Method of stabilizing protein

Abstract

The present inventors revealed that deamidation of an antibody can be suppressed without influencing its activity by substituting a glycine that is located adjacent to an asparagine with another amino acid.

1 . A method for stabilizing a protein, which comprises the step of substituting an amino acid that is located adjacent to an amino acid being deamidated with another amino acid.  
     
     
         2 . The method for stabilizing a protein of  claim 1 , wherein the amino acid being deamidated is asparagine.  
     
     
         3 . The method for stabilizing a protein of  claim 1 , wherein the amino acid that is located adjacent to the C-terminal side of the amino acid being deamidated is glycine.  
     
     
         4 . The method for stabilizing a protein of any one of  claims 1  to  3 , wherein the protein is an antibody.  
     
     
         5 . The method for stabilizing a protein of  claim 4 , wherein the antibody is humanized antibody.  
     
     
         6 . The method for stabilizing a protein of  claim 4  or  5 , wherein the amino acid being deamidated exists in the complementary determining region (CDR).  
     
     
         7 . The method for stabilizing a protein of  claim 6 , wherein the complementary determining region (CDR) is CDR2.  
     
     
         8 . The method for stabilizing a protein of any one of  claims 1  to  3 , wherein the protein is an antigen binding protein.  
     
     
         9 . The method for stabilizing a protein of any one of  claims 1  to  3 , wherein the protein belongs to the immunoglobulin superfamily.  
     
     
         10 . The method for stabilizing a protein of any one of  claims 1  to  3 , wherein the protein is a pharmaceutical agent.  
     
     
         11 . A protein stabilized by the method of any one of  claims 1  to  10 .  
     
     
         12 . The stabilized protein of  claim 11  whose antigen binding activity is 70% or more of the activity before the amino acid substitution.