Methods of treatment using a pentapeptide derived from the C-Terminus of Glucagon-Like Peptide 1 (GLP-1)

• US 10,137,171 B2
• Filed: 01/19/2017
• Issued: 11/27/2018
• Est. Priority Date: 07/06/2011
• 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., Tomas-Falco, Eva
• Primary Examiner(s): Cordero Garcia, Marcela M
• Assistant Examiner(s): Lee, Jia-Hai
• Application Number:
  US15/410,703
• Publication Number:
  US 20170136095A1
• Time in Patent Office: 677 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: A61K 38/08 Peptides having 5 to 11 amino acids A61K38/043 - A61K38/046 take precedence
• CPC Class Codes: A61K 38/26 Glucagons
• 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: C07K 14/605 Glucagons
• CPC Class Codes: C07K 2319/01 containing a localisation/targetting motif
• CPC Class Codes: C07K 2319/10 containing a tag for extracellular membrane crossing, e.g. TAT or VP22

Abstract

Methods of treating obesity, metabolic syndrome, hepatic and non-hepatic steatosis, and diabetes using a pentapeptide, LVKGRamide, derived from the C-terminus of Glucagon-Like Peptide 1 (GLP-1).

Claims

1. A method of treating obesity, metabolic syndrome, hepatic steatosis, non-hepatic steatosis, hypertriglyceridemia, or diabetes in a subject, the method comprising administering a therapeutically effective amount of a composition comprising an isolated peptide consisting of a sequence

2. The method of claim 1, wherein the subject is obese.

3. The method of claim 1, wherein the subject is obese due to consumption of a high fat diet.

4. The method of claim 1, wherein the C terminus of the isolated peptide is an Arg and the peptide is amidated.

5. The method of claim 1, wherein one or more amino acids of the isolated peptide are modified by attachment of a fatty acid.

6. The method of claim 5, wherein the fatty acid is selected from the group consisting of palmitate and oleate.

7. The method of claim 1, wherein Xaa is absent.

8. The method of claim 1, wherein Xaa is Gly.

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

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

11. The method of claim 1, wherein the isolated peptide is fused to a cell-penetrating peptide.

12. The method of claim 11, wherein the cell-penetrating peptide is fused on the C-terminus of the peptide of SEQ ID NO:

3.

13. The method of claim 11, wherein the cell-penetrating peptide is selected from the group consisting of HIV-derived TAT peptide, penetratins, transportans, SS peptides, and hCT derived cell-penetrating peptides.