Ang (1-7) derivative oligopeptides and methods for using and producing the same

Patent metadata

Field	Value
Publication number	US-11104706-B2
Application number	US-202016751120-A
Country	US
Kind code	B2
Filing date	Jan 23, 2020
Priority date	Jul 21, 2014
Publication date	Aug 31, 2021
Grant date	Aug 31, 2021

Abstract

The present invention provides oligopeptides, in particular, Ang-(1-7) derivatives, and methods for using and producing the same. In one particular embodiment, oligopeptides of the invention have higher blood-brain barrier penetration and/or in vivo half-life compared to the native Ang-(1-7), thereby allowing oligopeptides of the invention to be used in a wide variety of clinical applications including in treatment of cognitive dysfunction and/of impairment.

First claim

What is claimed is:

1. A method for treating cognitive dysfunction in a subject diagnosed as having a cognitive dysfunction comprising systemically administering to the subject a therapeutically effective amount of an octapeptide having the formula: A1-A2-A3-A4-A5-A6-A7-A8 (SEQ ID NO:1) wherein
A1 is aspartic acid;
A2 is arginine;
A3 is valine;
A4 is tyrosine;
A5 is isoleucine;
A6 is histidine;
A7 is proline; and
A8 is serine or glycosylated forms thereof.

2. The method of claim 1 , wherein the octapeptide comprises a monosaccharide or a disaccharide.

3. The method of claim 2 , wherein at least one of the monosaccharides or disaccharides is selected from the group consisting of glucose, galactose, xylose, fucose, rhamnose, lactose, cellobiose, and melibiose.

4. The method of claim 1 , wherein A8 is a serine that is terminated with an amino group.

5. The method of claim 4 , wherein A8 is a glycosylated serine that is terminated with an amino group.

6. The method of claim 1 , wherein the octapeptide has the formula of SEQ ID NO: 7, SEQ ID NO: 8, or SEQ ID NO:9.

7. The method of claim 1 , wherein the octapeptide comprises at least one D-amino acid.

8. The method of claim 1 , wherein the subject is diagnosed as having congestive heart failure.

9. The method of claim 1 , wherein the subject is diagnosed as having cardiovascular disease or hypertension.

10. The method of claim 1 , wherein the subject is diagnosed as having post-surgery dementia.

11. The method of claim 1 , wherein the subject is diagnosed as having dementia, Alzheimer's disease, trauma related cognitive impairment, age-related dementia, or post-operative delirium.

12. The method of claim 1 , wherein the octapeptide is administered to the subject by intravenous, intramuscular, or subcutaneous injection.

13. The method of claim 1 , wherein the octapeptide is administered to the subject by nasal insufflation.

14. The method of claim 1 , where in the cognitive dysfunction is caused by brain inflammation.

Assignees

• Univ Arizona

Inventors

• Hay Meredith
• Konhilas John
• Polt Robin L
• Jones Evan
• Szabo Lajos

Classifications

• C07K7/06 Primary

  having 5 to 11 amino acids · CPC title

• C07K9/001

  the peptide sequence having less than 12 amino acids and not being part of a ring structure · CPC title

• A61K38/085

  Angiotensins · CPC title

• A61K38/00

  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 title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title