Humanized antibody and process for preparing same

Abstract

A humanized antibody is produced by process comprising the steps of: (a) selecting a specificity determining residue (SDR) of the complementarity determining region (CDR) of murine monoclonal antibody heavy chain and light chain variable regions; and (b) grafting said SDR to at least one of the corresponding amino acid sequences in human antibody variable regions.

1 . (canceled) 
     
     
         2 . A process for preparing a humanized antibody consisting of the steps of:
 (a) first performing alanine scanning mutagenesis for replacing each amino acid residue in the entire complementarily determining region (CDR) of a murine monoclonal antibody heavy chain and light chain variable regions with alanine to produce a series of transformants, selecting a transformant that has a lower affinity to the human antigen (KD) than of the original murine antibody, and determining the replaced amino acid residue of said selected transformant as a specificity determining residue (SDR); and   (b) subsequently grafting all of the said SDR to the corresponding amino acid residues into human antibody variable regions.   
     
     
         3 . The process of  claim 2 , wherein the CDR is selected from the group consisting of HCDR1(aa 31-35), HCDR2(aa 50-65) and HCDR3(aa 95-102) of the heavy chain (SEQ ID NO: 2); and LCDR1(aa 24-34), LCDR2(aa 50-56) and LCDR3(aa 89-97) of the light chain (SEQ ID NO: 4) of the murine monoclonal antibody variable regions of that bind hepatitis B virus pre-S 1 antigen, selecting a transformant that has an affinity to antigen which is more than 3 times lower than the original murine antibody when replaced with alanine, determining the replaced amino acid residue of said transformant as an SDR, and grafting said SDR to the corresponding amino acid sequence in human antibody heavy chain and light chain. 
     
     
         4 - 24 . (canceled)