US010370455B2 (12 ) United States Patent (10 ) Patent No. : US 10 , 370 , 455 B2 Molloy et al. (45 ) Date of Patent: Aug . 6 , 2019 ( 54 ) IDENTIFICATION OF VSIG8 AS THE 4 ,517 , 288 A 5 / 1985 Giegel et al . PUTATIVE VISTA RECEPTOR ( V - R ) AND 4 ,522 ,811 A 6 / 1985 Eppstein et al . 4 , 596 , 556 A 6 / 1986 Morrow et al. USE THEREOF TO PRODUCE VISTANSIG8 4 ,676 , 980 A 6 / 1987 Segal et al . AGONISTS AND ANTAGONISTS 4 ,683 , 195 A 7 / 1987 Mullis et al. 4 ,683 , 202 A 7 / 1987 Mullis (71 ) Applicant: IMMUNEXT, INC ., Lebanon , NH 4 ,699 . 880 A 10 / 1987 Goldstein 4 ,736 , 866 A 4 / 1988 Leder et al. (US ) 4 ,790 , 824 A 12 / 1988 Morrow et al. 4 ,816 ,567 A 3 / 1989 Cabilly et al. (72 ) Inventors : Michael Molloy , Enfield , NH (US ) ; 4 , 837 , 168 A 6 / 1989 de Jaeger et al. Yalin Guo , Hanover, NH ( US ) ; Jay 4 ,870 ,009 A 9 / 1989 Evans et al. Rothstein , Norwich , VT (US ) ; Michael 4 ,873 , 191 A 10 / 1989 Wagner et al . 4 . 873 . 316 A 10 / 1989 Meade et al . Rosenzweig , Boston , MA (US ) 4 , 881 , 175 A 11/ 1989 Ladner 4 ,941 , 880 A 7 / 1990 Burns ( 73 ) Assignee : IMMUNEXT, INC ., Lebanon, NH 4 ,946 , 778 A 8 / 1990 Ladner et al. (US ) 4 , 954 ,617 A 9 / 1990 Fanger et al . 4 , 987 ,071 A 1 / 1991 Cech et al . ( * ) Notice : Subject to any disclaimer , the term of this 5 ,013 ,653 A 5 / 1991 Huston et al . patent is extended or adjusted under 35 5 , 064 ,413 A 11/ 1991 McKinnon et al. U . S . C . 154 (b ) by 355 days . 5 , 091 ,513 A 2 / 1992 Huston et al . (Continued ) (21 ) Appl. No. : 14 / 960, 973 FOREIGN PATENT DOCUMENTS (22 ) Filed : Dec . 7 , 2015 2383456 3 /2001 1753912 3 / 2006 (65 ) Prior Publication Data (Continued ) US 2016 /0159927 A1 Jun . 9 , 2016 Related U . S . Application Data OTHER PUBLICATIONS Le Mercier et al. ( 2014 ) VISTA Regulates the Development of (63 ) Continuation - in - part of application No . Protective Antitumor Immunity . Cancer Research 74 : 1933 - 1944. * PCT /US2015 / 064146 , filed on Dec . 5 , 2015 . Le Mercier et al. ( 2015 ) Beyond CTLA - 4 and PD - 1 , the generation ( 60 ) Provisional application No . 62/ 088 ,058 , filed on Dec . Z of negative checkpoint regulators . Front. Immunol. 6 :418 . doi : 5 , 2014 . 10 . 3389/ fimmu .2015 .00418 ; 1 - 15 . * Lines et al. (2014 ) VISTA Is an Immune Checkpoint Molecule for (51 ) Int . CI. Human T Cells . Cancer Research 74 : 1924 - 1932 . * COZK 16 / 28 ( 2006 .01 ) Liu et al . ( 2015 ) Immune -checkpoint proteins VISTA and PD - 1 A61K 39 / 395 ( 2006 .01 ) nonredundantly regulate murine T -cell responses . Proc. Natl. Acad . COOK 16 / 42 ( 2006 .01 ) Sci . USA 112 : 6682 - 6687 . * CO7K 14 / 705 ( 2006 .01 ) (Continued ) C12N 15 / 113 ( 2010 .01 ) A61K 39 /00 ( 2006 . 01 ) Primary Examiner — Ilia I Ouspenski (52 ) U . S . CI. ( 74) Attorney , Agent, or Firm — Robin L . Teskin ; CPC . .. .. CO7K 16 / 42 ( 2013 .01 ) ; CO7K 14 / 70503 LeClairRyan PLLC ( 2013 .01 ) ; C07K 16 / 2803 ( 2013 .01 ) ; COOK 16 / 2827 (2013 .01 ) ; C12N 15 / 1138 ( 2013 . 01 ) ; (57 ) ABSTRACT A61K 2039 / 505 ( 2013 . 01 ) ; COZK 2317 / 73 The receptor for VISTA is identified (VSIG8 ) as well as the ( 2013 . 01 ) ; COZK 2317 / 76 (2013 . 01 ) ; COOK use of this receptor in the identification or synthesis of 2319 / 30 (2013 .01 ) ; C12N 2310 / 14 (2013 .01 ) ; agonist or antagonist compounds, preferably antibodies , C12N 2310/ 531 ( 2013. 01 ) polypeptides and fusion proteins which agonize or antago ( 58 ) Field of Classification Search nize the effects of VSIG8 and / or VISTA and /or the VSIG8/ None VISTA binding interaction . These antagonists may be used See application file for complete search history . to suppress VISTA ' s suppressive effects on T cell immunity, and more particularly used in the treatment of cancer , or ( 56 ) References Cited infectious disease . 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