Claims
- 1. A recombinant adeno-associated virus (rAAV) vector comprising a polynucleotide encoding a fusion polypeptide comprising an extracellular domain of tumor necrosis factor receptor (TNFR) and a constant domain of an IgG1 molecule.
- 2. The rAAV vector of claim 1, wherein the TNFR extracellular domain is from p75 TNFR.
- 3. The rAAV vector of claim 1, wherein the polynucleotide encoding the TNFR polypeptide is operably linked to a heterologous promoter.
- 4. The rAAV vector of claim 1, wherein the polynucleotide encoding the TNFR polypeptide is operably linked to a constitutive promoter.
- 5. The rAAV vector of claim 1, wherein the polynucleotide encoding the TNFR polypeptide is operably linked to an inducible promoter.
- 6. The rAAV vector of claim 5, wherein the inducible promoter is from the TNFα gene.
- 7. The rAAV vector of claim 1, wherein the polynucleotide further encodes a polypeptide comprising an interleukin-1 (IL-1) antagonist.
- 8. The rAAV vector of claim 7 wherein the IL-1 antagonist is an IL-1 receptor polypeptide, wherein said IL-1 receptor polypeptide binds IL-1.
- 9. The rAAV vector of claim 8 wherein the IL-1 receptor polypeptide is a IL-1 receptor type II polypeptide.
- 10. A mammalian cell transfected with the rAAV vector of claim 1.
- 11. A mammalian cell transfected,with the rAAV vector of claim 7.
- 12. A composition comprising the rAAV of claim 1.
- 13. The composition of claim 12, further comprising a pharmaceutically acceptable excipient.
- 14. An rAAV virus particle comprising the rAAV vector of claim 1.
- 15. An rAAV virus particle comprising the rAAV vector of claim 7.
- 16. A method for reducing TNF levels in a mammal, comprising administering the rAAV vector of claim 1 to the mammal in an amount sufficient to reduce TNF levels in the mammal.
- 17. The method of claim 16, further comprising administering a TNF antagonist.
- 18. The method of claim 16, wherein said rAAV vector is administered by intra-articular injection.
- 19. The method of claim 16, wherein the rAAV is administered by injection to connective tissue selected from the group consisting of a synovium, a cartilage, a ligament, and a tendon of said mammal.
- 20. The method of claim 18, wherein said rAAV vector is administered to synovial cells lining a joint space of said mammal.
- 21. The method of claim 16, wherein said rAAV vector is administered by intramuscular injection.
- 22. The method of claim 16, wherein said rAAV vector is administered by intravenous injection.
- 23. A method for reducing an inflammatory response in a mammal, comprising administering the rAAV vector of claim 1 to the mammal in an amount sufficient to reduce the inflammatory response in the mammal.
- 24. The method of claim 23, further comprising administering a TNF antagonist.
- 25. The method of claim 23, wherein the inflammatory response occurs in a connective tissue.
- 26. The method of claim 23, wherein the inflammatory response occurs in a joint.
- 27. The method of claim 23, wherein said rAAV vector is administered by intra-articular injection.
- 28. The method of claim 23, wherein the rAAV is administered by injection to connective tissue selected from the group consisting of a synovium, a cartilage, a ligament, and a tendon of said mammal.
- 29. The method of claim 27, wherein said rAAV vector is administered to synovial cells lining a joint space of said mammal.
- 30. The method of claim 23, wherein said rAAV vector is administered by intramuscular injection.
- 31. The method of claim 23, wherein said rAAV vector is administered by intravenous injection.
- 32. A method for palliating a TNF-associated disorder in a mammal, comprising administering the rAAV vector of claim 1 to the mammal in an amount sufficient to palliate the TNF-associated disorder condition.
- 33. The method of claim 32, further comprising administering a TNF antagonist.
- 34. The method of claim 33, wherein said rAAV vector is administered by intra-articular injection.
- 35. The method of claim 32, wherein the rAAV is administered to connective tissue selected from the group consisting of a synovium, a cartilage, a ligament, and a tendon of said mammal.
- 36. The method of claim 32, wherein said rAAV vector is administered to synovial cells lining a joint space of said mammal.
- 37. The method of claim 32, wherein said rAAV vector is administered by intramuscular injection.
- 38. The method of claim 30, wherein the TNF-associated disorder in an inflammatory disorder.
- 39. The method of claim 32, wherein the inflammatory disorder is an arthritic condition.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the priority benefit of U.S. provisional patent application serial No. 60/150,688, filed May 28, 1999, which is incorporated by reference in its entirety.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60150688 |
May 1999 |
US |
Continuations (1)
|
Number |
Date |
Country |
Parent |
09579845 |
May 2000 |
US |
Child |
10313852 |
Dec 2002 |
US |