Polypeptide variants with altered effector function

Abstract

The present invention concerns polypeptides comprising a variant Fc region. More particularly, the present invention concerns Fc region-containing polypeptides that have altered effector function as a consequence of one or more amino acid modifications in the Fc region thereof.

1 . A polypeptide comprising a variant human IgG Fc region which is not a native sequence Fc region and has increased neonatal Fc receptor (FcRn) binding affinity, wherein the polypeptide comprises an amino acid modification at any one or more of amino acid positions 238, 256, 265, 272, 286, 303, 305, 307, 311, 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, 413, 424, or 434 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat.  
     
     
         2 . The polypeptide of  claim 1  which comprises an amino acid substitution at position 307.  
     
     
         3 . The polypeptide of  claim 1  which comprises an amino acid substitution at position 380.  
     
     
         4 . The polypeptide of  claim 1  which comprises an amino acid substitution at position 434.  
     
     
         5 . The polypeptide of  claim 1  which comprises amino acid substitutions at positions 380, and 434.  
     
     
         6 . The polypeptide of  claim 1  which comprises amino acid substitutions at positions 307, 380 and 434.  
     
     
         7 . The polypeptide of  claim 1  which comprises an antibody.  
     
     
         8 . The antibody of  claim 7  which binds to vascular endothelial growth factor (VEGF), HER2 receptor, CD20, IgE, or LFA-1.  
     
     
         9 . The polypeptide of  claim 1  which comprises an immunoadhesin.  
     
     
         10 . A polypeptide comprising a variant Fc region which is not a native sequence Fc region and has increased neonatal Fc receptor (FcRn) binding affinity, wherein the polypeptide comprises an amino acid modification at any one or more of amino acid positions 238, 256, 265, 272, 286, 303, 305, 307, 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, 413, or 424 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat.  
     
     
         11 . A polypeptide comprising a variant Fc region which is not a native sequence Fc region and has increased neonatal Fc receptor (FcRn) binding affinity, wherein the polypeptide comprises amino acid substitutions at any two or more of amino acid positions 238, 256, 265, 272, 286, 303, 305, 307, 311, 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, 413, 424, or 434 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat.  
     
     
         12 . The polypeptide of  claim 11  comprising substitutions at positions 380 and 434.  
     
     
         13 . The polypeptide of  claim 11  comprising substitutions at positions 307, 380 and 434.  
     
     
         14 . A polypeptide comprising a variant Fc region which is not a native sequence Fc region and has increased neonatal Fc receptor (FcRn) binding affinity, wherein the polypeptide comprises substitutions at positions 307, 380 and 434 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat.  
     
     
         15 . An antibody that binds CD20 comprising a variant Fc region which is not a native sequence Fc region and has increased neonatal Fc receptor (FcRn) binding affinity, wherein the polypeptide comprises amino acid substitutions at any two or more of amino acid positions 238, 256, 265, 272, 286, 303, 305, 307, 311, 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, 413, 424, or 434 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat.  
     
     
         16 . An antibody that binds vascular endothelial growth factor (VEGF) comprising a variant Fc region which is not a native sequence Fc region and has increased neonatal Fc receptor (FcRn) binding affinity, wherein the polypeptide comprises amino acid substitutions at any two or more of amino acid positions 238, 256, 265, 272, 286, 303, 305, 307, 311, 312, 317, 340, 356, 360, 362, 376, 378, 380, 382, 413, 424, or 434 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat.  
     
     
         17 . A composition comprising the polypeptide of  claim 1  and a pharmaceutically acceptable carrier.  
     
     
         18 . The composition of  claim 17  which is sterile.