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 - 73 . (canceled) 
     
     
         74 : A host cell engineered to express at least one nucleic acid encoding a polypeptide having β(1,4)-N-acetylglucosaminyltransferase III activity in an amount sufficient to modify the oligosaccharides in the Fc region of a polypeptide produced by said host cell, wherein said polypeptide is an antigen binding molecule comprising a sequence derived from the muring B-Ly1 antibody and a sequence from a heterologous polypeptide. 
     
     
         75 : The host cell of  claim 74 , wherein said polypeptide having β(1,4)-N-acetylglucosaminyltransferase III activity is a fusion polypeptide. 
     
     
         76 : The host cell of  claim 74 , wherein said antigen binding molecule is an antibody. 
     
     
         77 : The host cell of  claim 74 , wherein said antigen binding molecule is an antibody fragment. 
     
     
         78 : The host cell of  claim 74 , wherein said antigen binding molecule comprises a region equivalent to the Fc region of a human IgG. 
     
     
         79 : The host cell of  claim 74 , wherein said antigen binding molecule produced by said host cell exhibits increased Fc receptor binding affinity as a result of said modification. 
     
     
         80 : The host cell of  claim 74 , wherein said antibody produced by said host cell exhibits increased effector function as a result of said modification. 
     
     
         81 : The host cell according to  claim 75 , wherein said fusion polypeptide comprises the catalytic domain of β(1,4)-N-acetylglucosaminyltransferase III. 
     
     
         82 : The host cell according to  claim 75 , wherein said fusion polypeptide further comprises the Golgi localization domain of a heterologous Golgi resident polypeptide. 
     
     
         83 : The host cell according to  claim 82 , wherein said Golgi localization domain is the localization domain of mannosidase II. 
     
     
         84 : The host cell according to  claim 82 , wherein said Golgi localization domain is the localization domain of β(1,2)-N-acetylglucosaminyltransferase I. 
     
     
         85 : The host cell according to  claim 82 , wherein said Golgi localization domain is the localization domain of β(1,2)-N-acetylglucosaminyltransferase II. 
     
     
         86 : The host cell according to  claim 82 , wherein said Golgi localization domain is the localization domain of mannosidase I. 
     
     
         87 : The host cell according to  claim 82 , wherein said Golgi localization domain is the localization domain of α1-6 core fucosyltransferase. 
     
     
         88 : The host cell according to  claim 80 , wherein said increased effector function is increased Fc-mediated cellular cytotoxicity. 
     
     
         89 : The host cell according to  claim 80 , wherein said increased effector function is increased binding to NK cells. 
     
     
         90 : The host cell according to  claim 80 , wherein said increased effector function is increased binding to macrophages. 
     
     
         91 : The host cell according to  claim 80 , wherein said increased effector function is increased binding to polymorphonuclear cells. 
     
     
         92 : The host cell according to  claim 80 , wherein said increased effector function is increased binding to monocytes. 
     
     
         93 : The host cell according to  claim 80 , wherein said increased effector function is increased direct signaling inducing apoptosis. 
     
     
         94 : The host cell according to  claim 80 , wherein said increased effector function is increased dendritic cell maturation. 
     
     
         95 : The host cell according to  claim 80 , wherein said increased effector function is increased T cell priming. 
     
     
         96 : The host cell according to  claim 79 , wherein said Fc receptor is Fcγ activating receptor. 
     
     
         97 : The host cell according to  claim 79 , wherein said Fc receptor is FcγRIIIA receptor. 
     
     
         98 : The host cell according to  claim 74 , wherein said host cell is a CHO cell, a BHK cell, a NSO cell, a SP2/0 cell, a YO myeloma cell, a P3X63 mouse myeloma cell, a PER cell, a PER.C6 cell or a hybridoma cell. 
     
     
         99 : The host cell of  claim 74 , further comprising at least one transfected polynucleotide encoding a polypeptide derived from the murine B-Ly1 antibody and a sequence encoding a region equivalent to the Fc region of a human immunoglobulin. 
     
     
         100 : The host cell of  claim 74 , wherein said at least one nucleic acid encoding a polypeptide having β(1,4)-N-acetylglucosaminyltransferase III activity is operably linked to a constitutive promoter element. 
     
     
         101 : The host cell of  claim 100 , wherein said polypeptide having beta(1,4)-N-acetylglucosaminyltransferase III activity is a fusion polypeptide. 
     
     
         102 - 259 . (canceled)