Claims for Patent: 8,361,467

Summary for Patent: 8,361,467

Title:	Trans-capsular administration of high specificity cytokine inhibitors into orthopedic joints
Abstract:	The present invention relates to trans-capsularly administering into a diseased joint a high specificity antagonist selected from the group consisting of: i) an inhibitor of a pro-inflammatory interleukin; ii) an inhibitor of TNF-.alpha. synthesis; iii) an inhibitor of membrane-bound TNF-.alpha.; iv) an inhibitor of a natural receptor of TNF-.alpha.; v) an inhibitor of NO synthase, vi) an inhibitor of PLA.sub.2 enzyme; vii) an anti-proliferative agent; viii) an anti-oxidant; ix) an apoptosis inhibitor selected from the group consisting of EPO mimetic peptides, EPO mimetibodies, IGF-I, IGF-II, and caspase inhibitors, and x) an inhibitor of MMPs; and xi) an inhibitor of p38 kinase.
Inventor(s):	DiMauro; Thomas M. (Southboro, MA), Attawia; Mohamed (Canton, MA), Serhan; Hassan (South Easton, MA), Reynolds; Martin A. (Mansfield, MA), Grace; Melissa (Raynham, MA), Kadiyala; Sudhakar (South Easton, MA), Urbahns; David (Barrington, RI), Bruder; Scott (Sudbury, MA), Collins; Gregory (East Sandwich, MA), Brown; Laura J. (Hamilton Square, NJ), Geesin; Jeff (Doylestown, PA), Plouhar; Pamela L. (South Bend, IN), Smith; Catherine (East Falmouth, MA), Siekierka; John (Towaco, NJ)
Assignee:	DePuy Spine, Inc. (Raynham, MA)
Application Number:	10/630,227
Patent Claims:	1. A method of treating an inflamed orthopedic joint, said joint comprising i) opposing hyaline cartilage articular surfaces, ii) a peripheral collagenous capsule defining a central joint space and iii) synovial fluid contained within the joint space, comprising trans-capsularly administering into the joint space a formulation comprising an effective amount of an anti-TNF-.alpha. monoclonal antibody or antigen-binding fragment thereof such that the inflamed orthopedic joint is treated, the method further comprising providing a therapeutically effective amount of a Growth Differentiation Factor (GDF) to the joint. 2. The method of claim 1, wherein the joint is a knee joint. 3. The method of claim 1, wherein the joint is a hip joint. 4. The method of claim 1, wherein the joint is a spinal facet joint. 5. The method of claim 1, wherein the formulation further comprises a therapeutically effective amount of at least one growth factor. 6. The method of claim 1, wherein the formulation further comprises a liposomal delivery system. 7. The method of claim 1, wherein the formulation is administered in an amount of less than 1 cc. 8. The method of claim 1, wherein the anti-TNF-.alpha. monoclonal antibody or antigen-binding fragment thereof is present in the formulation in an amount of at least 100 mg/ml. 9. The method of claim 1, wherein the formulation is provided with a sustained release device. 10. The method of claim 9, wherein the sustained release device comprises a hydrogel. 11. The method of claim 9, wherein the sustained release device provides controlled release. 12. The method of claim 9, wherein the sustained release device provides continuous release. 13. The method of claim 9, wherein the sustained release device provides intermittent release. 14. The method of claim 9, wherein the sustained release device comprises microspheres having a plurality of degradation rates. 15. The method of claim 9, wherein the sustained release device maintains the administered anti-TNF-.alpha. monoclonal antibody or antigen-binding fragment thereof at a therapeutically effective level. 16. The method of claim 1, wherein the formulation is provided closely adjacent to the outer wall of the capsule. 17. The method of claim 1, wherein the anti-TNF-.alpha. monoclonal antibody or antigen-binding fragment thereof is present in the formulation in a maximum amount of 0.5 mg. 18. The method of claim 1, wherein the formulation further comprises a growth factor, which is provided by platelet concentrate. 19. The method of claim 1, wherein the anti-TNF-.alpha. monoclonal antibody or antigen-binding fragment thereof therapeutically inhibits the production of a cytokine. 20. The method of claim 1, wherein the formulation further comprises viable mesenchymal stem cells. 21. The method of claim 1, wherein the formulation is injected into the synovial fluid. 22. The method of claim 1, wherein the formulation includes a viscosupplement. 23. The method of claim 1, wherein a portion of the synovial fluid is removed prior to administration of the-anti-TNF-.alpha. monoclonal antibody or antigen-binding fragment thereof. 24. The method of claim 1, wherein the administration is performed through a needle. 25. The method of claim 1, wherein the formulation is administered through a drug pump. 26. The method of claim 1, wherein the formulation is administered in a volume of between 0.03 ml and 0.3 ml. 27. The method of claim 1, wherein the administration comprises providing the formulation in a patch attached to an outer wall of the capsule. 28. The method of claim 1, wherein the administration comprises providing the formulation in a depot at a location closely adjacent an outer wall of the capsule. 29. The method of claim 1, wherein the administration comprises providing the formulation in a depot at a location closely adjacent to an endplate of an adjacent bony body. 30. The method of claim 1, wherein the anti-TNF-.alpha. monoclonal antibody or antigen-binding fragment thereof is predominantly released from the formulation by diffusion of the high specificity antagonist through a sustained delivery device. 31. The method of claim 30, wherein the sustained delivery device is a polymer. 32. The method of claim 1, wherein the anti-TNF-.alpha. monoclonal antibody or antigen-binding fragment thereof is predominantly released from the formulation by biodegradation of a sustained delivery device. 33. The method of claim 1, wherein the formulation further comprises BMP-1, BMP-3, BMP-2, OP-1, BMP-2A, BMP-2B, or BMP-7. 34. The method of claim 1, wherein the formulation further comprises TGF-.beta.. 35. The method of claim 1, wherein said anti-TNF-.alpha. monoclonal antibody or antigen-binding fragment thereof is adalimumab. 36. The method of claim 1, wherein said anti-TNF-.alpha. monoclonal antibody or antigen-binding fragment thereof is CDP-571. 37. The method of claim 1, wherein said anti-TNF-.alpha. monoclonal antibody or antigen-binding fragment thereof is CDP-870. 38. A method of treating an inflamed orthopedic joint, said joint comprising i) opposing hyaline cartilage articular surfaces, ii) a peripheral collagenous capsule defining a central joint space and iii) synovial fluid contained within the joint space, comprising trans-capsularly administering into the joint space a formulation comprising an effective amount of infliximab, such that the inflamed orthopedic joint is treated, the method further comprising providing a therapeutically effective amount of a Growth Differentiation Factor (GDF) to the joint. 39. The method of claim 1, wherein the GDF is provided to the joint simultaneously with the TNF-.alpha. antibody or antigen binding fragment thereof. 40. The method of claim 39, wherein the GDF is provided in the formulation comprising the TNF-.alpha. antibody or antigen binding fragment thereof. 41. The method of claim 1, wherein the GDF is provided to the joint separately from the anti-TNF-.alpha. monoclonal antibody or antigen-binding fragment thereof. 42. The method of claim 1, wherein the joint is in a mammalian subject with ankylosing spondylitis.

Details for Patent 8,361,467

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Janssen Biotech, Inc.	REMICADE	infliximab	For Injection	103772	08/24/1998		2039-02-26
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	12/31/2002		2039-02-26
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	02/21/2008		2039-02-26
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	04/24/2013		2039-02-26