FC-Interferon-Beta Fusion Proteins

Abstract

Disclosed are Fc-interferon-beta (Fc-IFN-β) fusion proteins and nucleic acid molecules encoding them. The Fc-IFN-β fusion proteins include variants of the interferon-beta (IFN-β) protein that are altered to achieve enhanced biological activity, prolonged circulating half-life and greater solubility. Also disclosed are methods of producing the fusion proteins and methods of using the fusion proteins and/or nucleic acid molecules for treating diseases and conditions alleviated by the administration of interferon-beta.

1 . An Fc-interferon-β fusion protein comprising:
 an immunoglobulin Fc region; and 
 a human interferon-β protein linked by a peptide bond or a peptide linker sequence to the carboxy-terminus of the immunoglobulin Fc region, 
 wherein the interferon-β protein comprises SEQ ID NO: 2 and has the following substitutions: Cl7S, F50H, H131A, and either H140A or H140T. 
 
     
     
         2 . (canceled) 
     
     
         3 . (canceled) 
     
     
         4 . The fusion protein of  claim 1 , wherein the immunoglobulin Fc region comprises an immunoglobulin hinge region and an immunoglobulin heavy chain constant region. 
     
     
         5 . The fusion protein of  claim 1 , wherein the immunoglobulin Fc region is derived from IgG4, IgG2 or IgG1. 
     
     
         6 . The fusion protein of  claim 4 , wherein the immunoglobulin heavy chain constant region is derived from IgG4 and the immunoglobulin hinge region is derived from IgG1. 
     
     
         7 . The fusion protein of  claim 6 , wherein a cysteine residue of the hinge region has been mutated. 
     
     
         8 . The fusion protein of  claim 5 , wherein the immunoglobulin Fc region is derived from IgG1, and an alanine residue is substituted in place of a C-terminal lysine of the immunoglobulin Fc region. 
     
     
         9 . The fusion protein of  claim 4 , wherein the immunoglobulin heavy chain constant region is derived from IgG2, and the immunoglobulin hinge region is derived from IgG1. 
     
     
         10 . The fusion protein of  claim 9 , wherein a cysteine residue of the hinge region has been mutated. 
     
     
         11 . The fusion protein of  claim 5 , wherein the immunoglobulin Fc region is derived from IgG2, and an alanine residue is substituted in place of the C-terminal lysine of the immunoglobulin Fc region. 
     
     
         12 . The fusion protein of  claim 1 , wherein the peptide linker sequence is Gly 4 SerGly 4 SerGly 3 SerGly (SEQ ID NO: 1). 
     
     
         13 - 14 . (canceled) 
     
     
         15 . The fusion protein of  claim 1 , wherein the immunoglobulin Fc region comprises IgG1, IgG2, or IgG4. 
     
     
         16 . The fusion protein of  claim 1 , wherein the immunoglobulin Fc region comprises IgG4 and at least a portion of a hinge of IgG1. 
     
     
         17 - 22 . (canceled) 
     
     
         23 . The fusion protein of  claim 1 , wherein the interferon-β comprises the substitutions C17S, F50H, H131A, and H140A. 
     
     
         24 . The fusion protein of  claim 1 , wherein the interferon-β comprises the substitutions C17S, F50H, H131A, and H140T.