FUSION PROTEIN COMPRISING AN INTERLEUKIN 4 AND INTERLEUKIN
The invention is concerned with a fusion protein comprising interleukin 10 and interleukin 4, 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 . A fusion protein comprising an interleukin 4 and interleukin 10.
2 . A fusion protein according to claim 1 , wherein said interleukin 4 and said interleukin 10 are linked by a linker sequence.
3 . A fusion protein according to any one of claims 1 or 2 , wherein the interleukin 4 is fused N-terminal of the interleukin 10.
4 . A fusion protein according to any one of claims 1 or 2 , wherein the interleukin 10 is fused N-terminal of the interleukin 4.
5 . A fusion protein according to claim 1 , which further comprises one or more chemical modifications.
6 . A fusion protein according to claim 5 , wherein the chemical modification is selected from the group consisting of glycosylation, fucosylation, sialylation, and pegylation.
7 . A fusion protein according to claim 1 , wherein said interleukin 10 is human interleukin 10.
8 . A fusion protein according to claim 1 , wherein said interleukin 4 is human interleukin 4.
9 . A nucleic acid molecule comprising a polynucleotide encoding the fusion protein according to claim 1 .
10 . A vector comprising the nucleic acid molecule of claim 9 .
11 . A host cell comprising the nucleic acid molecule according to claim 9 or the vector according to claim 10 .
12 . A method for producing a fusion protein comprising an interleukin 4 and interleukin 10, said method comprising the steps of:
culturing a host cell according to claim 11 under conditions permitting the production of the fusion protein;
optionally, recovering the fusion protein.
13 . A pharmaceutical composition comprising the fusion protein according to claim 1 , and a pharmaceutically acceptable carrier.
14 . A fusion protein according to claim 1 for use as a medicament.
15 . A fusion protein according to claim 1 for use in the prevention or treatment of osteoarthritis, chronic pain, a condition characterized by local or systemic inflammation, immune activation, and/or lymphoproliferation.
16 . A fusion protein for use according to claim 14 , wherein said condition characterized by local or systemic inflammation, immune activation, lymphoproliferation and/or chronic pain is selected from the group consisting of: sepsis, adult respiratory distress syndrome, allo- and xenotransplantation, dermatitis, inflammatory bowel disease, sarcoidosis, allergies, psoriasis, ankylosing spondylarthitis, autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis, glomerolonephritis, immune complex-induced and other forms of vasculitis, multiple sclerosis, Sjogren's disease, gout, lymphoproliferative diseases such as non Hodgkin lymphoma and B cell chronic lymphocytic leukemia, burn injuries, multiple trauma, stroke, myocardial infarction, atherosclerosis, diabetes mellitus, extracorporeal dialysis and blood oxygenation, ischemia-reperfusion injuries, toxicity induced by the in vivo administration of cytokines or therapeutic monoclonal antibodies, chronic pain syndrome and neuropathic and/or inflammatory pain.
17 . A fusion protein according to claim 1 for use in the prevention or treatment of a clinical condition in a mammal, such as a human, for which interleukin 10 is indicated.
18 . A fusion protein according to claim 1 for use in the prevention or treatment of a clinical condition in a mammal, such as a human, for which interleukin 4 is indicated.
19 . A gene therapy vector according to claim 10 for use in the prevention or treatment of osteoarthritis, chronic pain, a condition characterized by local or systemic inflammation, immune activation, and/or lymphoproliferation.
20 . A vector for use according to claim 19 , wherein said condition characterized by local or systemic inflammation, immune activation, and/or lymphoproliferation is selected from the group consisting of: sepsis, adult respiratory distress syndrome, allo- and xenotransplantation, dermatitis, inflammatory bowel disease, sarcoidosis, allergies, psoriasis, ankylosing spondylarthitis, autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis, glomerolonephritis, immune complex-induced and other forms of vasculitis, multiple sclerosis, Sjogren's disease, gout, lymphoproliferatieve diseases such as non Hodgkin lymphoma and B cell chronic lymphocytic leukemia, burn injuries, multiple trauma, stroke, myocardial infarction, atherosclerosis, diabetes mellitus, extracorporeal dialysis and blood oxygenation, ischemia-reperfusion injuries, toxicity induced by the in vivo administration of cytokines or therapeutic monoclonal antibodies, chronic pain syndrome, and neuropathic and/or inflammatory pain.