Method for making humanized antibodies

Abstract

Variant immunoglobulins, particularly humanized antibody polypeptides are provided, along with methods for their preparation and use. Consensus immunoglobulin sequences and structural models are also provided.

1 . A humanized antibody variable domain having a non-human CDR incorporated into a human antibody variable domain, wherein the improvement comprises substituting an amino acid residue for the human residue at a site selected from the group consisting of: 
 4L, 35L, 36L, 38L, 43L, 44L, 46L, 58L, 62L, 63L, 64L, 65L, 66L, 67L, 68L, 69L, 60L, 71L, 73L, 85L, 87L, 98L, 2H, 4H, 24H, 36H, 37H, 39H, 43H, 45H, 49H, 58H, 60H, 67H, 68H, 69H, 70H, 73H, 74H, 75H, 76H, 78H, 91H, 92H, 93H, and 103H.    
     
     
         2 . The humanized antibody variable domain of  claim 1 , wherein the substituted residue is the residue found at the corresponding location of the non-human antibody from which the non-human CDR was obtained.  
     
     
         3 . The humanized antibody variable domain of  claim 1 , wherein no human FR residue other than those set forth in the group has been substituted.  
     
     
         4 . A humanized antibody that binds to human HER 2 .  
     
     
         5 . The humanized antibody of  claim 4  comprising huMAb4D5-8.  
     
     
         6 . A humanized HER 2  antibody comprising huMAb4D5-8.