Antibodies and fc fusion protein modifications with enhanced persistence or pharmacokinetic stability in vivo and methods of use thereof

Abstract

In certain embodiments, this present invention provides antibodies and Fc fusion proteins with enhanced pharmacokinetics, such as biotinylated antibodies or biotinylated Fc fusion polypeptides.

We claim: 
     
         1 . An Fc domain-containing fusion polypeptide, wherein said Fc domain comprises a conjugated biotin moiety, and wherein said Fc domain-containing fusion polypeptide has an increased half-life in vivo relative to the half-life of a corresponding Fc domain-containing fusion polypeptide that does not comprise a biotin moiety. 
     
     
         2 . The polypeptide of  claim 1 , wherein the Fc domain comprises a human Fc domain. 
     
     
         3 . The polypeptide of  claim 2 , wherein the human Fc domain of the Fc domain-containing fusion polypeptide is a human IgG Fc domain. 
     
     
         4 . The polypeptide of  claim 3 , wherein the human Fc domain is selected from the group consisting of the human Fc domains of IgG1, IgG2, IgG3, and IgG4. 
     
     
         5 . The polypeptide of  claim 2 , wherein the biotin moiety is covalently conjugated to the human Fc domain of the Fc fusion polypeptide. 
     
     
         6 . A method of treating a disorder in a subject in need thereof, the method comprising administering to the subject an effective amount of Fc fusion polypeptide comprising a human Fc domain fused to a heterologous fusion partner polypeptide, wherein said human Fc domain comprises a conjugated biotin moiety, and wherein said biotin moiety is conjugated to the Fc fusion polypeptide in an amount sufficient to increase the half-life of the Fc fusion polypeptide in vivo relative to the half-life of a corresponding Fc fusion polypeptide that does not comprise a biotin moiety. 
     
     
         7 . The method of  claim 6 , wherein the Fc domain comprises a human Fc domain. 
     
     
         8 . The method of  claim 7 , wherein the the human Fc domain is a human IgG Fc domain. 
     
     
         9 . The method of  claim 8 , wherein the human Fc domain is selected from the group consisting of IgG1, IgG2, IgG3, and IgG4.