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MAIMUITA IN ACUTUS010035853B2 CA UTI ON MUUNNI (12 ) United States Patent ( 10 ) Patent No. : US 10 ,035 ,853 B2 Arathoon et al. (45 ) Date of Patent: Jul. 31, 2018 ( 54 ) SITE -SPECIFIC ANTIBODY CONJUGATION 5 , 112 , 946 A 5 / 1992 Maione METHODS AND COMPOSITIONS 5 , 122 , 368 A 6 / 1992 Greenfield et al . 5 , 191 , 066 A 3 / 1993 Bieniarz et al . 5 , 223 , 409 A 6 / 1993 Ladner et al. (71 ) Applicant : ABBVIE STEMCENTRX LLC , North 5 ,336 ,603 A 8 / 1994 Capon et al. Chicago , IL (US ) 5 , 349 ,053 A 9 / 1994 Landolfi 5 , 359 , 046 A 10 / 1994 Capon et al. (72 ) Inventors : William Robert Arathoon , Los Altos 5 , 447 , 851 A 9 / 1995 Beutler et al. 5 , 530 , 101 A 6 / 1996 Queen Hills, CA (US ) ; Ishai Padawer , San 5 , 545 , 806 A 8 / 1996 Lonberg et al. Francisco , CA (US ) ; Luis Antonio 5 , 545 , 807 A 8 / 1996 Surani et al . Cano, Oakland , CA ( US ) ; Vikram 5 , 569 , 825 A 10 / 1996 Lonberg et al . Natwarsinhji Sisodiya , San Francisco , 5 .622 , 929 A 4 / 1997 Willner et al . CA (US ) ; Karthik Narayan Mani, San 5 ,625 , 126 A 4 / 1997 Lonberg et al . 5 ,633 , 425 A 5 / 1997 Lonberg et al . Francisco , CA (US ) ; David Liu , San 5 , 648 , 237 A 7 / 1997 Carter Francisco , CA (US ) 5 ,661 , 016 A 8 / 1997 Lonberg et al . 5 ,693 , 762 A 12 / 1997 Queen et al . ( 73 ) Assignee : AbbVie Stemcentrx LLC , North 5 , 750 , 373 A 5 / 1998 Garrard et al . 5 , 824 , 805 A 10 / 1998 King et al. Chicago , IL ( US ) 6 , 075 , 181 A 6 /2000 Kucherlapati et al . 6 , 150 , 584 A 11/ 2000 Kucherlapati et al . ( * ) Notice : Subject to any disclaimer, the term of this 6 , 180 , 370 B1 1 / 2001 Queen et al. patent is extended or adjusted under 35 6 ,214 , 345 Bi 4 / 2001 Firestone et al . U . S . C . 154 (b ) by 0 days . 6 , 300 , 064 B1 10 / 2001 Knappik et al. 6 , 362 , 331 B1 . 3 / 2002 Kamal et al. 6 , 376 , 217 B1 4 / 2002 Better (21 ) Appl. No .: 15 / 056 ,490 6 . 753 . 165 B16 / 2004 Cox 6 ,982 , 321 B2 1 / 2006 Winter ( 22 ) Filed : Feb . 29 , 2016 7 , 049 , 311 B1 5 / 2006 Thurston et al . 7 , 087 , 409 B2 8 / 2006 Barbas , III et al. (65 ) Prior Publication Data 7 , 189 , 710 B2 3 / 2007 Kamal et al . 7 , 279, 554 B2 10 / 2007 Chan et al . US 2016 /0176964 A1 Jun . 23, 2016 7 ,279 , 558 B2 10 / 2007 Ota et al . 7 , 407 , 951 B2 8 / 2008 Thurston et al. Related U . S . Application Data 7 , 422 , 739 B2 9 / 2008 Anderson et al . 7 , 429 , 658 B2 9 / 2008 Howard et al. (63 ) Continuation of application No . 7 , 521 , 541 B2 4 / 2009 Eigenbrot et al. PCT /US2014 / 053310 , filed on Aug . 28 , 2014 , which 7 , 557, 099 B2 7 /2009 Howard et al . is a continuation - in -part of application No . 7 , 608 , 429 B2 10 / 2009 Reilly PCT/ US2014 /053014 , filed on Aug. 27, 2014 . 7 , 619 , 068 B2 11/ 2009 Pilkington et al . 7 , 632 , 678 B2 12 / 2009 Hansford et al. (60 ) Provisional application No . 61/ 871 , 289 , filed on Aug . 7 , 659 , 241 B2 2 / 2010 Senter et al. 28 , 2013 , provisional application No. 61 /871 , 173 , 7 ,700 , 302 B2 4 / 2010 Hua et al. filed on Aug . 28 , 2013 . 7 ,723 , 485 B2 5 / 2010 Junutula 7 , 741 , 319 B2 6 / 2010 Howard et al. (51 ) Int. Cl. 7 , 825 ,267 B2 11 /2010 Koide et al. COZK 16 /28 ( 2006 .01 ) 7 , 837 , 980 B2 11/ 2010 Alley COZK 16 /30 ( 2006 .01 ) 7 , 855 ,275 B2 12/ 2010 Eigenbrot A61K 47 /48 ( 2006 . 01 ) ( Continued ) A6IK 39 / 395 ( 2006 . 01 ) CO7K 16 / 18 ( 2006 . 01 ) FOREIGN PATENT DOCUMENTS A61K 39 /00 (2006 . 01) EP 0307434 3 / 1989 (52 ) U . S . CI. EP 0367166 5 / 1990 CPC . .. .. CO7K 16 / 28 (2013 .01 ) ; A61K 47 / 48384 (Continued ) ( 2013 .01 ) ; A61K 47 / 48415 ( 2013 . 01 ) ; A61K 47 /48538 (2013 .01 ) ; A61K 47/ 48561 OTHER PUBLICATIONS ( 2013 .01 ) ; CO7K 16 / 18 (2013 .01 ) ; CO7K 16 / 2896 ( 2013 .01 ) ; C07K 16 / 30 ( 2013 .01 ) ; Accession No . NM _ 016941; “ Homo sapiens delta - like 3 A61K 2039 / 505 ( 2013 .01 ) ; CO7K 2317 / 24 (Drosophila ) ( DLL3) , transcript variant 1 , mRNA ” . ( 2013. 01 ) ; CO7K 2317 /53 (2013 . 01 ) ; CO7K (Continued ) 2317 /73 (2013 .01 ) (58 ) Field of Classification Search Primary Examiner — Julie Wu None ( 74 ) Attorney , Agent, or Firm — Womble Bond Dickinson See application file for complete search history . (US ) LLP ( 56 ) References Cited (57 ) ABSTRACT Provided are novel antibody drug conjugates (ADCs ), and U . S . PATENT DOCUMENTS methods of using such ADCs to treat proliferative disorders . 4 ,676 , 980 A 6 / 1987 Segal et al. 4 , 816 , 567 A 3 / 1989 Cabilly et al. 42 Claims, 19 Drawing Sheets US 10 ,035 ,853 B2 Page 2 (56 ) References Cited 2013 /0330350 A1 12 /2013 DiMasi 2014 /0106449 Al 4 / 2014 June et al . U . S . 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    (19) TZZ _T (11) EP 2 496 698 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: C07K 14/71 (2006.01) C12N 9/12 (2006.01) 09.01.2019 Bulletin 2019/02 (86) International application number: (21) Application number: 10829041.2 PCT/US2010/055329 (22) Date of filing: 03.11.2010 (87) International publication number: WO 2011/056894 (12.05.2011 Gazette 2011/19) (54) TRUNCATED EPIDERIMAL GROWTH FACTOR RECEPTOR (EGFRt) FOR TRANSDUCED T CELL SELECTION VERKÜRZTER REZEPTOR FÜR DEN EPIDERMALEN WACHSTUMSFAKTOR-REZEPTOR ZUR AUSWAHL UMGEWANDELTER T-ZELLEN RÉCEPTEUR DU FACTEUR DE CROISSANCE DE L’ÉPIDERME TRONQUÉ (EGFRT) POUR LA SÉLECTION DE LYMPHOCYTES T TRANSDUITS (84) Designated Contracting States: • LI ET AL.: ’Structural basis for inhibition of the AL AT BE BG CH CY CZ DE DK EE ES FI FR GB epidermal growth factor receptor by cetuximab.’ GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO CANCER CELL vol. 7, 2005, pages 301 - 311, PL PT RO RS SE SI SK SM TR XP002508255 • CHAKRAVERTY ET AL.: ’An inflammatory (30) Priority: 03.11.2009 US 257567 P checkpoint regulates recruitment of graft-versus-host reactive T cells to peripheral (43) Date of publication of application: tissues.’ JEM vol. 203, no. 8, 2006, pages 2021 - 12.09.2012 Bulletin 2012/37 2031, XP008158914 • POWELL ET AL.: ’Large-Scale Depletion of (73) Proprietor: City of Hope CD25+ Regulatory T Cells from Patient Duarte, CA 91010 (US) Leukapheresis Samples.’ J IMMUNOTHER vol. 28, no.