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Last Updated: March 29, 2024

Details for Patent: 6,872,700


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Title: Methods for glucagon suppression
Abstract:Methods for use of an exendin, an exendin agonist, or a modified exendin or exendin agonist having an exendin or exendin agonist linked to one or more polyethylene glycol polymers, for example, for lowering glucagon levels and/or suppressing glucagon secretion in a subject are provide. These methods are useful in treating hyperglucagonemia and other conditions that would be benefited by lowering plasma glucagon or suppressing glucagon secretion.
Inventor(s): Young; Andrew A. (La Jolla, CA), Gedulin; Bronislava (San Diego, CA)
Assignee: Amylin Pharmaceuticals, Inc. (San Diego, CA)
Filing Date:Dec 18, 2001
Application Number:09/889,331
Claims:1. A method of lowering plasma glucagon in a subject in need thereof, comprising: identifying a subject in need of therapeutic lowering of plasma glucagon levels; and administering to said subject a composition comprising a therapeutically effective glucagon lowering amount of an exendin, an exendin analog or combinations thereof; wherein said exendin and exendin analog each have amino acid sequence that is more than 30 amino acid residues in length.

2. The method of claim 1, wherein said subject is suffering from nocrolytic migratory erythema.

3. The method of claim 1, wherein said subject has a glucagonoma.

4. The method of claim 1, wherein the subject has a diabetes-related disorder.

5. The method of claim 4, wherein the subject has type 2 diabetes.

6. The method of any of claims 1-5, wherein said subject is a human.

7. The method of claim 1, wherein said composition is provided in a dosage unit form and further comprises another anti-glucagon agent.

8. The method of claim 1, wherein said composition comprises an exendin analog having an amino acid sequence selected from the sequences of SEQ ID NO: 47 and SEQ ID NO: 48.

9. The method of claim 8, wherein said amino acid sequence has a sequence of SEQ ID NO: 47, wherein the Xaa in position 1 is His; the Xaa in position 2 is Gly, the Xaa in position 6 is Phe or naphthylalanine; the Xaa in position 14 is Leu, pentylglycine or Met; the Xaa in position 22 is Phe or naphthylalanine; the Xaa in position 23 is Ile or Val; the Xaa in position 25 is Phe, Tyr, or naphthylalanine; the Xaa in positions 31, 36, 37, and 38 are independently selected from Pro, homoproline, thioproline, and N-alkylalanine; and the Xaa in position 39 is Ser or Tyr.

10. The method of claim 8, wherein said amino acid sequence has a sequence of SEQ ID NO: 47, wherein the Xaa in position 14 is Leu or pentylglycine; and the Xaa in position 22 is Phe or naphthylalanine.

11. The method of claim 8, wherein said amino acid sequence has a sequence of SEQ ID NO: 48, wherein the Xaa in positions 6 and 22 are independently selected from Phe and naphthylalanine; the Xaa in position 23 is Ile or Val; and the Xaa in positions 30, 36, 37, and 38 are independently selected from Pro, homoproline, thioproline, and N-alkylalanine.

12. The method of claim 1, wherein said composition comprises exendin-4.

13. A method of lowering plasma glucagon in a subject, comprising: identifying a subject in need of therapeutic lowering of plasma glucagon levels; and administering to said subject a composition consisting essentially of a therapeutically glucagon lowering amount of an exendin, an exendin analog or combinations thereof; wherein said exendin and exendin analog each have an amino acid sequence that is more than 30 amino acid residues in length.

14. The method of claim 13, wherein said subject is suffering from necrolytic migratory erythema.

15. The method of claim 13, wherein said subject has a glucaganoma.

16. The method of claim 13, wherein said composition consists essentially of exendin-4.

17. The method of claim 7, wherein said anti-glucagon agent comprises amylin.

18. The method of claim 13, wherein the subject has a diabetes-related disorder.

19. The method of claim 18, wherein the subject has type 2 diabetes.

20. The method of any of claims 13-19, wherein said subject is a human.

21. The method of claim 13, wherein said composition consists essentially of an exendin analog having an amino acid sequence selected from the sequences of SEQ ID NO: 47 and SEQ ID NO: 48.

22. The method of claim 21, wherein said amino acid sequence has a sequence of SEQ ID NO: 47, wherein the Xaa in position 1 is His; the Xaa in position 2 is Gly; the Xaa in position 6 is Phe or naphthylalanine; the Xaa in position 14 is Leu, pentylglycine or Met; the Xaa in position 22 is Phe or naphthylalanine; the Xaa in position 23 is Ile or Val; the Xaa in position 25 is Phe, Tyr, or naphthylalanine; the Xaa in positions 31, 36, 37, and 38 are independently selected from Pro, homoproline, thioproline, and N-alkylalanine; and the Xaa in position 39 is Ser or Tyr.

23. The method of claim 21, wherein said amino acid sequence has a sequence of SEQ ID NO: 47, wherein the Xaa in position 14 is Leu pentylglycine, and the Xaa in position 22 is Phe or naphthylalanine.

24. The method of claim 21, wherein said amino acid sequence has a sequence of SEQ ID NO: 48, wherein the Xaa in positions 6 and 22 are independently selected from Phe and naphthylalanine; the Xaa in position 23 is Ile or Val; and the Xaa in positions 30, 36, 37, and 38 are independently selected from Pro, homoproline, thioproline, and N-alkylalanine.

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