Optimized Fc Variants

Abstract

The present invention relates to Fc variants having decreased affinity for FcγRIIb, methods for their generation, Fc polypeptides comprising optimized Fc variants, and methods for using optimized Fc variants.

1 . (canceled) 
     
     
         2 . (canceled) 
     
     
         3 . An antibody comprising a variant IgG, said IgG being selected from IgG1 and IgG2, wherein said variant IgG comprises an amino acid substitution at position 228 and wherein numbering is according to the EU index. 
     
     
         4 . The antibody of  claim 3 , wherein said amino acid substitution is selected from the group consisting of P228E, P228G, P228K, P228Y. 
     
     
         5 . The antibody of  claim 3 , wherein said amino acid substitution is P228E. 
     
     
         6 . The antibody of  claim 3 , wherein said amino acid substitution is P228K. 
     
     
         7 . The antibody of  claim 3 , wherein said antibody is selected from the group consisting of a human antibody, a humanized antibody, and a monoclonal antibody. 
     
     
         8 . The antibody of  claim 3 , where said antibody comprises an engineered glycoform. 
     
     
         9 . The antibody of  claim 8 , wherein said engineered glycoform has a reduced level of fucose relative to a native human IgG. 
     
     
         10 . The antibody of  claim 3 , wherein said antibody has specificity for a target antigen selected from the group consisting of CD3, CD19, CD20, CD22, CD30, CD32, CD33, CD38, CD40, CD40L, CD52, Her2/neu, EGFR, EpCAM, MUC1, GD3, CEA, CA 125, HLA-DR, TNFalpha, MUC18, prostate specific membrane antigen (PMSA) and VEGF. 
     
     
         11 . The antibody of  claim 10 , wherein said antibody has specificity for a target antigen selected from CD3 and CD20. 
     
     
         12 . The antibody of  claim 11 , wherein said target antigen is CD3. 
     
     
         13 . The antibody of  claim 11 , wherein said target antigen is CD20. 
     
     
         14 . The antibody of  claim 3 , wherein said IgG is IgG1. 
     
     
         15 . The antibody of  claim 14  wherein said IgG1 is human. 
     
     
         16 . The antibody of  claim 3 , wherein said IgG is IgG2. 
     
     
         17 . The antibody of  claim 16 , wherein said IgG2 is human. 
     
     
         18 . A pharmaceutical composition comprising the antibody of  claim 3 , further comprising a pharmaceutically acceptable carrier. 
     
     
         19 . A nucleic acid encoding the antibody of  claim 3 . 
     
     
         20 . An expression vector comprising the nucleic acid of  claim 19 . 
     
     
         21 . A host cell comprising the nucleic acid of  claim 19   
     
     
         22 . A method of making an antibody, said method comprising:
 culturing a host cell transformed with the nucleic acid of  claim 19  under conditions appropriate for expression of the antibody;   expressing said nucleic acid, whereby the antibody is produced.