USE OF CDK9 INHIBITORS TO REDUCE CARTILAGE DEGRADATION

• US 20150105423A1
• Filed: 10/19/2012
• Published: 04/16/2015
• Est. Priority Date: 10/20/2011
• Status: Active Grant

• Current Assignee: Regents of the University of California (University of California)
• Original Assignee: Regents of the University of California (University of California)
• Inventors: Haudenschild, Dominik, Yik, Jasper, Christiansen, Blaine, Di Cesare, Paul
• Granted Patent: US 9,498,471 B2
• Time in Patent Office: Days
• US Class Current: 514/320
• CPC Class Codes: A01N 1/0226 Physiologically active agents, i.e. substances affecting physiological processes of cells and tissue to be preserved, e.g. anti-oxidants or nutrients
• CPC Class Codes: A61K 31/453 containing a six-membered ring with oxygen as a ring hetero atom
• CPC Class Codes: A61K 31/713 Double-stranded nucleic acids or oligonucleotides
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis

Abstract

The present invention relates to the use of cyclin-dependent kinase 9 (CDK9) inhibitors to reduce, inhibit and/or prevent cartilage degradation. CDK9 inhibitors can be used to reduce, inhibit and/or prevent cartilage degradation and loss of cartilage viability during allograft storage. CDK9 inhibitors can be used as a post-injury intervention treatment to reduce, inhibit and/or prevent the acute cellular responses that lead to future cartilage degradation and osteoarthritis.

Claims

1. A method of reducing, preventing or inhibiting cartilage degradation and/or chondrocyte death in a subject in need thereof, comprising administering to the subject an effective amount of an inhibitor of cyclin-dependent kinase 9 (CDK9), thereby reducing, preventing or inhibiting cartilage degradation and/or chondrocyte death in the subject.

3. The method of claim 1, wherein the subject has experienced a traumatic injury to cartilage tissue.

4. The method of claim 3, wherein the subject has undergone joint surgery.

5. The method of claim 1, wherein the inhibitor of CDK9 is administered within 24 hours after experiencing traumatic injury.

6. The method of claim 1, wherein the subject has undergone surgery to repair damaged cartilage tissue.

7. The method of claim 1, wherein the subject has received an osteochondral explant.

8. The method of claim 7, wherein the osteochondral explant is a cartilage allograft.

9. The method of claim 1, wherein the inhibitor of CDK9 is administered concurrently with or prior to surgery.

10. The method of claim 1, wherein the inhibitor of CDK9 is administered within 24 hours after surgery.

11. The method of claim 1, wherein the inhibitor of CDK9 is administered systemically.

12. The method of claim 11, wherein the inhibitor of CDK9 is administered intravenously.

13. The method of claim 1, wherein the inhibitor of CDK9 is administered directly to the site of injured cartilage tissue.

14. The method of claim 13, wherein the inhibitor of CDK9 is delivered from a matrix.

15. The method of claim 1, wherein the inhibitor of CDK9 is a small organic compound.

16. The method of claim 15, wherein the inhibitor of CDK9 is flavopiridol.

17. The method of claim 1, wherein the inhibitor of CDK9 is an inhibitory nucleic acid.

2. A method of reducing, preventing, delaying or inhibiting the onset and/or progression of post-traumatic osteoarthritis in a subject in need thereof, comprising administering to the subject an effective amount of an inhibitor of cyclin-dependent kinase 9 (CDK9), thereby reducing, preventing or inhibiting post-traumatic osteoarthritis in the subject.

18. A method of reducing, preventing or inhibiting degradation of an osteochondral explant and/or reducing, preventing or inhibiting chondrocyte death during storage, comprising storing the osteochondral explant and/or chondrocytes in a solution comprising an effective amount of an inhibitor of cyclin-dependent kinase 9 (CDK9).

19-22. -22. (canceled)

23. A composition comprising an osteochondral explant in a solution comprising an inhibitor of cyclin-dependent kinase 9 (CDK9).

28. A kit comprising the composition of claim 23.

24-27. -27. (canceled)