Method for decreasing immunogenicity

Abstract

A method for decreasing the immunogenicity of antibody variable domains is disclosed.

1 . An antibody variable domain comprising a variable light chain having a substitution at position 99, 101 and/or 148 (Aho numbering), and/or a variable heavy chain comprising substitutions at positions 12, 103, and 144 (AHo numbering), the antibody having reduced anti-drug antibody (ADA) reactivity compared with the ADA reactivity of the antibody containing the original amino acid at the substituted positions. 
     
     
         2 . The antibody variable domain of  claim 1 , being an scFv, an Fv fragment or a single domain antibody. 
     
     
         3 . The antibody variable domain of  claim 1 , being an scFv. 
     
     
         4 . The antibody variable domain of  claim 1 , wherein substitution of the variable light chain is at position 101 (AHo numbering). 
     
     
         5 . The antibody variable domain of  claim 4 , wherein substitution of the variable light chain at position 101 is a Serine (S). 
     
     
         6 . A pharmaceutical composition comprising the antibody variable domain of  claim 1 . 
     
     
         7 . An antibody variable domain comprising a variable light chain having a substitution at position 99, 101 and/or 148 (Aho numbering), and a variable heavy chain comprising Serine (S) at heavy chain amino acid position 12, Threonine (T) at heavy chain amino acid position 103, and Serine (S) at heavy chain amino acid position 144 (AHo numbering). 
     
     
         8 . The antibody variable domain of  claim 7 , being an scFv, an Fv fragment or a single domain antibody. 
     
     
         9 . The antibody variable domain of  claim 8 , being an scFv. 
     
     
         10 . The antibody variable domain of  claim 7 , wherein substitution of the variable light chain is at position 101 (AHo numbering). 
     
     
         11 . The antibody variable domain of  claim 10 , wherein substitution of the variable light chain at position 101 is a Serine (S). 
     
     
         12 . A pharmaceutical composition comprising the antibody variable domain of  claim 1 . 
     
     
         13 . A method of reducing anti-drug antibody (ADA) reactivity of an antibody variable domain comprising a variable light chain and a variable heavy chain, the method comprising making a substitution at position 99, 101 or 148 (Aho numbering) of the variable light chain, making a substitution of Serine (S) at heavy chain amino acid position 12, Serine (S) at heavy chain amino acid position 103, and Serine (S) at heavy chain amino acid position 144 (AHo numbering). 
     
     
         14 . The antibody variable domain of  claim 13 , being an scFv, an Fv fragment or a single domain antibody. 
     
     
         15 . The antibody variable domain of  claim 14 , being an scFv. 
     
     
         16 . The antibody variable domain of  claim 13 , wherein substitution of the variable light chain is at position 101 (AHo numbering). 
     
     
         17 . The antibody variable domain of  claim 16 , wherein substitution of the variable light chain at position 101 is a Serine (S). 
     
     
         18 . A pharmaceutical composition comprising the antibody variable domain of  claim 13 .