Binding molecules to the human ox40 receptor

Abstract

The present disclosure provides isolated binding molecules that bind to the human OX40R, nucleic acid molecules encoding an amino acid sequence of the binding molecules, vectors comprising the nucleic acid molecules, host cells containing the vectors, methods of making the binding molecules, pharmaceutical compositions containing the binding molecules, and methods of using the binding molecules or compositions.

1 .- 28 . (canceled) 
     
     
         29 . An isolated monoclonal antibody that binds to human OX40R, comprising:
 (a) a heavy chain CDR1 comprising an amino acid sequence of SEQ ID NO: 1; a heavy chain CDR2 comprising an amino acid sequence of SEQ ID NO: 2; and a heavy chain CDR3 comprising an amino acid sequence of SEQ ID NO: 3; or   (b) a heavy chain CDR1 comprising an amino acid sequence of SEQ ID NO: 13; a heavy chain CDR2 comprising an amino acid sequence of SEQ ID NO: 14; and a heavy chain CDR3 comprising an amino acid sequence of SEQ ID NO: 15,   
       wherein said isolated monoclonal antibody comprises 1, 2, 3 or 4 conservative amino acid substitutions in one or more heavy chain CDR sequences; and wherein said isolated monoclonal antibody:
 (a) binds to human OX40R with a K D  of 5×10 −9  M or less; and 
 (b) has agonist activity on human OX40R. 
 
     
     
         30 . The antibody according to  claim 29 , further comprising:
 (a) a light chain comprising a light chain CDR1 comprising an amino acid sequence of SEQ ID NO: 4; a light chain CDR2 comprising an amino acid sequence of SEQ ID NO: 5; and a light chain CDR3 comprising an amino acid sequence of SEQ ID NO: 6; or   (b) a light chain comprising a light chain CDR1 comprising an amino acid sequence of SEQ ID NO: 16; a light chain CDR2 comprising an amino acid sequence of SEQ ID NO: 17; and a light chain CDR3 comprising an amino acid sequence of SEQ ID NO: 18.   
     
     
         31 . The antibody according to  claim 29 , which is a human antibody, or a chimeric or humanized antibody. 
     
     
         32 . A composition comprising an antibody according to  claim 29  and optionally a pharmaceutically acceptable carrier. 
     
     
         33 . An isolated nucleic acid molecule comprising a nucleotide sequence that encodes an antibody according to  claim 29 . 
     
     
         34 . A vector comprising the nucleic acid molecule of  claim 33 . 
     
     
         35 . The vector according to  claim 34 , further comprising an expression control sequence operably linked to the nucleic acid molecule. 
     
     
         36 . A host cell comprising the vector according to  claim 34 . 
     
     
         37 . An in vitro method of inhibiting growth of tumor cells, comprising contacting the tumor cells with an antibody according to  claim 29 , wherein the antibody is in an amount effective to inhibit the growth of the tumor cells. 
     
     
         38 . A method of treating cancer in a mammal in need thereof, comprising administering to the mammal a therapeutically effective amount of the composition of  claim 32 . 
     
     
         39 . The method according to  claim 38 , wherein the cancer is selected from the group consisting of hepatocellular carcinoma, squamous cell carcinoma, head and neck cancer, renal cell carcinoma, melanoma, breast cancer, prostate cancer, colorectal cancer, lung cancer, and hematological cancer. 
     
     
         40 . The antibody according to  claim 30 , which is a human antibody, or a chimeric or humanized antibody. 
     
     
         41 . A composition comprising an antibody according to  claim 30  and optionally a pharmaceutically acceptable carrier. 
     
     
         42 . A method of enhancing an immune response in a mammal in need thereof, comprising administering to the mammal a therapeutically effective amount of the composition of  claim 32 . 
     
     
         43 . An isolated nucleic acid molecule comprising a nucleotide sequence that encodes an antibody according to  claim 30 . 
     
     
         44 . A vector comprising the nucleic acid molecule of  claim 43 . 
     
     
         45 . The vector according to  claim 34 , further comprising an expression control sequence operably linked to the nucleic acid molecule. 
     
     
         46 . A host cell comprising the vector according to  claim 45 . 
     
     
         47 . An in vitro method of inhibiting growth of tumor cells, comprising contacting the tumor cells with an antibody according to  claim 30 , wherein the antibody is in an amount effective to inhibit the growth of the tumor cells. 
     
     
         48 . A method of enhancing an immune response in a mammal in need thereof, comprising administering to the mammal a therapeutically effective amount of the composition of  claim 41 .