ANTIGEN BINDING MOLECULES WITH INCREASED Fc RECEPTOR BINDING AFFINITY AND EFFECTOR FUNCTION

Abstract

The present invention relates to antigen binding molecules (ABMs). In particular embodiments, the present invention relates to recombinant monoclonal antibodies, including chimeric, primatized or humanized antibodies specific for human CD20. In addition, the present invention relates to nucleic acid molecules encoding such ABMs, and vectors and host cells comprising such nucleic acid molecules. The invention further relates to methods for producing the ABMs of the invention, and to methods of using these ABMs in treatment of disease. In addition, the present invention relates to ABMs with modified glycosylation having improved therapeutic properties, including antibodies with increased Fc receptor binding and increased effector function.

1 - 101 . (canceled) 
     
     
         102 . A method for producing an antigen binding molecule having modified oligosaccharides in a host cell, said method comprising:
 a. culturing a host cell engineered to express at least one nucleic acid encoding a polypeptide having β(1,4)-N-acetylglucosaminyltransferase III activity under conditions which permit the production of said antigen binding molecule, and which permit the modification of the oligosaccharides present on the Fc region of said antigen binding molecule; and   b. isolating said antigen binding molecule wherein said antigen binding molecule is capable of competing with the murine B-Ly1 antibody for binding to CD20 and wherein said antigen binding molecule or fragment thereof is chimeric.   
     
     
         103 . The method according to  claim 102 , wherein said modified oligosaccharides have reduced fucosylation as compared to non-modified oligosaccharides. 
     
     
         104 . The method according to  claim 102 , wherein said modified oligosaccharides are hybrid. 
     
     
         105 . The method according to  claim 102 , wherein said modified oligosaccharides are complex. 
     
     
         106 . The method according to  claim 102 , wherein said recombinant antibody or fragment thereof produced by said host cell has an increased proportion of bisected, nonfucosylated oligosaccharides in the Fc region of said polypeptide. 
     
     
         107 . The method according to  claim 106 , wherein said bisected, nonfucosylated oligosaccharides are hybrid. 
     
     
         108 . The method according to  claim 106 , wherein said bisected, nonfucosylated oligosaccharides are complex. 
     
     
         109 . The method according to  claim 102 , wherein at least 20% of the oligosaccharides in the Fc region of said polypeptide are bisected, nonfucosylated. 
     
     
         110 . The method according to  claim 102 , wherein at least 30% of the oligosaccharides in the Fc region of said polypeptide are bisected, nonfucosylated. 
     
     
         111 . The method according to  claim 102 , wherein at least 35% of the oligosaccharides in the Fc region of said polypeptide are bisected, nonfucosylated. 
     
     
         112 - 259 . (canceled)