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Bispecific t-cell activator antibody

This invention relates to bispecific antibodies having combinations of linker and hinge sequences to create linker-hinge interface domains with biological significance. Such linker-hinge interface domains covalently join two molecules, maintain the
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  US 20130165629A1 19) United States 12) Patent Application Publication 10) Pub. No.: US 2013/0165629 A1 Hsu et al. 43) Pub. Date: Jun. 27, 2013 (54) BISPECIFIC T-CELL ACTIVATOR ANTIBODY Publication Classi?cation 71) ApplicantszDevelopment Center for 51) Int. Cl. Biotechnology, New aipei City (TW); C07K 6/46 (2006.01) DCB-USA LLC; Wilmington, DE (U ) C07K 7/06 (2006.01) C07K 7/08 (2006.01) 72) Inventors: Yu-Shen Hsu; NeW aipei City (TW); 52) us CL shew-Shall Shell, New aipei City CPC ............... .. C07K16/468 (2013.01); C07K 7/08 (TW); Mingi Chang, New aipei City 2013.01); C07K 7/06 (2013.01) (TW); Ming-Ch“an Chang, New aipei USPC ....................... 530/326; 530/3873; 530/328 City (TW); Ta-Tung Yuan; NeW aipei City (TW) 57) ABSTRACT This invention relates to bispeci?c antibodies having combi (73) Assigneesr DCB-USA LLC, Wilmington, DE (Us); nations of linker and hinge sequences to create linker-hinge DEVELOPMENT CENTER FOR interface domains With biological signi?cance. Such linker BIOTECHNOLOGY, NeW aipei City hinge interface domains covalently join tWo molecules; main (TW) tain the biological activities of linked molecules target bind ing); stabilize the biological characteristics of neW molecule (solubility and 40 C. stability); maintain the chemical; bio 21) Appl NO 13/720,573 chemical and physical properties cytotoxicity) of the linked molecules; and modulate the biological characteristics of the 22) Filed: Dec. 19, 2012 linked molecules activating T-lymphocytes Without signi? cant sign of roliferations). Both linker (GGGGS) and hinge CPPCP) sequences are required to establish functional Related U s Apphcatlon Data linker-hinge interface domains as deletion of any of the com (60) Provisional application No. 61/ 79,450; ?led on Dec. ponent resulted in signi?cant lost of T-lymphocyte mediated 22, 2011. activity.   301 oas ? ass“ ??véun 3? U 2013 0165629 A1 2:15 2”; 522: oting“ EEsH Jun. 27 2013 Sheet 0f 14 9 m muéqa EEEQ oming“; 5559 E ?mv £ Qmoue?dmHéowwiomswmoai SwE Patent Application Publication  Patent Application Publication Jun. 27 2 13 Sheet 2 0f 14 US 2013/0165629 A1 MB 2522: S31E83 EEFH 5.25 c?iwoua 5558 ‘ Axiom QU? EV 5 .25 5333.» ? :6 -255 mii E: Eu om u w mm NQUAES M? iommoqu dmwwowwcm ii : 55  Patent Application Publication Jun. 27 2 13 Sheet 3 0f 14 US 2013/0165629 A1 S325 a?a 3 25 25 min iim 051i NQOAEB MH ugen ating? EDH QMTQQL £ mam???mwowo?cmqéaowwiomsauai 5mm  5 m 0 25 i im bow nwakéum ? U 2013 0165629 A1 ESQ? is: ame wse EEQG wii x51 20 ”; 2522: izawou? 5555 Jun. 27 2013 Sheet 4 0f 14 2 20 ?5 ? 52.5 c?EmoR? EESH ., Patent Application Publication
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