US 20120301400A1 US 20120301400A1 (19) United States (12) Patent Application Publication oo) Pub. No.: US 2012/0301400 Al Williams et al. (43) Pub. Date: Nov. 29,2012 (54) MEDITOPES AND MEDITOPE-BINDING (30) Foreign Application Priority Data ANTIBODIES AND USES THEREOF Oct. 10, 2011 (US) ................. PCT/US2011/055656 (76) Inventors: John C. Williams, Monrovia, CA (US); David A. Horne, Duarte, CA Publication Classification (US); Yuelong Ma, Duarte, CA (51) Int. Cl. (US); Heng Wei Chang, Foster C07K16/18 (2006.01) City, CA (US); Joshua Michael C07K 7/08 (2006.01) Donaldson, Lumberton, NJ (US); C07K1/14 (2006.01) Cindy Zer, Duarte, CA (US); A61K 39/395 (2006.01) Krzysztof Bzymek, Pasadena, CA A61K 49/00 (2006.01) (US); Kendra Nicole Avery, C12N 5/071 (2010.01) Pasadena, CA (US); Jun Xie, C07K 7/06 (2006.01) Duarte, CA (US) C07K2/00 (2006.01) (21) Appl. No.: 13/443,804 (52) U.S. Cl......... 424/9.1; 530/387.9; 530/330; 530/329; 530/328; 530/327; 530/326; 530/321; 424/139.1; (22) Filed: Apr. 10, 2012 424/178.1; 435/331 Related U.S. Application Data (57) ABSTRACT (63) Continuation-in-part of application No. 13/270,207, Antibodies and meditopes that bind to the antibodies are filed on Oct. 10, 2011. provided, as well as complexes, compositions and combina­ (60) Provisional application No. 61/391,558, filed on Oct. tions containing the meditopes and antibodies, and methods 8, 2010, provisional application No. 61/597,708, filed of producing, using, testing, and screening the same, includ­ on Feb. 10, 2012. ing therapeutic and diagnostic methods and uses. Patent Application Publication Nov. 29, 2012 Sheet I of 79 US 2012/0301400 Al figure I Al v* Vt V fed! tope €h *·'·> ·■ . !*0 C ' Λίί ? 1O > ■? ' (S Q1 i " PatentApplicationPublication Nov. 29,2012 Sheet 2 of 79 US 2012/0301400 Al ISprei m Light Chain Kat>as Muonic 10 3S->_4S SS--I? iso—iss m I cmlps pffrr MStmM I I cpffcp 1c:#yf e I £}IC|1K« Ρ|ΥΥ I? Hmty Cltaln KaSst IKaaitef 33,,,,,.,,,44 BMm imsm m nsan CEMmimaM QStMM? TMi S PA .............■ ■ ■ ■ yP ^aaa SMi S PA trastua ama b QSSSKS TM E ES Patent Application Publication Nov. 29, 2012 Sheet 3 of 79 US 2012/0301400 Al Pigwt 3 Patent Application Publication Nov. 29, 2012 Sheet 4 of 79 US 2012/0301400 Al Fig»** 4 A-C Λ(·ΐϊ::ίί?ί· jsMA il-rj-R. -V i '·, C&w&mte J VAFsb I /I -;v Fafo .,.Domalrs Ifo ··: .·.·····:·:·. j· m n- F/adtepe FSTC Patent Application Publication Nov. 29, 2012 Sheet 5 of 79 US 2012/0301400 Al 0 0 211 48 m 80 100 fpll) wf:¥ Ii 2,0 Patent Application Publication Nov. 29, 2012 Sheet 6 of 79 US 2012/0301400 Al FigareS i;.-· 1® I Patent Application Publication Nov. 29, 2012 Sheet 7 of 79 US 2012/0301400 Al Fifttre $ ..... ' ' J >ϊ Ϊ JlliS i Mednope Meditopo w-Modi Iepe w Aleditope w?· Af\) j !Hill Patent Application Publication Nov. 29, 2012 Sheet 8 of 79 US 2012/0301400 Al figure 7 PfDlein A Patent Application Publication Nov. 29, 2012 Sheet 9 of 79 US 2012/0301400 Al Figure 8 Cetuximab TOPVIEW Matuzumab/425 Tumor Cell Multivalent Meditope Tumor Antigen Antibody "Daisy Chained" TOPVIEW Patent Application Publication Nov. 29, 2012 Sheet 10 of 79 US 2012/0301400 Al Wi fare 9 Fab variable light chain variable heavy chain Linkers PatentApplication Publication Nov. 29, 2012 Sheet 11 of 79 US 2012/0301400 Al FigtiM 1® PatentApplication Publication Nov. 29, 2012 Sheet 12 of 79 US 2012/0301400 Al Ftgmelt Tumor Association Protease Site Patent Application Publication Nov. 29, 2012 Sheet 13 of 79 US 2012/0301400 Al Figure 12 Momvglmt Modftopn TetmvMont Modiiopo ··;*· O- p β .,,,,;¾.- Oi* O .#·Λ Time iem tims md PatentApplication Publication Nov. 29, 2012 Sheet 14 of 79 US 2012/0301400 Al PigarK LI Ά KiCO3, H2N,. MO^JvOH 'NH3 3-bmrm>4fofftpyne I! J DMF ®C«Wft8 CDOMe COOMe 4 N » H tof ifimens linker € E! * H tar riknerie linker SRsOH for irimsrift lirskef ? R‘« Q''""''%,lef Himerift Sinfcer **■·.,V"··, ,ο,. YΛ'" Ον-·"·-..^·„0# FiTO DiEH iVti DMF I H H i Ff * H for sSmesks Iinfcer ISRi-HfofdsmeriRlfoksr S R' ~ irinsene SirHer 11 RF* t©f Himsrift inker Mj r~f,ft t i ^ Αν,χννΧ·.,#ί (PfO)ij I '" ISeriI C&SO4-fsssorbaie (I-Qfdlstrrlho O-QFOLSTRRLkvO ----------------------------------------* DiEA. DMF S-----------------------1 H2Oi ecetmttrlfo 2 QvmV^ θΐ§·: I H A tV >s%x<Ff 0¼ (EfO)D-Nfo*N R* 0¾¾! I O-QFOLSTR RLKvO om,RRTSLOFQ-Q i_____________ I 14 Fr » H, dimeric fSeemsceirs iabsfori Sadam «■ 'Xfo--Xx 14 Fr « s-ftLRgrsusfto-s- trimerfc ifoereseein Hfteieri lsefom Patent Application Publication Nov. 29, 2012 Sheet 15 of 79 US 2012/0301400 Al fiftire M m m m e »»»»»»»»»»»>»»»»»»»»»»»·_·: 1θ IS »3« :?-3 ;:i i I *1 I sI .T I I I 4Cii --::::.3 "I 3013343 I 3-2 2I wmjtm 33-0 /::4 3; ^■V! 3 543? 3000 3/332?? $4 < ΐ44 :2 s 3 - 4 . '3 .. .. .λ .w-:-4:-.;·:· ■■·;·;■ SCiS 300 iOOO OOO i 400 Patent Application Publication Nov. 29, 2012 Sheet 16 of 79 US 2012/0301400 Al ftgttre 14 L I «■""it ¥·® m ................. I !fill Il %|" I....................................ί i«·χ·χ·χ·:·:·:·:·:·:·:·:·:·:·:·:·:·:·:·:·:·:·:·:·:·:·:·:·:·:·:·: IbrZ * δ Expected MW: 858.8328 Found MW: 858.8294 PatentApplication Publication Nov. 29, 2012 Sheet 17 of 79 US 2012/0301400 Al Figure IS MedfcopeMFc (SEQ UD NOD miciefc acid aod SEQ ID NO; 4 αΜαά add) R; ex;; ;: a qR: R i: a a < x: R: <; I: ·;:: * a <; R: a:; a <: q a;; R .q: s a a i; ¢ :; a qqi: C 0' F "a R-" S F p' RR F K C F qAAAqaF AaqqR Re A.aqaR: AAqqaqqReqR aqqqqqcxxERaaF AFRAqqaaaqR.qqa Ra q S GFFFFF F F F FFFF F F F F F F :: q qq.:;R a. a q ; · c c:;:aq qq c q ·: q R qAR as q F < s a a::; q q aa a q q < a;c :;q <: F ;: i χ :a:. q a a a:q a: F a;s. F "a k" I'" F F FFFF F 'a F "f" f' F "f ' rr" F F q F aa; Raq a aqqa:: qqqq aaacqaa Fiaaqq aa a R.qq a aar FFaaaaiqq aaa aaaa aqa q 'v F F F F F K F a 'a F R,' Vi:" I F F x" f'"f 'p aaasF FF FFqqF Aqqqq a a.Ftqq aaaaFFF FqaFc aqqqqqF aaaaFF aaaRF aa a AaaF f I C F V F D F F F F D FEVK F FWFV a a a a q a q a aaa ¢:; fit aaa aaa a a a q q q q aaa a; q -a aa aa a aaaa q aa aa; a a F aa a a t F a a aa a D G F E V F W a K T K F F E F a a r;; a T ;; FFaaaatqaaataqqFaataiqsaiFK; agt; CKaaFq aaaaq';a:iaa;:.qqa IaaiFaaaaaaqaq:; F R V V F V L T F L F 0 a q a q; a r; E V a a aa q a a a a aa a aa aa a aa a a a a a at aaa; F a a a a aa a a a aa a aa. aa a aa Ra a a q aa. a aa q K C R F F F k ’ f. ’ I,' a F F F £ K X F S K ’ ’ F ’ a a aa a a a; a a aa a Aq aaa aa; aa; a a a aa: a Fa. aa a aaa R; F a; cq a;a; a a: a aaa a a a a; t aa a a ct. a; af; a K a F a- R F F Fi F V X L f" p F p'g p' e X a a aa a; a a a a AR a Ff cat; aa. a R a at; R R a FR aaa a a RRA R R a R a a aa q R a aaa a a F a rr a a FR a K W 0' V F R T F X:' "v K G P X p' a"P X A "v a a at rk:; q a RR Re a aa R aa a a a a a a-q qa a aa aa cr a R a a a a a aa a aa a a a q aaa a R a R R a aa a X F X a’ FR "p' 0 p' "a RR Ri P K T X p' F F R.· F R -CaxRARiRaiaRaaRAaiaR R eR.a R AR: Rq;a AR; RKFRqaiARxP:,aaa A RRAXiRxiAA qqR: AAiRAqqaA' F "a "0 Rr" P F I: X p' K" F X "a "a k' Rr" p' w" o' 0' q ARAqqq:: a Ra iaRccKcqcR AAiRRqqR ckraRx; AqaaaqR R aaa aa R aacR: a R A.aqca aaaa RC K V P a F a F RR RR R A G Ri W K X F Q K aqaqR AAqq At CRR.aqqciKqqqq a a kra A .R: a F a Ri a Patent Application Publication Nov. 29, 2012 Sheet 18 of 79 US 2012/0301400 Al I1psr« M PatentApplication Publication Nov. 29, 2012 Sheet 19 of 79 US 2012/0301400 Al Flgere 17 iSif-'-f'" "V. 3 I Meditope-Fc ·:·:·/ - SJ j K 1 SJ Meditope monomer sV kuX V QA ί»5 W Patent Application Publication Nov.
Details
-
File Typepdf
-
Upload Time-
-
Content LanguagesEnglish
-
Upload UserAnonymous/Not logged-in
-
File Pages253 Page
-
File Size-