Filovirus antibody

Abstract

The present invention addresses a need for antibodies useful for filovirus infections.

1 . An isolated humanized anti-filovirus glycoprotein pre-fusion core antibody comprising a framework region having a sequence of 95% or greater identity to a human antibody framework region, and comprising:
 (a) a heavy chain CDR1 comprising GFAFNYYDMF (SEQ ID NO:1); a heavy chain CDR2 comprising YIKPGGGNTYYADSV (SEQ ID NO:2); and a heavy chain CDR3 comprising QLYGNSFFDY (SEQ ID NO:3); and   (b) a light chain sequence CDR1 comprising DVTTA (SEQ ID NO:4); a light chain sequence CDR2 comprising WASTR (SEQ ID NO:5); and a light chain sequence CDR3 comprising HYSTPLT (SEQ ID NO:6).   
     
     
         2 . The humanized antibody of  claim 1 , wherein the light chain comprises the sequence: 
       
         
           
                 
               
                   (SEQ ID NO: 7) 
                 
                   DIQMTQSPSSLSASVGDRVTITCKASQDVTTAVAWYQQKPGKAPKLLIYW 
                 
                     
                 
                   ASTRHTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPLTFGQ 
                 
                     
                 
                   GTKVEIK. 
                 
             
                
                
                
                
                
                
               
            
           
         
       
     
     
         3 . The humanized antibody of  claim 1 , wherein the light chain comprises the sequence: 
       
         
           
                 
                 
               
                   (SEQ ID NO: 8) 
                     
                 
                   DIQMTQSPSSLSASVGDRVTITCKASQDVTTAVAWYQQKPGKAPKLLIYW 
                     
                 
                     
                 
                   ASTRHTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPLTFGQ 
                     
                 
                     
                 
                   GTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKV 
                     
                 
                     
                 
                   DNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQG 
                     
                 
                     
                 
                 
               
                   LSSPVTKSFNRGECGGS 
                 
                   or 
                 
                     
                 
                   (SEQ ID NO: 13) 
                 
                   DIQMTQSPSSLSASVGDRVTITCKASQDVTTAVAWYQQKPGKAPKLLIYW 
                 
                     
                 
                   ASTRHTGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCQQHYSTPLTFGQ 
                 
                     
                 
                   GTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKV 
                 
                     
                 
                   DNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQG 
                 
                     
                 
                   LSSPVTKSFNRGEC. 
                 
             
                
                
                
                
                
                
                
                
                
               
            
             
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         4 . The humanized antibody of  claim 1 , wherein the heavy chain comprises the sequence: 
       
         
           
                 
               
                   (SEQ ID NO: 9) 
                 
                   EVQLVESGGGLVQPGGSLRLSCAASGFAFNYYDMFWVRQAPGKGLEWVAY 
                 
                     
                 
                   IKPGGGNTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARQL 
                 
                     
                 
                   YGNSFFDYWGQGTLVTVSS 
                 
             
                
                
                
                
                
                
               
            
           
         
       
     
     
         5 . The humanized antibody of  claim 1 , wherein the heavy chain comprises the sequence: 
       
         
           
                 
               
                   (SEQ ID NO: 10) 
                 
                   EVQLVESGGGLVQPGGSLRLSCAASGFAFNYYDMFWVRQAPGKGLEWVAY 
                 
                     
                 
                   IKPGGGNTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARQL 
                 
                     
                 
                   YGNSFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD 
                 
                     
                 
                   YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTY 
                 
                     
                 
                   ICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGRPSVFLFPPKPK 
                 
                     
                 
                   DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS 
                 
                     
                 
                   TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV 
                 
                     
                 
                   YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL 
                 
                     
                 
                   DSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK, 
                 
                     
                 
                   (SEQ ID NO: 11) 
                 
                   EVQLVESGGGLVQPGGSLRLSCAASGFAFNYYDMFWVRQAPGKGLEWVAY 
                 
                     
                 
                   IKPGGGNTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARQL 
                 
                     
                 
                   YGNSFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD 
                 
                     
                 
                   YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTY 
                 
                     
                 
                   ICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGRPSVFLFPPKPK 
                 
                     
                 
                   DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS 
                 
                     
                 
                   TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV 
                 
                     
                 
                   YTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL 
                 
                     
                 
                   DSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG, 
                 
                   or 
                 
                     
                 
                   (SEQ ID NO: 12) 
                 
                   EVQLVESGGGLVQPGGSLRLSCAASGFAFNYYDMFWVRQAPGKGLEWVAY 
                 
                     
                 
                   IKPGGGNTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARQL 
                 
                     
                 
                   YGNSFFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKD 
                 
                     
                 
                   YFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTY 
                 
                     
                 
                   ICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPK 
                 
                     
                 
                   DTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNS 
                 
                     
                 
                   TYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQV 
                 
                     
                 
                   YTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVL 
                 
                     
                 
                   DSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPG. 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         6 . An antigen-binding fragment of the antibody of  claim 1 . 
     
     
         7 . A recombinant nucleic acid encoding the antibody of  claim 1 . 
     
     
         8 . A cell, wherein the cell is not in a human subject, transformed with the recombinant nucleic acid of  claim 7 . 
     
     
         9 . A composition comprising the antibody of  claim 1  or the antigen-binding fragment thereof. 
     
     
         10 . The composition of  claim 9 , comprising a pharmaceutically acceptably carrier. 
     
     
         11 . A method of treating a filovirus infection in a subject comprising administering to the subject an amount of the antibody of  claim 1  or the antigen-binding fragment thereof effective to treat a filovirus infection in a subject. 
     
     
         12 . The method of  claim 11 , wherein the antibody, antigen-binding fragment or composition are administered after the subject has been exposed to the filovirus. 
     
     
         13 . A method of inhibiting a filovirus infection of a subject comprising administering to the subject an amount of  claim 1  or the antigen-binding fragment thereof effective to inhibit a filovirus infection in a subject. 
     
     
         14 . The method of  claim 13 , wherein the antibody, antigen-binding fragment or composition are administered prior to the subject being exposed to the filovirus. 
     
     
         15 . The method of any of  claim 11 , wherein the filovirus is an Ebola virus. 
     
     
         16 . The method of  claim 15 , wherein the Ebola virus is the Sudan strain. 
     
     
         17 . The antibody of any of  claim 1  or the antigen-binding fragment thereof, wherein the antibody is a neutralizing antibody.