Monoclonal antibodies with reduced immunogenicity

Abstract

Antibodies having reduced immunogenicity and methods for making them are disclosed.

1 - 64 . (canceled)  
     
     
         65 . An antibody comprising: 
 a) a variable region comprising six complementarity determining regions (CDRs) from an antigen-specific donor antibody of a rodent and acceptor framework comprising amino acid residues from an Old World monkey, wherein at least one CDR-contacting amino acid residue from the acceptor framework is replaced with a corresponding residue from the donor framework, and wherein said CDR-contacting residue contacts a CDR residue within said antibody by the group selected from coming within the van der Waals radius of said CDR residue, a salt bridge and a hydrophobic interaction; and    b) at least one constant region from human, and    wherein said antibody has a specific binding avidity that is within about three-fold of the specific binding avidity of said antigen-specific donor antibody.    
     
     
         66 . The antibody of  claim 65 , wherein the rodent is mouse.  
     
     
         67 . The antibody of  claim 65 , wherein the rodent is rat.  
     
     
         68 . The antibody of  claim 65 , wherein the Old World monkey genus is  Macaca.    
     
     
         69 . The antibody of  claim 68  wherein the Old World monkey is  Macaca cynomolgus.    
     
     
         70 . The antibody of  claim 65 , wherein the acceptor framework comprises a light (VL) and heavy (VH) chain region each comprising four framework regions (framework I, II, III, and IV), and wherein the VH acceptor framework 1, 11, III and IV are from  cynomolgus.    
     
     
         71 . The antibody of  claim 70 , wherein the VH acceptor framework I, II and III comprise an amino acid sequence as set forth in SEQ ID NOs: 45, 46, 47, 48, 49, 50, 51 or 52 .  
     
     
         72 . The antibody of  claim 70 , wherein the VH acceptor IV comprises an amino acid sequence as set forth in SEQ ID NOs: 88, 89, 90, 91, 92 or 93.  
     
     
         73 . The antibody of  claim 70 , wherein the VL comprises segments Vκ and Vλ, and wherein Vκ comprises four acceptor framework regions (framework I, II, III, and IV), and wherein Vκ acceptor framework I, II, III and IV are from  cynomolgus.    
     
     
         74 . The antibody of  claim 70 , wherein VK acceptor framework I, II and III comprise an amino acid sequence as set forth in SEQ ID NOs: 59, 60, 61, 62, 63 or 64.  
     
     
         75 . The antibody of  claim 70 , wherein the Vκ acceptor framework IV comprises an amino acid sequence as set forth in SEQ ID NOs: 94, 95 or 96.