Human appetite control by glucagon-like peptide receptor binding compounds

• US 6,998,387 B1
• Filed: 03/16/1999
• Issued: 02/14/2006
• Est. Priority Date: 03/19/1998
• Status: Expired due to Term

• Current Assignee: Astrazeneca Pharmaceuticals LP (Astrazeneca PLC)
• Original Assignee: Amylin Pharmaceuticals Incorporated (Bristol-Myers Squibb Company)
• Inventors: Coolidge, Thomas R., Beglinger, Christoph, Goke, Burkhard
• Primary Examiner(s): Weber, Jon
• Assistant Examiner(s): Mohamed, Abdel A.
• Application Number:
  US09/646,433
• Time in Patent Office: 2,527 Days
• Field of Search: 514/12, 514/909, 530/308, 530/324
• US Class Current: 514/6.9
• CPC Class Codes: A61K 38/26 Glucagons

Abstract

A composition including a compound which binds to a receptor for glucagon-like peptide-1 and a pharmaceutical carrier. The amount of the compound present is effective to control appetite in a human. Also disclosed is a method for controlling appetite and for reducing food intake in a human by administering to the human a composition comprising a compound which binds to a receptor for glucagon-like peptide-1 and a pharmaceutical carrier.

Claims

1. A method for controlling appetite in a human comprising:

peripherally administering to a human a compound which binds to a receptor for glucagon-like peptide-1 and a pharmaceutical carrier, wherein said compound comprises GLP-1 (1–

37), GLP-1 (7–

37), GLP-1 (7–

36) or a biologically active analog of GLP-1 (1–

37), GLP-1 (7–

37), GLP-1 (7–

36) in an amount effective to control appetite in a human, wherein said biologically active analog of GLP-1 (1–

37), GLP-1 (7–

37), GLP-1 (7–

36) contains one or more substitutions, deletions or insertions of not more than five amino acids from the amino acid sequence of GLP-1 (1–

37), GLP-1 (7–

37), or GLP-1 (7–

36).

2. The method of claim 1 wherein the receptor-binding compound is glucagon-like peptide-1 (7–

37) comprising the sequence His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly Gln Ala Ala Lys Glu Phe His Ala Trp Leu Val Lys Gly Arg Gly (SEQ ID NO;

3).

3. The method of claim 1 wherein the receptor-binding compound is glucagon-like peptide-1 (7–

36) amide comprising the sequence His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly Gln Ala Ala Lys Glu Phe His Ala Trp Leu Val Lys Gly Arg (NH₂) (SEQ ID NO;

4).

4. The method of claim 1 wherein said administering comprises providing a graded dose regimen of doses in the range of from about 0.315 to about 2.0 pmol/kg per minute.

5. The method of claim 1 wherein said administering is in a manner selected from the group consisting of intravenous administration, single subcutaneous shot, continuous subcutaneous administration, a regimen of multiple subcutaneous injections, micropressure injection system, ambulatory pump, depot sustained-release injection, implant, deep lung sustained-release insufflation, skin patch, buccal patch and a sustained-release oral delivery dose form.

6. The method of claim 5 wherein said intravenous administration is in a dose range of from about 0.1 pmol to about 5.0 pmol/kg min.

7. The method of claim 5 wherein said single subcutaneous shot administration is in a dose range of from about 0.1 to about 5.0 nmol/kg.

8. The method of claim 5 wherein said continuous subcutaneous administration is in a dose range of from about 0.2 pmol to about 20 pmol/kg min.

9. A method for reducing food intake in a human comprising:

peripherally administering to a human a compound which binds to the receptor for glucagon-like peptide-1 and a pharmaceutical carrier, wherein said compound comprises GLP-1 (1–

37), GLP-1 (7–

37), GLP-1 (7–

36) or a biologically active analog of GLP-1 (1–

37), GLP-1 (7–

37), a human, wherein said biologically active analog of GLP-1 (1–

37), GLP-1 (7–

37), GLP-1(7–

36) contains one or more substitutions, deletions or insertions of not more than five amino acids from the amino acid sequence of GLP-1 (1–

37), GLP-1 (7–

37), or GLP-1 (7–

36).

10. The method of claim 9 wherein the receptor-binding compound is glucagon-like peptide-1 (7–

37) comprising the sequence His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly Gln Ala Ala Lys Glu Phe His Ala Trp Leu Val Lys Gly Arg Gly (SEQ ID NO;

3).

11. The method of claim 9 wherein the receptor-binding compound is glucagon-like peptide-1 (7–

36) amide comprising the sequence His Ala Glu Gly Thr Phe Thr Ser Asp Val Ser Ser Tyr Leu Glu Gly Gln Ala Ala Lys Glu Phe His Ala Trp Leu Val Lys Gly Arg (NH₂) (SEQ ID NO;

4).

12. The method of claim 9 wherein said administering comprises providing a graded dose regimen of doses in the range of from about 0.1 to about 20 pmol/kg per minute.

13. The method of claim 9 wherein the compound is effective to reduce spontaneous food intake in a human.

14. The method of claim 9 wherein said administering is in a manner selected from the group consisting of intravenous administration, single subcutaneous shot, continuous subcutaneous administration, a regimen of multiple subcutaneous injections, micropressure injection system, ambulatory pump, depot sustained-release injection, implant, deep lung sustained-release insufflation, skin patch, buccal patch and a sustained-release oral delivery dose form.

15. The method of claim 14 wherein said intravenous administration is in a dose range of from about 0.1 pmol to about 5.0 pmol/kg min.

16. The method of claim 14 wherein said single subcutaneous shot administration is in a dose range of from about 0.1 to about 5.0 nmol/kg.

17. The method of claim 14 wherein said continuous subcutaneous administration is in a dose range of from about 1.0 pmol to about 10 pmol/kg min.

18. A method for controlling appetite in a human with diabetes comprising:

peripherally administering to a human having diabetes a compound which binds to the receptor for glucagon-like peptide-1 and a pharmaceutical carrier, wherein said compound comprises GLP-1 (1–

37), GLP-1 (7–

37), GLP-1 (7–

36) or a biologically active analog of GLP-1 (1–

37), GLP-1 (7–

37), GLP-1 (7–

36) in an amount effective to control appetite in a human with diabetes, wherein said biologically active analog of GLP-1 (1–

37), GLP-1 (7–

37), GLP-1 (7–

36) contains one or more substitutions, deletions or insertions of not more than five amino acids from the amino acid sequence of GLP-1 (1–

37), GLP-1 (7–

37), or GLP-1 (7–

36).

19. A composition for suppressing appetite in a human comprising:

a compound prepared for intravenous administration in a dose range of from about 0.1 pmol to about 5.0 pmol/kg min which binds to a receptor for glucagon-like peptide-1, and a pharmaceutical carrier, wherein said compound comprises GLP-1(1–

37), GLP-1 (7–

37), GLP-1 (7–

36) or a biologically active analog of GLP-1 (1–

37), GLP-1 (7–

37), GLP-1 (7–

36) wherein said biologically active analog of GLP-1 (1–

37), GLP-1 (7–

37), GLP-1 (7–

36) contains one or more substitutions deletions or insertions of not more than five amino acids from the amino acid sequence of GLP-1 (1–

37), GLP-1 (7–

37), or GLP-1 (7–

36).