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( 12 ) United States Patent US010738128B2 (12 ) United States Patent ( 10 ) Patent No.: US 10,738,128 B2 Chappel et al. (45 ) Date of Patent : Aug. 11, 2020 ( 54 ) ANTIBODIES THAT BIND CD39 AND USES 5,571,698 A 11/1996 Ladner et al . THEREOF 5,580,717 A 12/1996 Dower et al . 5,624,821 A 4/1997 Winter et al . 5,648,260 A 7/1997 Winter et al. (71 ) Applicant: Surface Oncology , Inc., Cambridge, 5,658,727 A 8/1997 Barbas et al . MA (US ) 5,698,426 A 12/1997 Huse 5,733,743 A 3/1998 Johnson et al. (72 ) Inventors : Scott Chappel, Milton , MA (US ) ; 5,750,753 A 5/1998 Kimae et al. 5,780,225 A 7/1998 Wigler et al. Andrew Lake , Westwood , MA (US ) ; 5,821,047 A 10/1998 Garrard et al . Michael Warren , North Chelmsford , 5,858,358 A 1/1999 June et al. MA (US ) ; Austin Dulak , Reading , MA 5,883,223 A 3/1999 Gray (US ) ; Erik Devereaux, Hanover , MA 5,969,108 A 10/1999 McCafferty et al. (US ) ; Pamela M. Holland , Belmont, 6,001,329 A 12/1999 Buchsbaum et al. 6,005,079 A 12/1999 Casterman et al . MA (US ) ; Tauqeer Zaidi, Sharon , MA 6,194,551 B1 2/2001 Idusogie et al . (US ) ; Matthew Rausch , Cambridge , 6,300,064 B1 10/2001 Knappik et al . MA (US ) ; Bianka Prinz , Lebanon , NH 6,352,694 B1 3/2002 June et al . ( US ) ; Nels P. Nielson , Lebanon , NH 6,534,055 B1 3/2003 June et al . 6,692,964 B1 2/2004 June et al. (US ) ; Sonia Das, Cambridge , MA (US ) 6,797,514 B2 9/2004 Berenson et al. 6,867,041 B2 3/2005 Berenson et al . ( 73 ) Assignee: Surface Oncology, Inc. , Cambridge , 6,887,466 B2 5/2005 June et al . MA (US ) 6,905,680 B2 6/2005 June et al. 6,905,681 B1 6/2005 June et al. ( * ) Notice : Subject to any disclaimer, the term of this 6,905,874 B2 6/2005 Berenson et al. patent is extended or adjusted under 35 6,933,368 B2 8/2005 Co et al . 6,984,720 B1 1/2006 Korman et al. U.S.C. 154 ( b ) by 0 days . 6,995,259 B1 2/2006 Vargeese et al. 7,067,318 B2 6/2006 June et al. ( 21) Appl. No .: 16 / 352,589 7,144,575 B2 12/2006 June et al . 7,172,869 B2 2/2007 June et al. (22 ) Filed : Mar. 13 , 2019 7,175,843 B2 2/2007 June et al. 7,232,566 B2 6/2007 June et al. 7,411,057 B2 8/2008 Hanson et al . (65 ) Prior Publication Data 7,595,048 B2 9/2009 Honjo et al. US 2019/0284295 A1 Sep. 19 , 2019 7,943,743 B2 5/2011 Korman et al. 8,008,449 B2 8/2011 Korman et al. 8,114,845 B2 2/2012 Langermann et al. Related U.S. Application Data 8,354,509 B2 1/2013 Carven et al . (60 ) Provisional application No. 62 /803,235 , filed on Feb. (Continued ) 8 , 2019 , provisional application No. 62 /642,938 , filed on Mar. 14 , 2018 . FOREIGN PATENT DOCUMENTS EP 0133988 A2 3/1985 (51 ) Int. Ci. EP 0058481 B1 10/1986 A61K 39/395 ( 2006.01 ) A61P 35/00 ( 2006.01 ) (Continued ) COZK 16/28 ( 2006.01 ) C12N 15/85 (2006.01 ) OTHER PUBLICATIONS A61K 45/06 (2006.01 ) Ghebeh et al. , “ The B7 -H1 (PD -L1 ) T lymphocyte - inhibitory mol (52 ) U.S. CI. ecule is expressed in breast cancer patients with infiltrating ductal CPC CO7K 16/2896 ( 2013.01) ; A61P 35/00 carcinoma : correlation with important high - risk prognostic factors ” ( 2018.01) ; C12N 15/85 (2013.01 ) ; A61K 45/06 ( 2006 ) Neoplasia 8 : 190-198 . ( 2013.01 ) ; C07K 2317/52 ( 2013.01) ; COOK 2317/565 ( 2013.01) ; CO7K 2317/92 (2013.01 ) (Continued ) ( 58 ) Field of Classification Search None Primary Examiner Christine J Saoud See application file for complete search history . Assistant Examiner - Jon M Lockard ( 56 ) References Cited (74 ) Attorney , Agent, or Firm — McNeil Baur PLLC U.S. PATENT DOCUMENTS ( 57 ) ABSTRACT 3,710,795 A 1/1973 Higuchi et al. 3,773,919 A 11/1973 Boswell et al. The present disclosure relates to anti - CD39 antibodies, and 4,676,980 A 6/1987 Segal et al. antigen binding portions thereof and their use in treating 4,863,457 A 9/1989 Lee cancer . 5,223,409 A 6/1993 Ladner et al. 5,403,484 A 4/1995 Ladner et al . 5,427,908 A 6/1995 Dower et al. 5,501,856 A 3/1996 Ohtori et al. 19 Claims, 13 Drawing Sheets 5,516,637 A 5/1996 Huang et al. Specification includes a Sequence Listing . US 10,738,128 B2 Page 2 ( 56 ) References Cited Grinthal and Guidoti, “ Bilayer mechanical properties regulate transmembrane helix mobility and enzymatic state of CD39 ” ( 2007 ) U.S. PATENT DOCUMENTS Biochemistry 46 ( 1 ) :279-290 . Guesdon , J.-L. et al . , “ The use of avidin - biotin interaction in 8,728,474 B2 5/2014 Honjo et al. immunoenzymatic techniques ” 1979, J. Histochem . Cytochem . 27 : 8,779,105 B2 7/2014 Korman et al. 8,796,284 B2 8/2014 Gomez et al . 1131-1139 . 8,900,587 B2 12/2014 Carven et al. Gupta , et al. , " CD39 Expression Identifies Terminally Exhausted 8,952,136 B2 2/2015 Carven et al. CD8 + T Cells ” ( 2015 ) Plos Pathogens 11 ( 10 ) . 9,029,393 B2 5/2015 Schann et al . Hamanishi et al. , “ Programmed cell death 1 ligand 1 and tumor 9,067,999 B1 6/2015 Honjo et al . infiltrating CD8 + T lymphocytes are prognostic factors of human 9,073,994 B2 7/2015 Honjo et al . 9,133,197 B2 9/2015 Cabri et al. ovarian cancer ” ( 2007 ) Proc Nat Acad Sci USA 104 : 3360-3365 . 2005/0158280 A1 7/2005 Robson et al. Hanouska et al. “ Phase 1b dose escalation study of erlotinib in 2006/0121005 A1 6/2006 Berenson et al . combination with infusional 5 -Fluorouracil , leucovorin , and oxaliplatin 2008/0241223 A1 10/2008 Nivaggioli et al . in patients with advanced solid tumors ” ( 2007 ) Clin Cancer Res 2011/0287002 A1 11/2011 Bukhalid et al. 13 ( 2 , part 1 ) :523-531 . 2016/0129108 A1 5/2016 Sachsenmeier et al. Häusler et al . “ CD39 Wird in vivo und in vitro von Ovarialkarzinomzel 2016/0185861 A1 6/2016 Bedoya et al . len expirmiert und inhitiert die lytische Aktivitat von NK -Zellen ” 2017/0015758 A1 1/2017 Hammond et al . Geburtshilfe Frauenheilkunded 69 :P106 (2009 ) German . 2017/0335007 Al 11/2017 Chen et al . Häusler et al. “ CD39 Wird in vivo und in vitro von Ovarialkarzinomzel 2018/0009899 A1 1/2018 Griffin et al. len expirmiert und inhitiert die lytische Aktivitat von NK - Zellen " Geburtshilfe Frauenheilkunded 69 : P106 ( 2009 ) English . FOREIGN PATENT DOCUMENTS Häusler et al. “ Ectonucleotidases CD39 and CD73 on OvCA cells EP 0088046 B1 12/1987 are potent adenosine- generating enzymes responsible for adenosine EP 0143949 B1 10/1988 receptor 2A - dependent suppression of T cell function and NK cell EP 0036676 B2 9/1990 cytotoxicity ” Cancer Immunol Immunother 60 : 1405-1417 ( 2011) . EP 0488401 A1 6/1992 Häusler et al . Geburtshilfe Frauenheilkd ( 2009 ) 69 - A042 ( Abstract EP 0430539 B1 10/1994 for XXI. Akademische Tagung deutsch sprechender ochschullehrer EP 0404097 B1 9/1996 in der Gynakologie und Geburtshilfe — Innsbruck ) German . EP 1537878 A4 11/2006 Häusler et al . Geburtshilfe Frauenheilkd ( 2009 ) 69 - A042 ( Abstract EP 2170959 A1 4/2010 for XXI. Akademische Tagung deutsch sprechender ochschullehrer EP 2161336 B1 7/2013 in der Gynakologie und Geburtshilfe — Innsbruck ) English . EP 2654789B1 B1 5/2018 Häusler et al . , poster“ CD39 wird von humanen Ovarialkarzinomzel WO 1990002809 Al 3/1990 WO 1991010737 Al 7/1991 linien exprimiert und hemmt die immunologishe Tumorabwehr” ( WO 1992001047 A1 1/1992 date : 2008 ) English Translation . WO 1992018619 Al 10/1992 Häusler et al. , poster : " CD39 wird in vivo und in vitro von WO 1993001161 A1 1/1993 Ovarialkarzinomzellen exprimiert und inhibiert die lytische Aktivitiit WO 1993011236 A1 6/1993 von NK - Zellen ” ( date : 2009 ) English Translation . WO 1993015722 Al 8/1993 Häusler Geburtshilfe Frauenheilkd (2008 ) 68 : SI -S194 (68 :PO WO 1994004678 A1 3/1994 Onko_04.33) ( Abstract for Kongress der Deutschen Gesellschaft fur WO 1994020069 A1 9/1994 Gynakologie und Geburtshilfe Hamburg ) German . WO 1994025591 A1 11/1994 Häusler Geburtshilfe Frauenheilkd ( 2008 ) 68: SI- S194 (68 :PO WO 1994029351 A2 12/1994 Onko_04.33) ( Abstract for Kongress der Deutschen Gesellschaft fur WO 1995015982 A2 6/1995 Gynakologie und Geburtshilfe — Hamburg ) English Translation . WO 1995020401 A1 8/1995 WO 1996027011 Al 9/1996 Hetherington et al. “ Phase I dose escalation study to evaluate the WO 1999051642 A1 10/1999 safety and pharmacokinetic profile of tefibazumab in subjects with WO 2008024188 7/2008 end - stage renal disease requiring hemodialysis ” (2006 ) Antimicro WO 2009036379 A2 3/2009 bial Agents and Chemotherapy 50 ( 10 ) : 3499-3500 . WO 2007024715 A9 4/2009 Hino et al ., “ Tumor cell expression of programmed cell death - 1 WO 2009095478 A1 8/2009 ligand 1 is a prognostic factor for malignant melanoma” ( 2010 ) WO 2009156737 A1 12/2009 Cancer 116 ( 7 ) : 1757-1766 ) . WO 2010027827 A2 3/2010 Holland , P.“ Targeting the Adenosine Axis to Treat Cancer ” Brisbane WO 2010077634 A1 7/2010 Immunotherapy Conference May 2019 , poster. WO 2010105256 A1 9/2010 Hollinger et al ., “ Diabodies” : small bivalent and bispecific anti WO 2011066342 A3 7/2011 body fragments ” ( 1993 ) Proc . Natl . Acad . Sci. USA 90 :6444-6448 . 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