DOCSLIB.ORG

Patent Application Publication Oo) Pub. No.: US 2013/0260367 Al Lowery, JR

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Patent Application Publication Oo) Pub. No.: US 2013/0260367 Al Lowery, JR US 20130260367A1 (19) United States (12) Patent Application Publication oo) Pub. No.: US 2013/0260367 Al Lowery, JR. et al. (43) Pub. Date: Oct. 3,2013 (54) NMR SYSTEMS AND METHODS FOR THE (86) PCTNo.: PCT/US11/56936 RAPID DETECTION OF ANALYTES § 371 (c)(1), (2), (4) Date: Jun. 20, 2013 Related U.S. Application Data (75) Inventors: Thomas Jay Lowery, JR., Belmont, MA (US); Mark John Audeh, Brighton, (60) Provisional application No. 61/414,141, filed onNov. 16, 2010, provisional application No. 61/418,465, MA (US); Matthew Blanco, Boston, filed on Dec. I, 2010, provisional application No. MA (US); James Franklin Chepin, 61/497,374, filed on Jun. 15,2011. Arlington, MA (US); Vasiliki Demas, Arlington, MA (US); Rahul Dhanda, (30) Foreign Application Priority Data Needham, MA (US); Marilyn Lee Fritzemeier, Lexington, MA (US); Isaac Oct. 22, 2010 (US) .................................... 12/910594 Koh, Arlington, MA (US); Sonia Publication Classification Kumar, Cambridge, MA (US); Lori (51) Int. Cl. Anne Neely, Reading, MA (US); Brian GOlN 33/543 (2006.01) Mozeleski, Knox, ME (US); Daniella C12Q1/70 (2006.01) Lynn Plourde, Arlington, MA (US); GOlN 33/94 (2006.01) Charles William Rittershaus, Malden, C12Q1/68 (2006.01) MA (US); Parris Wellman, Reading, (52) U.S. Cl. MA (US) CPC ........ GOlN33/54326 (2013.01); C12Q1/6825 (2013.01); C12Q1/70 (2013.01); GOlN 33/9493 (2013.01); C12Q1/6895 (2013.01) USPC . 435/5; 436/501; 435/7.1; 435/6.11; 435/7.4; (73) Assignee: T2 Biosystems, Inc., Lexington, MA 435/287.2; 422/69; 422/554 (US) (57) ABSTRACT (21) Appl. No.: 13/384,051 This invention features systems and methods for the detection of analytes, and their use in the treatment and diagnosis of (22) PCT Filed: Oct. 19, 2011 disease. Patent Application Publication Oct. 3, 2013 Sheet I of 57 US 2013/0260367 Al Figure I A 100 r 102 #v s? s/ I\ * * * I t * ttft f/ 55 H 5! StfSfSff. /H f tf/f /' * t S ft ft ff RF OSCtLlATOR VOLTAGE (SIGNAL) Patent Application Publication Oct. 3, 2013 Sheet 2 of 57 US 2013/0260367 Al Figure IB Patent Application Publication Oct. 3, 2013 Sheet 3 of 57 US 2013/0260367 Al Figure 2 FIG, 2D 2D FIG, 2E FIG. Patent Application Publication Oct. 3, 2013 Sheet 4 of 57 US 2013/0260367 Al Figure 3 Patent Application Publication Oct. 3, 2013 Sheet 5 of 57 US 2013/0260367 Al Figure 4 1000 , ( b ) ' ( a ) I 900 $ 800 t 7°0 •: I [ I I I f I A00 O M- 500 / -100 ■ I \ .-- 3-00 I \ I 200 \ ^ - 100 , ' _________ 10 10 10 10 !o' “C 100 200 300 400 500 Pi=TtllIp 'IiJlTIPtOr InTl) Aortic!: D iam eter (nrm Figure 4A Figure 4B t I Mt' = 'X I J I : : r ! ,t: ^ or 'vt. "K ; \\ ______ ■ . - ■ 'I v ; > \ -Vv >' s t •>< \ v \ * c v • Figure 4C Figure 4D MotionaIAveraging ___ Slow Motion Regime Regime -M .:A> OtV iO> Figure 4E Patent Application Publication Oct. 3, 2013 Sheet 6 of 57 US 2013/0260367 Al Figure 5 Analyte (i.e. protein) Aggtomercitsvs santiw ich immunoassay Figure 5A Free drug Competitive immunoassay Figure 5B Figure 5 C Patent Application Publication Oct. 3, 2013 Sheet 7 of 57 US 2013/0260367 Al Figure 6 Patent Application Publication Oct. 3, 2013 Sheet 8 of 57 US 2013/0260367 Al Figure 7 Figure 7 A =NLT V-ODLLr FC=L -PA" = TD > =NLET VC'DL.E TOs CaSTF=DCE CN LEiT NL-LLAN FEALiAE-E LArEL SPAiT A TS-PaPv. VAC L-Ea L {EAST* 17-3021 S'; =NLriLsCOCLE EASE :PASfT * 5 7 -2 2 $ : CAS'=:R'DCE f == TNL-:=: Figure 7D Figure 7E Figure 7F Patent Application Publication Oct. 3, 2013 Sheet 9 of 57 US 2013/0260367 Al Figure 8 PatentApplicationPublication Oct. 3, 2013 Sheet 10 of 57 US 2013/0260367 Al Figure 9 Figure 9A Figure 9 C Patent Application Publication Oct. 3, 2013 Sheet 11 of 57 US 2013/0260367 Al Figure 10 (L)6.56”x(W)2.23”x(H)2.24” (Including Tube Holder Assembly) Figure 10B PatentApplicationPublication Oct. 3, 2013 Sheet 12 of 57 US 2013/0260367 Al Figure 11 Patent Application Publication Oct. 3, 2013 Sheet 13 of 57 US 2013/0260367 Al Figure 13 Figure 13 A Figure 13B Figure 13C PatentApplicationPublication Oct. 3, 2013 Sheet 14 of 57 US 2013/0260367 Al Figure 14 Figure 14 A Figure 14B Figure 14C PatentApplicationPublication Oct. 3, 2013 Sheet 15 of 57 US 2013/0260367 Al Figure 15 OR PatentApplicationPublication Oct. 3, 2013 Sheet 16 of 57 US 2013/0260367 Al Figure 16 PatentApplicationPublication Oct. 3, 2013 Sheet 17 of 57 US 2013/0260367 Al Figure 17 PatentApplicationPublication Oct. 3, 2013 Sheet 18 of 57 US 2013/0260367 Al Figure 18 .< st§ P MB*j g m J p f P - m b */ /7 / / / - / ^ / I________ Figure 18A Figure 18B Figure 18C PatentApplicationPublication Oct. 3, 2013 Sheet 19 of 57 US 2013/0260367 Al Figure 19 Figure 19 A Figure 19B Patent Application Publication Oct. 3, 2013 Sheet 20 of 57 US 2013/0260367 Al Figure 20 Sevspie Support '"or Dnvechstt a- ' ConpD :g & Dtiveshsft {hstKien) h<kr.:rt;!\s Piste Deve Mot»f Patent Application Publication Oct. 3, 2013 Sheet 21 of 57 US 2013/0260367 Al Figure 21 S-13 Ti: Sssu UrsSvgas. i\2 ; Lcsear S =Isi Sn Carr.sge stern SvlJ- ■ W p n n -tOr J r o v r RasS O-iyrsivv & Dr'v-eshat’t thidcen! Suoeo: t ror Onvivneft sWiisiSsisg Pane ^ ¾ ¾ Deve M s'tor Patent Application Publication Oct. 3, 2013 Sheet 22 of 57 US 2013/0260367 Al Figure 22 Ii::- v.-l »5. Sv:;, iXl-WiaS f « c u iif .f ?.h.T?t 'I p\:S O thef I: O :■ :t --;.::o ! -.:::0: - :::::. CfOvlKS biffs: MTtfc?:!-: o r - '•Tvoical --.Sffwi i ' H'', Oaf PTis can h a C-S'.-i-SSiiiS'f S--': c e s ip ie V ----- S C o u p S ittg -'AiiOVVS SO !'-S-SSiigtSPie::; 'Typica:: v hoiicat !.Oupiipv vH p t n a c e s v a rs iv !Mi-IsitOif Ksfse* hfieftS? 'T ypicalSv -.:■:■---■■■:.! ::: .-O.:::::.-'.-: '-V-to s'OVOOW 'T h e s e :i:e}i.::s fc-iv:: Pr: 'TotSeKv spsc’s a-'Pich aiiuw t -fce MtoTor to fihP a specific poioi in it's f e ta e c - f ' "loo.--.- !fis.it.:-' -ISfi-'-. a r t fco Mtoth-'- -:v :. Khtic.:-! CesfcSi?; it's u se ■?• ---C -astc: systems '■Suctctpa: MOfTsT sw itCWV fouSd aiSO PC -USfcfc Figure 22A X1Uvi-J :>!Vo r.voxxUvi ro visV ir •7.:$ V -!.-JvV- srxx iXv-Y V .v- r r > V -j Xo.: FXro :0::007 Offcity! VOw'd rooo.o .:oo> / ■ . - ■ -pO \ Ox 7vi v ovvvroo XV -.?--- '-i. s '; \ if* X O .O -HO i: Y ... 'W V O O U'.1 V '.7 <7 ''V" ' 7- L :o" x"-'" s c 4 en d MO 100.7 orX'Uj! j-.otx. $ % ,.-:XL.S V-X If S-' Oiivr ftf.fj of uoloxe w rw e o .fc IO C-.'7 iCcIiV V V w :y.! OvO.iO::: B'-XX vO t J ••70. ...XvN-- • -SMW-“' ? 7v->> #V i:7. end 70:7.7 : - W O-VO 70 - v 'Ti.; 0 : BAVPig .? 0::777, 7;-;r.<7.7:0 t<J L 77 dire .jv'Vv'-:- .¾ !-"V • ’• Uso \ vnien jveVv Vr F ::77 VYV:MS SOWO-i X. OW 7 MvOMtor. O v in e 4 O-O o e v ...o' bvvojv ihe i-yrxn; Figure 22B PatentApplicationPublication Oct. 3, 2013 Sheet 23 of 57 US 2013/0260367 Al Figure 23 Figure 23A Figure 23B Figure 23 C Patent Application Publication Oct. 3, 2013 Sheet 24 of 57 US 2013/0260367 Al Figure 24 Free Analyte antibody Analyte- coated Particle PatentApplicationPublication Oct. 3, 2013 Sheet 25 of 57 US 2013/0260367 Al Figure 25 Creatinine Competitive Assay in Serum 500 ••..................... I ............. 400 I------------- *•-. f 300 j----------------- p 200 I---------------- "T 10o [■--------------- 0 i------------------- 0.01 0.1 I 10 Crea, mg/dL Figure 25 A 12 Oustmni* Assay edits 2 Dsfferssti Asttibooy fAspa-atfem of IAOl SUaopdssS’rm i -¾- (-'rrpiaetssso a iprodssriiosy SOO SOi> A I £ t<50 £ 200 ■y O A 0 ,SatSSsody iOOOBHO’aOost. sig/fssi Figure 25 B Cmaimme Asttibody Titratfeso with AACs’2-3- 4, Creafsdesiwstfmd particles SOO - SGO '*00 y MvtilKWSf k s d 14H03 &Cm,5A a ■500 I ^OO <&• 4QQ v ^ £ & iOf> :•$ StJ on ny1 * I $ tiVb <r<y 30f> (¾ & (iiJC'Oi C -)1 i riy {vg/tr$ Figure 25 C PatentApplicationPublication Oct. 3, 2013 Sheet 26 of 57 US 2013/0260367 Al Figure 26 Effect of gMAA Processing Method on T2 510 490 Ij 600 ............. 470 | - i 500 ! f ' X " ] « * » 450 400 ■■ 77T JL 430 XControI ; I 300 i—— — LiJ 410 w -S-Twist : X 200 \ ! 390 0 1 8 0 ° turn X 100 i ............... ............. i ................................... ............. .............. 370 ■■ Remove 5s ; X 0 - ........... i 350 0 3 0 4 0.4 0 5 0.6 [AB] ng/mL [AB] |ig/mL Patent Application Publication Oct. 3, 2013 Sheet 27 of 57 US 2013/0260367 Al Figure 27 Creatinine Competitive Assay - sbgMAA Processing 450 r ................. 400 -- 350 j-.................. 300 j------------- -X- I 250 I.................. N 200 h ................. 150 j-.................. 100 F -.............. 50 ------------- 0 : 0.01 0.1 1 10 [Creat] mg/d L Patent Application Publication Oct. 3, 2013 Sheet 28 of 57 US 2013/0260367 Al Figure 28 AntigeirPrtftem Conjugate Jm Free Analyte Antibody-coated Particle Patent Application Publication Oct. 3, 2013 Sheet 29 of 57 US 2013/0260367 Al Figure 29 Tacrolimus Competitive Assay, Extracted Whole Blood • 5 PL Curve Fit Data 7 0 0 f I ■ 6 0 0 I- ...........
Load more

Recommended publications
  • Correlation of Cytokine Level with the Severity of Severe Fever With
    Liu et al. Virology Journal (2017) 14:6 DOI 10.1186/s12985-016-0677-1 RESEARCH Open Access Correlation of cytokine level with the severity of severe fever with thrombocytopenia syndrome Miao-Miao Liu1, Xiao-Ying Lei1, Hao Yu2, Jian-zhi Zhang3 and Xue-jie Yu1,4* Abstract Background: Severe fever with thrombocytopenia syndrome (SFTS) was an emerging hemorrhagic fever that was caused by a tick-borne bunyavirus, SFTSV. Although SFTSV nonstructural protein can inhibit type I interferon (IFN-I) production Ex Vivo and IFN-I played key role in resistance SFTSV infection in animal model, the role of IFN-I in patients is not investigated. Methods: We have assayed the concentration of IFN-α, a subtype of IFN-I as well as other cytokines in the sera of SFTS patients and the healthy population with CBA (Cytometric bead array) assay. Results: The results showed that IFN-α, tumor necrosis factor (TNF-α), granulocyte colony-stimulating factor (G-CSF), interferon-γ (IFN-γ), macrophage inflammatory protein (MIP-1α), interleukin-6 (IL-6), IL-10, interferon-inducible protein (IP-10), monocyte chemoattractant protein (MCP-1) were significantly higher in SFTS patients than in healthy persons (p < 0.05); the concentrations of IFN-α, IFN-γ, G-CSF, MIP-1α, IL-6, and IP-10 were significant higher in severe SFTS patients than in mild SFTS patients (p < 0.05). Conclusion: The concentration of IFN-α as well as other cytokines (IFN-γ, G-CSF, MIP-1α, IL-6, and IP-10) is correlated with the severity of SFTS, suggesting that type I interferon may not be significant in resistance SFTSV infection in humans and it may play an import role in cytokine storm.
    [Show full text]
  • Identification of Chalcone Derivatives As Putative Non-Steroidal Aromatase
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Online Publishing @ NISCAIR Indian Journal of Chemistry Vol. 59B, February 2020, pp. 283-293 Identification of chalcone derivatives as putative non-steroidal aromatase inhibitors potentially useful against breast cancer by molecular docking and ADME prediction Umang Shah*a, Samir Patela, Mehul Patela, Karan Gandhia & Ashish Patelb a Department of Pharmaceutical Chemistry, Ramanbhai Patel College of Pharmacy, Charotar University of Science and Technology, Changa 388 421, India b Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Parul University, P.O. Limda 391 760, Dist. Vadodara, India E-mail: [email protected] Received 30 August 2019; accepted (revised) 16 October 2019 Aromatase is an influential target to overcome estrogen receptor positive breast cancer, as the enzyme is responsible for conversion of androstenedione to estrone, a promising drug target for therapeutic management of breast cancer. Chalcones are prominent biosynthetic compounds and parent candidate for the synthesis of heterocycles with diversified biological activities. The prime objective of the present study is to evaluate the binding interaction of 2-hydroxyphenyl- prop-2-en-1- one (1A-1X), 2-hydroxy-4-methoxyphenyl- prop-2-en-1-one (3A-3X), 2,4-dihydroxyphenyl- prop-2-en-1-one (9A-9X) and 1-hydroxynaphthalen-2-yl-prop-2-en-1-one (5A-5X) derivatives with aromatase enzyme by molecular docking study and also check their ADME properties by maestro suit. The designed chalcones derivatives have been docked against our target protein with PDB id 3S7S retrieved from the protein data bank, whereas exemestane has been taken as the positive control.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2016/0367695A1 Wilson Et Al
    US 20160367695A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2016/0367695A1 Wilson et al. (43) Pub. Date: Dec. 22, 2016 (54) POLYPEPTIDE CONSTRUCTS AND USES (30) Foreign Application Priority Data THEREOF Oct. 28, 2011 (AU) ................................ 2011 9045O2 (71) Applicant: Teva Pharmaceuticals Australia Pty Ltd, Macquarie Park (AU) Publication Classification (72) Inventors: David S. Wilson, Freemont, CA (US); Sarah L. Pogue, Freemont, CA (US); (51) Int. Cl. Glen E. Mikesell, Pacifica, CA (US); A6II 47/48 (2006.01) Tetsuya Taura, Palo Alto, CA (US); C07K 6/28 (2006.01) Wouter Korver, Mountain View, CA (52) U.S. Cl. (US); Anthony G. Doyle, Drummoyne CPC ..... A61K 47/48269 (2013.01); C07K 16/2896 (AU); Adam Clarke, Five Dock (AU); (2013.01); C07K 231 7/565 (2013.01); C07K Matthew Pollard, Dural (AU): 2317/55 (2013.01); C07K 2317/92 (2013.01) Stephen Tran, Strathfield South (AU); Jack Tzu Chiao Lin, Redwood City, (57) ABSTRACT CA (US) (21) Appl. No.: 15/194,926 The present invention provides a polypeptide construct (22) Filed: Jun. 28, 2016 comprising a peptide or polypeptide signaling ligand linked to an antibody or antigen binding portion thereof which Related U.S. Application Data binds to a cell Surface-associated antigen, wherein the ligand (63) Continuation of application No. 14/262,841, filed on comprises at least one amino acid Substitution or deletion Apr. 28, 2014, which is a continuation of application which reduces its potency on cells lacking expression of said No. PCT/AU2012/001323, filed on Oct. 29, 2012. antigen. Patent Application Publication Dec.
    [Show full text]
  • Tanibirumab (CUI C3490677) Add to Cart
    5/17/2018 NCI Metathesaurus Contains Exact Match Begins With Name Code Property Relationship Source ALL Advanced Search NCIm Version: 201706 Version 2.8 (using LexEVS 6.5) Home | NCIt Hierarchy | Sources | Help Suggest changes to this concept Tanibirumab (CUI C3490677) Add to Cart Table of Contents Terms & Properties Synonym Details Relationships By Source Terms & Properties Concept Unique Identifier (CUI): C3490677 NCI Thesaurus Code: C102877 (see NCI Thesaurus info) Semantic Type: Immunologic Factor Semantic Type: Amino Acid, Peptide, or Protein Semantic Type: Pharmacologic Substance NCIt Definition: A fully human monoclonal antibody targeting the vascular endothelial growth factor receptor 2 (VEGFR2), with potential antiangiogenic activity. Upon administration, tanibirumab specifically binds to VEGFR2, thereby preventing the binding of its ligand VEGF. This may result in the inhibition of tumor angiogenesis and a decrease in tumor nutrient supply. VEGFR2 is a pro-angiogenic growth factor receptor tyrosine kinase expressed by endothelial cells, while VEGF is overexpressed in many tumors and is correlated to tumor progression. PDQ Definition: A fully human monoclonal antibody targeting the vascular endothelial growth factor receptor 2 (VEGFR2), with potential antiangiogenic activity. Upon administration, tanibirumab specifically binds to VEGFR2, thereby preventing the binding of its ligand VEGF. This may result in the inhibition of tumor angiogenesis and a decrease in tumor nutrient supply. VEGFR2 is a pro-angiogenic growth factor receptor
    [Show full text]
  • WO 2010/142017 Al
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date 16 December 2010 (16.12.2010) WO 2010/142017 Al (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every A61K 48/00 (2006.01) A61P 37/04 (2006.01) kind of national protection available): AE, AG, AL, AM, A61P 31/00 (2006.01) A61K 38/21 (2006.01) AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, (21) Number: International Application DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, PCT/CA20 10/000844 HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, (22) International Filing Date: KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, 8 June 2010 (08.06.2010) ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, (25) Filing Language: English SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR, (26) Publication Language: English TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: (84) Designated States (unless otherwise indicated, for every 61/185,261 9 June 2009 (09.06.2009) US kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, (71) Applicant (for all designated States except US): DE- ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, FYRUS, INC .
    [Show full text]
  • Differences Between the Non-Steroidal Aromatase Inhibitors Anastrozole and Letrozole – of Clinical Importance?
    British Journal of Cancer (2011) 104, 1059 – 1066 & 2011 Cancer Research UK All rights reserved 0007 – 0920/11 www.bjcancer.com Minireview Differences between the non-steroidal aromatase inhibitors anastrozole and letrozole – of clinical importance? ,1 J Geisler* 1 Institute of Clinical Medicine, University of Oslo, Faculty Division at Akershus University Hospital, Sykehusveien 27, Lørenskog N-1478, Norway Aromatase inhibition is the gold standard for treatment of early and advanced breast cancer in postmenopausal women suffering from an estrogen receptor-positive disease. The currently established group of anti-aromatase compounds comprises two reversible aromatase inhibitors (anastrozole and letrozole) and on the other hand, the irreversible aromatase inactivator exemestane. Although exemestane is the only widely used aromatase inactivator at this stage, physicians very often have to choose between either anastrozole or letrozole in general practice. These third-generation aromatase inhibitors (letrozole/Femara (Novartis Pharmaceuticals, Basel, Switzerland) and anastrozole/Arimidex (AstraZeneca, Pharmaceuticals, Macclesfield, Cheshire, UK)), have recently demonstrated superior efficacy compared with tamoxifen as initial therapy for early breast cancer improving disease-free survival. However, although anastrozole and letrozole belong to the same pharmacological class of agents (triazoles), an increasing body of evidence suggests that these aromatase inhibitors are not equipotent when given in the clinically established doses. Preclinical and clinical evidence indicates distinct pharmacological profiles. Thus, this review focuses on the differences between the non-steroidal aromatase inhibitors allowing physicians to choose between these compounds based on scientific evidence. Although we are waiting for the important results of a still ongoing head-to-head comparison in patients with early breast cancer at high risk for relapse (Femara Anastrozole Clinical Evaluation trial; ‘FACE-trial’), clinicians have to make their choices today.
    [Show full text]
  • WO 2017/112768 Al 29 June 2017 (29.06.2017) P O P C T
    (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2017/112768 Al 29 June 2017 (29.06.2017) P O P C T (51) International Patent Classification: Delaware 19707 (US). ZHUANG, Linghang; 3135 Fox C07D 471/10 (2006.01) A61K 31/47 (2006.01) Drive, Chalfont, Pennsylvania 18914 (US). C07D 487/10 (2006.01) A61K 31/519 (2006.01) (74) Agents: DAVEY, PH.D., Evan A. et al; Fish & Richard C07D 495/04 (2006.01) A61P 35/02 (2006.01) son P.C., P.O. Box 1022, Minneapolis, Minnesota 55440- C07D 513/04 (2006.01) 1022 (US). (21) International Application Number: (81) Designated States (unless otherwise indicated, for every PCT/US20 16/0680 16 kind of national protection available): AE, AG, AL, AM, (22) International Filing Date: AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, 2 1 December 2016 (21 .12.2016) BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DJ, DK, DM, DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (25) Filing Language: English HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KH, KN, (26) Publication Language: English KP, KR, KW, KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, (30) Priority Data: NI, NO, NZ, OM, PA, PE, PG, PH, PL, PT, QA, RO, RS, 62/270,973 22 December 201 5 (22. 12.2015) US RU, RW, SA, SC, SD, SE, SG, SK, SL, SM, ST, SV, SY, (71) Applicant: VITAE PHARMACEUTICALS, INC.
    [Show full text]
  • Aromatase and Its Inhibitors: Significance for Breast Cancer Therapy † EVAN R
    Aromatase and Its Inhibitors: Significance for Breast Cancer Therapy † EVAN R. SIMPSON* AND MITCH DOWSETT *Prince Henry’s Institute of Medical Research, Monash Medical Centre, Clayton, Victoria 3168, Australia; †Department of Biochemistry, Royal Marsden Hospital, London SW3 6JJ, United Kingdom ABSTRACT Endocrine adjuvant therapy for breast cancer in recent years has focussed primarily on the use of tamoxifen to inhibit the action of estrogen in the breast. The use of aromatase inhibitors has found much less favor due to poor efficacy and unsustainable side effects. Now, however, the situation is changing rapidly with the introduction of the so-called phase III inhibitors, which display high affinity and specificity towards aromatase. These compounds have been tested in a number of clinical settings and, almost without exception, are proving to be more effective than tamoxifen. They are being approved as first-line therapy for elderly women with advanced disease. In the future, they may well be used not only to treat young, postmenopausal women with early-onset disease but also in the chemoprevention setting. However, since these compounds inhibit the catalytic activity of aromatase, in principle, they will inhibit estrogen biosynthesis in every tissue location of aromatase, leading to fears of bone loss and possibly loss of cognitive function in these younger women. The concept of tissue-specific inhibition of aromatase expression is made possible by the fact that, in postmenopausal women when the ovaries cease to produce estrogen, estrogen functions primarily as a local paracrine and intracrine factor. Furthermore, due to the unique organization of tissue-specific promoters, regulation in each tissue site of expression is controlled by a unique set of regulatory factors.
    [Show full text]
  • ( 12 ) Patent Application Publication ( 10 ) Pub . No .: US 2020/0331966 A1 STOVER Et Al
    US 20200331966A1 IN ( 19 ) United States ( 12 ) Patent Application Publication ( 10 ) Pub . No .: US 2020/0331966 A1 STOVER et al . ( 43 ) Pub . Date : Oct. 22 , 2020 ( 54 ) FUSION PROTEIN COMPOSITION ( S ) Related U.S. Application Data COMPRISING MASKED TYPE I INTERFERONS ( IFNA AND IFNB ) FOR USE ( 60 ) Provisional application No. 62 / 920,140 , filed on Apr. IN THE TREATMENT OF CANCER AND 15 , 2019 . METHODS THEREOF Publication Classification ( 71 ) Applicant: Qwixel Therapeutics, Los Angeles, CA ( 51 ) Int. Ci . ( US ) CO7K 7/08 ( 2006.01 ) A61K 47/65 ( 2006.01 ) ( 72 ) Inventors : David STOVER , Encino, CA (US ) ; A61P 35/00 ( 2006.01 ) Sherie MORRISON , Los Angeles, CA ( 52 ) U.S. CI . ( US ) ; Alex VASUTHASAWAT , Los CPC CO7K 7/08 ( 2013.01 ) ; A61K 38/00 Angeles , CA ( US ) ; Kham TRINH , ( 2013.01 ) ; A61P 35/00 ( 2018.01 ) ; A61K 47/65 Porter Ranch , CA ( US ) ; George ( 2017.08 ) AYOUB , Los Angeles, CA ( US ) ( 57 ) ABSTRACT Fusion Protein compositions comprising masked IFNs and ( 73 ) Assignee : Qwixel Therapeutics, Los Angeles, CA methods of making masked IFNs are disclosed herein . ( US ) Consequently, the masked IFNs can be fused to a Mab or binding fragment thereof and be administered to patients as ( 21 ) Appl. No .: 16 /849,889 a therapeutic modality and provide a method of treating cancer, immunological disorders and other disease . ( 22 ) Filed : Apr. 15 , 2020 Specification includes a Sequence Listing . Matripase ST 14 Cleaves an IFN Mask from the Heavy Chain of an anti CD138 Fusion Ab . 1 2 3 1. ant - CD138 / Na 2. anti - C0138 IFNa mask 3. anti - C0138 FNa mask w / MST14 Patent Application Publication Oct.
    [Show full text]
  • United States Patent (10) Patent No.: US 9,464,124 B2 Bancel Et Al
    USOO9464124B2 (12) United States Patent (10) Patent No.: US 9,464,124 B2 Bancel et al. (45) Date of Patent: Oct. 11, 2016 (54) ENGINEERED NUCLEIC ACIDS AND 4,500,707 A 2f1985 Caruthers et al. METHODS OF USE THEREOF 4,579,849 A 4, 1986 MacCoSS et al. 4,588,585 A 5/1986 Mark et al. 4,668,777 A 5, 1987 Caruthers et al. (71) Applicant: Moderna Therapeutics, Inc., 4,737.462 A 4, 1988 Mark et al. Cambridge, MA (US) 4,816,567 A 3/1989 Cabilly et al. 4,879, 111 A 11/1989 Chong (72) Inventors: Stephane Bancel, Cambridge, MA 4,957,735 A 9/1990 Huang (US); Jason P. Schrum, Philadelphia, 4.959,314 A 9, 1990 Mark et al. 4,973,679 A 11/1990 Caruthers et al. PA (US); Alexander Aristarkhov, 5.012.818 A 5/1991 Joishy Chestnut Hill, MA (US) 5,017,691 A 5/1991 Lee et al. 5,021,335 A 6, 1991 Tecott et al. (73) Assignee: Moderna Therapeutics, Inc., 5,036,006 A 7, 1991 Sanford et al. Cambridge, MA (US) 9. A 228 at al. J. J. W. OS a 5,130,238 A 7, 1992 Malek et al. (*) Notice: Subject to any disclaimer, the term of this 5,132,418 A 7, 1992 °N, al. patent is extended or adjusted under 35 5,153,319 A 10, 1992 Caruthers et al. U.S.C. 154(b) by 0 days. 5,168,038 A 12/1992 Tecott et al. 5,169,766 A 12/1992 Schuster et al.
    [Show full text]
  • Refined Preparation of 1α,3-Dipyrrolidino-Androsta-3,5-Diene-17-One, a Key Intermediate in the Exemestane Synthesis
    ORIGINAL ARTICLES Pharmaceutical Research Institute1; Faculty of Chemistry, University of Warsaw, Warsaw, Poland Refined preparation of 1␣,3-dipyrrolidino-androsta-3,5-diene-17-one, a key intermediate in the exemestane synthesis Ł. Kaczmarek 1, M. Cybulski 1, M. Kubiszewski 1,A.Les´ 1,2 Received February 3, 2012, accepted March 31, 2012 Prof. Andrzej Le´s, Pharmaceutical Research Institute, Rydygiera 8, 01-793 Warsaw, Poland [email protected] Pharmazie 67: 899–905 (2012) doi: 10.1691/ph.2012.2025 A significant improvement of the patent route for exemestane synthesis has been achieved. The key inter- mediate 1␣,3-dipyrrolidino-androsta-3,5-diene-17-one (7) was obtained in a good yield and effectively used without further isolation in the next reaction step. The original analytical method for the identification and quantification of the substrate androsta-1,4-diene-3,17-dione (ADD, 6), intermediate 7 and 1-pyrrolidino- androsta-1,3,5-triene-17-one (9) impurity in the reaction mixture was applied. Due to the newly developed process, the economical synthesis of the final pharmaceutical product in a large scale was possible. In addition, the complete NMR characteristics of 7 was described for the first time. The experiments were also analyzed with the theoretical quantum mechanical density functional B3LYPcalculations for the energy outputs in model reactions. Based on these studies hypothetical routes of key intermediate (7) formation have been suggested. These predictions were consistent with the solutions of kinetic equations fitted to the experimental curves for time-dependence of three components of the reaction mixture. 1.
    [Show full text]
  • TOMMANNUUTTILIMINATIONUS009862693B2 (12 ) United States Patent ( 10 ) Patent No
    TOMMANNUUTTILIMINATIONUS009862693B2 (12 ) United States Patent ( 10 ) Patent No. : US 9 , 862, 693 B2 Pietras et al. (45 ) Date of Patent : Jan . 9 , 2018 ( 54 ) COMPOUNDS AND METHODS OF ( 56 ) References Cited TREATING CANCER U . S . PATENT DOCUMENTS (71 ) Applicant : The Regents of the University of 4 , 574 ,123 A * 3 / 1986 Edwards . .. .. C07C 279/ 28 California , Oakland , CA (US ) 162 / 161 4 , 861, 760 A 8 / 1989 Mazuel et al. ( 72 ) Inventors : Richard J . Pietras , Los Angeles , CA 4 ,911 , 920 A 3 / 1990 Jani et al . (US ) ; Michael E . Jung, Los Angeles , 5 ,212 , 162 A 5 / 1993 Missel et al. CA (US ) ; Diana C . Marquez -Garban , 5 , 403 , 841 A 4 / 1995 Lang et al . 6 ,699 ,989 B1 * 3 / 2004 Shetty CO7D 215 / 56 Los Angeles, CA (US ) ; Gang Deng, 540 /474 Los Angeles, CA (US ) 7 , 285 ,681 B2 * 10 /2007 Moinet .. .. .. CO7D 295/ 215 564 /233 ( 73 ) Assignee : The Regents of the University of 7 ,671 , 019 B2 * 3 /2010 Tobia A61K 8 /44 California , Oaklnad , CA (US ) 514 / 1 . 1 8 , 853, 259 B2 10 /2014 Mylari Subject to any disclaimer, the term of this 2010 / 0087544 A1 4 / 2010 Kim et al. ( * ) Notice : 2011 /0196015 A1 8 / 2011 Kim et al . patent is extended or adjusted under 35 2011 / 0207810 Al 8 / 2011 Kim et al . U . S . C . 154 (b ) by 40 days. 2015 /0126518 Al 5 /2015 Kim et al . ( 21) Appl . No. : 14 /566 ,055 FOREIGN PATENT DOCUMENTS ( 22 ) Filed : Dec . 10 , 2014 WO WO - 96 /05309 A2 2 / 1996 WO WO - 96 /05309 A3 2 / 1996 (65 ) Prior Publication Data WO WO - 2011 /083998 A2 7 / 2011 WO WO - 2011 /083998 A3 7 / 2011 US 2015 /0158832 A1 Jun .
    [Show full text]