COMPLEMENT INHIBITORY AGENTS AS THERAPEUTICS IN POSTTRAUMATIC AND DEGENERATIVE ARTHRITIS

• US 20090324585A1
• Filed: 06/11/2009
• Published: 12/31/2009
• Est. Priority Date: 06/12/2008
• Status: Abandoned Application

• Current Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.), United States of Government As Represented By The Department of Veterans Affairs, The Board of Regents of the University of Colorado (University of Colorado System)
• Original Assignee: The Trustees of The Leland Standford Junior University
• Inventors: Rozelle, Andrew L., Robinson, William H., Holers, V. Michael
• Application Number:
  US12/482,703
• Publication Number:
  US 20090324585A1
• Time in Patent Office: Days
• US Class Current: 514/1.1
• CPC Class Codes: A01K 2217/075 inducing loss of function, i.e. knock out
• CPC Class Codes: A01K 2217/15 Animals comprising multiple alterations of the genome, by transgenesis or homologous recombination, e.g. obtained by cross-breeding
• CPC Class Codes: A01K 2227/105 Murine
• CPC Class Codes: A01K 2267/03 Animal model, e.g. for test or diseases
• CPC Class Codes: A01K 2267/0368 Animal model for inflammation
• CPC Class Codes: A01K 67/0278 Knock-in vertebrates, e.g. humanised vertebrates
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 2039/545 characterised by the dose, timing or administration schedule
• CPC Class Codes: A61K 38/17 from animals; from humans enzyme inhibitors A61K38/005
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: C07K 16/18 against material from animals or humans

Abstract

The present disclosure is directed to methods and compositions for treating osteoarthritis and preventing osteoarthritis, by administering a compound that modulates one or more components in the complement system. In one embodiment, a compound that inhibits a component in the complement system is administered to prevent, delay the progression of, or treat osteoarthritis. In other embodiments, compounds with specific inhibition of a component in a particular pathway in the complement system, such as the alternative, mannose binding lectin, and/or classical pathway, are administered to a subject having osteoarthritis or at risk of developing osteoarthritis.

Claims

1. A method of treating a subject at risk of developing or currently having osteoarthritis, comprising

administering to the subject a complement inhibitor compound in a therapeutically effective amount

2. The method according to claim 1, wherein said administering is to a subject at risk for developing post-injury osteoarthritis.

3. The method according to claim 1, wherein said administering is to a subject with a genetic tendency to osteoarthritis.

4. The method according to claim 1, wherein said compound is an inhibitor of a molecule in the alternative complement pathway.

5. The method according to claim 1, wherein said compound is an inhibitor of a molecule in the classical complement pathway.

6. The method according to claim 1, wherein said compound is an inhibitor of a molecule in both the alternative and classical complement pathways.

7. The method according to claim 1, wherein said compound is an inhibitor of a molecule selected from C5, C5a, and C5b.

8. The method according to claim 1, wherein said compound is an inhibitor of the membrane attack complex.

9. The method according to claim 1, wherein the compound is a polypeptide.

10. The method according to claim 9, wherein the polypeptide is a CR2-Factor H fusion protein.

11. The method according to claim 9, wherein the polypeptide is a CR2-Crry fusion protein.

12. The method according to claim 1, wherein the compound is an antibody or functional fragment thereof.

13. The method according to claim 12, wherein the compound is an antibody specific for complement component C5.

14. The method according to claim 1, wherein the compound is a small molecule.

15. The method according to claim 1, wherein said compound prevents cleavage of a complement molecule to its fragments.

16. The method according to claim 15, wherein the compound prevents cleavage of C2, C3, C4, or C5.

17. The method according to claim 1, further comprising administering to the subject an anti-inflammatory agent, an analgesic, or a steroid.

18. The method according to claim 1, further comprising treating the patient with a physical therapy exercise.

19. A method of preventing, delaying, or reducing the probability of development of osteoarthritis in a human subject, comprising:

administering to the subject a complement inhibitor compound in a therapeutically effective amount.

20. A method of slowing or inhibiting the progression of osteoarthritis in a subject at risk of developing osteoarthritis or currently having osteoarthritis, comprising:

administering to the subject a complement inhibitor compound or a functional equivalent thereof in a prophylactically or therapeutically effective amount.