Anti-vegf antibodies

Abstract

Anti-VEGF antibodies and variants thereof, including those having high affinity for binding to VEGF, are disclosed. Also provided are methods of using phage display technology with naïve libraries to generate and select the anti-VEGF antibodies with desired binding and other biological activities. Further contemplated are uses of the antibodies in research, diagnostic and therapeutic applications.

1 - 20 . (canceled) 
     
     
         21 . An isolated nucleic acid molecule encoding an antibody, or an antibody fragment thereof, wherein the antibody, or antibody fragment thereof, binds to human VEGF and comprises a heavy chain variable domain (VH) and a light chain variable domain (VL),
 wherein the VH comprises a CDR-H1, CDR-H2, and CDR-H3, wherein:
 (a) CDR-H1 comprises the amino acid sequence DYWIH (SEQ ID NO: 261), 
 (b) CDR-H2 comprises the amino acid sequence GVTPAGGYTYYADSVKG (SEQ ID NO: 944), and 
 (c) CDR-H3 comprises the amino acid sequence FVFFLPYAMDY (SEQ ID NO: 475); or 
 (a) CDR-H1 comprises the amino acid sequence DYWIH (SEQ ID NO: 261), 
 (b) CDR-H2 comprises the amino acid sequence GVTPAGGYTAYADSVKG (SEQ ID NO: 945), and 
 (c) CDR-H3 comprises the amino acid sequence FVFFLPYAMDY (SEQ ID NO: 475); 
   and wherein the VL comprises a CDR-L1, CDR-L2, and CDR-L3, wherein:
 (d) CDR-L1 comprises the amino acid sequence RASQDVSTAVA (SEQ ID NO: 48), 
 (e) CDR-L2 comprises the amino acid sequence SASFLYS (SEQ ID NO: 49), and 
 (f) CDR-L3 comprises the amino acid sequence KQGFANPFT (SEQ ID NO: 946). 
   
     
     
         22 . The isolated nucleic acid molecule of  claim 21 , wherein the VH comprises the following amino acid sequence: 
       
         
           
                 
               
                   (SEQ ID NO: 35) 
                 
                   EVQLVESGGGLVQPGGSLRLSCAASGFTISDYWIHWVRQAPGKGLEWVAG 
                 
                     
                 
                   VTPAGGYTYYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFV 
                 
                     
                 
                   FFLPYAMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK 
                 
                     
                 
                   DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT 
                 
                     
                 
                   YICNVNHKPSNTKVDKKVEPKSCDKTH, 
                 
             
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
       and wherein the VL comprises the following amino acid sequence: 
       
         
           
                 
               
                   (SEQ ID NO: 34) 
                 
                   DIQMTQSPSSLSASVGDRVTITCRASQDVSTAVAWYQQKPGKAPKLLIYS 
                 
                     
                 
                   ASFLYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCKQGFANPFTFGQ 
                 
                     
                 
                   GTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKV 
                 
                     
                 
                   DNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQG 
                 
                     
                 
                   LSSPVTKSFNRGEC. 
                 
             
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         23 . The isolated nucleic acid molecule of  claim 21 , wherein the VH comprises the following amino acid sequence: 
       
         
           
                 
               
                   (SEQ ID NO: 36) 
                 
                   EVQLVESGGGLVQPGGSLRLSCAASGFTISDYWIHWVRQAPGKGLEWVAG 
                 
                     
                 
                   VTPAGGYTAYADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCARFV 
                 
                     
                 
                   FFLPYAMDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVK 
                 
                     
                 
                   DYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQT 
                 
                     
                 
                   YICNVNHKPSNTKVDKKVEPKSCDKTH. 
                 
             
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
       and wherein the VL comprises the following amino acid sequence: 
       
         
           
                 
               
                   (SEQ ID NO: 34) 
                 
                   DIQMTQSPSSLSASVGDRVTITCRASQDVSTAVAWYQQKPGKAPKLLIYS 
                 
                     
                 
                   ASFLYSGVPSRFSGSGSGTDFTLTISSLQPEDFATYYCKQGFANPFTFGQ 
                 
                     
                 
                   GTKVEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKV 
                 
                     
                 
                   DNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQG 
                 
                     
                 
                   LSSPVTKSFNRGEC. 
                 
             
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         24 . A vector comprising the nucleic acid of  claim 21 . 
     
     
         25 . A host cell comprising the vector of  claim 24 . 
     
     
         26 . A process of producing an antibody, or antibody fragment thereof, comprising culturing the host cell of  claim 25  so that the antibody is produced. 
     
     
         27 . The process of  claim 26 , wherein the antibody, or antibody fragment thereof, is recovered from the host cell medium.