C-terminal fragments of glucagon-like peptide-1 (GLP-1)

• US 10,118,955 B2
• Filed: 11/12/2014
• Issued: 11/06/2018
• Est. Priority Date: 11/07/2008
• Status: Active Grant

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Habener, Joel F., Yano, Tatsuya, Falco, Eva Tomas
• Primary Examiner(s): Bradley, Christina
• Assistant Examiner(s): Miknis, Zachary J
• Application Number:
  US14/539,578
• Publication Number:
  US 20150133384A1
• Time in Patent Office: 1,455 Days
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• 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 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 7/12 Antidiuretics, e.g. drugs for diabetes insipidus ADH A61P5/10
• CPC Class Codes: C07K 14/005 from viruses
• CPC Class Codes: C07K 14/605 Glucagons
• CPC Class Codes: C07K 2319/10 containing a tag for extracellular membrane crossing, e.g. TAT or VP22
• CPC Class Codes: C12N 2740/16033 Use of viral protein as therapeutic agent other than vaccine, e.g. apoptosis inducing or anti-inflammatory
• CPC Class Codes: C12N 7/00 Viruses; Bacteriophages; Compositions thereof; Preparation or purification thereof preparing medicinal viral antigen or antibody compositions, e.g. virus vaccines, A61K39/00

Abstract

C-Terminal Fragments of Glucagon-Like Peptide-1 (GLP 1), and methods of use thereof, e.g., for the treatment of obesity and obesity-related disorders, e.g., diabetes and the metabolic syndrome.

Claims

1. A method of treating metabolic syndrome in a subject, the method comprising administering to the subject a therapeutically effective amount of a peptide consisting of the amino acid sequence of (Phe/Tyr)-Ile-Ala-Trp-Leu-Val-(Lys/Arg)-Gly-Arg-Xaa (SEQ ID NO:

1), wherein Xaa is Gly-Arg or Gly-Arg-Gly, wherein one or more amino acids of the peptide are alkylated, acylated, or biotinylated.

2. The method of claim 1, wherein the peptide is amidated.

11. The method of claim 1, wherein Xaa is Gly-Arg.

15. The method of claim 1, wherein Xaa is Gly-Arg-Gly.

3. A method of treating obesity in a subject, the method comprising administering to the subject a therapeutically effective amount of a peptide consisting of the amino acid sequence of (Phe/Tyr)-Ile-Ala-Trp-Leu-Val-(Lys/Arg)-Gly-Arg-Xaa (SEQ ID NO:

1), wherein Xaa is Gly-Arg or Gly-Arg-Gly, wherein one or more amino acids of the peptide are alkylated, acylated, or biotinylated.

4. The method of claim 3, wherein the peptide is amidated.

12. The method of claim 3, wherein Xaa is Gly-Arg.

16. The method of claim 3, wherein Xaa is Gly-Arg-Gly.

5. A method of treating metabolic syndrome in a subject, the method comprising administering to the subject a therapeutically effective amount of a fusion peptide comprising a first portion consisting of the amino acid sequence of (Phe/Tyr)-Ile-Ala-Trp-Leu-Val-(Lys/Arg)-Gly-Arg-Xaa (SEQ ID NO:

1), wherein Xaa is Gly-Arg or Gly-Arg-Gly, fused to a cell-penetrating peptide, wherein one or more amino acids of the fusion peptide are alkylated, acylated, or biotinylated.

6. The method of claim 5, wherein the cell-penetrating peptide is fused to the C-terminus of the first portion.

7. The method of claim 5, wherein the cell-penetrating peptide is selected from the group consisting of HIV-derived TAT peptides, penetratins, transportans, SS peptides, and hCT derived cell-penetrating peptides.

13. The method of claim 5, wherein Xaa is Gly-Arg.

17. The method of claim 5, wherein Xaa is Gly-Arg-Gly.

8. A method of treating obesity in a subject, the method comprising administering to the subject a therapeutically effective amount of a fusion peptide comprising a first portion consisting of the amino acid sequence of (Phe/Tyr)-Ile-Ala-Trp-Leu-Val-(Lys/Arg)-Gly-Arg-Xaa (SEQ ID NO:

1), wherein Xaa is Gly-Arg or Gly-Arg-Gly, fused to a cell-penetrating peptide, wherein one or more amino acids of the fusion peptide are alkylated, acylated, or biotinylated.

9. The method of claim 8, wherein the cell-penetrating peptide is fused to the C-terminus of the first portion.

10. The method of claim 8, wherein the cell-penetrating peptide is selected from the group consisting of HIV-derived TAT peptides, penetratins, transportans, SS peptides, and hCT derived cell-penetrating peptides.

14. The method of claim 8, wherein Xaa is Gly-Arg.

18. The method of claim 8, wherein Xaa is Gly-Arg-Gly.