Patent Application Publication Oo) Pub. No.: US 2012/0301400 Al Williams Et Al

Patent Application Publication Oo) Pub. No.: US 2012/0301400 Al Williams Et Al

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,. 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