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 - 72 . (canceled) 
     
     
         73 : A method of treating a disorder treatable by B-cell depletion comprising administering a therapeutically effective amount of pharmaceutical composition comprising a) an antigen binding molecule comprising a polypeptide comprising a sequence derived from the murine B-Ly1 antibody and a sequence derived from a heterologous polypeptide, and b) a pharmaceutically acceptable carrier, to a human subject in need thereof. 
     
     
         74 - 133 . (canceled) 
     
     
         134 : A method of treating a disease treatable by B-cell depletion comprising administering a therapeutically effective amount of the antigen binding molecule to a human subject in need thereof, wherein the antigen binding molecule is engineered to have increased effector function by
 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.   
     
     
         135 - 146 . (canceled) 
     
     
         147 : The method of  claim 73 , wherein said disorder is a B cell lymphoma. 
     
     
         148 - 205 . (canceled) 
     
     
         206 : A method of treating a disorder treatable by B-cell depletion comprising administering a therapeutically effective amount of pharmaceutical composition comprising an antigen binding molecule and a pharmaceutically acceptable carrier to a human subject in need thereof,
 wherein the antigen binding molecule comprises a fusion polypeptide comprising a sequence selected from the group consisting of SEQ ID No:30; SEQ ID No:32; SEQ ID No:34; SEQ ID No:36; SEQ ID No:38; SEQ ID No:40; SEQ ID No:42; SEQ ID No:44; SEQ ID No:46; SEQ ID No:48; SEQ ID No:50; SEQ ID No:52; SEQ ID No:54; SEQ ID No:56; SEQ ID No:58; SEQ ID No:60; SEQ ID No:62; SEQ ID No:64; SEQ ID No:66; SEQ ID No:68; SEQ ID No:70; and SEQ ID No:72, or a variant thereof; and wherein said antigen binding molecule comprises an Fc region with modified oligosaccharides.   
     
     
         207 - 243 . (canceled) 
     
     
         244 : The method according to  claim 206 , wherein said disorder is a B cell lymphoma. 
     
     
         245 - 259 . (canceled)