Methods and materials for preparation of modified antibody variable domains and therapeutic uses thereof

Abstract

Methods are described for identifying the amino acid residues of an antibody variable domain which may be modified without diminishing the native affinity of the domain for antigen while reducing its immunogenicity with respect to a hereterologous species and for preparing so modified antibody variable domains which are useful for administration to heterologous species. Antibody variable regions prepared by the methods of the invention are also described.

1 . A method for determining the risk of changing an amino acid residue in an antibody variable domain, said method comprising 
 (a) aligning by computer the amino acid sequence of said variable domain with the amino acid sequence of an antibody light or heavy chain variable region or consensus sequence; and    (b) determining the risk assigned to changing said amino acid residue using the paired bind and bury lines as shown in FIG. 6A or  6 B.    
     
     
         2 . The method of  claim 1 , wherein said selected antibody variable region in part (b) is said light chain variable region.  
     
     
         3 . The method of  claim 1 , wherein said selected antibody variable region in part (b) is said heavy chain variable region.  
     
     
         4 . A method for determining the risk of changing an amino acid residue in an antibody variable region light chain sequence, said method comprising 
 (a) aligning by computer the amino acid sequence of said antibody variable domain light chain sequence with the amino acid sequence of an antibody light chain variable region sequence or consensus; and    (b) determining the risk assigned to changing said amino acid residue using the paired bind and bury lines as shown in FIG. 6A.    
     
     
         5 . A method for determining the risk of changing an amino acid residue in an antibody variable region heavy chain sequence, said method comprising 
 (a) aligning by computer the amino acid sequence of said antibody variable domain heavy chain sequence with the amino acid sequence of an antibody heavy chain variable region sequence or consensus; and    (b) determining the risk assigned to changing said amino acid residue using the paired bind and bury lines as shown in FIG. 6B.