Method for improving affinity of antibody for antigen and use thereof

Abstract

The present invention relates to a method for improving affinity of an antibody for an antigen. The present invention relates to a method for producing an antibody with improved affinity for an antigen as compared to an unmodified antibody. The present invention relates to a modified antibody with improved affinity for an antigen as compared to an unmodified antibody.

1 . A method for improving affinity of an antibody for an antigen, comprising:
 in an unmodified antibody, improving affinity for an antigen as compared to the unmodified antibody, by changing at least 3 amino acid residues selected from a group consisting of 60th, 63rd, 65th, 67th, 70th, 72nd, 74th, 76th, 77th, 79th and 81st amino acid residues of a light chain defined by Kabat method to charged amino acid residues,   wherein the 3 amino acid residues contain at least one selected from a group consisting of 60th, 74th, 76th, 77th, 79th and 81st amino acid residues of the light chain.   
     
     
         2 . A method for producing an antibody with improved affinity for an antigen as compared to an unmodified antibody, comprising:
 in an unmodified antibody, changing at least 3 amino acid residues selected from a group consisting of 60th, 63rd, 65th, 67th, 70th, 72nd, 74th, 76th, 77th, 79th and 81st amino acid residues of a light chain defined by Kabat method to charged amino acid residues; and   recovering the antibody obtained in the changing,   wherein the 3 amino acid residues contain at least one selected from a group consisting of 60th, 74th, 76th, 77th, 79th and 81st amino acid residues of the light chain.   
     
     
         3 . The method according to  claim 1  or  2 , wherein the at least 3 amino acid residues are selected from the group consisting of 60th, 74th, 76th, 77th, 79th and 81st amino acid residues of the light chain. 
     
     
         4 . The method according to any one of  claims 1  to  3 , wherein the at least 3 amino acid residues are 60th, 76th, and 77th amino acid residues of the light chain. 
     
     
         5 . A modified antibody with improved affinity for an antigen as compared to an unmodified antibody, wherein
 at least 3 amino acid residues selected from a group consisting of 60th, 63rd, 65th, 67th, 70th, 72nd, 74th, 76th, 77th, 79th and 81st amino acid residues of a light chain defined by Kabat method in the unmodified antibody are changed to charged amino acid residues, and the 3 amino acid residues contain at least one selected from a group consisting of 60th, 74th, 76th, 77th, 79th and 81st amino acid residues of the light chain.   
     
     
         6 . The modified antibody according to  claim 5 , wherein the at least 3 amino acid residues are at least 3 selected from the group consisting of 60th, 74th, 76th, 77th, 79th and 81st amino acid residues of the light chain. 
     
     
         7 . The modified antibody according to  claim 5  or  6 , wherein the at least 3 amino acid residues are 60th, 76th and 77th amino acid residues of the light chain. 
     
     
         8 . The method according to any one of  claims 1  to  4 , or the modified antibody according to any one of  claims 5  to  7 , wherein the charged amino acid residues are basic amino acid residues. 
     
     
         9 . The method according to any one of  claims 1  to  4  and  8 , or the modified antibody according to any one of  claims 5  to  8 , which is in a form of an antibody fragment. 
     
     
         10 . The method or modified antibody according to  claim 9 , wherein the antibody fragment is a Fab fragment, a F(ab′)2 fragment, a Fab′ fragment, a Fd fragment, a Fv fragment, a dAb fragment, scFv, or rIgG.