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 . An antibody comprising a variant human IgG1 Fc region, which antibody comprises an amino acid substitution at position 265 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 antibody of  claim 1  which comprises one amino acid substitution in the Fc region. 
     
     
         3 . The antibody of  claim 1  which consists of one amino acid substitution in the Fc region. 
     
     
         4 . The antibody of  claim 1  which comprises two amino acid substitutions in the Fc region. 
     
     
         5 . The antibody of  claim 1  which consists of two amino acid substitutions in the Fc region. 
     
     
         6 . The antibody of  claim 1  wherein the amino acid at position 265 is substituted with Ala. 
     
     
         7 . The antibody of  claim 1  wherein the amino acid at position 265 is substituted with Asn or Glu. 
     
     
         8 . The antibody of  claim 1  further comprising an amino acid substitution at position 297 of the Fc region. 
     
     
         9 . The antibody of  claim 8  wherein the amino acid at position 297 is substituted with Ala. 
     
     
         10 . The antibody of  claim 1  which binds to an integrin. 
     
     
         11 . The antibody of  claim 1  which binds a surface membrane protein or fragment thereof. 
     
     
         12 . A host cell comprising nucleic acid encoding an antibody comprising a variant human IgG1 Fc region, which antibody comprises an amino acid substitution at position 265 of the Fc region, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat. 
     
     
         13 . A method for producing an antibody comprising culturing the host cell of  claim 12  so that the nucleic acid is expressed. 
     
     
         14 . The method of  claim 13  further comprising recovering the antibody from the host cell culture. 
     
     
         15 . The method of  claim 13  wherein the antibody comprises one amino acid substitution in the Fc region. 
     
     
         16 . The method of  claim 13  wherein the antibody consists of one amino acid substitution in the Fc region. 
     
     
         17 . The method of  claim 13  wherein the antibody comprises two amino acid substitutions in the Fc region. 
     
     
         18 . The method of  claim 13  wherein the antibody consists of two amino acid substitutions in the Fc region. 
     
     
         19 . The method of  claim 13  wherein the amino acid at position 265 of the antibody is substituted with Ala. 
     
     
         20 . The method of  claim 13  wherein the amino acid at position 265 of the antibody is substituted with Asn or Glu. 
     
     
         21 . The method of  claim 13  wherein the antibody further comprises an amino acid substitution at position 297 of the Fc region. 
     
     
         22 . The method of  claim 21  wherein the amino acid at position 297 is substituted with Ala. 
     
     
         23 . The method of  claim 13  wherein the antibody binds to an integrin. 
     
     
         24 . The method of  claim 13  wherein the antibody binds a surface membrane protein or fragment thereof. 
     
     
         25 . A method for treating a disorder in a mammal comprising administering to the mammal a therapeutically effective amount of the antibody of  claim 1 .