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 - 2 . (canceled) 
     
     
         3 . A method of treatment comprising contacting effector cells expressing FcγRIIb with a polypeptide, wherein said polypeptide binds with greater affinity to the FcγRIIb receptor than a parent polypeptide and increases the inhibitory activity of the FcγRIIb receptor, and wherein said polypeptide comprises an Fc variant of said parent Fc polypeptide and wherein said Fc variant comprises an amino acid substitution S267E as compared to said parent Fc polypeptide, wherein said numbering is according to the EU index. 
     
     
         4 . The method according to  claim 3 , wherein said Fc variant has an affinity for FcγRIIb receptor that is more than 5-fold greater than that of said parent Fc polypeptide. 
     
     
         5 . The method according to  claim 3 , wherein said Fc variant has an affinity for FcγRIIb receptor that is between 5-fold and 300-fold greater than that of said parent Fc polypeptide. 
     
     
         6 . The method according to  claim 3 , wherein said polypeptide is an antibody. 
     
     
         7 . The method according to  claim 6 , wherein said antibody is selected from the group consisting of a human antibody, a humanized antibody, and a chimeric antibody. 
     
     
         8 . The method according to  claim 7 , wherein said antibody is a humanized antibody. 
     
     
         9 . The method according to  claim 7 , wherein said antibody is a chimeric antibody. 
     
     
         10 . The method according to  claim 6 , wherein said antibody further comprises an engineered glycoform. 
     
     
         11 . The method according to  claim 3 , wherein increasing inhibitory activity of the FcγRIIb receptor is used to treat autoimmune disease. 
     
     
         12 . The method according to  claim 3 , wherein increasing inhibitory activity of the FcγRIIb receptor is used to treat inflammatory disease. 
     
     
         13 . A method of treatment comprising contacting effector cells expressing FcγRIIb with a polypeptide, wherein said polypeptide binds with greater affinity to the FcγRIIb receptor than a parent polypeptide and increases the inhibitory activity of the FcγRIIb receptor, and wherein said polypeptide comprises an Fc variant of said parent Fc polypeptide and wherein said Fc variant comprises an amino acid substitution S267D as compared to said parent Fc polypeptide, wherein said numbering is according to the EU index. 
     
     
         14 . The method according to  claim 13 , wherein said Fc variant has an affinity for FcγRIIb receptor that is more than 5-fold greater than that of said parent Fc polypeptide. 
     
     
         15 . The method according to  claim 13 , wherein said Fc variant has an affinity for FcγRIIb receptor that is between 5-fold and 300-fold greater than that of said parent Fc polypeptide. 
     
     
         16 . The method according to  claim 13 , wherein said polypeptide is an antibody. 
     
     
         17 . The method according to  claim 16 , wherein said antibody is selected from the group consisting of a human antibody, a humanized antibody, and a chimeric antibody. 
     
     
         18 . The method according to  claim 17 , wherein said antibody is a humanized antibody. 
     
     
         19 . The method according to  claim 17 , wherein said antibody is a chimeric antibody. 
     
     
         20 . The method according to any one of  claim 16 , wherein said antibody further comprises an engineered glycoform. 
     
     
         21 . The method according to  claim 13 , wherein increasing inhibitory activity of the FcγRIIb receptor is used to treat autoimmune disease. 
     
     
         22 . The method according to  claim 13 , wherein increasing inhibitory activity of the FcγRIIb receptor is used to treat inflammatory disease. 
     
     
         23 . A method of enhancing the binding of an Fc polypeptide to the FcγRIIb receptor, said method comprising substituting in a parent Fc polypeptide the amino acid Ser at position 267 with the amino acid Glu to provide an Fc variant of the parent Fc polypeptide, wherein said numbering is according to the EU index. 
     
     
         24 . The method according to  claim 23 , wherein the polypeptide is an antibody. 
     
     
         25 . The method according to  claim 24 , wherein said antibody is selected from the group consisting of a human antibody, a humanized antibody, and a chimeric antibody. 
     
     
         26 . The method according to  claim 24 , wherein said antibody further comprises an engineered glycoform. 
     
     
         27 . The method according to  claim 24 , wherein the amino acid substitution is made by generating a nucleic acid that encodes said variant. 
     
     
         28 . A method of enhancing the binding of an Fc polypeptide to the FcγRIIb receptor, said method comprising substituting in a parent Fc polypeptide the amino acid Ser at position 267 with the amino acid Asp to provide an Fc variant of the parent Fc polypeptide, wherein said numbering is according to the EU index. 
     
     
         29 . The method according to  claim 28 , wherein the polypeptide is an antibody. 
     
     
         30 . The method according to  claim 29 , wherein said antibody is selected from the group consisting of a human antibody, a humanized antibody, and a chimeric antibody. 
     
     
         31 . The method according to  claim 29 , wherein said antibody further comprises an engineered glycoform. 
     
     
         32 . The method according to  claim 29 , wherein the amino acid substitution is made by generating a nucleic acid that encodes said variant.