Treatment of vascular, autoimmune and inflammatory diseases using low dosages of IMPDH inhibitors

• US 8,957,071 B2
• Filed: 05/05/2008
• Issued: 02/17/2015
• Est. Priority Date: 02/08/2005
• Status: Active Grant

• Current Assignee: Aspreva Pharmaceuticals Corporation (CSL Limited), Aspreva Pharmaceuticals S.A. (CSL Limited)
• Original Assignee: Aspreva Pharmaceuticals Corporation (CSL Limited), Aspreva Pharmaceuticals S.A. (CSL Limited)
• Inventors: Glickman, Richard, Hayden, Michael R., Hall, Noel
• Primary Examiner(s): PACKARD, BENJAMIN J
• Application Number:
  US12/115,464
• Publication Number:
  US 20090088427A1
• Time in Patent Office: 2,479 Days
• Field of Search: 514/232.5
• US Class Current: 514/232.5
• CPC Class Codes: A61K 31/343 condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
• CPC Class Codes: A61K 31/365 Lactones
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

The disclosure provides methods and compositions for treating a vascular, autoimmune, and/or inflammatory disease, or a condition associated therewith, with a dose of an inosine monophosphate dehydrogenase (IMPDH) inhibitor effective to treat the vascular, autoimmune and/or inflammatory disease, or associated condition but that does not produce immunosuppression sufficient to reduce the risk of allograft rejection. These lower doses of the immunosuppressant avoid the adverse consequences of severe immunosuppression while providing effective treatment of the vascular, autoimmune and/or inflammatory disease.

Claims

1. A method of treating atherosclerosis associated with a vascular, autoimmune and/or inflammatory disease, comprising administering to a human subject in need thereof an effective amount of mycophenolate mofetil (MMF), wherein the amount administered is less than 0.5 g/day.

2. The method of claim 1 in which the disease is a vascular disease.

3. The method of claim 1 in which the disease is an autoimmune disease.

4. The method of claim 3 in which the autoimmune disease is systemic lupus erythematosus (SLE), multiple sclerosis (MS), diabetes mellitus, or rheumatoid arthritis (RA).

5. The method of claim 1 in which the MMF is administered orally.

6. The method of claim 5 in which the MMF is administered once per day.

7. The method of claim 5 in which the MMF is administered twice per day.

8. The method of claim 1 in which the amount of MMF administered is about 0.05 to 2 mg/kg body weight/day.

9. The method of claim 8 in which the amount of MMF administered is about 0.05 to 0.30 mg/kg body weight/day.

10. The method of claim 8 in which the amount of MMF administered is about 0.05 to 0.50 mg/kg body weight/day.

11. The method of claim 8 in which the amount of MMF administered is about 0.05 to 0.90 mg/kg body weight/day.

12. The method of claim 8 in which the amount of MMF administered is about 0.05 to 1.50 mg/kg body weight/day.

13. The method of claim 1 in which the amount of MMF administered is about 1 to 4 mg/kg body weight/day.

14. The method of claim 13 in which the amount of MMF administered is about 1 to 2 mg/kg body weight/day.

15. The method of claim 13 in which the amount of MMF administered is about 1 to 3 mg/kg body weight/day.

16. The method of claim 1 in which the amount of MMF administered is 5 to 100 mg/day.

17. The method of claim 1 in which the amount of MMF administered is about 100, 125, 150, 175, 200, 225, 250, 300, 350, or 400 mg/day.

18. The method of claim 1 in which the amount of MMF administered is about 5, 10, 20, 25, 30, 40, 50, 60, 70, 75, 80, 90, or 100 mg/day.