryptophan, methionine and proline; R3A is OH; R4A is fluoro; R5A is fluoro or hydrogen; and B1A is an unsubstituted uracil; then R2A cannot be - OCH3; provided that when the dashed line ( ) of Formula (I) is absent; R1A is H; R3A is OH; R4A is fluoro; R5A is fluoro; and B1A is an unsubstituted cytosine; then R2A cannot be allenyl; provided that when the dashed line ( ) of Formula (I) is absent; R1A is H; R3A is OH; R4A is fluoro; R5A is hydrogen; and B1A is an unsubstituted thymine; then R2A cannot be Ci alkyl substituted with an N-amido; and provided that when the dashed line ( ) of Formula (I) is absent; R1A is H; R3A is OH; R4A is fluoro; R5A is fluoro; and B1A is an 69 unsubstituted cytosine; then R2A cannot be ethynyl. Claim 163. The use or method of Claim 162, wherein R1c is O" or OH. Claim 168. The use or method of Claim 162, wherein R1c i s an optionally substituted N - linked amino acid. Claim 169. The use or method of Claim 162, wherein R1c i s an optionally substituted N- linked amino acid ester derivative. Claim 170. The use or method of any one of Claims 162-169, wherein R2c i s O or OH. Claim 171. The use or method of any one of Claims 162-169, wherein R2c i s an optionally substituted C1-6 alkoxy. Claim 192. The use or method of any one of Claims 162-191, wherein R4C i s OH. Claim 193. The use or method of any one of Claims 162- 191 , wherein R4C is -OC(=0)R"C Claim 194. The use or method of Claim 193, wherein R4c is an optionally substituted C 1-8 alkyl. Claim 201 . The use or method of any one of Claims 162-200, wherein R6C is halogen. Claim 202. The use or method of any one of Claims 162-200, wherein R6C is hydrogen. Claim 203. The use or method of any one of Claims 162-202, wherein R6c is fluoro. Claim 205. The use or method of Claim 204, wherein the R7C and the R8C groups are all hydrogen. Claim 206. The use or method of Claim 204, wherein one R7C is halogen, one R8C is hydrogen and both R groups are all hydrogen. Claim 207. The use or method of Claim 204, wherein one R 7C is halogen, one R8C is hydrogen, one R is halogen and one R is hydrogen. Claim 212. The use or method of any one of Claims 162-211, wherein B is selected from the group consisting of:

from the group consisting of hydrogen, halogen, an optionally substituted Ci_6 alkyl, an optionally substituted C2_6 alkenyl and an optionally substituted C2_6 alkynyl; R EC2 is selected from the group consisting of hydrogen, hydroxy, an optionally substituted Ci_6 alkyl, an optionally substituted C3-8 cycloalkyl, -C(=0)R and - C(=0)ORSC2; R is selected from the group consisting of hydrogen, halogen, an optionally substituted Ci_6alkyl, an optionally substituted C2_6 alkenyl and an optionally substituted C2_6 alkynyl; Y2C and Y3C are independently N or CRIC2, wherein RIC2 is selected from the group consisting of hydrogen, halogen, an optionally substituted Ci_6-alkyl, an optionally substituted C2_6-alkenyl and an optionally substituted C2_6-alkynyl; R is an optionally substituted Ci_6 alkyl; R is hydrogen or NHR , wherein R is independently selected from the group consisting of hydrogen, -C(=0)RUC2 and -C(=0)ORVC2; and RKC2, RLC2, RMC2, RNC2, RPC2, RQC2 RRC2, RSC2 RUC2 and RVC2 are independently selected from the group consisting of Ci_6 alkyl, C2_6 alkenyl, C2_6 alkynyl, C3-6 cycloalkyl, C3-6 cycloalkenyl, C6-1o aryl, heteroaryl, heteroalicyclyl, aryl(Ci_6 alkyl), heteroaryl(Ci_6 alkyl) and heteroalicyclyl(Ci_6 alkyl).

Thus, it is clear that all elements of claim 1, IN201717025098 are covered in D2.

Therefore, claim 1 and all dependent claims lack novelty in view of D2 also.

Claim 2:

IN201717025098 D3: WO2013142525A1 CLAIM 2: The pharmaceutical composition of claim Claim 212. 1, wherein Q-R7 is OH. The use or method of any one of Claims 162-211, wherein B is selected from the group consisting of:

R EC2 is selected from the group consisting of hydrogen, hydroxy, an optionally substituted Ci_6 alkyl, an optionally substituted C3-8 cycloalkyl, -C(=0)R and - C(=0)ORSC2; R is selected from the group consisting of hydrogen, halogen, an optionally substituted Ci_6alkyl, an optionally substituted C2_6 alkenyl and an optionally substituted C2_6 alkynyl; Y2C and Y3C are independently N or CRIC2, wherein RIC2 is selected from the group consisting of hydrogen, halogen, an optionally substituted Ci_6-alkyl, an optionally substituted C2_6-alkenyl and an optionally substituted C2_6-alkynyl; R is an optionally substituted Ci_6 alkyl; R is hydrogen or NHR , wherein R is independently selected from the group consisting of hydrogen, -C(=0)RUC2 and -C(=0)ORVC2; and RKC2, RLC2, RMC2, RNC2, RPC2, RQC2 RRC2, RSC2 RUC2 and RVC2 are independently selected from the group consisting of Ci_6 alkyl, C2_6 alkenyl, C2_6 alkynyl, C3-6 cycloalkyl, C3-6 cycloalkenyl, C6-1o aryl, heteroaryl, heteroalicyclyl, aryl(Ci_6 alkyl), heteroaryl(Ci_6 alkyl) and heteroalicyclyl(Ci_6 alkyl). Claim 1 Use of an effective amount of a compound selected from Formula (I), Formula (II), and Formula (III), or a pharmaceutically acceptable salt of the foregoing, for amelioring or treating a viral infection caused by a virus selected from a henipavirus, a morbilli virus, a respirovirus, a rubulavirus and a metapneumovirus, wherein the compound is selected from Formula (I), Formula II), and Formula (III) has one of the following structures:

(I) (Π)

(HI) wherein: B1A, B1B, and B1C are independently an optionally substituted heterocyclic base or an optionally substituted heterocyclic base with a protected amino group; R1A is selected from the group consisting of hydrogen, an optionally substituted

N-linked amino acid and an optionally substituted N-linked amino acid ester derivative; R1C and R2C are independently selected from the group consisting of O-, OH, an

, an optionally substituted N-linked amino acid and an optionally substituted N-linked amino acid ester derivative; or optionally substituted C1-6 alkoxy

R2B and R are independently selected from the group consisting of an optionally substituted Ci_6 alkyl, an optionally substituted C2-6 alkenyl, an optionally substituted C2-6 alkynyl, an optionally substituted C3-6 cycloalkyl, an optionally substituted -0-C1-6 alkyl, an optionally substituted -O-C3-6 alkenyl, an optionally substituted -0-C3- 6 alkynyl and cyano; R4C is selected from the group consisting of OH, -OC(=0)R"c and an optionally substituted O-linked amino acid; R4A, R3B and R5C are independently a halogen; R5A, R4B and R6C are independently hydrogen or halogen; R6A, R7A and R8A are independently selected from the group consisting of absent, hydrogen, an optionally substituted Ci_24 alkyl, an optionally substituted C2-24 alkenyl, an optionally substituted C2-24 alkynyl, an optionally substituted C3-6 cycloalkyl, an optionally substituted C3-6 cycloalkenyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aryl(Ci_6 15A 16A alkyl), an optionally substituted *-(CR R )p-0-Ci_24 alkyl, an 17A 18A optionally substituted *-(CR R )q-0-Ci_24

R6A is and R7 is absent or hydrogen; or R and R , 7/AA are taken together to form a moiety selected from the group consisting of an optionally substituted

and an optionally substituted

wherein the oxygens connected to R6A and R7A, the phosphorus and the moiety form a six-membered to ten-membered ring system;. R9A is independently selected from the group consisting of an optionally substituted Ci_24 alkyl, an optionally substituted C2- 24 alkenyl, an optionally substituted C2-24 alkynyl, an optionally substituted C3_6 cycloalkyl, an optionally substituted 30A 31A C3_6 cycloalkenyl, NR R , an optionally substituted N-linked amino acid and an optionally substituted N-linked amino acid ester derivative; R10A and R11A are independently an optionally substituted N-linked amino acid or an optionally substituted N-linked amino acid ester derivative; R12A, R13A and R14A are independently absent or hydrogen; each R15A, each R16A, each R17A and each R18A are independently 19A 20A hydrogen, an optionally substituted Ci_24 alkyl or alkoxy; R , R , R22A, R23A, R5B, R6B, R8B, R9B, R9C, R10C, R12C and R13C are independently selected from the group consisting of hydrogen, an optionally substituted Ci_24 alkyl and an optionally substituted aryl; R2iA R24A R7B^ Ri

optionally substituted aryl; R1U", R^ and R are independently absent or hydrogen; R26A and R27A are independently -C≡N or an optionally substituted substituent selected from the group consisting of C2_8 organylcarbonyl, C2_8 alkoxycarbonyl and C2_8 organylaminocarbonyl; R28A is selected from the group consisting of hydrogen, an optionally substituted Ci_24-alkyl, an optionally substituted C2_24 alkenyl, an optionally substituted C2-24 alkynyl, an optionally substituted C3_6 cycloalkyl and an optionally substituted C3_6 cycloalkenyl; R30A and R31A are independently selected from the group consisting of hydrogen, an optionally substituted Ci_24-alkyl, an optionally substituted C2-24 alkenyl, an optionally substituted C2_24 alkynyl, an optionally substituted C3_6 cycloalkyl and an optionally substituted C3_6 cycloalkenyl; for Formula (III), is a single bond or a double bond; when is a single bond, each R and each R is independently hydrogen or halogen; and when is a double bond, each R is absent and each R is independently hydrogen or halogen; A "c R" and R are independently an optionally substituted Ci_24-alkyl; m and n are independently 0 or 1 ; p and q are independently selected from the group consisting of 1, 2 and 3; r is 1 or 2; Z1A, Z2A, Z3A, Z4A, Z1B, Z2B and Z1C are independently O or S; and provided that when the dashed line ( ) of Formula (I) is absent; R1A is

wherein R is an unsubstituted Ci_4 alkyl or phenyl optionally para- substituted with a halogen or methyl and R9A is methyl ester, ethyl ester, isopropyl ester, n-butyl ester, benzyl ester or phenyl ester of an amino acid selected from the group consisting of glycine, alanine, valine, leucine, phenylalanine, tryptophan, methionine and proline; R3A is OH; R4A is fluoro; R5A is fluoro or hydrogen; and B1A is an 2A unsubstituted uracil; then R cannot be -OCH3; provided that when the dashed line ( ) of Formula (I) is absent; R1A is H; R3A is OH; R4A is fluoro; R5A is fluoro; and B1A is an unsubstituted cytosine; then R2A cannot be allenyl; provided that when the dashed line ( ) of Formula (I) is absent; R1A is H; R3A is OH; R4A is fluoro; R5A is hydrogen; and B1A is an unsubstituted thymine; then R2A cannot be Ci alkyl substituted with an N-amido; and provided that when the dashed line ( ) of Formula (I) is absent; R1A is H; R3A is OH; R4A is fluoro; R5A is fluoro; and B1A is an unsubstituted cytosine; then R2A cannot be ethynyl.

Similar arguments are applicable to other independent claims 8 & 14.

Thus, all claims of IN201717025098 are anticipated by D3.

Claim 3

IN201717025098 D3: WO2013142525A1 CLAIM 3: The pharmaceutical composition of claim Claim 1 1, wherein R1 is Use of an effective amount of a compound selected from Formula (I), Formula (II), and Formula (III), or a pharmaceutically acceptable salt of the foregoing, for amelioring or treating a viral infection caused by a virus selected from a henipavirus, a morbilli virus, a respirovirus, a rubulavirus and a metapneumovirus, wherein the compound is selected from Formula (I), Formula II), and Formula (III) has one of the following structures:

R8 is hydrogen, hydroxy, or benzyloxy, and R9 is (C6-C22)alkyl.

(I) (Π)

N-linked amino acid and an optionally substituted N-linked amino acid ester derivative; R1C and R2C are independently selected from the group consisting of O-, OH, an

, an optionally substituted N-linked amino acid and an optionally substituted N-linked amino acid ester derivative; or optionally substituted C1-6 alkoxy

R2B and R are independently selected from the group consisting of an optionally substituted Ci_6 alkyl, an optionally substituted C2-6 alkenyl, an optionally substituted C2-6 alkynyl, an optionally substituted C3-6 cycloalkyl, an optionally substituted -0-C1-6 alkyl, 75 an optionally substituted -O-C3-6 alkenyl, an optionally substituted - 0-C3-6 alkynyl and cyano; R4C is selected from the group consisting of OH, -OC(=0)R"c and an optionally substituted O-linked amino acid; R4A, R3B and R5C are independently a halogen; R5A, R4B and R6C are independently hydrogen or halogen; R6A, R7A and R8A are independently selected from the group consisting of absent, hydrogen, an optionally substituted Ci_24 alkyl, an optionally substituted C2-24 alkenyl, an optionally substituted C2- 24 alkynyl, an optionally substituted C3-6 cycloalkyl, an optionally substituted C3-6 cycloalkenyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aryl(Ci_6 15A 16A alkyl), an optionally substituted *-(CR R )p-0-Ci_24 alkyl, an 17A 18A optionally substituted *-(CR R )q-0-Ci_24

R6A is and R7 is absent or hydrogen; or R and R , 7/AA are taken together to form a moiety selected from the group consisting of an optionally substituted

and an optionally substituted

when is a single bond, each R and each R is independently hydrogen or halogen; and when is a double bond, each R is absent and each R is independently hydrogen or halogen; A "c R" and R are independently an optionally substituted Ci_24-alkyl; m and n are independently 0 or 1 ; p and q are independently selected from the group consisting of 1, 2 and 3; r is 1 or 2; Z1A, Z2A, Z3A, Z4A, Z1B, Z2B and Z1C are independently O or S; and provided that when the dashed line ( ) of Formula (I) is absent; R1A is

Claim 4:

IN201717025098 D3: WO2013142525A1 CLAIM 4. A pharmaceutical composition comprising a Claim 1 pharmaceutically acceptable excipient and a compound of Use of an effective amount of a compound selected from formula IB, Formula (I), Formula (II), and Formula (III), or a pharmaceutically acceptable salt of the foregoing, for amelioring or treating a viral infection caused by a virus selected from a henipavirus, a morbilli virus, a respirovirus, a rubulavirus and a metapneumovirus, wherein the compound is selected from Formula (I), Formula II), and Formula (III) has one of the following structures:

Formula IB, or salts thereof, wherein V is absent, O, NH, NR15, S, CH2, or CHR15; X is CH2,CHMe, CMe2, CHF, CF2, or CD2; Y is H, D, F, Cl, Br, I, CH3, CD3, CF3, (C1-C6)alkyl, (I) (Π) acyl, (C2-C6)alkenyl, (C2-C6)alkynyl, hydroxyl, formyl or SCH3; R1

(HI) wherein: Monophosphate ester, B1A, B1B, and B1C are independently an optionally diphosphate ester substituted heterocyclic base or an optionally substituted heterocyclic base with a protected amino group; R1A is selected from the group consisting of hydrogen, an 77

optionally substituted

when the dashed line ( ) of Formula (I) is a single bond, R A is CH2, and R is O (oxygen); when the dashed line ( ) of Formula (I) is absent, RZA is selected from the group consisting of an optionally substituted alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, Ci_6 alkyl, an optionally substituted C2_6 alkenyl, an optionally formyl, substituted C2_6 alkynyl, an optionally substituted C3 carboxy, carbamoyl, carbanoyl, esteryl, alkoxy, cycloalkyl, an optionally substituted -O-C1-6 alkyl, an optionally substituted -0-C3_6 alkenyl, an optionally substituted (C1C22)alkylthio, (C1-C22)alkylamino, ((C1- 3A -O-C3-6 alkynyl and cyano, and R is selected from the group C22)alkyl)2amino, A (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- consistin of OH, -OC(=0)R" and an optionally substituted O- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or linked amino acid; heterocyclyl, or phosphoramidyl,wherein R1 is optionally substituted with one or more, the same or different, R20; Y1 is O or S; Y2 is OH, OR12, OAlkyl, or BH3-M+;

Y3 is OH or BH3-M+; N-linked amino acid and an optionally substituted N-linked R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, amino acid ester derivative; difluoromethyl, trifluoromethyl, hydroxymethyl, halogen, R1C and R2C are independently selected from the group nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, consisting of O-, OH, an carbamoyl, , (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1- C22)alkyl)2amino, (C1-C22)alkylsulfinyl, , (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; R5 is hydrogen, hydroxy, or halogen; , an optionally substituted N-linked amino acid and an R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2- optionally substituted N-linked amino acid ester derivative; C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, or optionally substituted C1-6 alkoxy hydroxy, benzyloxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1- C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-

C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- 2B C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R8 is R and R are independently selected from the group consisting optionally substituted with one or more, the same or of an optionally substituted Ci_6 alkyl, an optionally different, R20; substituted C2-6 alkenyl, an optionally substituted C2-6 alkynyl, R9 is hydrogen, methyl, ethyl, tert-butyl, (C1-C22)alkyl, an optionally substituted C3-6 cycloalkyl, an optionally halogen, nitro, cyano, hydroxy, amino,mercapto, formyl, substituted -0-C1-6 alkyl, an optionally substituted -O-C3-6 alkenyl, an optionally substituted -0-C3-6 alkynyl and cyano; carboxy, carbamoyl, cycloalkyl, (C1-C22)alkoxy, (C1- 4C C22)alkylthio, (C1-C22)alkylamino,((C1- R is selected from the group consisting of OH, - OC(=0)R"c and an optionally substituted O-linked amino acid; C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- 4A 3B 5C C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- R , R and R are independently a halogen; R5A, R4B and R6C are independently hydrogen or halogen; C6)carbocyclyl,(C6-C12)aryl,orheterocyclyl, wherein R9 is 6A 7A 8A optionally substituted with one or more, the same or R , R and R are independently selected from the group different, R20; consisting of absent, hydrogen, an optionally substituted Ci_24 R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, methyl, alkyl, an optionally substituted C2-24 alkenyl, an optionally ethyl, isopropyl, cyclopentyl, cyclohexyl, butyl, pentyl, substituted C2-24 alkynyl, an optionally substituted C3-6 hexyl, neopentyl, benzyl, halogen, nitro, cyano, hydroxy, cycloalkyl, an optionally substituted C3-6 cycloalkenyl, an amino, mercapto, formyl, carboxy,carbamoyl, (C1- optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aryl(Ci_6 alkyl), an optionally C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1- 15A 16A substituted *-(CR R )p-0-Ci_24 alkyl, an optionally C22)alkyl)2amino, (C1-C22)alkylsulfinyl,(C1- 17A 18A C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- substituted *-(CR R )q-0-Ci_24 C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R10 isoptionally substituted with one or more, the same or different, R20; R11 is hydrogen, deuterium, (C1-C22)alkyl, methyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio,

(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- R6A is and R7 is absent or hydrogen; or C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- R and R , 7/AA are taken together to form a moiety selected C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or from the group heterocyclyl, wherein R11 is optionally substituted with one consisting of an optionally substituted or more, the same or different, R20; R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl, 1- naphthyl, 2-naphthyl,aromatic, heteroaromatic, 4-substituted phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, and an optionally substituted 78 naphthyl, or heterocyclyl, wherein R12 is optionally substituted with one or more, the same or different, R20; R13 is hydrogen, deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, wherein the oxygens connected to R6A and R7A, the phosphorus hydroxy, amino, amido, mercapto, formyl, carboxy, and the moiety form a six-membered to ten-membered ring carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1- system;. C22)alkylthio, R9A is independently selected from the group consisting of an (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- optionally substituted Ci_24 alkyl, an optionally substituted C2- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- 24 alkenyl, an optionally substituted C2-24 alkynyl, an C12)arylsulfonyl,(C3-C6)carbocyclyl, (C6-C12)aryl, or optionally substituted C3_6 cycloalkyl, an optionally substituted 30A 31A heterocyclyl, wherein R13 is optionally substituted with one C3_6 cycloalkenyl, NR R , an optionally substituted N- or more, the linked amino acid and an optionally substituted N-linked amino same or different, R20; acid ester derivative; R14 is hydrogen, deuterium, (C1-C22)alkyl, (C2- R10A and R11A are independently an optionally substituted N- C22)alkenyl, (C12-C22)alkynyl, halogen, nitro, cyano, linked amino acid or an optionally substituted N-linked amino hydroxy, amino, amido, mercapto, formyl, carboxy, acid ester derivative; carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1- R12A, R13A and R14A are independently absent or hydrogen; C22)alkylthio, each R15A, each R16A, each R17A and each R18A are (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, alkylsulfinyl, independently hydrogen, an optionally substituted Ci_24 alkyl (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- or alkoxy; R19A, R20A, R22A, R23A, R5B, R6B, R8B, R9B, R9C, R10C, C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R14 R12C and R13C are independently selected from the group is optionally substituted with one or more, thesame or consisting of hydrogen, an optionally substituted Ci_24 alkyl different, R20; and an optionally substituted aryl; R15 is hydrogen, Lipid, -(C=O)Oalkyl(C1-C22), - R2iA R24A R7B^ Ri

wherein R is an unsubstituted Ci_4 alkyl or phenyl optionally para- substituted with a halogen or methyl and R9A is methyl

ester, ethyl ester, isopropyl ester, n-butyl ester, benzyl ester or phenyl ester of an amino acid selected from the group consisting of glycine, alanine, valine, leucine, phenylalanine, tryptophan, methionine and proline; R3A is OH; R4A is fluoro; R5A is fluoro or hydrogen; and B1A is an unsubstituted uracil; 2A then R cannot be -OCH3; provided that when the dashed line ( ) of Formula (I) is absent; R1A is H; R3A is OH; R4A is fluoro; R5A is fluoro; and B1A is an unsubstituted cytosine; then R2A cannot be allenyl; provided that when the dashed line ( ) of Formula (I) is absent; R1A is H; R3A is OH; R4A is fluoro; R5A is hydrogen; and B1A is an unsubstituted thymine; then R2A cannot be Ci alkyl substituted with an N-amido; and provided that when the dashed line ( ) of Formula (I) is absent; R1A is H; R3A is OH; R4A is fluoro; R5A is fluoro; and B1A is an unsubstituted cytosine; then R2A cannot be ethynyl.

Claim 212. The use or method of any one of Claims 162-211, wherein B is selected from the group consisting of:

wherein: R is selected from the group consisting of hydrogen, halogen and NHR' KC2 wherein R is selected from the group consisting of hydrogen, -C(=0)R U and C(=0)OR^ ; R is halogen or NHR , wherein R is selected from the group consisting of hydrogen, an optionally substituted Ci_6 alkyl, an optionally substituted C2-6 alkenyl, an optionally substituted MC2 NC2 C3_8 cycloalkyl, -C(=0)R and -C(=0)OR ; RDC2 is hydrogen or NHR , wherein R is selected from the group consisting of hydrogen, -C(=0)RPC2 and -C(=0)ORQC2; R is selected from the group consisting of hydrogen, halogen, an optionally substituted Ci_6 alkyl, an optionally substituted C2_6 alkenyl and an optionally substituted C2_6 alkynyl; R EC2 is selected from the group consisting of hydrogen, hydroxy, an optionally substituted Ci_6 alkyl, an optionally substituted C3-8 cycloalkyl, -C(=0)R and - C(=0)ORSC2; R is selected from the group consisting of hydrogen, halogen, an optionally substituted Ci_6alkyl, an optionally substituted C2_6 alkenyl and an optionally substituted C2_6 alkynyl; Y2C and Y3C are independently N or CRIC2, wherein RIC2 is selected from the group consisting of hydrogen, halogen, an optionally substituted Ci_6-alkyl, an optionally substituted C2_6-alkenyl and an optionally substituted C2_6-alkynyl; R is an optionally substituted Ci_6 alkyl; R is hydrogen or NHR , wherein R is independently selected from the group consisting of hydrogen, -C(=0)RUC2 and - C(=0)ORVC2; and RKC2, RLC2, RMC2, RNC2, RPC2, RQC2 RRC2, RSC2 RUC2 and RVC2 are independently selected from the group consisting of Ci_6 alkyl, C2_6 alkenyl, C2_6 alkynyl, C3-6 cycloalkyl, C3-6 cycloalkenyl, C6-1o aryl, heteroaryl, heteroalicyclyl, aryl(Ci_6 alkyl), heteroaryl(Ci_6 alkyl) and heteroalicyclyl(Ci_6 alkyl).

Claim 5

IN201717025098 D3: WO2013142525A1 CLAIM 5 Claim 5 is dependent on claim 3 which is dependent on The composition of claim 3, wherein the compound is selected from: claim 1. Hence arguments of claim 1 apply here as such. 1-(3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)- 4((nonanoyloxy)amino)pyrimidin- 2-one, 1-(3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)- 4-((((heptyloxy)carbonyl)oxy)amino)pyrimidin-2-one, and isopropyl(((3,4-dihydroxy-5-(4-(hydroxyamino)-2- oxopyrimidin-1(2H)-yl)tetrahydrofuran-2- yl)methoxy)(phenoxy)phosphoryl)alaninate.

Claim 6

IN201717025098 D3: WO2013142525A1 CLAIM 6 Claim 1 A pharmaceutical composition comprising a Use of an effective amount of a compound selected from pharmaceutically acceptable excipient and a compound of Formula (I), Formula (II), and Formula (III), or a Formula IC, pharmaceutically acceptable salt of the foregoing, for amelioring or treating a viral infection caused by a virus selected from a henipavirus, a morbilli virus, a respirovirus, a rubulavirus and a metapneumovirus, wherein the compound is selected from Formula (I), Formula II), and Formula (III) has one of the following structures:

or salts thereof, wherein

X is CH2,CHMe, CMe2, CHF, CF2, or CD2; (I) (Π) Y is H, D, F, Cl, Br, I, CH3, CD3, CF3, alkyl, acyl, alkenyl, alkynyl, hydroxyl, formyl or SCH3; R1 is hydrogen, monophosphate, diphosphate, triphosphate,

when the dashed line ( ) of Formula (I) is a single bond, R A is CH2, and R is O (oxygen); when the dashed line ( ) of Formula (I) is absent, RZA is selected from the group consisting of an optionally substituted Ci_6 alkyl, an optionally substituted C2_6 alkenyl, an optionally substituted C2_6 alkynyl, an optionally substituted C3 cycloalkyl, an optionally substituted -O-C1- 6 alkyl, an optionally substituted -0-C3_6 alkenyl, an 3A alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, optionally substituted -O-C3-6 alkynyl and cyano, and R is A formyl, selected from the group consistin of OH, -OC(=0)R" and an carboxy, carbamoyl, carbanoyl, esteryl, alkoxy, (C1- optionally substituted O-linked amino acid; C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, 81

(C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, or phosphoramidyl, or wherein R1 is optionally substituted with one or more, the same or different, R20; N-linked amino acid and an optionally substituted N-linked Y1 is O or S; amino acid ester derivative; Y2 is OH, OR12, OAlkyl, or BH3-M+; R1C and R2C are independently selected from the group Y3 is OH or BH3-M+; consisting of O-, OH, an R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxymethyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio,(C1- C22)alkylamino, ((C1-C22)alkyl)2amino,(C1-

C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6- , an optionally substituted N-linked amino acid and an C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or optionally substituted N-linked amino acid ester derivative; heterocyclyl; or optionally substituted C1-6 alkoxy R5 is hydrogen, hydroxy, or halogen; R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, benzyloxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1- R2B and R are independently selected from the group C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- consisting of an optionally substituted Ci_6 alkyl, an C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- optionally substituted C2-6 alkenyl, an optionally substituted C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C2-6 alkynyl, an optionally substituted C3-6 cycloalkyl, an C12)aryl,orheterocyclyl, wherein R8 is optionally optionally substituted -0-C1-6 alkyl, an optionally substituted substituted with one or more, the same or different, R20; -O-C3-6 alkenyl, an optionally substituted -0-C3-6 alkynyl and R9 is hydrogen, methyl, ethyl, tert-butyl, (C1-C22)alkyl, cyano; halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, R4C is selected from the group consisting of OH, - carboxy, carbamoyl, cycloalkyl, (C1-C22)alkoxy, (C1- OC(=0)R"c and an optionally substituted O-linked amino acid; C22)alkylthio, (C1-C22)alkylamino,((C1-C22)alkyl)2amino, R4A, R3B and R5C are independently a halogen; (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- R5A, R4B and R6C are independently hydrogen or halogen; C12)arylsulfonyl, (C3-C6)carbocyclyl,(C6- R6A, R7A and R8A are independently selected from the group C12)aryl,orheterocyclyl, wherein R9 is optionally consisting of absent, hydrogen, an optionally substituted substituted with one or more, the same or different, R20; Ci_24 alkyl, an optionally substituted C2-24 alkenyl, an R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, methyl, optionally substituted C2-24 alkynyl, an optionally ethyl, isopropyl, cyclopentyl, cyclohexyl,butyl, pentyl, substituted C3-6 cycloalkyl, an optionally substituted C3-6 hexyl, neopentyl, benzyl, halogen, nitro, cyano, hydroxy, cycloalkenyl, an optionally substituted aryl, an optionally amino, mercapto, formyl, carboxy,carbamoyl, (C1- substituted heteroaryl, an optionally substituted aryl(Ci_6 15A 16A C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1- alkyl), an optionally substituted *-(CR R )p-0-Ci_24 alkyl, 17A 18A C22)alkyl)2amino, (C1-C22)alkylsulfinyl,(C1- an optionally substituted *-(CR R )q-0-Ci_24 C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R10 isoptionally substituted with one or more, the same or different, R20; R11 is hydrogen, deuterium, (C1-C22)alkyl, methyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio,

C22)alkenyl, (C12-C22)alkynyl, halogen, nitro, cyano, R10A and R11A are independently an optionally substituted N- hydroxy, amino, amido, mercapto, formyl, carboxy, linked amino acid or an optionally substituted N-linked carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1-C22)alkylthio, amino acid ester derivative; (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, alkylsulfinyl, R12A, R13A and R14A are independently absent or hydrogen; (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- each R15A, each R16A, each R17A and each R18A are C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R14 independently hydrogen, an optionally substituted 19A 20A 22A 23A 5B 6B 8B 9B is optionally substituted with one or more, the same or Ci_24 alkyl or alkoxy; R , R , R , R , R , R , R , R , different, R20; R9C, R10C, R12C and R13C are independently selected from the R15 is hydrogen, Lipid, -(C=O)Oalkyl(C1-C22), - group consisting of hydrogen, an optionally substituted (C=O)alkyl(C1-C22), -(C=O)NHalkyl(C1-C22), - (C=O)N- Ci_24 alkyl and an optionally substituted aryl; dialkyl(C1-C22), -(C=O)Salkyl(C1-C22), hydroxy, (C1- R2iA R24A R7B^ Ri

absent; R1A is H; R3A is OH; R4A is fluoro; R5A is hydrogen; and B1A is an unsubstituted thymine; then R2A cannot be Ci alkyl substituted with an N-amido; and provided that when the dashed line ( ) of Formula (I) is absent; R1A is H; R3A is OH; R4A is fluoro; R5A is fluoro; and B1A is an unsubstituted cytosine; then R2A cannot be ethynyl.

Claim 212. The use or method of any one of Claims 162-211, wherein B is selected from the group consisting of:

wherein: R is selected from the group consisting of hydrogen, halogen and NHR' KC2 wherein R is selected from the group consisting of hydrogen, -C(=0)R U and C(=0)OR^ ; R is halogen or NHR , wherein R is selected from the group consisting of hydrogen, an optionally substituted Ci_6 alkyl, an optionally substituted C2-6 alkenyl, an optionally MC2 NC2 substituted C3_8 cycloalkyl, -C(=0)R and -C(=0)OR ; RDC2 is hydrogen or NHR , wherein R is selected from the group consisting of hydrogen, -C(=0)RPC2 and -C(=0)ORQC2; R is selected from the group consisting of hydrogen, halogen, an optionally substituted Ci_6 alkyl, an optionally substituted C2_6 alkenyl and an optionally substituted C2_6 alkynyl; R EC2 is selected from the group consisting of hydrogen, hydroxy, an optionally substituted Ci_6 alkyl, an optionally substituted C3-8 cycloalkyl, -C(=0)R and - C(=0)ORSC2; R is selected from the group consisting of hydrogen, halogen, an optionally substituted Ci_6alkyl, an optionally substituted C2_6 alkenyl and an optionally substituted C2_6 alkynyl; Y2C and Y3C are independently N or CRIC2, wherein RIC2 is selected from the group consisting of hydrogen, halogen, an optionally substituted Ci_6-alkyl, an optionally substituted C2_6-alkenyl and an optionally substituted C2_6-alkynyl; R is an optionally substituted Ci_6 alkyl; R is hydrogen or NHR , wherein R is independently selected from the group consisting of hydrogen, -C(=0)RUC2 and - C(=0)ORVC2; and RKC2, RLC2, RMC2, RNC2, RPC2, RQC2 RRC2, RSC2 RUC2 and RVC2 are independently selected from the group consisting of Ci_6 alkyl, C2_6 alkenyl, C2_6 alkynyl, C3-6 cycloalkyl, C3-6 cycloalkenyl, C6-1o aryl, heteroaryl, heteroalicyclyl, aryl(Ci_6 alkyl), heteroaryl(Ci_6 alkyl) and heteroalicyclyl(Ci_6 alkyl).

Claim 7

IN201717025098 D3: WO2013142525A1 CLAIM 7 Claim 1 7. A pharmaceutical composition comprising a Use of an effective amount of a compound selected from pharmaceutically acceptable excipient and a compound Formula (I), Formula (II), and Formula (III), or a of Formula ID, pharmaceutically acceptable salt of the foregoing, for amelioring or treating a viral infection caused by a virus selected from a henipavirus, a morbilli virus, a respirovirus, a rubulavirus and a metapneumovirus, wherein the compound is selected from Formula (I), Formula II), and Formula (III) has one of the following structures:

Formula ID, or salt thereof, wherein W is CH2, NH, S or O; (I) (Π) X is CH2,CHMe, CMe2, CHF, CF2, or CD2; Y is N or CR”; Z is N or CR”; each R” is independently selected from is H, D, F, Cl, Br, I, CH3, CD3, CF3, alkyl, acyl, alkenyl, alkynyl, hydroxyl, formyl or SCH3; R1 is hydrogen, monophosphate, diphosphate, (HI) triphosphate, wherein: alkyl, halogen, nitro, B1A, B1B, and B1C are independently an optionally cyano, hydroxy, amino, mercapto, formyl, carboxy, substituted heterocyclic base or an optionally substituted heterocyclic base with a protected amino group; carbamoyl, carbanoyl, esteryl, alkoxy, (C1- 1A C22)alkylthio, (C1-C22)alkylamino, ((C1- R is selected from the group consisting of hydrogen, an C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- optionally substituted C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, or phosphoramidyl, or wherein R1 is optionally substituted with one or more, the same or different, R20; when the dashed line ( ) of Formula (I) is a single bond, R A is Y1 is O or S; CH2, and R is O (oxygen); Y2 is OH, OR12, OAlkyl, or BH3-M+; when the dashed line ( ) of Formula (I) is absent, RZA is selected Y3 is OH or BH3-M+; from the group consisting of an optionally substituted Ci_6 alkyl, R2 is hydrogenor hydroxy; an optionally substituted C2_6 alkenyl, an optionally substituted R3 is hydrogen, hydroxy, alkyl, halogen, nitro, cyano, C2_6 alkynyl, an optionally substituted C3 cycloalkyl, an hydroxy, amino, mercapto, formyl, carboxy, optionally substituted -O-C1-6 alkyl, an optionally substituted -0- carbamoyl, alkoxy, (C1-C22)alkylthio, alkylamino, C3_6 alkenyl, an optionally substituted -O-C3-6 alkynyl and (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, cyano, and R3A is selected from the group consistin of OH, - arylsulfonyl,carbocyclyl, aryl, or heterocyclyl; OC(=0)R"A and an optionally substituted O-linked amino acid; R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxymethyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1- C22)alkylthio,(C1-C22)alkylamino, ((C1- C22)alkyl)2amino,(C1-C22)alkylsulfinyl,(C1- N-linked amino acid and an optionally substituted N-linked C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- amino acid ester derivative; 1C 2C C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; R and R are independently selected from the group - R5 is hydrogen, hydroxy, or halogen; consisting of O , OH, an R6 is hydrogen, hydroxy, alkoxy, alkyl, ethynyl, allenyl, halogen, nitro, cyano, amino, mercapto,formyl, carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl; , an optionally substituted N-linked amino acid and an optionally R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2- substituted N-linked amino acid ester derivative; or C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, optionally substituted C1-6 alkoxy hydroxy, benzyloxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1- C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- R2B and R are independently selected from the group consisting C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein of an optionally substituted Ci_6 alkyl, an optionally substituted R8 is optionally substituted with one or more, the same C2-6 alkenyl, an optionally substituted C2-6 alkynyl, an 85 or different, R20; optionally substituted C3-6 cycloalkyl, an optionally substituted - R9 is hydrogen, methyl, ethyl, tert-butyl, (C1- 0-C1-6 alkyl, an optionally substituted -O-C3-6 alkenyl, an C22)alkyl, halogen, nitro, cyano, hydroxy, optionally substituted -0-C3-6 alkynyl and cyano; amino,mercapto, formyl, carboxy, carbamoyl, R4C is selected from the group consisting of OH, - cycloalkyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1- OC(=0)R"c and an optionally substituted O-linked amino acid; C22)alkylamino,((C1-C22)alkyl)2amino, (C1- R4A, R3B and R5C are independently a halogen; C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- R5A, R4B and R6C are independently hydrogen or halogen; C12)arylsulfonyl, (C3-C6)carbocyclyl, R6A, R7A and R8A are independently selected from the group (C6-C12)aryl,orheterocyclyl, wherein R9 is optionally consisting of absent, hydrogen, an optionally substituted Ci_24 substituted with one or more, the same or different, alkyl, an optionally substituted C2-24 alkenyl, an optionally R20; substituted C2-24 alkynyl, an optionally substituted C3-6 R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, cycloalkyl, an optionally substituted C3-6 cycloalkenyl, an methyl, ethyl, isopropyl, cyclopentyl, cyclohexyl,butyl, optionally substituted aryl, an optionally substituted heteroaryl, pentyl, hexyl, neopentyl, benzyl, halogen, nitro, cyano, an optionally substituted aryl(Ci_6 alkyl), an optionally 15A 16A hydroxy, amino, mercapto, formyl, carboxy,carbamoyl, substituted *-(CR R )p-0-Ci_24 alkyl, an optionally 17A 18A (C1-C22)alkoxy, (C1-C22)alkylthio, (C1- substituted *-(CR R )q-0-Ci_24 C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl,orheterocyclyl, wherein R10 is optionally substituted with one or more, the same or different, R20; R11 is hydrogen, deuterium, (C1-C22)alkyl, methyl, R6A is and R7 is absent or hydrogen; or halogen, nitro, cyano, hydroxy, amino, /A mercapto,formyl, carboxy, carbamoyl, (C1- R and R , 7 A are taken together to form a moiety selected from C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, the group ((C1-C22)alkyl)2amino,(C1-C22)alkylsulfinyl, (C1- consisting of an optionally substituted C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R11 is optionally substituted with one or and an optionally substituted more, the same or different, R20; R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl, 1-naphthyl, 2- naphthyl,aromatic,heteroaromatic, 4-substituted wherein the oxygens connected to R6A and R7A, the phosphorus phenyl, 4-fluorophenyl, 4-chlorophenyl, 4- and the moiety form a six-membered to ten-membered ring bromophenyl, naphthyl, or system;. heterocyclyl, wherein R12 is optionally substituted R9A is independently selected from the group consisting of an with one or more, the same or different, R20; optionally substituted Ci_24 alkyl, an optionally substituted C2- R13 is hydrogen, deuterium, (C1-C22)alkyl, (C2- 24 alkenyl, an optionally substituted C2-24 alkynyl, an optionally C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, substituted C3_6 cycloalkyl, an optionally substituted 30A 31A hydroxy, amino, amido, mercapto, formyl, carboxy, C3_6 cycloalkenyl, NR R , an optionally substituted N-linked carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1- amino acid and an optionally substituted N-linked amino acid C22)alkylthio,(C1-C22)alkylamino, ((C1- ester derivative; C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- R10A and R11A are independently an optionally substituted N- C22)alkylsulfonyl, (C6-C12)arylsulfonyl,(C3- linked amino acid or an optionally substituted N-linked amino C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, acid ester derivative; wherein R13 is optionally substituted with one or R12A, R13A and R14A are independently absent or hydrogen; more, the same or different, R20; each R15A, each R16A, each R17A and each R18A are independently 19A R14 is hydrogen, deuterium, (C1-C22)alkyl, (C2- hydrogen, an optionally substituted Ci_24 alkyl or alkoxy; R , C22)alkenyl, (C12-C22)alkynyl, halogen, nitro, R20A, R22A, R23A, R5B, R6B, R8B, R9B, R9C, R10C, R12C and R13C are cyano,hydroxy, amino, amido, mercapto, formyl, independently selected from the group consisting of hydrogen, an carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy, optionally substituted Ci_24 alkyl and an optionally substituted (C1-C22)alkylthio,(C1-C22)alkylamino, ((C1- aryl; C22)alkyl)2amino, alkylsulfinyl, (C1- R2iA R24A R7B^ Ri

(C=O)Ndialkyl(C1-C22), -(C=O)Salkyl(C1-C22), consisting of hydrogen, an optionally substituted Ci_24-alkyl, an hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl, halogen, optionally substituted C2-24 alkenyl, an optionally substituted nitro, cyano, amino,mercapto, formyl, carboxy, C2_24 alkynyl, an optionally substituted C3_6 cycloalkyl and an carbamoyl, (C1-C22)alkylthio, (C1-C22)alkylamino, optionally substituted C3_6 cycloalkenyl; ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- for Formula (III), is a single bond or a double bond; C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- when is a single bond, each R and each R is independently C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; hydrogen or halogen; and R15 and R15’ can form a ring that is optionally when is a double bond, each R is absent and each R is substituted with one or more, the same or different, independently hydrogen or halogen; A "c R20; R" and R are independently an optionally substituted Ci_24- R20 is deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, alkyl; (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, m and n are independently 0 or 1 ; amino, amido, mercapto, formyl, carboxy, carbamoyl, p and q are independently selected from the group consisting of azido, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1- 1, 2 and 3; C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- r is 1 or 2; C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- Z1A, Z2A, Z3A, Z4A, Z1B, Z2B and Z1C are independently O or S; C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, and or heterocyclyl; and provided that when the dashed line ( ) of Formula (I) is absent; wherein the lipid comprises a C6-22 alkyl, (C6- R1A is C22)alkoxy, polyethylene glycol, or (C6-C12)aryl substituted with an (C1-C22)alkyl group heterocyclylis acarbocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur, and heteroaromatic is an aromatic heterocyclylcomprising 1-4 heteroatoms selected from nitrogen,oxygen, or sulfur and at least 1 carbon atom. wherein R is an unsubstituted Ci_4 alkyl or phenyl optionally para- substituted with a halogen or methyl and R9A is methyl ester, ethyl ester, isopropyl ester, n-butyl ester, benzyl ester or phenyl ester of an amino acid selected from the group consisting of glycine, alanine, valine, leucine, phenylalanine, tryptophan, methionine and proline; R3A is OH; R4A is fluoro; R5A is fluoro or hydrogen; and B1A is an unsubstituted uracil; then R2A cannot be -OCH3; provided that when the dashed line ( ) of Formula (I) is absent; R1A is H; R3A is OH; R4A is fluoro; R5A is fluoro; and B1A is an unsubstituted cytosine; then R2A cannot be allenyl; provided that when the dashed line ( ) of Formula (I) is absent; R1A is H; R3A is OH; R4A is fluoro; R5A is hydrogen; and B1A is an unsubstituted thymine; then R2A cannot be Ci alkyl substituted with an N-amido; and provided that when the dashed line ( ) of Formula (I) is absent; R1A is H; R3A is OH; R4A is fluoro; R5A is fluoro; and B1A is an unsubstituted cytosine; then R2A cannot be ethynyl.

Claim 212. The use or method of any one of Claims 162-211, wherein B is selected from the group consisting of:

RDC2 is hydrogen or NHR , wherein R is selected from the group consisting of hydrogen, -C(=0)RPC2 and -C(=0)ORQC2; R is selected from the group consisting of hydrogen, halogen, an optionally substituted Ci_6 alkyl, an optionally substituted C2_6 alkenyl and an optionally substituted C2_6 alkynyl; R EC2 is selected from the group consisting of hydrogen, hydroxy, an optionally substituted Ci_6 alkyl, an optionally substituted C3-8 cycloalkyl, -C(=0)R and - C(=0)ORSC2; R is selected from the group consisting of hydrogen, halogen, an optionally substituted Ci_6alkyl, an optionally substituted C2_6 alkenyl and an optionally substituted C2_6 alkynyl; Y2C and Y3C are independently N or CRIC2, wherein RIC2 is selected from the group consisting of hydrogen, halogen, an optionally substituted Ci_6-alkyl, an optionally substituted C2_6- alkenyl and an optionally substituted C2_6-alkynyl; R is an optionally substituted Ci_6 alkyl; R is hydrogen or NHR , wherein R is independently selected from the group consisting of hydrogen, -C(=0)RUC2 and - C(=0)ORVC2; and RKC2, RLC2, RMC2, RNC2, RPC2, RQC2 RRC2, RSC2 RUC2 and RVC2 are independently selected from the group consisting of Ci_6 alkyl, C2_6 alkenyl, C2_6 alkynyl, C3-6 cycloalkyl, C3-6 cycloalkenyl, C6-1o aryl, heteroaryl, heteroalicyclyl, aryl(Ci_6 alkyl), heteroaryl(Ci_6 alkyl) and heteroalicyclyl(Ci_6 alkyl).

Claim 8

IN201717025098 D3: WO2013142525A1 CLAIM 8 Claim 1 8. A pharmaceutical composition comprising a Use of an effective amount of a compound selected from pharmaceutically acceptable excipient and a compound Formula (I), Formula (II), and Formula (III), or a of Formula IE, pharmaceutically acceptable salt of the foregoing, for amelioring or treating a viral infection caused by a virus selected from a henipavirus, a morbilli virus, a respirovirus, a rubulavirus and a metapneumovirus, wherein the compound is selected from Formula (I), Formula II), and Formula (III) has one of the following structures:

Formula IE, or salt thereof, wherein (I) (Π) Q is O, -O(C=O)-, -O(C=O)Lipid, -O(C=O)V-, NH, or NR7; V is O, NH, NR7, S, CH2, or CHR7; W is CH2, NH, S or O; X is CH2,CHMe, CMe2, CHF, CF2, or CD2; Y is N or CR”; Z is N or CR”; (HI) each R” is independently selected from is H, D, F, Cl, wherein: Br, I, CH3, CD3, CF3, alkyl, acyl, alkenyl, alkynyl, B1A, B1B, and B1C are independently an optionally hydroxyl, formyl or SCH3; substituted heterocyclic base or an optionally substituted heterocyclic base with a protected amino group; R2 is hydrogen, alkyl, alkenyl, alkynyl, ethynyl, 1A fluoromethyl, difluoromethyl, trifluoromethyl, R is selected from the group consisting of hydrogen, an chloromethyl, hydroxymethyl, halogen, nitro, cyano, optionally substituted hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, azido, or heterocyclyl;

R3 is hydrogen, hydroxy, alkyl, halogen, nitro, cyano, when the dashed line ( ) of Formula (I) is a single bond, R A is hydroxy, amino, mercapto, formyl, carboxy, CH2, and R is O (oxygen); carbamoyl, alkoxy, (C1-C22)alkylthio, alkylamino, when the dashed line ( ) of Formula (I) is absent, RZA is selected alkyl)2amino, alkylsulfinyl, alkylsulfonyl, from the group consisting of an optionally substituted Ci_6 alkyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl; an optionally substituted C2_6 alkenyl, an optionally substituted R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, 88 difluoromethyl, trifluoromethyl, hydroxymethyl, C2_6 alkynyl, an optionally substituted C3 cycloalkyl, an halogen, nitro, cyano, hydroxy, amino, mercapto, optionally substituted -O-C1-6 alkyl, an optionally substituted -0- formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1- C3_6 alkenyl, an optionally substituted -O-C3-6 alkynyl and C22)alkylthio,(C1-22)alkylamino, ((C1- cyano, and R3A is selected from the group consistin of OH, - C22)alkyl)2amino,(C1-C22)alkylsulfinyl,(C1- OC(=0)R"A and an optionally substituted O-linked amino acid; 22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; R5 is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, alkynyl, ethynyl, fluoromethyl, difluoromethyl,trifluoromethyl, hydroxymethyl, allenyl, halogen, nitro, cyano, amino, mercapto, N-linked amino acid and an optionally substituted N-linked formyl, carboxy, carbamoyl,alkoxy, (C1- amino acid ester derivative; R1C and R2C are independently selected from the group C22)alkylthio, alkylamino, (alkyl)2amino, - alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, consisting of O , OH, an aryl,or heterocyclyl; R6 is hydrogen, hydroxy, alkoxy, alkyl, ethynyl, allenyl, halogen, nitro, cyano, amino, mercapto,formyl, carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio, lkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl,arylsulfonyl, carbocyclyl, aryl, or , an optionally substituted N-linked amino acid and an optionally heterocyclyl; substituted N-linked amino acid ester derivative; or each R7 is independently selected from absent, optionally substituted C1-6 alkoxy hydrogen, -(C=O)Oalkyl, -(C=O)alkyl, - (C=O)NHalkyl, -(C=O)N-dialkyl, -(C=O)Salkyl, hydroxy, alkoxy, alkyl, higher alkyl, (C6-C16)alkyl, (C6-C22)alkyl, halogen, nitro, cyano, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, (C1- R2B and R3c are independently selected from the group consisting C22)alkylthio,alkylamino, (alkyl)2amino, of an optionally substituted Ci_6 alkyl, an optionally substituted alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, C2-6 alkenyl, an optionally substituted C2-6 alkynyl, an aryl, or heterocyclyl, whereineach R7 is optionally optionally substituted C3-6 cycloalkyl, an optionally substituted - substituted with one or more, the same or different, 0-C1-6 alkyl, an optionally substituted -O-C3-6 alkenyl, an R20; optionally substituted -0-C3-6 alkynyl and cyano; R15 is hydrogen, -(C=O)Oalkyl(C1-C22), - R4C is selected from the group consisting of OH, - (C=O)alkyl(C1-C22), -C=O)NHalkyl(C1-C22), - OC(=0)R"c and an optionally substituted O-linked amino acid; (C=O)Ndialkyl(C1-C22), -(C=O)Salkyl(C1-C22), R4A, R3B and R5C are independently a halogen; hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl, halogen, R5A, R4B and R6C are independently hydrogen or halogen; nitro, cyano, amino,mercapto, formyl, carboxy, R6A, R7A and R8A are independently selected from the group carbamoyl, (C1-C22)alkylthio, (C1-C22)alkylamino, consisting of absent, hydrogen, an optionally substituted Ci_24 ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- alkyl, an optionally substituted C2-24 alkenyl, an optionally C22)alkylsulfonyl, (C6-12)arylsulfonyl, (C3- substituted C2-24 alkynyl, an optionally substituted C3-6 C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl,wherein cycloalkyl, an optionally substituted C3-6 cycloalkenyl, an R15 is optionally substituted with one or more, the optionally substituted aryl, an optionally substituted heteroaryl, same or different, R20; an optionally substituted aryl(Ci_6 alkyl), an optionally 15A 16A R15’ is hydrogen, -(C=O)Oalkyl(C1-C22), - substituted *-(CR R )p-0-Ci_24 alkyl, an optionally 17A 18A (C=O)alkyl(C1-C22), -C=O)NHalkyl(C1-C22), - substituted *-(CR R )q-0-Ci_24 (C=O)Ndialkyl(C1-C22), -(C=O)Salkyl(C1-C22), hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl, halogen, nitro, cyano, amino, mercapto, formyl, carboxy, carbamoyl, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1- C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- R6A is and R7 is absent or hydrogen; or C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; /A R15 and R15’ can form a ring that is optionally R and R , 7 A are taken together to form a moiety selected from substituted with one or more, the same or the group different,R20; consisting of an optionally substituted If Q = -O(C=O)V- and V = NR7 then the R7s can together form a ring that is optionally substitutedwith one or more, the same or different, R20; and an optionally substituted R20 is deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy,amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1-C22)alkylthio, wherein the oxygens connected to R6A and R7A, the phosphorus (C1-C22)alkylamino, ((C1-22)alkyl)2amino, (C1- and the moiety form a six-membered to ten-membered ring C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- system;. C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, R9A is independently selected from the group consisting of an or heterocyclyl; and optionally substituted Ci_24 alkyl, an optionally substituted C2- wherein lipid comprises a C6-22 alkyl, (C6- 24 alkenyl, an optionally substituted C2-24 alkynyl, an optionally C22)alkoxy, polyethylene glycol, or (C6-C12)aryl substituted C3_6 cycloalkyl, an optionally substituted 30A 31A substituted with an (C1-C22)alkyl group, C3_6 cycloalkenyl, NR R , an optionally substituted N-linked heterocyclylis carbocyclyl comprising 1-4 heteroatoms amino acid and an optionally substituted N-linked amino acid 89 selected from nitrogen, oxygen, or sulfur, ester derivative; and heteroaromatic is an aromatic R10A and R11A are independently an optionally substituted N- heterocyclylcomprising 1-4 heteroatoms selected from linked amino acid or an optionally substituted N-linked amino nitrogen,oxygen, or sulfur and at least 1 carbon atom. acid ester derivative; R12A, R13A and R14A are independently absent or hydrogen; each R15A, each R16A, each R17A and each R18A are independently 19A hydrogen, an optionally substituted Ci_24 alkyl or alkoxy; R , R20A, R22A, R23A, R5B, R6B, R8B, R9B, R9C, R10C, R12C and R13C are independently selected from the group consisting of hydrogen, an optionally substituted Ci_24 alkyl and an optionally substituted aryl; R2iA R24A R7B^ Ri

wherein R is an unsubstituted Ci_4 alkyl or phenyl optionally para- substituted with a halogen or methyl and R9A is methyl ester, ethyl ester, isopropyl ester, n-butyl ester, benzyl ester or phenyl ester of an amino acid selected from the group consisting of glycine, alanine, valine, leucine, phenylalanine, tryptophan, methionine and proline; R3A is OH; R4A is fluoro; R5A is fluoro or hydrogen; and B1A is an unsubstituted uracil; then R2A cannot be -OCH3; provided that when the dashed line ( ) of Formula (I) is absent; R1A is H; R3A is OH; R4A is fluoro; R5A is fluoro; and B1A is an unsubstituted cytosine; then R2A cannot be allenyl; provided that when the dashed line ( ) of Formula (I) is absent; R1A is H; R3A is OH; R4A is fluoro; R5A is hydrogen; and B1A is an unsubstituted thymine; then R2A cannot be Ci alkyl substituted with an N-amido; and provided that when the dashed line ( ) of Formula (I) is absent;

R1A is H; R3A is OH; R4A is fluoro; R5A is fluoro; and B1A is an unsubstituted cytosine; then R2A cannot be ethynyl.

Claim 212. The use or method of any one of Claims 162-211, wherein B is selected from the group consisting of:

wherein: R is selected from the group consisting of hydrogen, halogen and NHR' KC2 wherein R is selected from the group consisting of hydrogen, -C(=0)R U and C(=0)OR^ ; R is halogen or NHR , wherein R is selected from the group consisting of hydrogen, an optionally substituted Ci_6 alkyl, an optionally substituted C2-6 alkenyl, an optionally substituted MC2 NC2 C3_8 cycloalkyl, -C(=0)R and -C(=0)OR ; RDC2 is hydrogen or NHR , wherein R is selected from the group consisting of hydrogen, -C(=0)RPC2 and -C(=0)ORQC2; R is selected from the group consisting of hydrogen, halogen, an optionally substituted Ci_6 alkyl, an optionally substituted C2_6 alkenyl and an optionally substituted C2_6 alkynyl; R EC2 is selected from the group consisting of hydrogen, hydroxy, an optionally substituted Ci_6 alkyl, an optionally substituted C3-8 cycloalkyl, -C(=0)R and - C(=0)ORSC2; R is selected from the group consisting of hydrogen, halogen, an optionally substituted Ci_6alkyl, an optionally substituted C2_6 alkenyl and an optionally substituted C2_6 alkynyl; Y2C and Y3C are independently N or CRIC2, wherein RIC2 is selected from the group consisting of hydrogen, halogen, an optionally substituted Ci_6-alkyl, an optionally substituted C2_6- alkenyl and an optionally substituted C2_6-alkynyl; R is an optionally substituted Ci_6 alkyl; R is hydrogen or NHR , wherein R is independently selected from the group consisting of hydrogen, -C(=0)RUC2 and - C(=0)ORVC2; and RKC2, RLC2, RMC2, RNC2, RPC2, RQC2 RRC2, RSC2 RUC2 and RVC2 are independently selected from the group consisting of Ci_6 alkyl, C2_6 alkenyl, C2_6 alkynyl, C3-6 cycloalkyl, C3-6 cycloalkenyl, C6-1o aryl, heteroaryl, heteroalicyclyl, aryl(Ci_6 alkyl), heteroaryl(Ci_6 alkyl) and heteroalicyclyl(Ci_6 alkyl).

Claim 9

IN201717025098 D3: WO2013142525A1 CLAIM 9 A pharmaceutical composition comprising a Claim 1 pharmaceutically acceptable excipient and a compound of Use of an effective amount of a compound selected from Formula II, Formula (I), Formula (II), and Formula (III), or a pharmaceutically acceptable salt of the foregoing, for amelioring or treating a viral infection caused by a virus selected from a henipavirus, a morbilli virus, a respirovirus, a rubulavirus and a metapneumovirus, wherein the compound is selected from Formula (I), Formula II), and Formula (III) has one of the following structures:

(I) (Π)

or salt thereof, wherein

Q is O, -O(C=O)-, -O(C=O)Lipid, -O(C=O)V-, NH, or (HI) NR7; wherein: V is O, NH, NR7, S, CH2, or CHR7; B1A, B1B, and B1C are independently an optionally W is CH2, NH, S or O; substituted heterocyclic base or an optionally substituted X is CH2 or O; heterocyclic base with a protected amino group; Y is N or CR”; R1A is selected from the group consisting of hydrogen, an Z is N or CR”; optionally substituted each R” is independently selected from is H, D, F, Cl, Br, I, CH3, CD3, CF3, alkyl, acyl, alkenyl, alkynyl, hydroxyl, formyl or SCH3; R1 is monophosphate, diphosphate, triphosphate,

N-linked amino acid and an optionally substituted N-linked amino acid ester derivative; R1C and R2C are independently selected from the group consisting of O-, OH, an

Y1 is O or S; Y2 is OH, OR12, OAlkyl, or BH3-M+; Y3 is OH or BH3-M+; R2 is hydrogen, alkyl, alkenyl, alkynyl, ethynyl, fluoromethyl, difluoromethyl, , an optionally substituted N-linked amino acid and an trifluoromethyl,chloromethyl, hydroxymethyl, halogen, optionally substituted N-linked amino acid ester derivative; nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, or optionally substituted C1-6 alkoxy carbamoyl, alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl,azido, or heterocyclyl; R3 is hydrogen, hydroxy, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, R2B and R3c are independently selected from the group alkoxy, (C1-C22)alkylthio, alkylamino, alkyl)2amino, consisting of an optionally substituted Ci_6 alkyl, an alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, optionally substituted C2-6 alkenyl, an optionally substituted or heterocyclyl; C2-6 alkynyl, an optionally substituted C3-6 cycloalkyl, an R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, optionally substituted -0-C1-6 alkyl, an optionally substituted - difluoromethyl, rifluoromethyl, hydroxymethyl,halogen, O-C3-6 alkenyl, an optionally substituted -0-C3-6 alkynyl and nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, cyano; carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio,(C1- R4C is selected from the group consisting of OH, - C22)alkylamino, ((C1-C22)alkyl)2amino,(C1- OC(=0)R"c and an optionally substituted O-linked amino C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6- acid; C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or R4A, R3B and R5C are independently a halogen; heterocyclyl; R5A, R4B and R6C are independently hydrogen or halogen; R5 is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, alkynyl, R6A, R7A and R8A are independently selected from the group ethynyl, fluoromethyl, difluoromethyl,trifluoromethyl, consisting of absent, hydrogen, an optionally substituted Ci_24 hydroxymethyl, allenyl, halogen, nitro, cyano, amino, alkyl, an optionally substituted C2-24 alkenyl, an optionally 92 mercapto, formyl, carboxy, carbamoyl,alkoxy, (C1- substituted C2-24 alkynyl, an optionally substituted C3-6 C22)alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, cycloalkyl, an optionally substituted C3-6 cycloalkenyl, an alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl,or optionally substituted aryl, an optionally substituted heteroaryl, heterocyclyl; an optionally substituted aryl(Ci_6 alkyl), an optionally 15A 16A R6 is hydrogen, hydroxy, alkoxy, alkyl, ethynyl, allenyl, substituted *-(CR R )p-0-Ci_24 alkyl, an optionally 17A 18A halogen, nitro, cyano, amino, mercapto,formyl, carboxy, substituted *-(CR R )q-0-Ci_24 carbamoyl, alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl,arylsulfonyl, carbocyclyl, aryl, or heterocyclyl; each R7 is independently selected from absent, hydrogen, -(C=O)Oalkyl, -(C=O)alkyl, - (C=O)NHalkyl, -(C=O)N- dialkyl, -(C=O)Salkyl, hydroxy, alkoxy, alkyl, higher alkyl, (C6-C16)alkyl, (C6-C22)alkyl, halogen, nitro, R6A is and R7 is absent or hydrogen; or cyano, amino, mercapto, formyl, carboxy, carbamoyl, /A alkoxy, (C1-C22)alkylthio,alkylamino, (alkyl)2amino, R and R , 7 A are taken together to form a moiety selected alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, from the group or heterocyclyl, wherein each R7 is optionally substituted consisting of an optionally substituted with one or more, the same or different, R20; R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, and an optionally substituted cyano,hydroxy, benzyloxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1- C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- wherein the oxygens connected to R6A and R7A, the phosphorus 22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- and the moiety form a six-membered to ten-membered ring C6)carbocyclyl, (C6-12)aryl,orheterocyclyl, wherein R8 is system;. optionally substituted with one or more, the same or R9A is independently selected from the group consisting of an different, R20; optionally substituted Ci_24 alkyl, an optionally substituted C2- R9 is hydrogen, methyl, ethyl, tert-butyl, (C1-C22)alkyl, 24 alkenyl, an optionally substituted C2-24 alkynyl, an halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, optionally substituted C3_6 cycloalkyl, an optionally 30A 31A carboxy, carbamoyl, cycloalkyl, (C1-C22)alkoxy, (C1- substituted C3_6 cycloalkenyl, NR R , an optionally C22)alkylthio, (C1-C22)alkylamino,((C1- substituted N-linked amino acid and an optionally substituted C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- N-linked amino acid ester derivative; C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- R10A and R11A are independently an optionally substituted N- C6)carbocyclyl,(C6-C12)aryl,orheterocyclyl, wherein R9 linked amino acid or an optionally substituted N-linked amino is optionally substituted with one or more, the same or acid ester derivative; different, R20; R12A, R13A and R14A are independently absent or hydrogen; R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, methyl, each R15A, each R16A, each R17A and each R18A are ethyl, isopropyl, cyclopentyl, cyclohexyl,butyl, pentyl, independently hydrogen, an optionally substituted Ci_24 alkyl hexyl, neopentyl, benzyl, halogen, nitro, cyano, hydroxy, or alkoxy; R19A, R20A, R22A, R23A, R5B, R6B, R8B, R9B, R9C, R10C, amino, mercapto, formyl, carboxy,carbamoyl, (C1- R12C and R13C are independently selected from the group C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, consisting of hydrogen, an optionally substituted Ci_24 alkyl ((C1-C22)alkyl)2amino, (C1-22)alkylsulfinyl,(C1- and an optionally substituted aryl; C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- R2iA R24A R7B^ Ri

R14 is hydrogen, deuterium, (C1-C22)alkyl, (C2- independently hydrogen or halogen; A "c C22)alkenyl, (C12-C22)alkynyl, halogen, nitro, R" and R are independently an optionally substituted Ci_24- cyano,hydroxy, amino, amido, mercapto, formyl, carboxy, alkyl; arbamoyl, lipid, azido, (C1-C22)alkoxy, (C1- m and n are independently 0 or 1 ; C22)alkylthio,(C1-C22)alkylamino, ((C1- p and q are independently selected from the group consisting C22)alkyl)2amino, alkylsulfinyl, (C1-C22)alkylsulfonyl, of 1, 2 and 3; (C6-12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or r is 1 or 2; heterocyclyl, wherein R14 is optionally substituted with Z1A, Z2A, Z3A, Z4A, Z1B, Z2B and Z1C are independently O or S; one or more, the same or different, R20; and If Q = -O(C=O)V- and V = NR7 then the R7s can together provided that when the dashed line ( ) of Formula (I) is absent; form a ring that is optionally substituted with one or more, R1A is the same or different, R20; R20 is deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2- C22)alkynyl, halogen, nitro, cyano, hydroxy,amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- wherein R is an unsubstituted Ci_4 alkyl or phenyl optionally C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; and 9A wherein lipid comprises a C6-22 alkyl, (C6-C22)alkoxy, para- substituted with a halogen or methyl and R is methyl polyethylene glycol, or (C6-C12)aryl substituted ester, ethyl ester, isopropyl ester, n-butyl ester, benzyl ester or with an (C1-C22)alkyl group, heterocyclylis phenyl ester of an amino acid selected from the group consisting of glycine, alanine, valine, leucine, phenylalanine, acarbocyclylcomprising 1-4 heteroatoms selected from 3A 4A nitrogen, oxygen, or sulfur, and tryptophan, methionine and proline; R is OH; R is fluoro; R5A is fluoro or hydrogen; and B1A is an unsubstituted uracil; heteroaromatic is an aromatic heterocyclylcomprising 1-4 2A heteroatoms selected from nitrogen,oxygen, or sulfur and then R cannot be -OCH3; provided that when the dashed line ( ) of Formula (I) is absent; at least 1 carbon atom. 1A 3A 4A 5A 1A R is H; R is OH; R is fluoro; R is fluoro; and B is an unsubstituted cytosine; then R2A cannot be allenyl; provided that when the dashed line ( ) of Formula (I) is absent; R1A is H; R3A is OH; R4A is fluoro; R5A is hydrogen; and B1A is an unsubstituted thymine; then R2A cannot be Ci alkyl substituted with an N-amido; and provided that when the dashed line ( ) of Formula (I) is absent; R1A is H; R3A is OH; R4A is fluoro; R5A is fluoro; and B1A is an unsubstituted cytosine; then R2A cannot be ethynyl.

Claim 212. The use or method of any one of Claims 162-211, wherein B is selected from the group consisting of:

R is selected from the group consisting of hydrogen, halogen, an optionally substituted Ci_6alkyl, an optionally substituted C2_6 alkenyl and an optionally substituted C2_6 alkynyl; Y2C and Y3C are independently N or CRIC2, wherein RIC2 is selected from the group consisting of hydrogen, halogen, an optionally substituted Ci_6-alkyl, an optionally substituted C2_6-alkenyl and an optionally substituted C2_6-alkynyl; R is an optionally substituted Ci_6 alkyl; R is hydrogen or NHR , wherein R is independently selected from the group consisting of hydrogen, -C(=0)RUC2 and - C(=0)ORVC2; and RKC2, RLC2, RMC2, RNC2, RPC2, RQC2 RRC2, RSC2 RUC2 and RVC2 are independently selected from the group consisting of Ci_6 alkyl, C2_6 alkenyl, C2_6 alkynyl, C3-6 cycloalkyl, C3-6 cycloalkenyl, C6-1o aryl, heteroaryl, heteroalicyclyl, aryl(Ci_6 alkyl), heteroaryl(Ci_6 alkyl) and heteroalicyclyl(Ci_6 alkyl).

Claim 10

IN201717025098 D3: WO2013142525A1 CLAIM 10 The pharmaceutical composition of claim Claim 10 is dependent on claim 3 which is dependent on claim 1.

1,further comprising a propellant. Hence, the arguments applicable for claim 1are applicable here

too. Propellant as such is no new invention.

Claim 11

IN201717025098 D3: WO2013142525A1 CLAIM 11 The pharmaceutical composition of claim 10, Claim 11 is dependent on claim 10 which is dependent on claim 1. wherein the propellant is compressed air, ethanol, Hence, the arguments applicable for claim 1 & 10 are applicable nitrogen, carbon dioxide, nitrous oxide, here too. Propellant as such is no new invention. hydrofluoroalkanes (HFA), 1,1,1,2,-tetrafluoroethane,

1,1,1,2,3,3,3-heptafluoropropane or combinations thereof.

Claim 12

IN201717025098 D3: WO2013142525A1 CLAIM 12 The composition of claim 1, wherein the Claim 1 compound has a structure according to Formula IA Use of an effective amount of a compound selected from Formula (I), Formula (II), and Formula (III), or a pharmaceutically acceptable salt of the foregoing, for amelioring or treating a viral infection caused by a virus selected from a henipavirus, a morbilli virus, a respirovirus, a rubulavirus and a metapneumovirus, wherein the compound is selected from Formula (I), Formula II), and Formula (III) has one of the following structures: or salt thereof, wherein R7 is H, X is CH2, CHMe, CMe2, CHF, CF2, or CD2; Y is independently selected from is H, D, F, Cl, Br, I, CH3, CD3, CF3, alkyl, acyl, alkenyl, alkynyl, hydroxyl, formyl or SCH3; (I) (Π) R1 is

monophosphate ester, diphosphate ester (HI) wherein: B1A, B1B, and B1C are independently an optionally substituted heterocyclic base or an optionally substituted heterocyclic base with a protected amino group; R1A is selected from the group consisting of hydrogen, an optionally substituted

A when the dashed line ( ) of Formula (I) is a single bond, R is CH2, and R is O (oxygen); when the dashed line ( ) of Formula (I) is absent, RZA is selected from the group consisting of an optionally substituted Ci_6 alkyl, an optionally substituted C2_6 alkenyl, an optionally substituted C2_6 alkynyl, an optionally substituted C3 cycloalkyl, an optionally substituted -O-C amino, mercapto, formyl, carboxy, carbanoyl, 1- 6 alkyl, an optionally substituted -0-C3_6 alkenyl, an optionally esteryl, alkoxy, (C1- 3A substituted -O-C3-6 alkynyl and cyano, and R is selected from the C22)alkylthio, (C1-C22)alkylamino, ((C1- group consistin of OH, -OC(=0)R"A and an optionally substituted O- C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- linked amino acid; C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, or phosphoramidyl, wherein R1 is optionally substituted with one or more, the same or different, R20, Y1 is O or S; Y2 is OH, OR12, OAlkyl, or BH3-M+; N-linked amino acid and an optionally substituted N-linked amino acid Y3 is OH or BH3-M+; ester derivative; R4 is hydrogen, hydroxy, (C1-C22)alkyl, R1C and R2C are independently selected from the group consisting of fluoromethyl, difluoromethyl, trifluoromethyl, O-, OH, an hydroxymethyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- , an optionally substituted N-linked amino acid and an optionally C12)aryl, or heterocyclyl, wherein R4 is optionally substituted N-linked amino acid ester derivative; or optionally substituted with one or more, the same or different, substituted C1-6 alkoxy R20; R5 is hydrogen, hydroxy, or halogen; R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2- C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, benzyloxy, amino, amido, R2B and R3c are independently selected from the group consisting of an mercapto, formyl, carboxy, carbamoyl, azido, (C1- optionally substituted Ci_6 alkyl, an optionally substituted C2-6 alkenyl, C22)alkoxy, (C1-C22)alkylthio, (C1- an optionally substituted C2-6 alkynyl, an optionally substituted C3-6 C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- cycloalkyl, an optionally substituted -0-C1-6 alkyl, an optionally C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- substituted -O-C3-6 alkenyl, an optionally substituted -0-C3-6 alkynyl and C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- cyano; C12)aryl,orheterocyclyl, wherein R8 is optionally R4C is selected from the group consisting of OH, -OC(=0)R"c and an substituted with one or more, the same or different, optionally substituted O-linked amino acid; R20; R4A, R3B and R5C are independently a halogen; R9 is hydrogen, methyl, ethyl, tert-butyl, (C1- R5A, R4B and R6C are independently hydrogen or halogen; C22)alkyl, halogen, nitro, cyano, hydroxy, amino, R6A, R7A and R8A are independently selected from the group consisting of mercapto, formyl, carboxy, carbamoyl, cycloalkyl, absent, hydrogen, an optionally substituted Ci_24 alkyl, an optionally (C1-C22)alkoxy, (C1-C22)alkylthio, (C1- substituted C2-24 alkenyl, an optionally substituted C -24 alkynyl, an C22)alkylamino,((C1-C22)alkyl)2amino, (C1- 2 optionally substituted C3-6 cycloalkyl, an optionally substituted C3-6 C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- cycloalkenyl, an optionally substituted aryl, an optionally substituted C12)arylsulfonyl, (C3-C6)carbocyclyl,(C6- heteroaryl, an optionally substituted aryl(Ci_6 alkyl), an optionally C12)aryl,orheterocyclyl, wherein R9 is optionally 15A 16A substituted *-(CR R )p-0-Ci_24 alkyl, an optionally substituted *- substituted with one or more, the same or different, (CR17AR18A) -0-Ci_ R20; q 24 R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, methyl, ethyl, isopropyl, cyclopentyl, cyclohexyl,butyl, pentyl, hexyl, neopentyl, benzyl, halogen, nitro, cyano, hydroxy, amino, mercapto, 96 formyl, carboxy,carbamoyl, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1- C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R10 is optionally substituted with one or more, the same or different, R20; R6A is and R7 is absent or hydrogen; or R11 is hydrogen, deuterium, (C1-C22)alkyl, methyl, /A halogen, nitro, cyano, hydroxy, amino, mercapto, R and R , 7 A are taken together to form a moiety selected from the formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1- group C22)alkylthio, (C1-C22)alkylamino, ((C1- consisting of an optionally substituted C22)alkyl)2amino,(C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, and an optionally substituted wherein R11 is optionally substituted with one or more, the same or different, R20; R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl, 1-naphthyl, 2-naphthyl, aromatic, wherein the oxygens connected to R6A and R7A, the phosphorus and the heteroaromatic, 4-substituted phenyl, 4- moiety form a six-membered to ten-membered ring system;. fluorophenyl, 4-chlorophenyl, 4-bromophenyl, R9A is independently selected from the group consisting of an optionally naphthyl, or heterocyclyl, wherein R12 is optionally substituted Ci_24 alkyl, an optionally substituted C2-24 alkenyl, an substituted with one or more, the same or different, optionally substituted C2-24 alkynyl, an optionally substituted 30A 31A R20; C3_6 cycloalkyl, an optionally substituted C3_6 cycloalkenyl, NR R , R13 is hydrogen, deuterium, (C1-C22)alkyl, (C2- an optionally substituted N-linked amino acid and an optionally C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, substituted N-linked amino acid ester derivative; cyano, hydroxy, amino, amido, mercapto, formyl, R10A and R11A are independently an optionally substituted N-linked carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy, amino acid or an optionally substituted N-linked amino acid ester (C1-C22)alkylthio, derivative; (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- R12A, R13A and R14A are independently absent or hydrogen; C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- each R15A, each R16A, each R17A and each R18A are independently 19A 20A C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- hydrogen, an optionally substituted Ci_24 alkyl or alkoxy; R , R , C12)aryl, or heterocyclyl, wherein R13 is optionally R22A, R23A, R5B, R6B, R8B, R9B, R9C, R10C, R12C and R13C are substituted with one or more, the same or different, independently selected from the group consisting of hydrogen, an R20; optionally substituted Ci_24 alkyl and an optionally substituted aryl; R14 is hydrogen, deuterium, (C1-C22)alkyl, (C2- R2iA R24A R7B^ Ri

wherein R is an unsubstituted Ci_4 alkyl or phenyl optionally para- substituted with a halogen or methyl and R9A is methyl ester, ethyl ester, isopropyl ester, n-butyl ester, benzyl ester or phenyl ester of an amino acid selected from the group consisting of glycine, alanine, valine, leucine, phenylalanine, tryptophan, methionine and proline; R3A is OH; R4A is fluoro; R5A is fluoro or hydrogen; and B1A is an unsubstituted 2A uracil; then R cannot be -OCH3; provided that when the dashed line ( ) of Formula (I) is absent; R1A is H; R3A is OH; R4A is fluoro; R5A is fluoro; and B1A is an unsubstituted cytosine; then R2A cannot be allenyl; provided that when the dashed line ( ) of Formula (I) is absent; R1A is H; R3A is OH; R4A is fluoro; R5A is hydrogen; and B1A is an unsubstituted thymine; then R2A cannot be Ci alkyl substituted with an N-amido; and provided that when the dashed line ( ) of Formula (I) is absent; R1A is H; R3A is OH; R4A is fluoro; R5A is fluoro; and B1A is an unsubstituted cytosine; then R2A cannot be ethynyl.

Claim 212. The use or method of any one of Claims 162-211, wherein B is selected from the group consisting of:

wherein: R is selected from the group consisting of hydrogen, halogen and NHR' KC2 wherein R is selected from the group consisting of hydrogen, - C(=0)R U and C(=0)OR^ ; R is halogen or NHR , wherein R is selected from the group consisting of hydrogen, an optionally substituted Ci_6 alkyl, an optionally substituted MC2 C2-6 alkenyl, an optionally substituted C3_8 cycloalkyl, -C(=0)R and - C(=0)ORNC2; RDC2 is hydrogen or NHR , wherein R is selected from the group consisting of hydrogen, -C(=0)RPC2 and -C(=0)ORQC2; R is selected from the group consisting of hydrogen, halogen, an optionally substituted Ci_6 alkyl, an optionally substituted C2_6 alkenyl and an optionally substituted C2_6 alkynyl; R EC2 is selected from the group consisting of hydrogen, hydroxy, an optionally substituted Ci_6 alkyl, an optionally substituted C3-8 cycloalkyl, -C(=0)R and - C(=0)ORSC2; R is selected from the group consisting of hydrogen, halogen, an optionally substituted Ci_6alkyl, an optionally substituted C2_6 alkenyl and an optionally substituted C2_6 alkynyl; Y2C and Y3C are independently N or CRIC2, wherein RIC2 is selected from the group consisting of hydrogen, halogen, an optionally substituted Ci_6-alkyl, an optionally substituted C2_6-alkenyl and an optionally substituted C2_6-alkynyl; R is an optionally substituted Ci_6 alkyl; R is hydrogen or NHR , wherein R is independently selected from the group consisting of hydrogen, -C(=0)RUC2 and -C(=0)ORVC2; and RKC2, RLC2, RMC2, RNC2, RPC2, RQC2 RRC2, RSC2 RUC2 and RVC2 are independently selected from the group consisting of Ci_6 alkyl, C2_6 alkenyl, C2_6 alkynyl, C3-6 cycloalkyl, C3-6 cycloalkenyl, C6-1o aryl, heteroaryl, heteroalicyclyl, aryl(Ci_6 alkyl), heteroaryl(Ci_6 alkyl) and heteroalicyclyl(Ci_6 alkyl).

Claim 13

IN201717025098 D3: WO2013142525A1 CLAIM 13 Claim 13 is dependent on claim 1 so the arguments applicable for The composition of claim 1, wherein R4 is hydrogen, claim 1are applicable here too hydroxy, alkyl, halogen, or fluoro.

Claim 14

IN201717025098 D3: WO2013142525A1 CLAIM 14 Claim 13 is dependent on claim 1 so the arguments applicable for The composition of claim 1, wherein R5 is hydrogen, claim 1are applicable here too hydroxy, alkoxy, alkyl, methyl, ethynyl, or allenyl.

D. Opponent further introduces prior art EP2615101B1 (D4) to Junbiao Chang to contest the

novelty of the invention. EP2615101B1 having priority date of Sept 7, 2010 is a

permissible prior art for IN20717025098 having priority date of Dec 26, 2014.

iv. Lack of novelty in view of EP2615101B1 (D4) to Junbiao Chang

D4 discloses fluorinated and azido-substituted pyrimidine nucleoside derivatives, and preparation methods and uses thereof. The structural formula is as shown (I). These compounds can be used for preparing medicaments for treating diseases such as tumors and viral infections, and can be used separately or in combination with other medicaments. The compounds also have effective activity against diseases such as tumors and viral infections.

IN201717025098 D4: EP2615101B1 CLAIM 1: A pharmaceutical composition comprising a pharmaceutically acceptable [0001] The present invention relates to 4’-azido-2’-deoxy-2’- excipient and a compound having Formula I β-fluoropyrimidine nucleoside derivatives, preparation methods thereof, and uses thereof for preparing anti-tumor and anti-virus medicaments.

[030]

Monophosphate Formula I, or salt thereof, wherein Q is O, -O(C=O)-, -O(C=O)V-, or NR7; ester, V is O, NH, NR7, CH2, or CHR7; diphosphate [031] 5-07 R1=NHOCH3, 5-08 R1=NHOEt, 5-17 R1= NHOH, W is O; X is CH2,CHMe, CMe2, CHF, CF2, or CD2; ester Y is CR”; Z is CR”; 5-30 R1= , 5-31 R1=CH3NHNH each R” is independently selected from is H, D, F, Cl, Br, I, CH3, CD3, CF3, C1-22alkyl, acyl, C2- 22alkenyl, C2-22alkynyl, hydroxyl, formyl or SCH3; [032] Compound 5-07: HRMS(ESI) calcd for C10H13FN6O5Na R1 is [M + Na]+ 339.0829, found 339.0831. Compound 5-08: HRMS(ESI) calcd for C11H15FN6O5Na [M + Na]+ 353.0986, found 353.0986 Compound 5-30: 1H NMR (300 MHz, CD4O): δ 3.85 (2H, s, 5’- CH2), 4.49 (1H, dd, J = 21.8 and 4.7, 3’-H), 5.21 (1H,d, J = 53.6, 2’-H), 5.93 (1H, s, 5-H), 6.47 (1H, dd, J = 11.9 and 4.9, 1’-H), 99

7.61 (1H, s, 6-H); 13C NMR (75 MHz, CD4O): δ 63.4 (5’-CH2), 76.4 (3’-CH, d, J 24.9), 84.6 (1’-CH), 92.6 (5-CH), 96.2 (2’-CH, d, JFC 192.4), 98.6 (4’-C),144.1 (6-CH), 156.7 (4-C), 161.9 (CO); HRMS (ESI) calcd for C10H13FN8O5Na [M + Na]+ 367.0891, found 367.0912 (calcd for C13H20FN6O6 [M + H]+ 345.1071, found 345.1103). Claim 4 The 4'-azido-2'-deoxy-2'-β-fluoropyrimidine nucleoside derivative of alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, claim 1, wherein when carbanoyl, esteryl, alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1- C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, or phosphoramidyl wherein R1 is optionally substituted with one or more, the same or different, R20; Y1 is O or S; the following compounds in which R2 =H and Y2 is OH, OR12, OAlkyl, or BH3 - M+; Y3 is OH or BH3 - M+; R1 is one of the following groups are preferred, entry R1 5-01 R2 is hydrogen or hydroxy; EtNH 5-02 NHCH2CH2NH2 5-03 R3 is hydrogen, hydroxy, (C1-C22)alkyl, halogen, nitro, cyano, hydroxy, amino, Figure imgb0164 mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio, , (C1- 5-04 NEt2 5-05 C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, Figure imgb0165 (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; 5-06 R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, difluoromethyl, Figure imgb0166 trifluoromethyl, hydroxymethyl, halogen, nitro, cyano, hydroxy, amino, mercapto, 5-07 NHOCH3 5-08 NHOEt 5-09 formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, Figure imgb0167 ((C1-C22)alkyl)2amino,(C1-C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6- 5-10 C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; Figure imgb0168 R5 is hydrogen, hydroxy, or halogen; 5-11 R6 is hydrogen, hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl, ethynyl, allenyl, halogen, Figure imgb0169 nitro, cyano, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1- 5-12 C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, Figure imgb0170 (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl,orheterocyclyl; 5-13 each R7 is independently selected from absent, hydrogen, -(C=O)Oalkyl(C1-C22), - Figure imgb0171 (C=O)alkyl(C1- C22), -(C=O)NHalkyl(C1-C22), -(C=O)N-dialkyl(C1-C22), - 5-14 (C=O)Salkyl(C1-C22), hydroxy, (C1-C22)alkoxy, (C1- C22)alkyl, halogen, nitro, cyano, Figure imgb0172 amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1- 127 5-15 C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- Figure imgb0173 C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- 5-16 C12)aryl,orheterocyclyl, wherein each R7 is optionally substituted with one or more, Figure imgb0174 the same or different, R20; 5-17 NHOH 5-18 R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-C22)alkynyl, halogen, Figure imgb0175 nitro, cyano, hydroxy, benzyloxy, amino, amido, mercapto, formyl, carboxy, 5-19 carbamoyl, azido, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1- Figure imgb0176 C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, 5-20 (C3-C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R8 is optionally substituted Figure imgb0177 with one or more, the same or different, R20; 5-21 N(CH3)2 5-22 R9 is hydrogen, methyl, ethyl, tert-butyl, (C1-C22)alkyl, halogen, nitro, cyano, Figure imgb0178 hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, cycloalkyl, (C1-C22)alkoxy, 5-23 (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, Figure imgb0179 (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- 5-24 NH(CH2)4CH3 5-25 NH(CH2)5CH3 5-26 NH(CH2)6CH3 5- C12)aryl,orheterocyclyl, wherein R9 is optionally substituted with one or more, the 27 NH(CH2)7CH3 5-28 NHCH3 5-29 same or different, R20; Figure imgb01= R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, methyl, ethyl, isopropyl, 5-30 cyclopentyl, cyclohexyl, butyl, pentyl, hexyl, neopentyl, benzyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6- C12)aryl,orheterocyclyl, 5-31 CH3NHNH wherein R10 is optionally substituted with one or more, the same or different, R20; R11 is hydrogen, deuterium, (C1-C22)alkyl, methyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R11 is optionally substituted with one or more, the same or different, R20; R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl, 1-naphthyl, 2- naphthyl,aromatic, heteroaromatic, 4-substituted phenyl, 4-fluorophenyl, 4- chlorophenyl, 4-bromophenyl, naphthyl, or heterocyclyl, wherein R12 is optionally substituted with one or more, the same or different, R20; R13 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1- C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R13 is optionally substituted with one or more, the same or different, R20; R14 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C12-C22)alkynyl, 100 halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1- C22)alkyl)2amino, alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R14 is optionally substituted with one or more, the same or different, R20; R20 is deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; and wherein the lipid comprises a C6-22 alkyl, (C1- C22)alkoxy, polyethylene glycol, or (C6-C12)aryl substituted with an (C1-C22)alkyl group, heterocyclylis acarbocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur, and heteroaromatic is an aromatic heterocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur and at least 1 carbon atom.

CLAIM 2: The pharmaceutical composition of claim 1, wherein Q-R7 is [031] 5-07 R1=NHOCH3, 5-08 R1=NHOEt, 5-17 R1= OH. NHOH,

5-30 R1= , 5-31 R1=CH3NHNH

CLAIM 3: The pharmaceutical composition of claim 1, wherein R1 is Claim dependent on claim 1 so the arguments of claim 1 apply as such

R8 is hydrogen, hydroxy, or benzyloxy, and R9 is (C6-C22)alkyl. CLAIM 4. [0001] The present invention relates to 4’-azido-2’- A pharmaceutical composition comprising a pharmaceutically acceptable deoxy-2’-β-fluoropyrimidine nucleoside derivatives, excipient and a compound of formula IB, preparation methods thereof, and uses thereof for preparing anti-tumor and anti-virus medicaments.

Monophosphate ester, diphosphate ester

alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, carbanoyl, esteryl, alkoxy, (C1C22)alkylthio, (C1- 101

C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, or phosphoramidyl,wherein R1 is optionally substituted with one or more, the same or different, R20; Y1 is O or S; Y2 is OH, OR12, OAlkyl, or BH3-M+; Y3 is OH or BH3-M+; R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxymethyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, , (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, , (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; R5 is hydrogen, hydroxy, or halogen; R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2- C22)alkynyl, halogen, nitro, cyano, hydroxy, benzyloxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R8 is optionally substituted with one or more, the same or different, R20; R9 is hydrogen, methyl, ethyl, tert-butyl, (C1-C22)alkyl, halogen, nitro, cyano, hydroxy, amino,mercapto, formyl, carboxy, carbamoyl, cycloalkyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino,((C1- C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl,(C6-C12)aryl,orheterocyclyl, wherein R9 is optionally substituted with one or more, the same or different, R20; R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, methyl, ethyl, isopropyl, cyclopentyl, cyclohexyl, butyl, pentyl, hexyl, neopentyl, benzyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy,carbamoyl, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R10 isoptionally substituted with one or more, the same or different, R20; R11 is hydrogen, deuterium, (C1-C22)alkyl, methyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R11 is optionally substituted with one or more, the same or different, R20; R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl, 1-naphthyl, 2- naphthyl,aromatic, heteroaromatic, 4-substituted phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, naphthyl, or heterocyclyl, wherein R12 is optionally substituted with one or more, the same or different, R20; R13 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2- C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl,(C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R13 is optionally substituted with one or more, the same or different, R20; R14 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C12- C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R14 is optionally substituted with one or more, thesame or different, R20; R15 is hydrogen, Lipid, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1-C22), - (C=O)NHalkyl(C1-C22), -(C=O)N-dialkyl(C1-C22), -(C=O)Salkyl(C1-C22), hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl, halogen, nitro, cyano,amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R15 is optionally substituted with one or more, the same or different, R20; R20 is deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-C22)alkynyl, halogen, 102 nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; and wherein the lipid comprises a C6-22 alkyl, (C6-C22)alkoxy, polyethylene glycol, or (C6-C12)aryl substituted with an alkyl group,heterocyclylis acarbocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur, and heteroaromatic is an aromatic heterocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur and at least 1 carbon atom. CLAIM 5 Claim dependent on claim 3 which depends on claim 1, The composition of claim 3, wherein the compound is selected from: so the arguments of claim 1 apply as such here. 1-(3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)- 4((nonanoyloxy)amino)pyrimidin- 2-one, 1-(3,4-dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-4- ((((heptyloxy)carbonyl)oxy)amino)pyrimidin-2-one, and isopropyl(((3,4-dihydroxy-5-(4-(hydroxyamino)-2-oxopyrimidin-1(2H)- yl)tetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)alaninate. CLAIM 6 [0001] The present invention relates to 4’-azido-2’- A pharmaceutical composition comprising a pharmaceutically acceptable deoxy-2’-β-fluoropyrimidine nucleoside derivatives, excipient and a compound of Formula IC, preparation methods thereof, and uses thereof for preparing anti-tumor and anti-virus medicaments.

or salts thereof, wherein X is CH2,CHMe, CMe2, CHF, CF2, or CD2; Y is H, D, F, Cl, Br, I, CH3, CD3, CF3, alkyl, acyl, alkenyl, alkynyl, hydroxyl, formyl or SCH3; R1 is hydrogen, monophosphate, diphosphate, triphosphate,

alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, carbanoyl, esteryl, alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, or phosphoramidyl, or wherein R1 is optionally substituted with one or more, the same or different, R20; Y1 is O or S; Y2 is OH, OR12, OAlkyl, or BH3-M+; Y3 is OH or BH3-M+; R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, difluoromethyl, 103 trifluoromethyl, hydroxymethyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1- C22)alkylthio,(C1-C22)alkylamino, ((C1-C22)alkyl)2amino,(C1- C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; R5 is hydrogen, hydroxy, or halogen; R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2- C22)alkynyl, halogen, nitro, cyano, hydroxy, benzyloxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R8 is optionally substituted with one or more, the same or different, R20; R9 is hydrogen, methyl, ethyl, tert-butyl, (C1-C22)alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, cycloalkyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino,((C1- C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl,(C6-C12)aryl,orheterocyclyl, wherein R9 is optionally substituted with one or more, the same or different, R20; R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, methyl, ethyl, isopropyl, cyclopentyl, cyclohexyl,butyl, pentyl, hexyl, neopentyl, benzyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy,carbamoyl, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R10 isoptionally substituted with one or more, the same or different, R20; R11 is hydrogen, deuterium, (C1-C22)alkyl, methyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino,(C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, orheterocyclyl, wherein R11 is optionally substituted with one or more, the same or different, R20; R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl, 1-naphthyl, 2- naphthyl,aromatic,heteroaromatic, 4-substituted phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, naphthyl, or heterocyclyl, wherein R12 is optionally substituted with one or more, the same or different, R20; R13 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2- C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R13 is optionally substituted with one or more, the same or different, R20; R14 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C12- C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R14 is optionally substituted with one or more, the same or different, R20; R15 is hydrogen, Lipid, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1-C22), - (C=O)NHalkyl(C1-C22), - (C=O)N-dialkyl(C1-C22), -(C=O)Salkyl(C1-C22), hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl, halogen, nitro, cyano,amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino,(C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R15 is optionally substituted with one or more, the same or different, R20; R20 is deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; and wherein the lipid comprises a C6-22 alkyl, (C6-C22)alkoxy, polyethylene glycol, or (C6-C12)aryl substituted with an alkyl group,heterocyclylis acarbocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen, 104 or sulfur, and heteroaromatic is an aromatic heterocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur and at least 1 carbon atom. CLAIM 7 [0001] The present invention relates to 4’-azido-2’- 7. A pharmaceutical composition comprising a pharmaceutically deoxy-2’-β-fluoropyrimidine nucleoside derivatives, acceptable excipient and a compound of Formula ID, preparation methods thereof, and uses thereof for preparing anti-tumor and anti-virus medicaments.

Formula ID, or salt thereof, wherein W is CH2, NH, S or O; X is CH2,CHMe, CMe2, CHF, CF2, or CD2; Y is N or CR”; Z is N or CR”; each R” is independently selected from is H, D, F, Cl, Br, I, CH3, CD3, CF3, alkyl, acyl, alkenyl, alkynyl, hydroxyl, formyl or SCH3; R1 is hydrogen, monophosphate, diphosphate, triphosphate, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, carbanoyl, esteryl, alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1- C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, or phosphoramidyl, or wherein R1 is optionally substituted with one or more, the same or different, R20; Y1 is O or S; Y2 is OH, OR12, OAlkyl, or BH3-M+; Y3 is OH or BH3-M+; R2 is hydrogenor hydroxy; R3 is hydrogen, hydroxy, alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl,carbocyclyl, aryl, or heterocyclyl; R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxymethyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1- C22)alkylthio,(C1-C22)alkylamino, ((C1-C22)alkyl)2amino,(C1- C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; R5 is hydrogen, hydroxy, or halogen; R6 is hydrogen, hydroxy, alkoxy, alkyl, ethynyl, allenyl, halogen, nitro, cyano, amino, mercapto,formyl, carboxy, carbamoyl, alkoxy, (C1- C22)alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, or heterocyclyl; R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2- C22)alkynyl, halogen, nitro, cyano, hydroxy, benzyloxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1- C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R8 is optionally substituted with one or more, the same or different, R20; R9 is hydrogen, methyl, ethyl, tert-butyl, (C1-C22)alkyl, halogen, nitro, cyano, hydroxy, amino,mercapto, formyl, carboxy, carbamoyl, cycloalkyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino,((C1- C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R9 is optionally substituted with one or more, the same or different, R20; R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, methyl, ethyl, isopropyl, cyclopentyl, cyclohexyl,butyl, pentyl, hexyl, neopentyl, benzyl, halogen, 105 nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy,carbamoyl, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R10 is optionally substituted with one or more, the same or different, R20; R11 is hydrogen, deuterium, (C1-C22)alkyl, methyl, halogen, nitro, cyano, hydroxy, amino, mercapto,formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino,(C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R11 is optionally substituted with one or more, the same or different, R20; R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl, 1-naphthyl, 2- naphthyl,aromatic,heteroaromatic, 4-substituted phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, naphthyl, or heterocyclyl, wherein R12 is optionally substituted with one or more, the same or different, R20; R13 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2- C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1- C22)alkylthio,(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl,(C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R13 is optionally substituted with one or more, the same or different, R20; R14 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C12- C22)alkynyl, halogen, nitro, cyano,hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1- C22)alkylthio,(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R14 is optionally substituted with one or more, the same or different, R20; R15 is hydrogen, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1-C22), - (C=O)NHalkyl(C1-C22), -(C=O)Ndialkyl(C1-C22), -(C=O)Salkyl(C1-C22), hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl, halogen, nitro, cyano, amino,mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl,wherein R15 is optionally substituted with one or more, the same or different, R20; R15’ is hydrogen, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1-C22), - (C=O)NHalkyl(C1-C22), -(C=O)Ndialkyl(C1-C22), -(C=O)Salkyl(C1-C22), hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl, halogen, nitro, cyano, amino,mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; R15 and R15’ can form a ring that is optionally substituted with one or more, the same or different, R20; R20 is deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1- C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; and wherein the lipid comprises a C6-22 alkyl, (C6-C22)alkoxy, polyethylene glycol, or (C6-C12)aryl substituted with an (C1-C22)alkyl group heterocyclylis acarbocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur, and heteroaromatic is an aromatic heterocyclylcomprising 1-4 heteroatoms selected from nitrogen,oxygen, or sulfur and at least 1 carbon atom. CLAIM 8 [0001] The present invention relates to 4’-azido-2’- 8. A pharmaceutical composition comprising a pharmaceutically deoxy-2’-β-fluoropyrimidine nucleoside derivatives, acceptable excipient and a compound of Formula IE, preparation methods thereof, and uses thereof for preparing anti-tumor and anti-virus medicaments.

[030] 106

Formula IE, [031] 5-07 R1=NHOCH3, 5-08 R1=NHOEt, 5-17 R1= or salt thereof, wherein NHOH, Q is O, -O(C=O)-, -O(C=O)Lipid, -O(C=O)V-, NH, or NR7; V is O, NH, NR7, S, CH2, or CHR7; W is CH2, NH, S or O; 5-30 R1= , 5-31 R1=CH3NHNH X is CH2,CHMe, CMe2, CHF, CF2, or CD2; Y is N or CR”; [032] Compound 5-07: HRMS(ESI) calcd for Z is N or CR”; C10H13FN6O5Na [M + Na]+ 339.0829, found each R” is independently selected from is H, D, F, Cl, Br, I, CH3, CD3, CF3, 339.0831. alkyl, acyl, alkenyl, alkynyl, hydroxyl, formyl or SCH3; Compound 5-08: HRMS(ESI) calcd for R2 is hydrogen, alkyl, alkenyl, alkynyl, ethynyl, fluoromethyl, C11H15FN6O5Na [M + Na]+ 353.0986, found 353.0986 difluoromethyl, trifluoromethyl, chloromethyl, hydroxymethyl, halogen, Compound 5-30: 1H NMR (300 MHz, CD4O): δ 3.85 nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (2H, s, 5’-CH2), 4.49 (1H, dd, J = 21.8 and 4.7, 3’-H), alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, 5.21 (1H,d, J = 53.6, 2’-H), 5.93 (1H, s, 5-H), 6.47 (1H, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl, azido, or heterocyclyl; dd, J = 11.9 and 4.9, 1’-H), 7.61 (1H, s, 6-H); 13C NMR R3 is hydrogen, hydroxy, alkyl, halogen, nitro, cyano, hydroxy, amino, (75 MHz, CD4O): δ 63.4 (5’-CH2), 76.4 (3’-CH, d, J mercapto, formyl, carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio, 24.9), 84.6 (1’-CH), 92.6 (5-CH), 96.2 (2’-CH, d, JFC alkylamino, alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, 192.4), 98.6 (4’-C),144.1 (6-CH), 156.7 (4-C), 161.9 carbocyclyl, aryl, or heterocyclyl; (CO); HRMS (ESI) calcd for C10H13FN8O5Na [M + Na]+ R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, difluoromethyl, 367.0891, found 367.0912 (calcd for C13H20FN6O6 trifluoromethyl, hydroxymethyl, halogen, nitro, cyano, hydroxy, amino, [M + H]+ 345.1071, found 345.1103). mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1- Claim 4 C22)alkylthio,(C1-22)alkylamino, ((C1-C22)alkyl)2amino,(C1- The 4'-azido-2'-deoxy-2'-β-fluoropyrimidine nucleoside C22)alkylsulfinyl,(C1-22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- derivative of C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; claim 1, wherein when R5 is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, alkynyl, ethynyl, fluoromethyl, difluoromethyl,trifluoromethyl, hydroxymethyl, allenyl, halogen, nitro, cyano, amino, mercapto, formyl, carboxy, carbamoyl,alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl,or heterocyclyl; the following compounds in which R2 =H R6 is hydrogen, hydroxy, alkoxy, alkyl, ethynyl, allenyl, halogen, nitro, and R1 is one of the following groups are preferred, cyano, amino, mercapto,formyl, carboxy, carbamoyl, alkoxy, (C1- entry R1 5-01 EtNH 5-02 NHCH2CH2NH2 5-03 C22)alkylthio, lkylamino, (alkyl)2amino, alkylsulfinyl, Figure imgb0164 alkylsulfonyl,arylsulfonyl, carbocyclyl, aryl, or heterocyclyl; 5-04 NEt2 5-05 each R7 is independently selected from absent, hydrogen, -(C=O)Oalkyl, - Figure imgb0165 (C=O)alkyl, -(C=O)NHalkyl, -(C=O)N-dialkyl, -(C=O)Salkyl, hydroxy, alkoxy, 5-06 alkyl, higher alkyl, (C6-C16)alkyl, (C6-C22)alkyl, halogen, nitro, cyano, Figure imgb0166 amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, (C1- 5-07 NHOCH3 5-08 NHOEt 5-09 C22)alkylthio,alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, Figure imgb0167 arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, whereineach R7 is optionally 5-10 substituted with one or more, the same or different, R20; Figure imgb0168 R15 is hydrogen, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1-C22), - 5-11 C=O)NHalkyl(C1-C22), -(C=O)Ndialkyl(C1-C22), -(C=O)Salkyl(C1-C22), Figure imgb0169 hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl, halogen, nitro, cyano, 5-12 amino,mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1- Figure imgb0170 C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- 5-13 C22)alkylsulfonyl, (C6-12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or Figure imgb0171 heterocyclyl,wherein R15 is optionally substituted with one or more, the 5-14 same or different, R20; Figure imgb0172 R15’ is hydrogen, -(C=O)Oalkyl(C1-C22), -(C=O)alkyl(C1-C22), - 5-15 C=O)NHalkyl(C1-C22), -(C=O)Ndialkyl(C1-C22), -(C=O)Salkyl(C1-C22), Figure imgb0173 hydroxy, (C1-C22)alkoxy, (C1-C22)alkyl, halogen, nitro, cyano, amino, 5-16 mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkylthio, (C1- Figure imgb0174 C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- 5-17 NHOH 5-18 C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or Figure imgb0175 heterocyclyl; 5-19 R15 and R15’ can form a ring that is optionally substituted with one or Figure imgb0176 more, the same or different,R20; 5-20 107

If Q = -O(C=O)V- and V = NR7 then the R7s can together form a ring that is Figure imgb0177 optionally substitutedwith one or more, the same or different, R20; 5-21 N(CH3)2 5-22 R20 is deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-C22)alkynyl, halogen, Figure imgb0178 nitro, cyano, hydroxy,amino, amido, mercapto, formyl, carboxy, 5-23 carbamoyl, azido, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, Figure imgb0179 ((C1-22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- 5-24 NH(CH2)4CH3 5-25 NH(CH2)5CH3 5-26 C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; and NH(CH2)6CH3 5-27 NH(CH2)7CH3 5-28 NHCH3 5-29 wherein lipid comprises a C6-22 alkyl, (C6-C22)alkoxy, polyethylene glycol, Figure imgb0180 or (C6-C12)aryl substituted with an (C1-C22)alkyl group, heterocyclylis 5-30 carbocyclyl comprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur, and heteroaromatic is an aromatic heterocyclylcomprising 1-4 heteroatoms selected from nitrogen,oxygen, or sulfur and at least 1 5-31 CH3NHNH carbon atom. CLAIM 9 A pharmaceutical composition comprising a pharmaceutically [0001] The present invention relates to 4’-azido-2’- acceptable excipient and a compound of Formula II, deoxy-2’-β-fluoropyrimidine nucleoside derivatives, preparation methods thereof, and uses thereof for preparing anti-tumor and anti-virus medicaments.

[030]

or salt thereof, wherein Q is O, -O(C=O)-, -O(C=O)Lipid, -O(C=O)V-, NH, or NR7; V is O, NH, NR7, S, CH2, or CHR7; [031] 5-07 R1=NHOCH3, 5-08 R1=NHOEt, 5-17 R1= W is CH2, NH, S or O; NHOH, X is CH2 or O; Y is N or CR”; Z is N or CR”; each R” is independently selected from is H, D, F, Cl, Br, I, CH3, CD3, CF3, 5-30 R1= , 5-31 R1=CH3NHNH alkyl, acyl, alkenyl, alkynyl, hydroxyl, formyl or SCH3; R1 is monophosphate, diphosphate, triphosphate, [032] Compound 5-07: HRMS(ESI) calcd for C10H13FN6O5Na [M + Na]+ 339.0829, found 339.0831. Compound 5-08: HRMS(ESI) calcd for C11H15FN6O5Na [M + Na]+ 353.0986, found 353.0986 Compound 5-30: 1H NMR (300 MHz, CD4O): δ 3.85 (2H, s, 5’-CH2), 4.49 (1H, dd, J = 21.8 and 4.7, 3’-H), 5.21 (1H,d, J = 53.6, 2’-H), 5.93 (1H, s, 5-H), 6.47 (1H, dd, J = 11.9 and 4.9, 1’-H), 7.61 (1H, s, 6-H); 13C NMR (75 MHz, CD4O): δ 63.4 (5’-CH2), 76.4 (3’-CH, d, J 24.9), 84.6 (1’-CH), 92.6 (5-CH), 96.2 (2’-CH, d, JFC 192.4), 98.6 (4’-C),144.1 (6-CH), 156.7 (4-C), 161.9 (CO); HRMS (ESI) calcd for C10H13FN8O5Na [M + Na]+ 367.0891, found 367.0912 (calcd for C13H20FN6O6 [M + H]+ 345.1071, found 345.1103). Claim 4 The 4'-azido-2'-deoxy-2'-β-fluoropyrimidine nucleoside derivative of claim 1, wherein when

Y1 is O or S; Y2 is OH, OR12, OAlkyl, or BH3-M+; the following compounds in which R2 =H Y3 is OH or BH3-M+; and R1 is one of the following groups are preferred, R2 is hydrogen, alkyl, alkenyl, alkynyl, ethynyl, fluoromethyl, entry R1 5-01 EtNH 5-02 NHCH2CH2NH2 5-03 difluoromethyl, trifluoromethyl,chloromethyl, hydroxymethyl, halogen, Figure imgb0164 nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, 5-04 NEt2 5-05 alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, Figure imgb0165 alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl,azido, or heterocyclyl; 5-06 R3 is hydrogen, hydroxy, alkyl, halogen, nitro, cyano, hydroxy, amino, Figure imgb0166 mercapto, formyl, carboxy, carbamoyl, alkoxy, (C1-C22)alkylthio, 5-07 NHOCH3 5-08 NHOEt 5-09 108 alkylamino, alkyl)2amino, alkylsulfinyl, alkylsulfonyl, arylsulfonyl, Figure imgb0167 carbocyclyl, aryl, or heterocyclyl; 5-10 R4 is hydrogen, hydroxy,(C1-C22)alkyl, fluoromethyl, difluoromethyl, Figure imgb0168 rifluoromethyl, hydroxymethyl,halogen, nitro, cyano, hydroxy, amino, 5-11 mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1- Figure imgb0169 C22)alkylthio,(C1-C22)alkylamino, ((C1-C22)alkyl)2amino,(C1- 5-12 C22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- Figure imgb0170 C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; 5-13 R5 is hydrogen, hydroxy, alkoxy, alkyl, alkenyl, alkynyl, ethynyl, Figure imgb0171 fluoromethyl, difluoromethyl,trifluoromethyl, hydroxymethyl, allenyl, 5-14 halogen, nitro, cyano, amino, mercapto, formyl, carboxy, Figure imgb0172 carbamoyl,alkoxy, (C1-C22)alkylthio, alkylamino, (alkyl)2amino, 5-15 alkylsulfinyl, alkylsulfonyl, arylsulfonyl, carbocyclyl, aryl,or heterocyclyl; Figure imgb0173 R6 is hydrogen, hydroxy, alkoxy, alkyl, ethynyl, allenyl, halogen, nitro, 5-16 cyano, amino, mercapto,formyl, carboxy, carbamoyl, alkoxy, (C1- Figure imgb0174 C22)alkylthio, alkylamino, (alkyl)2amino, alkylsulfinyl, 5-17 NHOH 5-18 alkylsulfonyl,arylsulfonyl, carbocyclyl, aryl, or heterocyclyl; Figure imgb0175 each R7 is independently selected from absent, hydrogen, -(C=O)Oalkyl, - 5-19 (C=O)alkyl, - (C=O)NHalkyl, -(C=O)N-dialkyl, -(C=O)Salkyl, hydroxy, alkoxy, Figure imgb0176 alkyl, higher alkyl, (C6-C16)alkyl, (C6-C22)alkyl, halogen, nitro, cyano, 5-20 amino, mercapto, formyl, carboxy, carbamoyl, alkoxy, (C1- Figure imgb0177 C22)alkylthio,alkylamino, (alkyl)2amino, alkylsulfinyl, alkylsulfonyl, 5-21 N(CH3)2 5-22 arylsulfonyl, carbocyclyl, aryl, or heterocyclyl, wherein each R7 is Figure imgb0178 optionally substituted with one or more, the same or different, R20; 5-23 R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2- Figure imgb0179 C22)alkynyl, halogen, nitro, cyano,hydroxy, benzyloxy, amino, amido, 5-24 NH(CH2)4CH3 5-25 NH(CH2)5CH3 5-26 mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1- NH(CH2)6CH3 5-27 NH(CH2)7CH3 5-28 NHCH3 5-29 C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- Figure imgb0180 C22)alkylsulfinyl, (C1-22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- 5-30 C6)carbocyclyl, (C6-12)aryl,orheterocyclyl, wherein R8 is optionally substituted with one or more, the same or different, R20; R9 is hydrogen, methyl, ethyl, tert-butyl, (C1-C22)alkyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, cycloalkyl, 5-31 CH3NHNH (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino,((C1- C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3-C6)carbocyclyl,(C6-C12)aryl,orheterocyclyl, wherein R9 is optionally substituted with one or more, the same or different, R20; R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, methyl, ethyl, isopropyl, cyclopentyl, cyclohexyl,butyl, pentyl, hexyl, neopentyl, benzyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy,carbamoyl, (C1- C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-22)alkylsulfinyl,(C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R10 is optionally substituted with one or more, the same or different, R20; R11 is hydrogen, deuterium, (C1-C22)alkyl, methyl, halogen, nitro, cyano, hydroxy, amino, mercapto,formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino,(C1- 22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R11 is optionally substituted with one or more, the same or different, R20; R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl, 1-naphthyl, 2- naphthyl,aromatic,heteroaromatic, 4-substituted phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, naphthyl, or heterocyclyl, wherein R12 is optionally substituted with one or more, the same or different, R20; R13 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2- C22)alkynyl, halogen, nitro, cyano,hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1- C22)alkylthio,(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl,(C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R13 is optionally substituted with one or more, the same or different, R20; R14 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C12- C22)alkynyl, halogen, nitro, cyano,hydroxy, amino, amido, mercapto, formyl, carboxy, arbamoyl, lipid, azido, (C1-C22)alkoxy, (C1- C22)alkylthio,(C1-C22)alkylamino, ((C1-C22)alkyl)2amino, alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R14 is optionally substituted with one or more, the 109 same or different, R20; If Q = -O(C=O)V- and V = NR7 then the R7s can together form a ring that is optionally substituted with one or more, the same or different, R20; R20 is deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2-C22)alkynyl, halogen, nitro, cyano, hydroxy,amino, amido, mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- C12)arylsulfonyl, (C3- C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl; and wherein lipid comprises a C6-22 alkyl, (C6-C22)alkoxy, polyethylene glycol, or (C6-C12)aryl substituted with an (C1-C22)alkyl group, heterocyclylis acarbocyclylcomprising 1-4 heteroatoms selected from nitrogen, oxygen, or sulfur, and heteroaromatic is an aromatic heterocyclylcomprising 1-4 heteroatoms selected from nitrogen,oxygen, or sulfur and at least 1 carbon atom.

CLAIM 10 The pharmaceutical composition of claim 1,further comprising a Claim 10 is dependent on claim 1 so the arguments of propellant. claim 1 apply as such here. Propellant as such no invention CLAIM 11 The pharmaceutical composition of claim 10, wherein the Claim 10 is dependent on claim 1 so the arguments of propellant is compressed air, ethanol, nitrogen, carbon dioxide, nitrous claim 1 apply as such here. Propellant as such no oxide, hydrofluoroalkanes (HFA), 1,1,1,2,-tetrafluoroethane, 1,1,1,2,3,3,3- invention heptafluoropropane or combinations thereof. CLAIM 12 The composition of claim 1, wherein the compound has a [0001] The present invention relates to 4’-azido-2’- structure according to Formula IA deoxy-2’-β-fluoropyrimidine nucleoside derivatives, preparation methods thereof, and uses thereof for preparing anti-tumor and anti-virus medicaments.

[030]

[031] 5-07 R1=NHOCH3, 5-08 R1=NHOEt, 5-17 R1= NHOH, monophosphate ester, diphosphate ester 5-30 R1= , 5-31 R1=CH3NHNH

[032] Compound 5-07: HRMS(ESI) calcd for C10H13FN6O5Na [M + Na]+ 339.0829, found 339.0831. Compound 5-08: HRMS(ESI) calcd for C11H15FN6O5Na [M + Na]+ 353.0986, found 353.0986 Compound 5-30: 1H NMR (300 MHz, CD4O): δ 3.85 (2H, s, 5’-CH2), 4.49 (1H, dd, J = 21.8 and 4.7, 3’-H), 5.21 (1H,d, J = 53.6, 2’-H), 5.93 (1H, s, 5-H), 6.47 (1H, dd, J = 11.9 and 4.9, 1’-H), 7.61 (1H, s, 6-H); 13C NMR (75 MHz, CD4O): δ 63.4 (5’-CH2), 76.4 (3’-CH, d, J 24.9), 84.6 (1’-CH), 92.6 (5-CH), 96.2 (2’-CH, d, JFC 192.4), 98.6 (4’-C),144.1 (6-CH), 156.7 (4-C), 161.9 (CO); HRMS (ESI) calcd for C10H13FN8O5Na [M + Na]+ 367.0891, found 367.0912 (calcd for C13H20FN6O6 [M + H]+ 345.1071, found 345.1103). amino, mercapto, formyl, carboxy, carbanoyl, esteryl, alkoxy, (C1- Claim 4 C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- The 4'-azido-2'-deoxy-2'-β-fluoropyrimidine nucleoside C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- derivative of C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, or phosphoramidyl, wherein claim 1, wherein when R1 is optionally substituted with one or more, the same or different, R20, Y1 is O or S; Y2 is OH, OR12, OAlkyl, or BH3-M+; Y3 is OH or BH3-M+; 110

R4 is hydrogen, hydroxy, (C1-C22)alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxymethyl, halogen, nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or the following compounds in which R2 =H heterocyclyl, wherein R4 is optionally substituted with one or more, the and R1 is one of the following groups are preferred, same or different, R20; entry R1 5-01 EtNH 5-02 NHCH2CH2NH2 5-03 R5 is hydrogen, hydroxy, or halogen; Figure imgb0164 R8 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2- 5-04 NEt2 5-05 C22)alkynyl, halogen, nitro, cyano, hydroxy, benzyloxy, amino, amido, Figure imgb0165 mercapto, formyl, carboxy, carbamoyl, azido, (C1-C22)alkoxy, (C1- 5-06 C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1- Figure imgb0166 C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- 5-07 NHOCH3 5-08 NHOEt 5-09 C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R8 is optionally Figure imgb0167 substituted with one or more, the same or different, R20; 5-10 R9 is hydrogen, methyl, ethyl, tert-butyl, (C1-C22)alkyl, halogen, nitro, Figure imgb0168 cyano, hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, cycloalkyl, 5-11 (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino,((C1- Figure imgb0169 C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6- 5-12 C12)arylsulfonyl, (C3-C6)carbocyclyl,(C6-C12)aryl,orheterocyclyl, wherein Figure imgb0170 R9 is optionally substituted with one or more, the same or different, R20; 5-13 R10 is hydrogen, (C1-C22)alkyl, cycloalkyl, lipid, methyl, ethyl, isopropyl, Figure imgb0171 cyclopentyl, cyclohexyl,butyl, pentyl, hexyl, neopentyl, benzyl, halogen, 5-14 nitro, cyano, hydroxy, amino, mercapto, formyl, carboxy,carbamoyl, (C1- Figure imgb0172 C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, 5-15 (C1-C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- Figure imgb0173 C6)carbocyclyl, (C6-C12)aryl,orheterocyclyl, wherein R10 is optionally 5-16 substituted with one or more, the same or different, R20; Figure imgb0174 R11 is hydrogen, deuterium, (C1-C22)alkyl, methyl, halogen, nitro, cyano, 5-17 NHOH 5-18 hydroxy, amino, mercapto, formyl, carboxy, carbamoyl, (C1-C22)alkoxy, Figure imgb0175 (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino,(C1- 5-19 C22)alkylsulfinyl, (C1-C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3- Figure imgb0176 C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R11 is optionally 5-20 substituted with one or more, the same or different, R20; Figure imgb0177 R12 is hydrogen, (C1-C22)alkyl, (C6-C12)aryl, phenyl, 1-naphthyl, 2- 5-21 N(CH3)2 5-22 naphthyl, aromatic, heteroaromatic, 4-substituted phenyl, 4-fluorophenyl, Figure imgb0178 4-chlorophenyl, 4-bromophenyl, naphthyl, or heterocyclyl, wherein R12 is 5-23 optionally substituted with one or more, the same or different, R20; Figure imgb0179 R13 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C2- 5-24 NH(CH2)4CH3 5-25 NH(CH2)5CH3 5-26 C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, NH(CH2)6CH3 5-27 NH(CH2)7CH3 5-28 NHCH3 5-29 formyl, carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1-C22)alkylthio, Figure imgb0180 (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, (C1-C22)alkylsulfinyl, (C1- 5-30 C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R13 is optionally substituted with one or more, the same or different, R20; R14 is hydrogen, deuterium, (C1-C22)alkyl, (C2-C22)alkenyl, (C12- 5-31 CH3NHNH C22)alkynyl, halogen, nitro, cyano, hydroxy, amino, amido, mercapto, formyl, carboxy, carbamoyl, lipid, azido, (C1-C22)alkoxy, (C1-C22)alkylthio, (C1-C22)alkylamino, ((C1-C22)alkyl)2amino, alkylsulfinyl, (C1- C22)alkylsulfonyl, (C6-C12)arylsulfonyl, (C3-C6)carbocyclyl, (C6-C12)aryl, or heterocyclyl, wherein R14 is optionally substituted with one or more, the same or different, R20;

CLAIM 13 Claim dependent on claim 1 so the arguments of claim The composition of claim 1, wherein R4 is hydrogen, hydroxy, alkyl, 1 apply as such halogen, or fluoro. CLAIM 14 Claim dependent on claim 1 so the arguments of claim The composition of claim 1, wherein R5 is hydrogen, hydroxy, alkoxy, alkyl, 1 apply as such methyl, ethynyl, or allenyl.

Therefore, it may be concluded that all claims of IN201717025098 are anticpated by contents

of D4 as well apart from D1-D3.

111

From the above comparison it is amply clear that none of the claims of opposed application are novel wrt to D1-D4 independently as per Section 2(1)(l) of the IPA.

Therefore, Learned Examiner is request to reject the case on grounds of Section 25(1)(b)&

GROUND II:

II) Section 25(1)(e): Lack of inventive step

The invention so far as claimed in any claim of the complete specification is obvious and clearly does not involve any inventive step, having regard to the matter published as mentioned in clause (b) or having regard to what was used in India before the priority date of the claim.

It is submitted that the invention lacks any inventive step and on this ground alone should be rejected.

As such, when none of the claims 1-14 as submitted by Applicant in response to FER (Annexure 2) are novel for the reasons as aforesaid, claims lack inventive step without a doubt. However for sake of clarity, Applicant has discussed lack of inventive step wrt to each citation.

Applicant shall rely on following prior art while discussing lack of inventive step in the impugned application:

D1: US 2003/0087873 D2: US20140235566A1 D3: WO2013142525A1 D4: EP2615101B1 D5: US2004/0171860A1 D6: US 2014/0273023 D7: WO 2009/143011A1 D8: US5349947A1

112

Opponent shall consider the problem solution approach to clarify his stand as following:

The problem in the prior art as anticipated by opponent (as there is no mention of the same in the specification of impugned application) could be the need of new antiviral drugs and antivirals with broader coverage.

Considering both D1 & D2 are from Emory University only, its very obvious for a person to use the background technology available with their institute and find new uses of the existing compounds known to be having antiviral properties. That is clearly what the Applicant has done in the current case. Completely overlapping compounds of impugned application with compounds of D1 & D2 alone or combined for same usage proves opponent’s point.

Further discussing the lack of inventive step in the impugned application, wrt to Graham’s factors of inventive step as laid in Graham v. John Deere Co.

Graham’s Factors Facts The scope and content of the prior art; D1-D4 and are clearly identified prior art The level of ordinary skill in the art; Ordinary skilled in the art has access to information available in public domain to make the β-D or β-L nucleosides to be used as antivirals. Applicant being from the same institute as of D1, D2 had the privilege of readily available background technology to work on. The differences between the claimed invention and Contents of impugned application seem to be the prior art. completely anticipating the consent of the opposed application. Applicant seems to be claiming the prior art as no improvements over existing prior art are reported.

Further, there have been no multiple failed efforts to answer the need of the prior art. Even

Emory University, the Applicant in this application and of D1 & D2, has been working in the area and filing patents in the same set of compounds for past 15 years.

Thus, the invention lacks novelty in view of D1, D2, D3, and D4 independently and so the fact obviously renders invention not having inventive alone or when combined.

i) Obviousness of the invention wrt to D1 US 2003/0087873

113

D1 discloses a β-D or β-L nucleosides or its pharmaceutically acceptable salt or prodrug for the treatment of a host infected with a virus belonging to the Flaviviridae infection including all members of the Hepacivirus genus (HCV), Pestivirus genus (BVDV, CSFV, BDV), or

Flavivirus genus (Dengue virus, Japanese encephalitis virus group (including West Nile

Virus), and Yellow Fever virus); Orthomyxoviridae including all members of the Influenza

A, B genus, in particular influenza A and all relevant subtypes - including H1N1 and H3N2 - and Influenza B; and Paramyxoviridae family including Respiratory Syncytial Virus (RSV) infection or for the treatment of abnormal cellular proliferation including malignant tumors.

All claims of IN201717025098 are clearly anticipated by D1 as described above in context of novelty. Thus IN201717025098 offers no technical advancement over D1 and is clearly obvious over D1 alone. ii) Obviousness of the invention wrt to D2 2014/23556

D2 discloses compounds and compositions for treating and preventing cancer and viral infections such as HIV, HCV, Norovirus, Saporovirus, cytomegalovirus (CMV), herpes viruses (HSV-1, HSV-2), Dengue virus, Yellow fever, or HBV in human patients or other animal hosts, using N4-hydroxycytidine nucleosides derivatives, modified monophosphate and phosphonates prodrugs analogs, and pharmaceutically acceptable, salts, prodrugs, and other derivatives thereof of the Formula (I),

X1 is H, C1-C6 alkyl, C1-C6haloalkyl, C1-C6alkoxy, C2-C 6 alkenyl, C2-C6alkynyl, COR1, or COOR1; X2 is hydrogen, COR1, or COOR1 wherein each R1 is, independently, CH2-O(CO)-X5; CH2-O(CO)O-X5, C1-20alkyl, the carbon chain derived from a fatty 114 alcohol or C1-20alkyl substituted with a C1-C6alkyl, alkoxy, di(C1- C6alkyl)-amino, fluoro, C3-C10cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aryl, heteroaryl, substituted aryl, or substituted heteroaryl; wherein the substituents are C1-6 alkyl, or C1-6 alkyl substituted with a C1-C6 alkyl, C1 –C6alkoxy, di(C1-C6alkyl)-amino, fluoro, or C3-10cycloalkyl; X5 is independently, C1-20 alkyl, the carbon chain derived from a fatty alcohol or C alkyl substituted with a C1–C6 alkyl, alkoxy, C3-10cycloalkyl, cycloalkyl alkyl, cycloheteroalkyl, aryl, heteroaryl, substituted aryl, or substituted heteroaryl; wherein the substituents are C1-6alkyl, or C1-6alkyl substituted with a C1-C6alkyl, C1-C6alkoxy, di(C1- C6alkyl)-amino, fluoro, or C cycloalkyl each X3 and X4 is independently H, C1-6alkyl, C2- C6 alkenyl, C2-C6alkynyl, aryl, alkylaryl, halogen, NH2, OH, SH, CN, or NO2;

Wherein the sugar moiety is ribose or modified ribose of the general Formula (II),

wherein:

D is H, C(O)R1, C(O)OR1, diphosphate ester, or triphosphate

ester; R1 is as defined above;

W is CL2 or CL2CL2, wherein L independently is selected from the group consisting

of H, C1-6alkyl, C2-6alkenyl, and C2-6 alkynyl, wherein C1-C6 alkyl, C2-6 alkenyl,

and C2-6alkynyl can each optionally contain one or more heteroatoms; A is O, S,

CH2, CHF, CF2, C=CH2, C=CHF, or C=CF2;

R4', R5, R5', R6, R6', and R7 are independently selected from the group consisting of

H, F, CI, Br, I, OH, SH, NH2, NHOH, NHNH2, N3, C(O)OH, CN, CH2OH,

C(O)NH2, C(S)NH2, C(O)OR, R, OR, SR,SSRNHR,andNR2;

R5’andR6’ can come together to form a ring; wherein: when A is O or CH2, D is H or acyl, W is CH2, R4' and R7’are H then, R5,

R5', R6, R6' cannot be H, halogen, OH, SH, OCH3 , SCH3, NH2, NHCH3, CH3,

CH=CH2, CN, CH2NH2, CH2OH, COOH when A is O or S, R7cannot be OH, SH,

NH2, NHOH,

115

NHNH2, OR, SR, SSR, NHR, or NR2, and R is independently a C1-C6alkyl, C2-

6alkenyl, C2-6alkynyl, C3-6 cycloalkyl, (C3-C6cycloalkyl) aryl, alkylaryl, or

arylalkyl, wherein the groups can be substituted with one or more substituents as

defined above.

The Opponent states that the antiviral compounds having the core N4-hydroxycytidine nucleoside moiety covered under the Markush structure in pharmaceutical composition of independent claim(s) 1, 4, 6, 7, 8 and 9 of the impugned Patent Application wherein the variables are as defined in the amended claims with identical properties and functions are prior disclosed in D2.

Therefore all the claims of the impugned application are obvious and lack any inventive feature over D2 alone.

iii) Obviousness of the invention wrt to D3 WO2013142525A1 to etal

D3 discloses Formula (I), Formula (II), and Formula (III), or a pharmaceutically acceptable salt of the foregoing, for ameliorating or treating a viral infection caused by a virus selected from a henipavirus, a morbilli virus, a respirovirus, a rubulavirus and a metapneumovirus, wherein the compound is selected from Formula (I), Formula II), and Formula (III) has one of the following structures:

(I) (Π)

(HI) wherein: 116

B B and B are independently an optionally substituted heterocyclic base or an optionally substituted heterocyclic base with a protected amino group; R1A is selected from the group consisting of hydrogen, an optionally substituted

N-linked amino acid and an optionally substituted N-linked amino acid ester derivative; R1C and R2C are independently selected from the group consisting of O", OH, an

, an optionally substituted N-linked amino acid and an optionally substituted N-linked amino acid ester derivative; or

117

R2B and R are independently selected from the group consisting of an optionally substituted Ci_6 alkyl, an optionally substituted C2-6 alkenyl, an optionally substituted C2-6 alkynyl, an optionally substituted C3-6 cycloalkyl, an optionally substituted -0-C1-6 alkyl, an optionally substituted -O-C3-6 alkenyl, an optionally substituted -0-C3-6 alkynyl and cyano; R4C is selected from the group consisting of OH, -OC(=0)R"c and an optionally substituted O-linked amino acid; R4A, R3B and R5C are independently a halogen; R5A, R4B and R6C are independently hydrogen or halogen; R6A, R7A and R8A are independently selected from the group consisting of absent, hydrogen, an optionally substituted Ci_24 alkyl, an optionally substituted C2-24 alkenyl, an optionally substituted C2-24 alkynyl, an optionally substituted C3-6 cycloalkyl, an optionally substituted C3-6 cycloalkenyl, an optionally substituted aryl, an optionally substituted heteroaryl, an optionally substituted aryl(Ci_6 alkyl), an optionally substituted *- 15A 16A 17A 18A (CR R )p-0-Ci_24 alkyl, an optionally substituted *-(CR R )q-0-

Ci_24

R6A is and R7 is absent or hydrogen; or R and R , 7/AA are taken together to form a moiety selected from the group consisting of an optionally substituted

and an optionally substituted

wherein the oxygens connected to R6A and R7A, the phosphorus and the moiety form a six-membered to ten- membered ring system;.

9A R is independently selected from the group consisting of an optionally substituted Ci_24 alkyl, an optionally substituted C2-24 alkenyl, an optionally substituted C2-24 alkynyl, an optionally substituted C3_6 cycloalkyl, an 30A 31A optionally substituted C3_6 cycloalkenyl, NR R , an optionally substituted N-linked amino acid and an optionally substituted N-linked amino acid ester derivative;

R10A and R11A are independently an optionally substituted N-linked amino acid or an optionally substituted N- linked amino acid ester derivative;

R12A, R13A and R14A are independently absent or hydrogen;

15A 16A 17A 18A each R , each R , each R and each R are independently hydrogen, an optionally substituted Ci_24 alkyl or alkoxy; R19A, R20A, R22A, R23A, R5B, R6B, R8B, R9B, R9C, R10C, R12C and R13C are independently selected from the group consisting of hydrogen, an optionally substituted Ci_24 alkyl and an optionally substituted aryl; R2iA R24A R7B^ Ri

118

R25A R29A RHB and R15C are independently selected from the group consisting of hydrogen, an optionally substituted Ci_24 alkyl and an optionally substituted aryl;

R1U", R^ and R are independently absent or hydrogen;

R26A and R27A are independently -C≡N or an optionally substituted substituent selected from the group consisting of C2_8 organylcarbonyl, C2_8 alkoxycarbonyl and C2_8 organylaminocarbonyl;

R28A is selected from the group consisting of hydrogen, an optionally substituted Ci_24-alkyl, an optionally substituted C2_24 alkenyl, an optionally substituted C2-24 alkynyl, an optionally substituted C3_6 cycloalkyl and an optionally substituted C3_6 cycloalkenyl;

R30A and R31A are independently selected from the group consisting of hydrogen, an optionally substituted Ci_24-alkyl, an optionally substituted C2-24 alkenyl, an optionally substituted C2_24 alkynyl, an optionally substituted C3_6 cycloalkyl and an optionally substituted C3_6 cycloalkenyl; for Formula (III), is a single bond or a double bond; when is a single bond, each R and each R is independently hydrogen or halogen; and when is a double bond, each R is absent and each R is independently hydrogen or halogen; A "c R" and R are independently an optionally substituted Ci_24-alkyl; m and n are independently 0 or 1 ; p and q are independently selected from the group consisting of 1, 2 and 3; r is 1 or 2;

Z1A, Z2A, Z3A, Z4A, Z1B, Z2B and Z1C are independently O or S; and provided that when the dashed line ( ) of Formula (I) is absent; R1A is

wherein R is an unsubstituted Ci_4 alkyl or phenyl optionally para- substituted with a halogen or methyl and R9A is methyl ester, ethyl ester, isopropyl ester, n-butyl ester, benzyl ester or phenyl ester of an amino acid selected from the group consisting of glycine, alanine, valine, leucine, phenylalanine, tryptophan, methionine and proline; R3A is OH; R4A is fluoro; R5A is fluoro or hydrogen; and B1A is an unsubstituted uracil; then 2A R cannot be -OCH3; provided that when the dashed line ( ) of Formula (I) is absent; R1A is H; R3A is OH; R4A is fluoro; R5A is fluoro; and B1A is an unsubstituted cytosine; then R2A cannot be allenyl; provided that when the dashed line ( ) of Formula (I) is absent; R1A is H; R3A is OH; R4A is fluoro; R5A is hydrogen; and B1A is an unsubstituted thymine; then R2A cannot be Ci alkyl substituted with an N-amido; and provided that when the dashed line ( ) of Formula (I) is absent; R1A is H; R3A is OH; R4A is fluoro; R5A is fluoro; and B1A is an unsubstituted cytosine; then R2A cannot be ethynyl.

Therefore, all the claims of IN201717025098 do not offer any technological advancement over D3 alone rendering it obvious. iv) Obviousness of the invention wrt to D4 EP2615101B1 to Junbiao Chang

D4 discloses fluorinated and azido-substituted pyrimidine nucleoside derivatives, particularly compounds of the formula shown below:

119

Also disclosed are methods of preparation and uses for these compounds. The compounds can be used for preparing medicaments for treating diseases such as tumors and viral infections, and can be used separately or in combination with other medicaments. The compounds also have effective activity against diseases such as tumors and viral infections, while having few side effects, and thus have potential application value.

Thus, it is clear from aforesaid discussion about novelty that that D4 not only affects novelty of the invention it also makes the invention obvious over it.

Therefore, it may be concluded that opposed application was obvious to a person practicing in the field on its priority date given the teachings of D1,D2, D3, D4 and other cited prior art when each is considered even alone.

The mosaicism of the prior art renders all the features of IN201717025098 completely overlapping with the prior art not involving any inventive step and not offering any technical advancement over existing prior art.

IN201717025098 merely reclaims the prior art, offering yet another way of producing antivirals without any technical advancement over the prior art.

120

N4 hydroxycytidine nucleoside compound(s) and derivatives thereof covered under the Markush claims of the impugned Patent Application being pertinently prior disclosed in D1 and D2 with a similar core structure and with broad spectrum anti-viral activity, a person of ordinary skill in art will easily be motivated to use a pharmaceutical composition comprising the N4 hydroxycytidine nucleoside against viral infections.

Hence, there seems to be enough motivation to the Applicant to try out activity of existing compounds against new virus groups, with teachings available within the organization (not even suggestions).

Further when teachings of D1, D2, D3 or D4 alone or combined, there is no burden over a person skilled in the art to come up with invention as disclosed in IN201717025098.

Opponent further refers to D5-D8 as relevant document rendering contents of opposed application as obvious. Since arguments using D1-D4 are enough to prove the fact that the invention is not involving an inventive step, D5-D8 have been not discussed again for sake of brevity and not being repetitive.

Further, attention of Learned Examiner is sought towards response to FER filed by Applicant Annexure 1, on Sept 18, 2020 page 6, first para reading “The Applicant submits herewith amended set of claims wherein claims have been amended to exclude compounds that are recited in D1-D8 and are therefore believed to be novel and inventive as submitted in above paragraph under head “Novelty and Inventive step”. Effectively, Applicant himself confesses overlap of his invention with standing prior art in FER. Even after the amendments, which include only removal of few variables from the main compound of the impugned invention, the main compound still is the same which lacks novelty and inventive step as admitted by the Applicant in response to FER. It is also obvious that adding few variables in the existing compounds without any proved advantage of doing the same cannot make the invention novel or inventive.

As such Opponent has proved the point of lack of novelty and inventive step wrt D1-D4 in above paragraphs.

Therefore, the claims of impugned applications lack inventive step as per section 2(1)(ja) of the Act and renders it non patentable. Hence the application should be rejected being obvious

121 and lacking in inventive step under Section 25(1)(e) apart from lacking novelty totally as per Section 2(1)(l) of the IPA.

GROUND III

III) Section 25(1)(f): The subject of any claim of the complete specification is not an invention within the meaning of this Act, or is not patentable under this Act.

It is submitted that considering all the aforesaid arguments contesting novelty of the invention under Ground I, the invention lacks novelty as per section 2(1)(l) of the Act.

Further, considering the obviousness arguments, under Ground the invention does not involve an inventive step as per section 2(1)(ja) of the Act, hence renders it unpatentable.

Therefore the invention does not qualify to be an invention under section 2(1)(j) of the Act and is therefore not patentable.

Further, Opponent pleads that the contents of the opposed application attract the provisions of Section 3 of the Indian Patents Act, 1970 and hence are non-patentable. The reasons are as following:

a. Section 3(d): Section 3(d) of 'the Act reads as “the mere discovery of a new form of a known substance which does not result in the enhancement of the known efficacy of that substance or the mere discovery of any new property or new use for a known substance or of the mere use at a known process, machine or apparatus unless such known process results in a new product or employs at least one new reactant’ is not patentable under the Act.

Explanation:- For the purpose of this clause, salts, esters, ethers, polymorphs, metabolites, pure form, particle size, isomers, mixtures of isomers, complexes, combinations and other derivatives of known substance shall be considered to be the same substance, unless they differ significantly in properties with regard to efficacy.”

122

It is clear from aforesaid arguments that the compounds disclosed in opposed application are not novel, inventive and merely an attempt to reclaim the prior art. Further, Opponent states that the alleged Applicant has failed to demonstrate enhancement in the therapeutic efficacy of the plethora of compounds, covered under the Markush structure, as broad spectrum antivirals in the as filed impugned patent application over the known compounds disclosed in said prior art documents.

D1 has disclosed the antiviral effect of the N4 hydroxycytidine nucleoside compounds on various cell lines at active concentration of low-micromolar range on pages 184-201.

D2 has disclosed the antiviral activity of the N4 hydroxycytidine nucleoside compounds in low micromolar range against HCV on page 131.

Learned Controller’s attention is sought to following points in the reply to FER filed by Applicant on Sept 18, 2020:

i. Applicant has disclaimed the compounds covered under the Markush structure

of Formula (I) and in Formula IA (newly added claim 12) in the as filed

complete specification by virtue of deletion of the group ‘H’ atom from the

variable R1 in the amended claims as on record attached as Annexure 2.

Hence, the claim to compound(s) covered under the Markush structure of

Formula I or Formula IA, wherein R1 is hydrogen and provided in the

examples (shown below) as antiviral agents now stand invalid. Therefore, the

data provided by the Applicant to support the claim of improved efficacy does

not hold good.

ii. The Opponent further submits that the anti-viral activity efficacy data

provided by the alleged Applicant in the FER response pages 6 to 10

attached as Annexure 1 for the compound EIDD-1931 is confusing since

123

the Applicant has disclaimed the compound by deletion of the group ‘H’

atom from the R1 variable of Formula I (claim 1) and Formula (IA) in

newly added Claim 12. iii. Applicant on page 6 of the FER response filed on Sept 18, 2020 first para

mentions “The Applicant submits herewith amended set of claims wherein

claims have been amended to exclude compounds that are recited in D1-

D8 and are therefore believed to be novel and inventive as submitted in

above paragraph under head “Novelty and Inventive step”. Therefore,

Applicant himself confesses that the deleted variables of the markush were

not novel and hence any data related to the same cannot be used to

establish enhance efficacy over the prior art. iv. Applicant on page 10, first para of the response to FER refers to

“PCT/US2018/064503 (Example 33) demonstrates the efficacy of EIDD-

1931 against Togaviridae, particularly against CHIKV, EEEV, VEEV, and

WEEV.” To support its arguments of improved efficacy.

PCT/US2018/064503 by Emory University has an Indian counterpart

202017019418 published on Aug 14, 2020. Applicant is citing support

from data of application filed in 2020 during prosecution of his application

claiming priority of 2014. This is clear evidence to believe that Applicant

is trying to keep molecules of potential value always under patent

protection thus evergreening the molecule for around 10 yrs or so. This

itself defeats the purpose of inclusion of Section 3(d) of the IPA and

should be the ground alone to reject the opposed Application.

v. Applicant mentions “It is therefore incorrect to assume that because D1

compounds (as an example) treat Flaviviridae virus infection, then the

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same compounds would be effective against other RNA virus infections,

such as those caused by MERS coronavirus, Eastern equine encephalitis

virus, and the like. Even more, it is unseemly to assume that after

structural modifications to a known antiviral compound, the modified

compound would still possess any or similar antiviral activity.”on page 4

second last para of the response Annexure 1. Applicant seems to be

contradicting his own statement when he cites his 202017019418 data to

support this application against Section 3(d) objections. This actually

opens up a question as to compounds of 202017019418 & currently

opposed application are same that the Applicant expects results of one to

be used for other or else his quoted statement is not valid. If the statement

of extrapolating results of 202017019418 is meant to be true, then same

logic applies to D1-D4 and these results could be applicable to compounds

therein, thus anticipating antiviral properties against all viral families as

attempted by Applicant. If this is the case, then compounds of D1-D4

render markush of currently opposed application as not novel only, as per

his own admission. vi. Applicant may be tempted to revive his interest in antiviral compounds of

currently opposed application, given the pandemic, but can the data being

cited to support the claims be treated as part of specification as per section

10(4) (a) of the Indian Patent Act is left to Learned Examiner’s wise

judgement. vii. This could be a case of double patenting by Applicant’s own admission so

either of the application should be dropped by the Applicant on his own.

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Section 3(e):

The Opponent submits that the impugned claims 1 to 14 (as amended) fall within the ambit of section 3(e) and hence are not patentable.

The Opponent submits that the alleged Applicant has failed to demonstrate the synergy of the pharmaceutical composition containing the compounds covered under the Markush structure in the amended claims. Hence, the provision of section 3(e) of the Patents Act is also attracted. The complete specification and the claims of the impugned patent application indicate that the pharmaceutical compounds are obtained by mere admixture resulting only in the aggregation of the properties of the component thereof or a process of producing the substance. There is no synergism as reflected by absence of any supporting data in the patent application and it ought to be rejected.

Opponent humbly submits that the Applicant is merely attempting to reclaim the prior art without establishing any efficacy or synergy over the prior art. Therefore, it should be rejected as being under the provision of Section 3 (e) of the IPA, 1970.

Further, the Opponent has come to know that there have been concerns about similar drugs having mutagenic (DNA damaging) properties. A previous company, Pharmasset, that had investigated the drug's active ingredient had abandoned it. Source: https://en.wikipedia.org/wiki/Molnupiravir . Negishi K, Harada C, Ohara Y, Oohara K, Nitta

N, Hayatsu H. 1983. N4-aminocytidine, a nucleoside analog that has an exceptionally high mutagenic activity. Nucleic Acids Res 11:5223–5233. doi:10.1093/nar/11.15.522

In this context, Opponent has as humble submission that Applicant should be asked to submit the safety data available else the application may attract the provisions of Section 3(b) of the

IPA, reading “an invention the primary or intended use or commercial exploitation of 126 which could be contrary public order or morality or which causes serious prejudice to human” . While opponent is not bringing this objection right now but reserves the right to recall this objection during the opposition proceedings while looking at the data made available by the Applicant.

GROUND IV

IV) Section 25(1)(g): The complete specification does not sufficiently and clearly describe the invention or the method by which it is to be performed:

It is submitted that the complete specification of the impugned patent application

contains a plurality of possibilities and no clarity as to what exactly is claimed.

It is further submitted that the alleged Applicant has failed to describe the plethora of

compounds covered under the Markush structure of the impugned claims 1 to 14 and

the anti-viral activity in the as filed complete specification.

Claims mention “pharmaceutical composition comprising a pharmaceutically

acceptable excipient” however what is actual composition and what are the excipients,

dosage etc. are not defined.

There is no supporting antiviral activity data for the kind of the breadth of antiviral

activity claimed by Applicant.

Therefore, it is submitted that the impugned claims are not sufficiently enabled by

way of description as per the requirement of section 25(1)(g) read with section 10(4)

of the Patent Act, 1970 and hence be rejected on this ground alone.

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GROUND V

V. Section 25 (1)(i): The complete specification does not disclose or wrongly mentions the source or geographical origin of biological material used for the invention

The specification does not state that the source and geographical origin of the biological materials hydrogenated castor oil or hydrogenated vegetable oil, or mixtures used in the invention.

In view of the above serious defects in the claims and specification, all the claims are liable to be rejected.

P R A Y E R

In the facts and circumstances of the case the Petitioner prays as follows:

(i) That the Patent Application No. IN201717025098 filed by the Applicant

be rejected in toto and the grant of Patent to the Applicant is refused;

(ii) That the Opponent be granted a hearing under section 25(1) read with Rule

55(1) and the Opponent be informed immediately of any response filed by

the Applicant to this Opposition;

(iii) That the Opponent be provided the Reply Statement along with evidence,

if any, filed by the Patent Applicant under Rule 55(4);

(iv) That the Opponent be granted leave to file further arguments and evidence

(rejoinder) against the impugned application of the Applicant;

(v) That the Opponent be allowed to oppose with documents and further

evidence any amendments or changes that the Applicant may make to the

Complete Specifications or claims;

(vi) For costs;

(vii) Such other and further relief/s be granted to the Opponent, as the Ld.

Controller may deem fit in the facts and circumstances of this case.

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All communications relating to these proceedings may be sent to the

following address in India:-

Poorvashree Joshi

100, NCL Innovation Park,

Dr Homi Bhabha Rd,

Pune, Maharashtra 411008

E-mail address: [email protected]

Dated this 31st day of March 2021

Poorvashree Joshi IN/PA- 4071 On behalf of Opponent The Controller of Patents The Patent Office, DELHI

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