Use of leptin to treat metabolic abnormalities associated with lipoatrophy

• US 8,318,666 B2
• Filed: 05/09/2011
• Issued: 11/27/2012
• Est. Priority Date: 10/22/2001
• Status: Expired due to Term

• Current Assignee: Amgen Inc., The United States of America As Represented By The Secretary of Agriculture, Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Amgen Inc., United States Department Of Health And Human Services, Board of Regents of the University of Texas System (University of Texas System)
• Inventors: DePaoli, Alexander M., Taylor, Simeon I., Garg, Abhimanyu, Oral, Elif Arioglu
• Primary Examiner(s): Chandra, Gyan
• Application Number:
  US13/103,294
• Publication Number:
  US 20110306540A1
• Time in Patent Office: 568 Days
• Field of Search: None
• US Class Current: 514/5.8
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 31/426 1,3-Thiazoles
• CPC Class Codes: A61K 38/2264 Obesity-gene products, e.g. leptin
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 Antihyperlipidemics
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• 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
• CPC Class Codes: G01N 33/68 involving proteins, peptides or amino acids involving lipoproteins G01N33/92
• CPC Class Codes: G01N 33/74 involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors

Abstract

Leptin, leptin analogs, and leptin derivatives are used to treat patients with lipoatrophy. Leptin is effective against conditions of lipoatrophy for both genetic and acquired forms of the disease. A therapeutically effective amount of leptin can be administered in a variety of ways, including subcutaneously and using gene therapy methods. Methods of the present invention contemplate administration of leptin, leptin analogs, and leptin derivatives to patients having a leptin level of approximately 4 ng/ml or less before treatment.

Claims

1. A method of treating diabetes associated with an inherited or an acquired form of lipoatrophy in a human in need thereof comprising administering to the human a therapeutically effective amount of recombinant methionyl human leptin to treat the diabetes.

2. The method of claim 1, wherein the human has a leptin level of 4 ng/mi or less before administration of recombinant methionyl human leptin.

3. The method of claim 1, wherein the human has a leptin level of 2 ng/ml or less before administration of recombinant methionyl human leptin.

4. The method of claim 1, wherein the lipoatrophy is an acquired form of lipoatrophy.

5. The method of claim 1, wherein the lipoatrophy is an inherited, form of lipoatrophy.

6. The method of claim 5, wherein the inherited form of lipoatrophy is congenital generalized, lipoatrophy or familial partial lipodystrophy (FPLD).

7. The method of claim 1, wherein the recombinant methionyl human leptin is administered subcutaneously.

8. The method of claim 1, wherein the recombinant methionyl human leptin is administered together with at least one of a pharmaceutically acceptable carrier and a pharmaceutically acceptable diluent.

9. The method of claim 1, wherein the method further comprises administering at least one compound selected from the group consisting of a thiazolidinedione, a fibrate, a statin and metformin.

10. A method of treating hypertriglyceridemia associated with an inherited or an acquired form of lipoatrophy in a human in need thereof comprising administering to the human a therapeutically effective amount of recombinant methionyl human leptin to treat the hypertriglyceridemia.

11. The method of claim 10, wherein the human has a leptin level of 4 ng/ml or less before administration of recombinant methionyl human leptin.

12. The method of claim 10, wherein the human has a leptin level of 2 ng/ml or less before administration of recombinant methionyl human leptin.

13. The method of claim 10, wherein the lipoatrophy is an acquired form of lipoatrophy.

14. The method of claim 10, wherein the lipoatrophy is an inherited form of lipoatrophy.

15. The method of claim 10, Wherein the recombinant methionyl human leptin is administered subcutaneously.

16. The method of claim 10, wherein the recombinant methionyl human leptin is administered together with at least one of a pharmaceutically acceptable carrier and a pharmaceutically acceptable diluent.

17. The method of claim 10, wherein the method further comprises administering at least one compound selected from the group consisting of a thiazolidinedione, fibrate, a statin and metformin.

18. A method of treating a metabolic abnormality associated with an inherited or an acquired fowl of lipoatrophy in a human in need thereof comprising administering to the human a therapeutically effective amount of recombinant methionyl human leptin to treat the metabolic abnormality.

19. The method of claim 18, wherein the human has a leptin, level of 4 ng/ml or less before administration of recombinant methionyl human leptin.

20. The method of claim 18, wherein the human has a leptin level of 2 ng/ml or less before administration of recombinant meihionyl human leptin.

21. The method of claim 18, wherein the lipoatrophy is an acquired form of lipoatrophy.

22. The method of claim 18, wherein the lipoatrophy is an inherited form of lipoatrophy.

23. The method of claim 18, wherein the metabolic abnormality is diabetes, hypertriglyceridemia, hyperglycemia, dyslipidemia, hyperlipidemia, hypercholesterolemia, atherosclerosis, restenosis, fatty liver, steatohepatitis, hepatomegaly, or insulin resistance.

24. The method of claim 18, wherein the metabolic abnormality is dyslipidemia.

25. The method of claim 18, wherein the metabolic abnormality is hyperlipidemia.

26. The method of claim 18, wherein the metabolic abnormality is hypercholesterolemia.

27. The method of claim 18, wherein the metabolic abnormality is atherosclerosis.

28. The method of claim 18, wherein the metabolic abnormality is vascular restenosis.

29. The method of claim 18, wherein the metabolic abnormality is fatty liver.

30. The method of claim 18, wherein the metabolic abnormality is steatohepatitis.

31. The method of claim 18, wherein the metabolic abnormality is hepatomegaly.

32. The method of claim 18, wherein the metabolic abnormality is insulin resistance.

33. The method of claim 18, wherein the recombinant methionyl human leptin is administered subcutaneously.

34. The method of claim 18, wherein the recombinant methionyl human leptin is administered together with at least one of a pharmaceutically acceptable carrier and a pharmaceutically acceptable diluent.

35. The method of claim 18, wherein the method further comprises administering at least one compound selected from the group consisting of a thiazolidinedione, a fibrate, a statin and metformin.