Ifnar2 mutants, their production and use

Abstract

The present invention relates to mutant polypeptides of the beta chain of the type I IFN receptor (IFNAR2 mutant) with enhanced affinity for IFNβ as compared to the wild type protein for prolonging the effect of IFNβ in vivo.

1 . A method for augmenting the anti-cancer, immune modulating or anti-viral properties of interferon-β (IFNβ) comprising administering to a patient in need thereof a therapeutically effective amount of a composition comprising a fusion protein comprising (1) an IFNAR2 portion consisting of the sequence of SEQ ID NO: 2 and (2) an immunoglobulin portion consisting of an immunoglobulin or fragment thereof, wherein the affinity of said fusion protein for IFN-β is synergistically increased 25 to 100-fold compared to the affinity of wild type human IFNAR2 for IFN-β. 
     
     
         2 . The method of  claim 1 , wherein the composition further comprises IFNβ. 
     
     
         3 . The method of  claim 1  or  2 , wherein the method is for the treatment of an autoimmune disease selected from multiple sclerosis, rheumatoid arthritis, myasthenia gravis, diabetes, lupus and ulcerative colitis. 
     
     
         4 . The method of  claim 1  or  2 , wherein the method is for the treatment of a cancer selected from hairy cell leukemia, Kaposi's sarcoma, multiple myeloma, chronic myelogenous leukemia, non-Hodgkin's lymphoma and melanoma. 
     
     
         5 . The method of  claim 1  or  2 , wherein the method is for the treatment of a viral disease selected from the group consisting of chronic granulomatous disease, condyloma acuminatum, juvenile laryngeal papillomatosis, hepatitis A, and chronic infection with hepatitis B and C viruses. 
     
     
         6 . The method of  claim 2 , wherein the fusion protein and IFNβ are covalently linked. 
     
     
         7 . A method for augmenting the anti-cancer, immune modulating or anti-viral properties of IFNβ comprising administering to a patient in need thereof a therapeutically effective amount of a composition comprising an isolated polypeptide consisting of the sequence of SEQ ID NO: 2. 
     
     
         8 . The method of  claim 7 , wherein the composition further comprises IFNβ. 
     
     
         9 . The method of  claim 7  or  8 , wherein the method is for the treatment of an autoimmune disease selected from multiple sclerosis, rheumatoid arthritis, myasthenia gravis, diabetes, lupus and ulcerative colitis. 
     
     
         10 . The method of  claim 7  or  8 , wherein the method is for the treatment of a cancer selected from hairy cell leukemia, Kaposi's sarcoma, multiple myeloma, chronic myelogenous leukemia, non-Hodgkin's lymphoma and melanoma. 
     
     
         11 . The method of  claim 7  or  8 , wherein the method is for the treatment of a viral disease selected from the group consisting of chronic granulomatous disease, condyloma acuminatum, juvenile laryngeal papillomatosis, hepatitis A, and chronic infection with hepatitis B and C viruses. 
     
     
         12 . The method of  claim 8 , wherein the polypeptide and IFNβ are covalently linked. 
     
     
         13 . A method for inhibiting the activity of IFNβ comprising administering to a patient in need thereof a therapeutically effective amount of a composition comprising a fusion protein comprising (1) an IFNAR2 portion consisting of the sequence of SEQ ID NO: 2 and (2) an immunoglobulin portion consisting of an immunoglobulin or fragment thereof, wherein the affinity of said fusion protein for IFN-β is synergistically increased 25 to 100-fold compared to the affinity of wild type human IFNAR2 for IFN-β. 
     
     
         14 . A method for inhibiting the activity of IFNβ comprising administering to a patient in need thereof a therapeutically effective amount of a composition comprising an isolated polypeptide consisting of the sequence of SEQ ID NO: 2. 
     
     
         15 . The method of  claim 13  or  14  wherein the composition further comprises an IFNβ antagonist.