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 region, said polypeptide having a higher anti-inflammatory activity and a lower cytotoxic activity as compared to an unpurified antibody and methods of production of such polypeptide.

1 . A polypeptide containing at least one IgG Fc region, said polypeptide having a higher anti-inflammatory activity and a lower cytotoxic activity as compared to an unpurified antibody. 
     
     
         2 . The polypeptide of  claim 1  comprising a human IgG1, IgG2, IgG3 or IgG4 Fc region, said polypeptide having a higher sialic acid content as compared to an unpurified antibody. 
     
     
         3 . The polypeptide of  claim 1  or  2  having an increased anti-inflammatory activity in vitro. 
     
     
         4 . The polypeptide of any one of  claims 1 - 3 , having an increased anti-inflammatory activity in vivo. 
     
     
         5 . The polypeptide of any one of  claims 1 - 4 , derived from a naturally occurring antibody source. 
     
     
         6 . The polypeptide of any one of  claims 1 - 4 , derived from a recombinant antibody source. 
     
     
         7 . The polypeptide of any one of  claims 1 - 6 , having greater percent sialic acid content as compared to unmodified antibody, wherein said unmodified antibody comprises IVIG. 
     
     
         8 . The antibody of any one of  claims 1 - 7 , derived from a cell line having an enhanced protein sialylation activity. 
     
     
         9 . The antibody of any one of  claims 1 - 8 , modified by treatment with sialyltransferase. 
     
     
         10 . The antibody of any one of  claims 1 - 9 , which is purified. 
     
     
         11 . A pharmaceutical formulation comprising the antibody of any  claims 1 - 10  in combination with a suitable carrier or diluent. 
     
     
         12 . A method of preparation of a polypeptide containing at least one Fc region, said polypeptide having a higher anti-inflammatory activity and a lower cytotoxicity than an unpurified antibody, said method comprising:
 providing an unpurified source of the polypeptide containing at least one Fc region, said unpurified source of the polypeptide containing at least one Fc region comprising a plurality of the polypeptides containing at least one Fc region having sialic acid and a plurality of the polypeptides containing at least one Fc region lacking sialic acid; and   increasing the ratio of the plurality of the polypeptides containing at least one Fc region having sialic acid to the plurality of the polypeptide containing at least one Fc region lacking sialic acid.   
     
     
         13 . The method of  claim 12 , wherein said unpurified source of the polypeptide containing at least one Fc region comprises a human unpurified IgG antibody. 
     
     
         14 . The method of  claim 12  or  13 , wherein the unpurified source of the polypeptide containing at least one Fc region is provided from expressing a vector comprising a nucleic acid sequence in an expression system, wherein said nucleic acid sequence is translated into an IgG antibody. 
     
     
         15 . The method of  claim 14 , wherein the expression system comprises modified host expression systems capable of N-linked glycosylation selected from the group consisting of fungal, plant, vertebrate and invertebrate expression systems, and any combinations thereof. 
     
     
         16 .- 22 . (canceled)