Anti-cd39 antibodies, compositions comprising anti-cd39 antibodies and methods of using anti-cd39 antibodies

Abstract

Provided herein are antibodies that selectively bind to CD39 and its isoforms and homologs, and compositions comprising the antibodies. Also provided are methods of using the antibodies, such as therapeutic and diagnostic methods.

1 .- 13 . (canceled) 
     
     
         14 . An isolated antibody molecule capable of binding to human CD39 (hCD39), comprising a heavy chain variable region (V H ) and a light chain variable region (V L ), V H  and/or V L  comprising 1, 2, 3, 4, 5, or 6 of:
 a) a VHCDR1 having the sequence set forth in SEQ ID NOs: 1-45,   b) a VHCDR2 having the sequence set forth in SEQ ID NOs: 46-81,   c) a VHCDR3 having the sequence set forth in SEQ ID NOs: 82-109,   d) a VLCDR1 having the sequence set forth in SEQ ID NOs: 110-124,   e) a VLCDR2 having the sequence set forth in SEQ ID NOs: 125-140, and   f) a VLCDR3 having the sequence set forth in SEQ ID NOs: 141-166.   
     
     
         15 . (canceled) 
     
     
         16 . An isolated nucleic acid encoding an antigen binding protein according to  claim 14 . 
     
     
         17 . An expression vector comprising the nucleic acid according to  claim 16 . 
     
     
         18 . A prokaryotic or eukaryotic host cell comprising the vector of  claim 17 . 
     
     
         19 . An oncolytic virus encoding the nucleic acid of  claim 16 . 
     
     
         20 . A method for the production of a recombinant protein comprising the steps of expressing a nucleic acid according to  claim 16  in a prokaryotic or eukaryotic host cell and recovering the protein from the cell or the cell culture supernatant. 
     
     
         21 . A method for treatment of a subject suffering from cancer, a chronic infection, or from an inflammatory disease, comprising the step of administering to the subject a pharmaceutical composition comprising an effective amount of the the isolated antibody molecule of  claim 14 . 
     
     
         22 . The method of  claim 21 , wherein the cancer is a solid cancer. 
     
     
         23 . The method of  claim 21 , wherein the cancer is a hematological cancer. 
     
     
         24 .- 29 . (canceled) 
     
     
         30 . The method of  claim 21 , wherein the method further comprises one or more of the following
 a) administering chemotherapy;   b) administering radiation therapy; and/or   c) administering one or more additional therapeutic agents.   
     
     
         31 . The method of  claim 30 , wherein the one or more additional therapeutic agents comprise one or more immunostimulatory agents. 
     
     
         32 . The method of  claim 31 , wherein the one or more immunostimulatory agents comprise an antagonist to an inhibitory receptor of an immune cell. 
     
     
         33 . The method of  claim 32 , wherein the inhibitory receptor is at least one of CTLA-4, PD-1, PD-L1, PD-L2, LAG-3, Tim3, neuritin, BTLA, CECAM-1, CECAM-5, VISTA, LAIR1, CD160, 2B4, TGF-R, and/or Killer cell immunoglobulin-like receptor (KIR). 
     
     
         34 . The method of  claim 31 , wherein the one or more immunostimulatory agents comprise an agonist of a co-stimulatory receptor of an immune cell. 
     
     
         35 . The method of  claim 34 , wherein the co-stimulatory receptor is OX40, CD2, CD27, CDS, ICAM-1, LFA-1, ICOS (CD278), 4-1BB (CD137), GITR, CD28, CD30, CD40, BAFFR, HVEM, CD7, LIGHT, NKG2C, SLAMF7, NKp80, CD160, B7-H3, or a CD83 ligand. 
     
     
         36 . The method of  claim 35 , wherein the costimulatory receptor or ligand LFA-1 further comprises an LFA-1 P-chains CD18 and/or an LFA-1 a-chain CD11a. 
     
     
         37 . The method of  claim 31 , wherein the one or more immunostimulatory agents comprise a cytokine. 
     
     
         38 . The method of  claim 37 , wherein the cytokine is at least one of IL-2, IL-5, IL-7, IL-12, IL-15, and/or IL-21. 
     
     
         39 . The method of  claim 31 , wherein the one or more immunostimulatory agents comprise an oncolytic virus. 
     
     
         40 . The method of  claim 39 , wherein the oncolytic virus is a Herpes simplex virus, a Vesicular stomatitis virus, an adenovirus, a Newcastle disease virus, a vaccinia virus, or a maraba virus. 
     
     
         41 . The method of  claim 31 , wherein the one or more immunostimulatory agents comprise a chimeric antigen engineered T cell. 
     
     
         42 . The method of  claim 31 , wherein the one or more immunostimulatory agents comprise a bi- or multispecific T cell directed antibody. 
     
     
         43 .- 49 . (canceled) 
     
     
         50 . An isolated antibody molecule capable of binding to human CD39 (hCD39), comprising a heavy chain and a light chain, the heavy chain comprising one or more molecules having a sequence consisting of one of SEQ ID NO: 255, SEQ ID NO: 257, SEQ ID NO: 259, SEQ ID NO: 261, SEQ ID NO: 263, SEQ ID NO: 265, SEQ ID NO: 267, SEQ ID NO: 269, SEQ ID NO: 271, SEQ ID NO: 273, SEQ ID NO: 275, SEQ ID NO: 277, SEQ ID NO: 279, SEQ ID NO: 281, SEQ ID NO: 283, SEQ ID NO: 285, SEQ ID NO: 287, SEQ ID NO: 289, SEQ ID NO: 291, SEQ ID NO: 293, or SEQ ID NO: 295 and the light chain comprising one or more molecules having a sequence consisting of one of SEQ ID NO: 256, SEQ ID NO: 258, SEQ ID NO: 260, SEQ ID NO: 262, SEQ ID NO: 264, SEQ ID NO: 266, SEQ ID NO: 268, SEQ ID NO: 270, SEQ ID NO: 272, SEQ ID NO: 274, SEQ ID NO: 276, SEQ ID NO: 278, SEQ ID NO: 280, SEQ ID NO: 282, SEQ ID NO: 284, SEQ ID NO: 286, SEQ ID NO: 288, SEQ ID NO: 290, SEQ ID NO: 292, SEQ ID NO: 294, or SEQ ID NO: 296. 
     
     
         51 . The isolated antibody molecule capable of binding to human CD39 (hCD39) according to  claim 50 , wherein,
 a) the heavy chain comprises one or more molecules, each molecule having a a sequence consisting of SEQ ID NO: 255 and the light chain comprises one or more, each molecule having a sequence consisting of SEQ ID NO: 256;   b) the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 257 and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 258;   c) the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 259 and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 260;   d) the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 261 and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 262;   e) the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 263 and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 264;   f) the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 265 and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 266;   g) the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 267 and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 268;   h) the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 269 and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 270;   i) the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 271 and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 272;   j) the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 273 and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 274;   k) the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 275 and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 276;   l) the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 277 and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 278   m) the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 279 and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 280;   n) the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 281 and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 282;   o) the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 283 and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 284;   p) the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 285 and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 286;   q) the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 287 and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 288;   r) the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 289 and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 290;   s) the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 291 and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 292;   t) the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 293 and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 294; or   u) the heavy chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 295 and the light chain comprises one or more molecules, each molecule having a sequence consisting of SEQ ID NO: 296.   
     
     
         52 .- 53 . (canceled)