Anti-pd-1 antibodies and their uses

Abstract

The present disclosure provides novel anti-PD-1 antibodies, compositions including the new antibodies, nucleic acids encoding the antibodies, and methods of making and using the same.

What is claimed is: 
     
         1 . An anti-PD-1 binding protein which comprises (i) a V H  chain comprising three CDRs; and (ii) a V L  chain comprising three CDRs, wherein: 
       
         
           
                 
                 
               
                     
                   V H  CDR#1 is 
                 
                     
                   (SEQ ID NO: 11) 
                 
                     
                   GYTFTHYGMN; 
                 
                     
                     
                 
                     
                   V H  CDR#2 is 
                 
                     
                   (SEQ ID NO: 12) 
                 
                     
                   WVNTYTGEPTYADDFKG; 
                 
                     
                     
                 
                     
                   V H  CDR#3 is 
                 
                     
                   (SEQ ID NO: 13) 
                 
                     
                   EGEGLGFGD; 
                 
                     
                     
                 
                     
                   V L  CDR#1 is 
                 
                     
                   (SEQ ID NO: 14) 
                 
                     
                   RSSQSIVHSHGDTYLE; 
                 
                     
                     
                 
                     
                   V L  CDR#2 is 
                 
                     
                   (SEQ ID NO: 15) 
                 
                     
                   KVSNRFS; 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   V L  CDR#3 is 
                 
                     
                   (SEQ ID NO: 16) 
                 
                     
                   FQGSHIPVT. 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         2 . The anti-PD-1 binding protein of  claim 1 , which is humanized. 
     
     
         3 . The anti-PD-1 binding protein of  claim 2 , which comprises a V H  chain corresponding in sequence to SEQ ID NO:36; and a V L  chain corresponding in sequence to SEQ ID NO:42. 
     
     
         4 . The anti-PD-1 binding protein of  claim 3 , which is an IgG. 
     
     
         5 . The anti-PD-1 binding protein of  claim 4 , which is an IgG 1 . 
     
     
         6 . The anti-PD-1 binding protein of  claim 5  comprising a variant CH2 domain having amino acid substitutions L234A and L235A. 
     
     
         7 . The anti-PD-1 binding protein of  claim 4 , which is an IgG 4 . 
     
     
         8 . The anti-PD-1 binding protein of  claim 7  comprising a variant Fc region having an amino acid substitution S228P. 
     
     
         9 . The anti-PD-1 binding protein of  claim 3  comprising a kappa light constant region. 
     
     
         10 . The anti-PD-1 binding protein of  claim 3  which comprises a heavy chain corresponding in sequence to SEQ ID NO:51 or SEQ ID NO:52, and a light chain corresponding in sequence to SEQ ID NO:61. 
     
     
         11 . The anti-PD-1 binding protein of  claim 1  which has a K D  of less than about 100 nM. 
     
     
         12 . The anti-PD-1 binding protein of  claim 11  which has a K D  of less than about 10 nM. 
     
     
         13 . A pharmaceutical composition comprising the anti-PD-1 binding protein of  claim 1 , and a pharmaceutically acceptable carrier. 
     
     
         14 . A nucleic acid comprising a nucleotide sequence encoding an anti-PD-1 binding protein, wherein the binding protein comprises (i) a V H  chain comprising three CDRs; and (ii) a V L  chain comprising three CDRs, wherein: 
       
         
           
                 
                 
               
                     
                   V H  CDR#1 is 
                 
                     
                   (SEQ ID NO: 11) 
                 
                     
                   GYTFTHYGMN; 
                 
                     
                     
                 
                     
                   V H  CDR#2 is 
                 
                     
                   (SEQ ID NO: 12) 
                 
                     
                   WVNTYTGEPTYADDFKG; 
                 
                     
                     
                 
                     
                   V H  CDR#3 is 
                 
                     
                   (SEQ ID NO: 13) 
                 
                     
                   EGEGLGFGD; 
                 
                     
                     
                 
                     
                   V L  CDR#1 is 
                 
                     
                   (SEQ ID NO: 14) 
                 
                     
                   RSSQSIVHSHGDTYLE; 
                 
                     
                     
                 
                     
                   V L  CDR#2 is 
                 
                     
                   (SEQ ID NO: 15) 
                 
                     
                   KVSNRFS; 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   V L  CDR#3 is 
                 
                     
                   (SEQ ID NO: 16) 
                 
                     
                   FQGSHIPVT. 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         15 . A vector comprising the nucleic acid of  claim 14 . 
     
     
         16 . A prokaryotic host cell transformed with the vector of  claim 15 . 
     
     
         17 . A eukaryotic host cell transformed with the vector of  claim 15 . 
     
     
         18 . A eukaryotic host cell engineered to express the nucleic acid of  claim 14 . 
     
     
         19 . The eukaryotic host cell of  claim 18  which is a mammalian host cell. 
     
     
         20 . A method of producing an anti-PD-1 binding protein thereof, comprising: (a) culturing the host cell of  claim 19  and (b) recovering the anti-PD-1 binding protein. 
     
     
         21 . A method of activating the immune system, comprising administering to a patient in need thereof an effective amount of an anti-PD-1 binding protein expressed by the host cell of  claim 18 . 
     
     
         22 . A method of treating a cancer, comprising administering to a patient in need thereof a therapeutically effective amount of an anti-PD-1 binding protein, wherein the binding protein comprises (i) a V H  chain comprising three CDRs; and (ii) a V L  chain comprising three CDRs, wherein: 
       
         
           
                 
                 
               
                     
                   V H  CDR#1 is 
                 
                     
                   (SEQ ID NO: 11) 
                 
                     
                   GYTFTHYGMN; 
                 
                     
                     
                 
                     
                   V H  CDR#2 is 
                 
                     
                   (SEQ ID NO: 12) 
                 
                     
                   WVNTYTGEPTYADDFKG; 
                 
                     
                     
                 
                     
                   V H  CDR#3 is 
                 
                     
                   (SEQ ID NO: 13) 
                 
                     
                   EGEGLGFGD; 
                 
                     
                     
                 
                     
                   V L  CDR#1 is 
                 
                     
                   (SEQ ID NO: 14) 
                 
                     
                   RSSQSIVHSHGDTYLE; 
                 
                     
                     
                 
                     
                   V L  CDR#2 is 
                 
                     
                   (SEQ ID NO: 15) 
                 
                     
                   KVSNRFS; 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   V L  CDR#3 is 
                 
                     
                   (SEQ ID NO: 16) 
                 
                     
                   FQGSHIPVT. 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         23 . The method of  claim 22 , wherein the cancer is selected from bladder cancer, breast cancer, head and neck cancer, kidney cancer, lung cancer, lymphoma, melanoma, and stomach cancer. 
     
     
         24 . The method of  claim 23 , wherein the lung cancer is non-small cell lung cancer. 
     
     
         25 . The method of  claim 21 , in which the anti-PD-1 binding protein is administered intravenously.