Use of leptin for treating human lipoatrophy and method of determining predisposition to said treatment

• US 7,183,254 B2
• Filed: 07/18/2003
• Issued: 02/27/2007
• Est. Priority Date: 10/22/2001
• Status: Active Grant

• Current Assignee: Amgen Inc., The United States of America As Represented By The Secretary of Agriculture, United States Secretary of Health and Human Services is the head of the United States Department of Health and Human Services, Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Amgen Inc.
• Inventors: Oral, Elif A., DePaoli, Alexander M., Taylor, Simeon I., Garg, Abhimanyu
• Primary Examiner(s): O'Hara; Eileen B.
• Application Number:
  US10/623,189
• Publication Number:
  US 20050020496A1
• Time in Patent Office: 1,320 Days
• Field of Search: None
• US Class Current: 514/1.9
• 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 a human patient with a condition of lipoatrophy, which comprises administering to the patient a dose of leptin, leptin analog or leptin derivative effective to treat the condition of lipoatrophy.

2. The method of claim 1, wherein said leptin, leptin analog or leptin derivative is administered together with a pharmaceutically acceptable carrier.

3. The method of claim 1, wherein said leptin, leptin analog or leptin derivative is administered in a pharmaceutically acceptable diluent.

4. The method of claim 1, wherein the patient has a leptin level of 4 ng/ml or less before administration of leptin, leptin analog, or leptin derivative.

5. The method of claim 4, wherein the patient has a leptin level of 2 ng/ml or less before administration of leptin, leptin analog, or leptin derivative.

6. The method of claim 1, wherein the patient has an acquired form of lipoatrophy.

7. The method of claim 6, wherein the patient is HIV positive.

8. The method of claim 7, wherein the acquired form of lipoatrophy is related to treating the HIV positive patient with highly active antiretroviral therapy (HAART).

9. The method of claim 1, wherein the patient has a genetic form of lipoatrophy.

10. The method of claim 9, wherein the genetic form of lipoatrophy is congenital generalized lipoatrophy.

11. The method of claim 1, wherein the condition of lipoatrophy comprises metabolic abnormalities.

12. The method of claim 11, wherein the metabolic abnormalities are selected from a group consisting of hyperglycemia, dyslipidemia, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, atherosclerosis, vascular restenosis, and insulin resistance.

13. The method of claim 11, wherein the metabolic abnormalities comprise diabetes.

14. The method of claim 11, wherein the metabolic abnormalities comprise insulin resistance.

15. The method of claim 11, wherein the metabolic abnormalities comprise hypertriglyceridemia.

16. The method of claim 1, wherein the condition of lipoatrophy comprises hepatomegaly.

17. The method of claim 1, wherein the condition of lipoatrophy comprises an abnormality in the distribution of fat tissue.

18. The method of claim 1, wherein said leptin, leptin analog, or leptin derivative is administered subcutaneously.

19. The method of claim 18, wherein the leptin is selected from the group consisting of recombinant human leptin of SEQ ID NO:

1 and SEQ ID NO;

2.

20. The method of claim 19, wherein said leptin is administered together with a pharmaceutically acceptable carrier.

21. The method of claim 19, wherein said leptin is administered in a pharmaceutically acceptable diluent.

22. The method of claim 1, wherein said leptin is recombinant human leptin.

23. The method of claim 22, wherein said recombinant human leptin is SEQ ID NO:

1.

24. A method of determining a predisposition of a lipoatrophic patient to respond to treatment with leptin, leptin analog, or leptin derivative, the method comprising:

(a) determining a leptin level in the patient prior to said treatment; and

(b) ascertaining whether the leptin level is less than or equal to approximately 4 ng/ml.

25. The method of claim 24, wherein said patient is a male and said leptin level is less than or equal to approximately 2 ng/ml prior to treatment.

26. The method of claim 24, wherein said patient is a female.

27. A method of determining a predisposition of a lipoatrophic patient to respond to treatment with leptin, leptin analog, or leptin derivative, the method comprising:

(a) determining a leptin level in the patient prior to said treatment; and

(b) ascertaining whether the leptin level of (i) a male patient is less than or equal to approximately 2 ng/ml, or (ii) a female patient is less than or equal to approximately 4 ng/ml.

28. A method for treating a patient with a condition of lipoatrophy, comprising administering to the patient a pharmaceutical regimen comprising a combination of protease inhibitor and leptin, leptin analog, or leptin derivative effective to treat the condition of lipoatrophy.

29. A method for treating a patient with a condition of lipoatrophy, comprising administering to the patient a pharmaceutical regimen comprising a combination of leptin, leptin analog, or leptin derivative and at least one compound selected from the group consisting of thiazolidinediones, fibrates, statins and metformin, wherein the regimen is effective to treat the condition of lipoatrophy.

30. A method of treating a human with a metabolic abnormality associated with lipoatrophy, comprising administering leptin, leptin analog, or leptin derivative at a dose effective to treat the metabolic abnormality associated with lipoatrophy.