Anti-cd40 antibody and their uses

Abstract

The present disclosure provides novel anti-CD40 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-CD40 antibody or binding fragment 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 selected from:   
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 6) 
                 
                     
                   GYTFTSYWMH, 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 7) 
                 
                     
                   GYTFTDYYIN, 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 8) 
                 
                     
                   GYSITSNYYWN, 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 9) 
                 
                     
                   GYSISSNYYWN, 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 10) 
                 
                     
                   GYDITSNYYWN; 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         V H  CDR #2 is selected from: 
       
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 17) 
                 
                     
                   WIFPGSGSVYCNEQFKG, 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 18) 
                 
                     
                   YIRYDGSNNYNPSLKN, 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 19) 
                 
                     
                   NIDPSNGETHYAQKFQG, 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 20) 
                 
                     
                   WIFPGSGSVYSNEQFKG, 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 21) 
                 
                     
                   YIRYDGSNNYNPSLKS, 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 22) 
                 
                     
                   YIRYDGSNNYNPSLKG; 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         V H  CDR #3 is selected from: 
       
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 35) 
                 
                     
                   LDY, 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 36) 
                 
                     
                   ERIYYSGSTYDGYFDV, 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 37) 
                 
                     
                   SLGKFAY; 
                 
             
                
                
                
                
                
                
                
                
                
               
            
           
         
         V L  CDR #1 is selected from: 
       
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 56) 
                 
                     
                   SASSSLSYMH, 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 57) 
                 
                     
                   KASQSVVTAVA, 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 58) 
                 
                     
                   RSSQSLENTNGNTFLN; 
                 
             
                
                
                
                
                
                
                
                
                
               
            
           
         
         V L  CDR #2 is selected from: 
       
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 66) 
                 
                     
                   DTSKLAS, 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 67) 
                 
                     
                   SASNRYT, 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 68) 
                 
                     
                   RVSNRFS; 
                 
             
                
                
                
                
                
                
                
                
                
               
            
           
         
         V L  CDR #3 is selected from: 
       
       
         
           
                 
                 
               
                     
                   (SEQ ID NO: 86) 
                 
                     
                   QQWSSNPWT, 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 87) 
                 
                     
                   QQYSSYPYT, 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   (SEQ ID NO: 88) 
                 
                     
                   LQVTHVPFT. 
                 
             
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         2 . The anti-CD40 antibody or binding fragment of  claim 1  which comprises CDRS having the sequences of SEQ ID NOS: 8, 18, 35, 58, 68, and 88. 
     
     
         3 . The anti-CD40 antibody or binding fragment of  claim 1  which is human or humanized. 
     
     
         4 . The anti-CD40 antibody or binding fragment of  claim 1 , which comprises a V H  chain corresponding in sequence to any one of SEQ ID NOS:110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, or 123; and a V L  chain corresponding in sequence to any one of SEQ ID NOS:161, 162, 163, 164, 165, 166, 167, 168, 169, 170, or 171. 
     
     
         5 . The anti-CD40 antibody or binding fragment of  claim 1  which comprises a V H  chain corresponding to the sequence of SEQ ID NO:117 and a V L  chain corresponding to the sequence of SEQ ID NO:170. 
     
     
         6 . The anti-CD40 antibody or binding fragment of  claim 1 , which is an IgG, optionally an IgG 1 . 
     
     
         7 . The anti-CD40 antibody of  claim 6 , which is an IgG 1  and comprises a variant CH2 region comprising the amino acid substitution V273E or V273Y. 
     
     
         8 . The anti-CD40 antibody of  claim 6 , which is an IgG 1  and comprises a variant Fc region comprising the amino acid substitutions D356E and L358M. 
     
     
         9 . The anti-CD40 antibody of  claim 6  comprising a kappa light chain constant region. 
     
     
         10 . The anti-CD40 antibody of  claim 1  having a heavy chain sequence according to any one of SEQ ID NOS:130-135, and light chain sequence according to any one of SEQ ID NOS:140-142. 
     
     
         11 . The anti-CD40 antibody of  claim 10  having a heavy chain sequence according to SEQ ID NOS:130 or 131, and a light chain sequence according to SEQ ID NO:140. 
     
     
         12 . The anti-CD40 antibody of  claim 10  having a heavy chain sequence according to SEQ ID NOS:132 or 133, and a light chain sequence according to SEQ ID NO:141. 
     
     
         13 . The anti-CD40 antibody of  claim 10  having a heavy chain sequence according to SEQ ID NOS:132 or 133, and a light chain sequence according to SEQ ID NO:142. 
     
     
         14 . A pharmaceutical composition comprising an anti-CD40 antibody or binding fragment of  claim 1 , and a pharmaceutically acceptable carrier. 
     
     
         15 . A method of treating a cancer, comprising administering to a patient in need thereof an anti-CD40 antibody or binding fragment of  claim 1 . 
     
     
         16 . A nucleic acid comprising a nucleotide sequence encoding an anti-CD40 antibody or binding fragment of  claim 1 . 
     
     
         17 . A vector comprising the nucleic acid of  claim 16 . 
     
     
         18 . A prokaryotic host cell transformed with the vector of  claim 17 . 
     
     
         19 . A eukaryotic host cell transformed with the vector of  claim 17 . 
     
     
         20 . A eukaryotic host cell engineered to express the nucleic acid of  claim 16 . 
     
     
         21 . The eukaryotic host cell of  claim 20  which is a mammalian host cell. 
     
     
         22 . A method of producing an anti-CD40 antibody or binding fragment thereof, comprising: (a) culturing the host cell of  claim 20  and (b) recovering the antibody or binding fragment. 
     
     
         23 . A method of activating the immune system, comprising administering to a patient in need thereof an anti-CD40 antibody or binding fragment of  claim 1 .