Combination for treating an inflammatory disorder
The invention provides a combination of a source of a CD39 and of a source of a CD73.
1. A method for treating an inflammatory condition or disease selected from: rheumatoid arthritis (RA), juvenile rheumatoid arthritis, osteoarthritis (OA), gout, spondlyarthritis (SpA), psoriasis, psoriatic arthritis, ankylosing spondylitis, inflammatory bowel disease including Crohn's disease or ulcerative colitis, hepatitis, sepsis, alcoholic liver disease, and non-alcoholic steatosis, pain, ischemic disorder, glaucoma, asthma, arthritis, cancer, neurodegenerative disorders, chronic disorders, acute inflammation, blood clotting disorders, heart failure, and disorder of platelet function, the method comprising administering to a person in need thereof a combination of:
(a) a source of a CD39 comprising a nucleic acid molecule encoding the CD39 and
(b) a source of a CD73 comprising a nucleic acid molecule encoding the CD73,
wherein the nucleic acid molecules encoding the CD39 and the CD73 are present in a nucleic acid construct comprising a viral expression construct selected from a retrovirus vector, an adenovirus vector, an adeno-associated virus vector, a herpesvirus vector, a polyoma virus vector or a vaccinia virus vector.
2. The method according to claim 1 , wherein the inflammatory condition or disease is selected from: rheumatoid arthritis (RA), juvenile rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, inflammatory bowel disease including Crohn's disease or ulcerative colitis, hepatitis, sepsis, alcoholic liver disease, and non-alcoholic steatosis.
3. The method according to claim 1 , wherein the source of a CD39 is administered sequentially or simultaneously with the source of a CD73.
4. The method according to claim 1 , wherein the source of a CD39 and the source of a CD73 are present in one single composition or wherein the source of a CD39 is present in one composition and the source of a CD73 is present in distinct compositions.
5. The method according to claim 1 , wherein the source of a CD39 encodes a soluble CD39 and/or the source of a CD73 encodes a soluble CD73.
6. The method according to claim 1 , wherein the source of a CD39 and the source of a CD73 encodes a fusion protein comprising a CD39 protein or part thereof and a CD73 protein or part thereof.
7. The method according to claim 6 , wherein the fusion protein comprises an amino acid sequence that has at least 60% sequence identity or similarity with the amino acid sequence of SEQ ID NO: 17 and/or 19.
8. The method according to claim 1 , wherein the nucleic acid construct is a fusion construct comprising a nucleic acid molecule encoding CD39 fused to a nucleic acid molecule encoding CD73 via a 2A sequence.
9. The method according to claim 8 , wherein the fusion construct has at least 60% sequence identity or similarity with the nucleotide sequence of SEQ ID NO: 54 or SEQ ID NO: 57.
10. The method according to claim 1 , wherein the adeno-associated virus vector comprising a source of a CD39 and/or the adeno-associated virus vector comprising a source of a CD73 comprises a rAAV2 or rAAV5 or a rAAV8 vector comprising rAAV2 or rAAV5 ITR.
11. The method according to claim 1 , wherein the combination is administrated as a pharmaceutical composition comprising the combination and a pharmaceutically acceptable carrier, adjuvant, diluents, solubilizer, filler, preservative and/or excipient.
12. The method according to claim 1 , wherein the inflammatory condition or disease is selected from the group consisting of: rheumatoid arthritis (RA), juvenile rheumatoid arthritis, osteoarthritis (OA), gout, spondlyarthritis (SpA), psoriatic arthritis and ankylosing spondylitis.