Compositions comprising an interleukin construct

Abstract

The invention is concerned with a fusion protein, a nucleic acid molecule encoding such fusion protein, a vector comprising such nucleic acid molecule, and a host cell comprising such nucleic acid molecule or such vector. The invention further pertains to a method for producing such fusion protein. The fusion protein or a gene therapy vector encoding the fusion protein may be used in the prevention or treatment of osteoarthritis, chronic pain, a condition characterized by local or systemic inflammation, immune activation, and/or lymphoproliferation.

1 - 20 . (canceled) 
     
     
         21 . A method of treating pain, inflammation, or osteoarthritis in a subject in need thereof, comprising administering to the subject a fusion protein comprising, from N- to C-terminus, an IL-4 polypeptide and an IL-10 polypeptide; or from N- to C-terminus, the IL-10 polypeptide and the IL-4 polypeptide. 
     
     
         22 . The method of  claim 21 , wherein chronic pain is treated in the subject. 
     
     
         23 . The method of  claim 21 , wherein neuropathic pain is treated in the subject. 
     
     
         24 . The method of  claim 21 , wherein the osteoarthritis is treated in the subject. 
     
     
         25 . The method of  claim 21 , wherein the inflammation is treated in the subject. 
     
     
         26 . The method of  claim 25 , wherein the inflammation is associated with osteoarthritis. 
     
     
         27 . The method of  claim 21 , wherein cartilage damage is reduced in the subject. 
     
     
         28 . The method of  claim 21 , wherein the IL-4 polypeptide is a mammalian wild type IL-4. 
     
     
         29 . The method of  claim 21 , wherein the IL-4 polypeptide is a human wild type IL-4. 
     
     
         30 . The method of  claim 21 , wherein the IL-10 polypeptide is a mammalian wild type IL-10. 
     
     
         31 . The method of  claim 21 , wherein the IL-10 polypeptide is a human wild type IL-10. 
     
     
         32 . The method of  claim 21 , wherein the fusion protein further comprises a linker that joins the IL-4 polypeptide and the IL-10 polypeptide. 
     
     
         33 . The method of  claim 32 , wherein the linker comprises the amino acid sequence of SEQ ID NO: 3. 
     
     
         34 . The method of  claim 32 , wherein the linker consists of the amino acid sequence of SEQ ID NO: 3. 
     
     
         35 . The method of  claim 34 , wherein the fusion protein comprises an amino acid sequence that consists of, from N- to C-terminus, the IL-4 polypeptide, the linker, and the IL-10 polypeptide. 
     
     
         36 . The method of  claim 34 , wherein the fusion protein comprises an amino acid sequence that consists of, from N- to C-terminus, the IL-10 polypeptide, the linker, and the IL-4 polypeptide. 
     
     
         37 . The method of  claim 21 , wherein the fusion protein is in a monomeric form. 
     
     
         38 . The method of  claim 21 , wherein the fusion protein is in a dimeric form. 
     
     
         39 . The method of  claim 21 , wherein the fusion protein is glycosylated. 
     
     
         40 . The method of  claim 21 , wherein the fusion protein is not glycosylated. 
     
     
         41 . The method of  claim 21 , wherein the fusion protein is fucosylated, sialylated, pegylated, or a combination thereof. 
     
     
         42 . The method of  claim 21 , wherein upon administration of the fusion protein to the subject, the pain, the inflammation, or the osteoarthritis is reduced to a greater extent than upon administration of an equivalent dose of a combination of the IL-4 polypeptide in a free form and the IL-10 polypeptide in a free form. 
     
     
         43 . The method of  claim 21 , wherein upon administration of the fusion protein to the subject, the pain, the inflammation, or the osteoarthritis is reduced for a longer period of time than upon administration of equivalent doses of a combination of the IL-4 polypeptide in a free form and the IL-10 polypeptide in a free form. 
     
     
         44 . The method of  claim 21 , wherein the fusion protein is administered intrathecally. 
     
     
         45 . The method of  claim 21 , wherein the fusion protein is administered by an intraarticular route. 
     
     
         46 . The method of  claim 21 , wherein the fusion protein is administered by a subcutaneous, intracapsular, intravenous, subarachnoid, or epidural route. 
     
     
         47 . A fusion protein comprising, from N- to C-terminus, an IL-4 polypeptide, a linker, and an IL-10 polypeptide; or from N- to C-terminus, the IL-10 polypeptide, the linker, and the IL-4 polypeptide. 
     
     
         48 . The fusion protein of  claim 47 , wherein the IL-4 polypeptide is a mammalian wild type IL-4 and the IL-10 polypeptide is a mammalian wild type IL-10. 
     
     
         49 . The fusion protein of  claim 47 , wherein the linker consists of the amino acid sequence of SEQ ID NO: 3. 
     
     
         50 . The fusion protein of  claim 49 , wherein the fusion protein comprises an amino acid sequence that consists of, from N- to C-terminus, the IL-4 polypeptide, the linker, and the IL-10 polypeptide. 
     
     
         51 . The fusion protein of  claim 49 , wherein the fusion protein comprises an amino acid sequence that consists of, from N- to C-terminus, the IL-10 polypeptide, the linker, and the IL-4 polypeptide. 
     
     
         52 . A pharmaceutical composition comprising the fusion protein of  claim 47  and a pharmaceutically-acceptable excipient.