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 - 8 . (canceled) 
     
     
         9 . A method comprising administering to a patient a polypeptide comprising a variant Fc region comprising an amino acid substitution at position 271 of the Fc region as compared to a parent Fc region, wherein said variant Fc region exhibits enhanced binding affinity to FcγRIIb as compared with the parent Fc region, wherein numbering is according to the EU index. 
     
     
         10 . The method according to  claim 9  wherein said amino acid substitution is selected from the group consisting of aspartic acid, glutamic acid, asparagine, glutamine, lysine, arginine, serine, threonine, histidine, alanine, valine, leucine, isoleucine, phenylalanine, methionine, tyrosine, tryptophan, and glycine. 
     
     
         11 . The method according to  claim 9 , wherein said polypeptide comprises an engineered glycoform. 
     
     
         12 . The method according to  claim 9  wherein said parent Fc region is a human IgG1Fc region. 
     
     
         13 . The method of  claim 9 , wherein said polypeptide is an antibody. 
     
     
         14 . The method of  claim 12 , wherein said polypeptide is an antibody. 
     
     
         15 . The method of  claim 14 , wherein said antibody is selected from the group consisting of a chimeric antibody, a humanized antibody, a monoclonal antibody, and a human antibody. 
     
     
         16 . The method of  claim 9 , wherein said polypeptide is an immunoadhesin. 
     
     
         17 . A method comprising administering to a patient a polypeptide comprising a variant Fc region comprising an amino acid substitution at position 271 of the Fc region as compared to a parent Fc region, wherein the amino acid substitution is glycine, wherein said variant Fc region exhibits enhanced binding affinity to FcγRIIb as compared with the parent Fc region, wherein numbering is according to the EU index. 
     
     
         18 . The method according to  claim 9  wherein said parent Fc region is a human IgG1Fc region. 
     
     
         19 . The method of  claim 17 , wherein said polypeptide is an antibody. 
     
     
         20 . The method of  claim 17 , wherein said antibody is selected from the group consisting of a chimeric antibody, a humanized antibody, a monoclonal antibody, and a human antibody. 
     
     
         21 . The method of  claim 9 , wherein said polypeptide is an immunoadhesin. 
     
     
         22 . A nucleic acid encoding a polypeptide comprising a variant Fc region comprising an amino acid substitution at position 271 of the Fc region as compared to a parent Fc region, wherein said variant Fc region exhibits enhanced binding affinity to FcγRIIb as compared with the parent Fc region, wherein numbering is according to the EU index. 
     
     
         23 . An expression vector comprising the nucleic acid of  claim 22 . 
     
     
         24 . A host cell comprising the expression vector of  claim 23 . 
     
     
         25 . A method of making a polypeptide, said method comprising culturing the host cell according to  claim 24  under conditions whereby said polypeptide is expressed.