Fc VARIANTS WITH ALTERED BINDING TO FcRn

Abstract

The present application relates to a variant Fc region comprising at least one modification relative to a wild-type human Fc region, where the modification selected from the group consisting of 434S, 252Y/428L, 252Y/434S, and 428L/434S, and the numbering is according to the EU index.

We claim: 
     
         1 . A variant Fc region comprising at least one modification relative to a wild-type human Fc region, wherein said modification selected from the group consisting of: 434S, 252Y/428L, 252Y/434S, and 428L/434S, wherein numbering is according to the EU index. 
     
     
         2 . A variant according to  claim 1 , wherein said modification is 434S. 
     
     
         3 . A variant according to  claim 1 , wherein said modification is 428L/434S. 
     
     
         4 . A variant according to  claim 1 , wherein said modification is 252Y/428L. 
     
     
         5 . A variant according to  claim 1 , wherein said modification is 252Y/434S. 
     
     
         6 . A variant according to  claim 1 , wherein said variant comprises an antibody or immunoadhesin, and wherein said Fc region is selected from the group consisting of: IgG1, IgG2, IgG3, and IgG4. 
     
     
         7 . A variant according to  claim 6 , wherein said variant comprises an IgG1 Fc region. 
     
     
         8 . A variant according to  claim 6 , wherein said variant comprises an IgG2 Fc region. 
     
     
         9 . A variant according to  claim 6 , wherein said variant has longer serum half-life in a mammal relative to said antibody or immunoadhesin with said wild-type Fc region. 
     
     
         10 . A variant according to  claim 9 , wherein said mammal is a mouse expressing human FcRn or a non-human primate. 
     
     
         11 . A variant according to  claim 9 , wherein said mammal is human. 
     
     
         12 . A variant according to  claim 6 , wherein said antibody or immunoadhesin has specificity for an antigen selected from the group consisting of: vascular endothelial growth factor (VEGF), tumor necrosis factor α (TNF-α), CD25, epidermal growth factor receptor (EGFR) and IgE. 
     
     
         13 . A variant antibody or variant immunoadhesin comprising a variant of an IgG2 Fc region, wherein said variant antibody or immunoglobulin comprises between one and five modifications relative to the wild-type IgG2 Fc region, wherein at least one of said modifications is at position 434, wherein numbering is according to the EU index, and wherein said variant antibody or variant immunoadhesin has longer serum half-life in a mammal relative to said antibody or immunoadhesin with said wild-type IgG2 Fc region. 
     
     
         14 . A variant antibody or variant immunoadhesin according to  claim 13 , wherein said modification is 434S. 
     
     
         15 . A variant according to  claim 14 , wherein said variant additionally comprises at least one modification at a position selected from the group consisting of: 252 and 428. 
     
     
         16 . A variant according to  claim 13 , wherein said mammal is a mouse expressing human FcRn or a non-human primate. 
     
     
         17 . A variant according to  claim 13 , wherein said mammal is human. 
     
     
         18 . A variant Fc region comprising at least two modifications relative to a wild-type human Fc region, wherein at least one modification is 428L, and at least one modification is at position 252 or 434, wherein numbering is according to the EU index, 
     
     
         19 . A variant according to  claim 18 , wherein said Fc region comprises an antibody or immunoadhesin, and wherein said antibody or immunoadhesin comprises an IgG1 or IgG2 Fc region, and wherein said variant has longer serum half-life in a mammal relative to said antibody or immunoadhesin with said wild-type human Fc region, wherein said mammal is a mouse expressing human FcRn, a non-human primate, or in humans.