Process for the modulation of the antagonistic activity of a monoclonal antibody

Abstract

The present disclosure relates to the antibody engineering field and, more particularly, to a process for the screening of antibodies and/or the modulation of the agonistic/antagonistic activity of antibodies. More particularly, the disclosure concerns a process of improving the antagonistic activity of a monoclonal antibody directed against a specific target molecule, or a divalent functional fragment or derivative thereof, the antibody being capable of inhibiting one or more of the biological activities of the target molecule, wherein the process comprises a stage of reconfiguration of the hinge region consisting of a modification of the amino acid sequence of the hinge region by the deletion, the addition or the substitution of at least one amino acid. The disclosure also relates to polypeptides useful for such a modulation method and the obtained antibodies.

1 .- 25 . (canceled) 
     
     
         26 . An isolated monoclonal antibody comprising an amino acid sequence selected from 
       
         
           
                 
                 
               
                     
                   SEQ ID No. 2 
                 
                     
                   (PKSCGCKPCICT), 
                 
                     
                     
                 
                     
                   SEQ ID NO. 3 
                 
                     
                   (PKSCGCKPCICP), 
                 
                     
                     
                 
                     
                   SEQ ID No. 4 
                 
                     
                   (PRDCGCKPCPPCP), 
                 
                     
                     
                 
                     
                   SEQ ID NO. 5 
                 
                     
                   (PRDCGCHTCPPCP), 
                 
                     
                     
                 
                     
                   SEQ ID No. 6 
                 
                     
                   (PKSCDCHCPPCP), 
                 
                     
                     
                 
                     
                   SEQ ID No. 22 
                 
                     
                   (CKSCDKTHTCPPCP), 
                 
                     
                     
                 
                     
                   SEQ ID NO. 23 
                 
                     
                   (PCSCDKTHTCPPCP), 
                 
                     
                     
                 
                     
                   SEQ ID No. 24 
                 
                     
                   (PKCCDKTHTCPPCP), 
                 
                     
                     
                 
                     
                   SEQ ID NO. 25 
                 
                     
                   (PKSCCKTHTCPPCP), 
                 
                     
                     
                 
                     
                   SEQ ID No. 26 
                 
                     
                   (PKSCDCTHTCPPCP), 
                 
                     
                     
                 
                     
                   SEQ ID No. 28 
                 
                     
                   (PKSCDKTCTCPPCP), 
                 
                     
                     
                 
                     
                   SEQ ID NO. 29 
                 
                     
                   (PKSCDKTHCCPPCP), 
                 
                     
                     
                 
                     
                   SEQ ID NO. 33 
                 
                     
                   (PSCDKTHTCPPCP), 
                 
                     
                     
                 
                     
                   SEQ ID NO. 35 
                 
                     
                   (PKSCDKTHCPPCP), 
                 
                     
                     
                 
                     
                   SEQ ID No. 36 
                 
                     
                   (KCDKTHTCPPCP), 
                 
                     
                     
                 
                     
                   SEQ ID NO. 37 
                 
                     
                   (PSCKTHTCPPCP), 
                 
                     
                     
                 
                     
                   SEQ ID No. 38 
                 
                     
                   (PKSCDTHCPPCP), 
                 
                     
                     
                 
                     
                   SEQ ID NO. 39 
                 
                     
                   (PKSCTHTCPPCP), 
                 
                     
                     
                 
                     
                   SEQ ID NO. 41 
                 
                     
                   (PKSCDKTHCPPC), 
                 
                     
                     
                 
                     
                   SEQ ID No. 42 
                 
                     
                   (PKSCDCHTCPPCP), 
                 
                     
                     
                 
                     
                   SEQ ID NO. 43 
                 
                     
                   (PKSCDCTHCPPCP), 
                 
                     
                     
                 
                     
                   SEQ ID No. 44 
                 
                     
                   (PCSCKHTCPPCP), 
                 
                     
                     
                 
                     
                   SEQ ID NO. 45 
                 
                     
                   (PSCCTHTCPPCP), 
                 
                     
                     
                 
                     
                   SEQ ID No. 46 
                 
                     
                   (PSCDKHCCPPCP), 
                 
                     
                     
                 
                     
                   SEQ ID NO. 47 
                 
                     
                   (PKSTHTCPPCP), 
                 
                     
                     
                 
                     
                   SEQ ID No. 48 
                 
                     
                   (PKSCTCPPCP), 
                 
                     
                   and 
                 
                     
                     
                 
                     
                   SEQ ID No. 49 
                 
                     
                   (PKSCDKCVECPPCP); 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
         or a divalent fragment of, or a derivative of, said antibody. 
       
     
     
         27 . The isolated monoclonal antibody according to  claim 26 , wherein said antibody is a human antibody. 
     
     
         28 . The isolated monoclonal antibody according to  claim 26 , wherein said antibody is an IgG1 antibody. 
     
     
         29 . An isolated nucleic acid encoding for a monoclonal antibody according to  claim 26 . 
     
     
         30 .- 31 . (canceled)