Interferon-beta fusion proteins and uses

Abstract

A fusion polypeptide is described having the amino acid sequence X-Y-Z, or portion thereof, comprising the amino acid sequence of a glycosylated interferon-beta (X); Y is an optional linker moiety; and Z is a polypeptide comprising at least a portion of a polypeptide other than glycosylated interferon-beta. It is preferred that X is human interferon-beta-1a. Mutants of interferon-beta-1a are also described.

1 . An isolated polypeptide having the amino acid sequence X-Y-Z, wherein X is a polypeptide having the amino acid sequence, or portion thereof, comprising the amino acid sequence of a glycosylated interferon-beta; Y is an optional linker moiety; and Z is a polypeptide comprising at least a portion of a polypeptide other than glycosylated interferon-beta. 
     
     
         2 . The isolated polypeptide of  claim 1 , wherein X is interferon-beta-1a. 
     
     
         3 . The isolated polypeptide of  claim 1 , wherein X is a mutant having at least one of the following properties: (a) the mutant has a higher antiviral activity than wild type interferon beta 1a, wherein the antiviral activity is measured by viral induced lysis of cells; (b) the mutant has, relative to wild type interferon-beta-1a, greater antiviral activity than antiproliferative activity; (c) the mutant binds interferon receptor but has, when compared to wild type interferon-beta-1a, lowered antiviral activity and lowered antiproliferative activity relative to its receptor binding activity. 
     
     
         4 . The isolated polypeptide of  claim 2 , wherein the interferon beta-1a is derivatized. 
     
     
         5 . The isolated polypeptide of  claim 4 , wherein the derivative is a polyalkylglycol polymer. 
     
     
         6 . The isolated polypeptide of  claim 1 , wherein Z is at least a portion of a constant region of an immunoglobulin. 
     
     
         7 . The isolated polypeptide of  claim 6 , wherein said at least a portion of the constant region is derived from an immunoglobulin of the class selected from classes IgM, IgG, IgD, IgA, and IgE. 
     
     
         8 . The isolated polypeptide of  claim 7 , wherein the class is IgG. 
     
     
         9 . The isolated polypeptide of  claim 6 , wherein the at least a portion of the constant region comprises at least a hinge, CH2 and CH3 domains. 
     
     
         10 . A fusion protein having an amino terminal region consisting of the amino acid sequence of a glycosylated interferon-beta or a portion thereof and having a carboxy terminal region comprising at least a portion of a protein other than glycosylated interferon-beta. 
     
     
         11 . The isolated protein of  claim 10 , wherein X is interferon-beta-1a. 
     
     
         12 . The isolated protein of  claim 10 , wherein X is a mutant having at least one of the following properties: (a) the mutant has a higher antiviral activity than wild type inteferon beta 1a, wherein the antiviral activity is measured by viral induced lysis of cells; (b) the mutant has, relative to wild type interferon-beta-1a, greater antiviral activity than antiproliferative activity; (c) the mutant binds interferon receptor but has, compared to wild type interferon-beta-1a, lowered antiviral activity and lowered antiproliferative activity relative to its receptor binding activity. 
     
     
         13 . The isolated protein of  claim 11 , wherein the interferon-beta-1a is derivatized. 
     
     
         14 . The isolated protein of  claim 13 , wherein the derivative is a polyalkylglycol polymer. 
     
     
         15 . The isolated protein of  claim 10 , wherein the at least a portion of the protein other than interferon beta is at least a portion of a constant region of an immunoglobulin. 
     
     
         16 . The isolated protein of  claim 15 , wherein said at least a portion of the constant region is derived from an immunoglobulin of the class selected from classes IgM, IgG, IgD, IgA, and IgE. 
     
     
         17 . The isolated protein of  claim 16 , wherein the class is IgG. 
     
     
         18 . The isolated protein of  claim 15 , wherein the at least a portion of the constant region is comprises at least a hinge, CH2 and CH3 domains. 
     
     
         19 - 31 . (canceled)