Anti-ox40l antibodies and methods using same

Abstract

The invention provides anti-OX40L antibodies, and compositions comprising and methods of using these antibodies.

1 . An anti-OX40L antibody comprising: at least one, two, three, four, five, and/or six hypervariable region (HVR) sequences selected from the group consisting of:
 (a) HVR-L1 comprising sequence RSSQSIVHGNGNTYLE (SEQ ID NO:1) or RSSQSPVHSNGNTYLH (SEQ ID NO:2);   (b) HVR-L2 comprising sequence RVSNRFS (SEQ ID NO:3) or KVSNRFS (SEQ ID NO:4);   (c) HVR-L3 comprising sequence FQGSHVPYT (SEQ ID NO:5) or SQSTHIPWT (SEQ ID NO:6);   (d) HVR-H1 comprising sequence SYWLN (SEQ ID NO:7) or SYWMH (SEQ ID NO:8);   (e) HVR-H2 comprising sequence MIDPSDSETHYNQVFKD (SEQ ID NO:9) or EIDPSNGRTNYNEKFKS (SEQ ID NO:10); and   (f) HVR-H3 comprising sequence GRGNFYGGSHAMEY (SEQ ID NO:11) or ERSPRYFDV (SEQ ID NO:12),   wherein the anti-OX40L antibody binds OX40L.   
     
     
         2 . The anti-OX40L antibody of  claim 1 , wherein the antibody comprises: at least one, two, three, four, five, and/or six hypervariable region (HVR) sequences selected from the group consisting of:
 (a) HVR-L1 comprising sequence RSSQSIVHGNGNTYLE (SEQ ID NO:1);   (b) HVR-L2 comprising sequence RVSNRFS (SEQ ID NO:3);   (c) HVR-L3 comprising sequence FQGSHVPYT (SEQ ID NO:5);   (d) HVR-H1 comprising sequence SYWLN (SEQ ID NO:7);   (e) HVR-H2 comprising sequence MIDPSDSETHYNQVFKD (SEQ ID NO:9); and   (f) HVR-H3 comprising sequence GRGNFYGGSHAMEY (SEQ ID NO:11).   
     
     
         3 . The anti-OX40L antibody of  claim 1 , wherein the antibody comprises: at least one, two, three, four, five, and/or six hypervariable region (HVR) sequences selected from the group consisting of:
 (a) HVR-L1 comprising sequence RSSQSPVHSNGNTYLH (SEQ ID NO:2);   (b) HVR-L2 comprising sequence KVSNRFS (SEQ ID NO:4);   (c) HVR-L3 comprising sequence SQSTHIPWT (SEQ ID NO:6);   (d) HVR-H1 comprising sequence SYWMH (SEQ ID NO:8);   (e) HVR-H2 comprising sequence EIDPSNGRTNYNEKFKS (SEQ ID NO:10); and   (f) HVR-H3 comprising sequence ERSPRYFDV (SEQ ID NO:12).   
     
     
         4 . The anti-OX40L antibody of  claim 1 , wherein the antibody comprises: a light chain comprising at least one, at least two or all three of HVR sequences selected from the group consisting of RSSQSIVHGNGNTYLE (SEQ ID NO:1), RVSNRFS (SEQ ID NO:3), and FQGSHVPYT (SEQ ID NO:5). 
     
     
         5 . The anti-OX40L antibody of  claim 1 , wherein the antibody comprises: a heavy chain comprising at least one, at least two or all three of HVR sequences selected from the group consisting of SYWLN (SEQ ID NO:7), MIDPSDSETHYNQVFKD (SEQ ID NO:9), and GRGNFYGGSHAMEY (SEQ ID NO:11). 
     
     
         6 . The anti-OX40L antibody of  claim 1 , wherein the antibody comprises:
 (a) a light chain comprising at least one, at least two or all three of HVR sequences selected from the group consisting of RSSQSIVHGNGNTYLE (SEQ ID NO:1), RVSNRFS (SEQ ID NO:3), and FQGSHVPYT (SEQ ID NO:5), and   (b) a heavy chain comprising at least one, at least two or all three of HVR sequences selected from the group consisting of SYWLN (SEQ ID NO:7), MIDPSDSETHYNQVFKD (SEQ ID NO:9), and GRGNFYGGSHAMEY (SEQ ID NO:11).   
     
     
         7 . The anti-OX40L antibody of  claim 1 , wherein the antibody comprises: a light chain comprising at least one, at least two or all three of HVR sequences selected from the group consisting of RSSQSPVHSNGNTYLH (SEQ ID NO:2), KVSNRFS (SEQ ID NO:4), and SQSTHIPWT (SEQ ID NO:6). 
     
     
         8 . The anti-OX40L antibody of  claim 1 , wherein the antibody comprises: a heavy chain comprising at least one, at least two or all three of HVR sequences selected from the group consisting of SYWMH (SEQ ID NO:8), EIDPSNGRTNYNEKFKS (SEQ ID NO:10, and ERSPRYFDV (SEQ ID NO:12). 
     
     
         9 . The anti-OX40L antibody of  claim 1 , wherein the antibody comprises:
 (a) a light chain comprising at least one, at least two or all three of HVR sequences selected from the group consisting of RSSQSPVHSNGNTYLH (SEQ ID NO:2), KVSNRFS (SEQ ID NO:4), and SQSTHIPWT (SEQ ID NO:6); and   (b) a heavy chain comprising at least one, at least two or all three of HVR sequences selected from the group consisting of SYWMH (SEQ ID NO:8), EIDPSNGRTNYNEKFKS (SEQ ID NO:10, and ERSPRYFDV (SEQ ID NO:12).   
     
     
         10 . The anti-OX40L antibody of  claim 1 , wherein the antibody comprises: a light chain variable domain having the sequence: 
       
         
           
                 
               
                   (SEQ ID NO: 13) 
                 
                   DILMTQTPLSLPVSLGDQASISCRSSQSIVHGNGNTYLEWHLQKPGQSP 
                 
                     
                 
                   KLLIYRVSNRFSGVPDRFSGSGSGTDFTLKINRVEAEDLGVYYCFQGSH 
                 
                     
                 
                   VPYTFGGGTKVEIKR. 
                 
             
                
                
                
                
                
                
               
            
           
         
       
     
     
         11 . The anti-OX40L antibody of  claim 1 , wherein the antibody comprises: a heavy chain variable domain having the sequence: 
       
         
           
                 
               
                   (SEQ ID NO: 15) 
                 
                   QVQLQQPGAELVRPGASVkLSCKASGYTFTSYWLNWVKQRPGQGLEWIV 
                 
                     
                 
                   MIDPSDSETHYNQVFKDKATLTVDKSSSTAYMQLSSLTSEDSAVYYCIR 
                 
                     
                 
                   GRGNFYGGSHAMEYWGQGTLLTVSS. 
                 
             
                
                
                
                
                
                
               
            
           
         
       
     
     
         12 . The anti-OX40L antibody of  claim 1 , wherein the antibody comprises:
 (a) a light chain variable domain having the sequence:   DILMTQTPLSLPVSLGDQASISCRSSQSIVHGNGNTYLEWHLQKPGQSPKLLIYRVSNRFSGVPDRFSGSGSG TDFTLKINRVEAEDLGVYYCFQGSHVPYTFGGGTKVEIKR (SEQ ID NO:13); and   (b) a heavy chain variable domain having the sequence:   
       
         
           
                 
               
                   (SEQ ID NO: 15) 
                 
                   QVQLQQPGAELVRPGASVKLSCKASGYTFTSYWLNWVKQRPGQGLEWIV 
                 
                     
                 
                   MIDPSDSETHYNQVFKDKATLTVDKSSSTAYMQLSSLTSEDSAVYYCIR 
                 
                     
                 
                   GRGNFYGGSHAMEYWGQGTLLTVSS. 
                 
             
                
                
                
                
                
                
               
            
           
         
       
     
     
         13 . The anti-OX40L antibody of  claim 1 , wherein the antibody comprises: a light chain variable domain having the sequence: 
       
         
           
                 
               
                   (SEQ ID NO: 14) 
                 
                   DIVMTQTPLSLPVSLGDQASMYCRSSQSPVHSNGNTYLHWYLQKPGQSP 
                 
                     
                 
                   KELIYKVSNRFSGVPDRFSGSGSGTDFTLKISRVEAEDLGVYFCSQSTH 
                 
                     
                 
                   IPWTFGGGTKVEIKR. 
                 
             
                
                
                
                
                
                
               
            
           
         
       
     
     
         14 . The anti-OX40L antibody of  claim 1 , wherein the antibody comprises: a heavy chain variable domain having the sequence: 
       
         
           
                 
               
                   (SEQ ID NO: 16) 
                 
                   QVQLQQPGAELVKPGTSVKLSCKASGYSFTSYWMHGVRQRPGQGLEWIG 
                 
                     
                 
                   EIDPSNGRTNYNEKFKSKATLTVDKSSSTAYIQLSSLTSEDSAVYYCTR 
                 
                     
                 
                   ERSPRYFDVWGAGTTLTVSS. 
                 
             
                
                
                
                
                
                
               
            
           
         
       
     
     
         15 . The anti-OX40L antibody of  claim 1 , wherein the antibody comprises:
 (a) a light chain variable domain having the sequence: DIVMTQTPLSLPVSLGDQASMYCRSSQSPVHSNGNTYLHWYLQKPGQSPKWYKVSNRFSGVPDRFSGSGS GTDFTLKISRVEAEDLGVYFCSQSTHIPWTFGGGTKVEIKR (SEQ ID NO:14); and   (b) a heavy chain variable domain having the sequence:   
       
         
           
                 
               
                   (SEQ ID NO: 16) 
                 
                   QVQLQQPGAELVKPGTSVKLSCKASGYSFTSYWMHGVRQRPGQGLEWIG 
                 
                     
                 
                   EIDPSNGRTNYNEKFKSKATLTVDKSSSTAYIQLSSLTSEDSAVYYCTR 
                 
                     
                 
                   ERSPRYFDVWGAGTTLTVSS. 
                 
             
                
                
                
                
                
                
               
            
           
         
       
     
     
         16 . An isolated antibody that binds to a same epitope on human OX40L as the antibody of  claim 12 . 
     
     
         17 . An isolated antibody that binds to a same epitope on human OX40L as the antibody of  claim 15 . 
     
     
         18 . An isolated antibody that competes with an antibody of  claim 12 . 
     
     
         19 . An isolated antibody that competes with an antibody of  claim 15 . 
     
     
         20 . The antibody of  claim 1 ,  2 ,  3 ,  9 ,  12  or  15 , wherein the antibody is a monoclonal antibody. 
     
     
         21 . The antibody of  claim 1 ,  2 ,  3 ,  9 ,  12  or  15 , wherein the antibody is selected from the group consisting of a chimeric antibody, a humanized antibody, an affinity matured antibody, a human antibody, and a bispecific antibody. 
     
     
         22 . The antibody of  claim 1 ,  2 ,  3 ,  9 ,  12  or  15 , wherein the antibody is an antibody fragment. 
     
     
         23 . A polynucleotide encoding an antibody of any of  claim 1 ,  2 ,  3 ,  9 ,  12  or  15 . 
     
     
         24 . A vector comprising the polynucleotide of  claim 23 . 
     
     
         25 . The vector of  claim 24 , wherein the vector is an expression vector. 
     
     
         26 . A host cell comprising a vector of  claim 24  or  25 . 
     
     
         27 . The host cell of  claim 26 , wherein the host cell is prokaryotic. 
     
     
         28 . The host cell of  claim 26 , wherein the host cell is eukaryotic. 
     
     
         29 . The host cell of  claim 26 , wherein the host cell is mammalian. 
     
     
         30 . A method for making an anti-OX40L antibody, said method comprising (a) expressing a vector of  claim 25  in a suitable host cell, and (b) recovering the antibody. 
     
     
         31 . The method of  claim 30 , wherein the host cell is prokaryotic. 
     
     
         32 . The method of  claim 30 , wherein the host cell is eukaryotic. 
     
     
         33 . A method for treating or preventing an immune disorder, the method comprising administering an effective amount of the anti-OX40L antibody of any of  claim 1 ,  2 ,  3 ,  9 ,  12  or  15  to a subject in need of such treatment. 
     
     
         34 . The method of  claim 33 , wherein the immune disorder is an autoimmune disorder. 
     
     
         35 . The method of  claim 33 , wherein the immune disorder is asthma, atopic dermatitis, allergic rhinitis, inflammatory bowel disease, graft-verses-host disease, multiple sclerosis, or systemic lupus erythematosus. 
     
     
         36 . The method of  claim 35 , wherein the immune disorder is asthma, atopic dermatitis or allergic rhinitis. 
     
     
         37 . A composition comprising an anti-OX40L antibody of any of  claim 1 ,  2 ,  3 ,  9 ,  12  or  15 . 
     
     
         38 . A composition comprising a polynucleotide of  claim 22 .