Polypeptides With Enhanced Anti-Inflammatory And Decreased Cytotoxic Properties And Relating Methods

Abstract

The invention provides a polypeptide containing at least one IgG Fc region, wherein said at least one IgG Fc region is glycosylated with at least one galactose moiety connected to a respective terminal sialic acid moiety by a α 2,6 linkage, and wherein said polypeptide having a higher anti-inflammatory activity as compared to an unpurified antibody.

1 . An isolated polypeptide containing at least one IgG Fc region, having altered properties compared to an unpurified antibody preparation, wherein sialylation of the isolated polypeptide is higher than the sialylation of the unpurified antibody preparation. 
     
     
         2 . The isolated polypeptide of  claim 1 , wherein said at least one IgG Fc region is glycosylated with at least one galactose moiety connected to a respective terminal sialic acid moiety by a α 2,6 linkage, and wherein said polypeptide having a higher anti-inflammatory activity as compared to an unpurified antibody preparation. 
     
     
         3 . The isolated polypeptide of  claim 1 , wherein said at least one IgG Fc region is glycosylated with at least one galactose moiety connected to a respective terminal sialic acid moiety by a α 2,6 linkage, and wherein said polypeptide having a reduced binding to an Fc activating receptor as compared to an unpurified antibody preparation. 
     
     
         4 . The isolated polypeptide of  claim 3 , wherein the Fc activating receptor is selected from the group consisting of FcγRIIA, FcγRIIC and FcγRIIIA. 
     
     
         5 . The isolated polypeptide of  claim 1 , comprising a human IgG1, IgG2, IgG3 or IgG4 Fc region, said polypeptide having a higher content of the at least one galactose moiety connected to the respective terminal sialic acid moiety by a α 2,6 linkage as compared to an unpurified antibody. 
     
     
         6 . The isolated polypeptide of  claim 1 , having an increased anti-inflammatory activity in vitro. 
     
     
         7 . The isolated polypeptide of  claim 1 , having an increased anti-inflammatory activity in vivo. 
     
     
         8 . The isolated polypeptide of  claim 1 , derived from a naturally occurring antibody source. 
     
     
         9 . The isolated polypeptide of  claim 1 , derived from a recombinant antibody source. 
     
     
         10 . The isolated polypeptide of  claim 1 , wherein said unmodified antibody comprises IVIG. 
     
     
         11 . The isolated polypeptide of  claim 1 , derived from a cell line having an enhanced activity of creating α 2,6 linkages between at least one galactose moiety and a respective terminal sialic acid in a protein's polysaccharide chain. 
     
     
         12 . The isolated polypeptide of  claim 1 , modified by treatment with α2-6 sialyltransferase. 
     
     
         13 . The isolated polypeptide of  claim 1 , which is purified. 
     
     
         14 . A pharmaceutical formulation comprising the isolated polypeptide of  claim 1  in combination with a suitable carrier or diluent. 
     
     
         15 .- 31 . (canceled)