Anti-ox40 antibodies and their uses

Abstract

The present disclosure provides novel anti-OX40 antibodies, compositions including the antibodies, nucleic acids encoding the antibodies, and methods of making and using the same.

What is claimed is: 
     
         1 . An anti-OX40 antibody which comprises (i) a V H  chain comprising three CDRs; and (ii) a V L  chain comprising three CDRs, wherein: 
       
         
           
                 
                 
               
                     
                   V H  CDR#1 has an amino acid sequence: 
                 
                     
                   (SEQ ID NO: 101) 
                 
                     
                   GFTFSRYGMS, 
                 
                     
                     
                 
                     
                   V H  CDR#2 has an amino acid sequence: 
                 
                     
                   (SEQ ID NO: 102) 
                 
                     
                   TINSNGGRTYYPDSVKG, 
                 
                     
                     
                 
                     
                   V H  CDR#3 has an amino acid sequence: 
                 
                     
                   (SEQ ID NO: 103) 
                 
                     
                   EGITTAYAMDY, 
                 
                     
                     
                 
                     
                   V L  CDR#1 has an amino acid sequence: 
                 
                     
                   (SEQ ID NO: 104) 
                 
                     
                   KASQSVDYDGDSYMH, 
                 
                     
                     
                 
                     
                   V L  CDR#2 has an amino acid sequence: 
                 
                     
                   (SEQ ID NO: 105) 
                 
                     
                   AASILES, 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   V L  CDR#3 has an amino acid sequence: 
                 
                     
                   (SEQ ID NO: 106) 
                 
                     
                   QQSNEDPRT. 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         2 . The anti-OX40 antibody of  claim 1 , which is monoclonal. 
     
     
         3 . The anti-OX40 antibody of  claim 1 , which is humanized. 
     
     
         4 . The anti-OX40 antibody of  claim 3 , which comprises a V H  chain having an amino acid sequence according to: 
       
         
           
                 
               
                   (SEQ ID NO: 22) 
                 
                   EVQLVESGGGLVQPGGSLRLSCAASGFTFSRYGMSWVRQAPGKGLELVA 
                 
                     
                 
                   TINSNGGRTYYPDSVKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCAR 
                 
                     
                 
                   EGITTAYAMDYWGQGTTVTVSS; 
                 
             
                
                
                
                
                
                
               
            
           
         
         and a V L  chain having an amino acid sequence according to: 
       
       
         
           
                 
               
                   (SEQ ID NO: 32) 
                 
                   DIVMTQSPDSLAVSLGERATINCKASQSVDYDGDSYMHWYQQKPGQPPK 
                 
                     
                 
                   LLIYAASILESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQQSNED 
                 
                     
                 
                   PRTFGGGTKVEIK. 
                 
             
                
                
                
                
                
                
               
            
           
         
       
     
     
         5 . The anti-OX40 antibody of  claim 3 , which is an IgG. 
     
     
         6 . The anti-OX40 antibody of  claim 5 , which is an IgG 1 . 
     
     
         7 . The anti-OX40 antibody of  claim 3  comprising a kappa light chain constant region. 
     
     
         8 . The anti-OX40 antibody of  claim 1  which comprises a heavy chain having an amino acid sequence according to SEQ ID NOS: 41 or 42; and a light chain having an amino acid sequence according to SEQ ID NO: 51. 
     
     
         9 . The anti-OX40 antibody of  claim 1  which has a k d  against human OX40 (SEQ ID NO:1) of less than about 1 sec −1 . 
     
     
         10 . The anti-OX40 antibody of  claim 1  which has a K D  against human OX40 (SEQ ID NO:1) of less than about 100 nM. 
     
     
         11 . A pharmaceutical composition comprising the anti-OX40 antibody of  claim 1 , and a pharmaceutically acceptable carrier. 
     
     
         12 . A nucleic acid comprising a nucleotide sequence encoding an anti-OX40 antibody which comprises (i) a V H  chain comprising three CDRs; and (ii) a V L  chain comprising three CDRs, wherein: 
       
         
           
                 
                 
               
                     
                   V H  CDR#1 has an amino acid sequence: 
                 
                     
                   (SEQ ID NO: 101) 
                 
                     
                   GFTFSRYGMS, 
                 
                     
                     
                 
                     
                   V H  CDR#2 has an amino acid sequence: 
                 
                     
                   (SEQ ID NO: 102) 
                 
                     
                   TINSNGGRTYYPDSVKG, 
                 
                     
                     
                 
                     
                   V H  CDR#3 has an amino acid sequence: 
                 
                     
                   (SEQ ID NO: 103) 
                 
                     
                   EGITTAYAMDY, 
                 
                     
                     
                 
                     
                   V L  CDR#1 has an amino acid sequence: 
                 
                     
                   (SEQ ID NO: 104) 
                 
                     
                   KASQSVDYDGDSYMH, 
                 
                     
                     
                 
                     
                   V L  CDR#2 has an amino acid sequence: 
                 
                     
                   (SEQ ID NO: 105) 
                 
                     
                   AASILES, 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   V L  CDR#3 has an amino acid sequence: 
                 
                     
                   (SEQ ID NO: 106) 
                 
                     
                   QQSNEDPRT. 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         13 . A vector comprising the nucleic acid of  claim 12 . 
     
     
         14 . A prokaryotic host cell transformed with the vector of  claim 12 . 
     
     
         15 . A eukaryotic host cell transformed with the vector of  claim 12 . 
     
     
         16 . The eukaryotic host cell of  claim 15  which is a mammalian host cell. 
     
     
         17 . A method of producing an anti-OX40 antibody, comprising: (a) culturing the host cell of  claim 16  and (b) recovering the anti-OX40 antibody. 
     
     
         18 . A method of treating a cancer, comprising administering to a patient in need thereof an effective amount of an anti-OX40 antibody which comprises (i) a V H  chain comprising three CDRs; and (ii) a V L  chain comprising three CDRs, wherein: 
       
         
           
                 
                 
               
                     
                   V H  CDR#1 has an amino acid sequence: 
                 
                     
                   (SEQ ID NO: 101) 
                 
                     
                   GFTFSRYGMS, 
                 
                     
                     
                 
                     
                   V H  CDR#2 has an amino acid sequence: 
                 
                     
                   (SEQ ID NO: 102) 
                 
                     
                   TINSNGGRTYYPDSVKG, 
                 
                     
                     
                 
                     
                   V H  CDR#3 has an amino acid sequence: 
                 
                     
                   (SEQ ID NO: 103) 
                 
                     
                   EGITTAYAMDY, 
                 
                     
                     
                 
                     
                   V L  CDR#1 has an amino acid sequence: 
                 
                     
                   (SEQ ID NO: 104) 
                 
                     
                   KASQSVDYDGDSYMH, 
                 
                     
                     
                 
                     
                   V L  CDR#2 has an amino acid sequence: 
                 
                     
                   (SEQ ID NO: 105) 
                 
                     
                   AASILES, 
                 
                     
                   and  
                 
                     
                     
                 
                     
                   V L  CDR#3 has an amino acid sequence: 
                 
                     
                   (SEQ ID NO: 106) 
                 
                     
                   QQSNEDPRT. 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         19 . The method of  claim 18 , wherein the cancer is selected from bladder cancer, breast cancer, head and neck cancer, gastric cancer, kidney cancer, liver cancer, lung cancer, ovarian cancer, skin cancer, and a tumor with evidence of DNA mismatch repair deficiency. 
     
     
         20 . The method of  claim 19 , wherein the lung cancer is small cell lung cancer, non-small cell lung cancer, or mesothelioma.