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US009993566B2MULT MAIMULOQOTI TAITE (12 ) United States Patent ( 10 ) Patent No. : US 9 , 993 ,566 B2 Liu et al. (45 ) Date of Patent : * Jun. 12 , 2018 ( 54 ) SEZ6 MODULATORS AND METHODS OF ( 56 ) References Cited USE U . S . PATENT DOCUMENTS @(71 ) Applicant : AbbVie Stemcentrx LLC , North 5 , 112 , 946 A 5 / 1992 Maione Chicago , IL (US ) 5 ,336 ,603 A 8 / 1994 Capon et al. 5 , 349 ,053 A 9 / 1994 Landolfi @(72 ) Inventors : David Liu , South San Francisco , CA 5 , 359 ,046 A 10 / 1994 Capon et al. (US ) ; Deepti Rokkam , Sunnyvale , CA 5 , 447 , 851 A 9 / 1995 Beutler et al. (US ) ; Sheila Bheddah , San Francisco , 5 , 530 , 101 A 6 / 1996 Queen et al. 5 ,622 , 929 A 4 / 1997 Willner et al . CA (US ) ; Javier Lopez -Molina , New 5 ,693 , 762 A 12 / 1997 Queen et al . York , NY (US ) ; Laura Saunders, San 6 ,180 , 370 B1 1 / 2001 Queen et al . 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No. : 14 /915 , 563 8 , 163, 736 B2 . 4 /2012 Gauzy et al . 8 ,788 ,213 B2 7 / 2014 Bright ( 22 ) PCT Filed : Aug . 27, 2014 8 , 889 ,833 B2 11/ 2014 Yue et al. 9 ,676 ,850 B2 * 6 /2017 Saunders . C07K 16 / 28 ( 86 ) PCT No. : PCT/ US2014 / 053014 2003 /0211991 Al 11 /2003 Su $ 371 ( c ) ( 1 ), (Continued ) ( 2 ) Date : Feb . 29 , 2016 FOREIGN PATENT DOCUMENTS ( 87 ) PCT Pub . No . : W02015 / 031541 CN 1343774 A 4 / 2002 EP 0367166 5 / 1990 PCT Pub . Date : Mar. 5 , 2015 (Continued ) (65 ) Prior Publication Data US 2016 / 0287720 A1 Oct . 6 , 2016 OTHER PUBLICATIONS Gorlov et al. Seizure 6 - like (SEZÓL ) gene and risk for lung cancer . Related U . S . Application Data Cancer Research 67 ( 17 ) : 8406 -8411 , Sep . 1 , 2007. * ( 60 ) Provisional application No . 61 / 871, 289 , filed on Aug . Gussow et al . (Methods in Enzymology . 1991 ; 203 : 99 - 121) . * George et al . (Circulation . 1998 ; 97 : 900 - 906 ) . * 28 , 2013 NM _ 001098635 — Homo sapiens seizure related 6 homolog (51 ) Int . Ci. (SEZ6 ) , transcript variant 2 , mRNA . NM _ 021286 — Mus musculus seizure related gene 6 (Sezo ) , tran CO7K 16 / 00 ( 2006 .01 ) script variant 1 , mRNA . A61K 4748 ( 2006 . 01) NM _ 178860 — Homo sapiens seizure related 6 homolog (SEZO ) , CO7K 16 / 28 ( 2006 .01 ) transcript variant 1 , mRNA . GOIN 33 / 574 ( 2006 .01 ) NP _ 001092105 — seizure protein 6 homolog isoform 2 precursor CO7K 16 / 18 ( 2006 .01 ) [Homo sapiens ] . A61K 47 /68 ( 2017 . 01 ) NP _ 001099224 — seizure protein 6 homolog precursor [Rattus A61K 39 / 00 ( 2006 . 01 ) norvegicus ] . ( 52 ) U . S . CI. (Continued ) CPC . .. A61K 47 /48384 ( 2013 .01 ) ; A61K 47/ 6803 ( 2017 .08 ) ; A61K 47 /6843 ( 2017 .08 ); A61K 47 /6849 ( 2017 . 08 ) ; CO7K 16 / 18 ( 2013 .01 ) ; Primary Examiner — Brad Duffy CO7K 16 / 28 ( 2013 .01 ) ; GOIN 33 / 57407 (74 ) Attorney , Agent, or Firm — Womble Bond Dickinson (2013 .01 ) ; GOIN 33 /57423 ( 2013 .01 ) ; A61K (US ) LLP 2039 / 505 ( 2013 .01 ) ; CO7K 2317 /20 ( 2013 .01 ) ; CO7K 2317 / 24 ( 2013 .01 ) ; CO7K 2317 / 33 (57 ) ABSTRACT ( 2013 .01 ) ; CO7K 2317 / 34 ( 2013 .01 ) ; CO7K 2317 / 565 (2013 . 01 ) ; COZK 2317 /73 ( 2013 .01 ) ; Novel modulators , including antibodies and derivatives CO7K 2317 /77 (2013 .01 ) thereof , and methods of using such modulators to treat (58 ) Field of Classification Search proliferative disorders are provided . None See application file for complete search history . 41 Claims, 72 Drawing Sheets US 9 ,993 ,566 B2 Page 2 ( 56 ) References Cited Bork et al ., “ The CUB domain . 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