Proteoglycan mimetics for enhanced wound healing, angiogenesis, and vascular repair

Patent metadata

Field	Value
Publication number	US-12485182-B2
Application number	US-202318168792-A
Country	US
Kind code	B2
Filing date	Feb 14, 2023
Priority date	Apr 5, 2018
Publication date	Dec 2, 2025
Grant date	Dec 2, 2025

Abstract

The present disclosure provides pro-angiogenic proteoglycan mimetics that can provide a provisional, pro-angiogenic scaffold to support tissue regeneration while limiting systemic exposure to VEGF activity. These mimetics can protect a collagen matrix from rapid degradation, and in conjunction with EPCs promote angiogenesis in order to accelerate ischemic wound healing. For example, the provided compounds can be delivered from the end of a catheter following balloon angioplasty to coat the collagen exposed areas, prevent platelet binding and thrombosis, support capture of EPCs from blood to facilitate reendothelialization, and reduce late-lumen loss (neointimal hyperplasia).

First claim

What is claimed is:

1 . A method for improving endothelialization and vascularization of endothelial cells and/or endothelial progenitor cells in a subject, the method comprising administering to the subject a composition comprising a first compound, the first compound comprising:
one or more P1 subunits, wherein P1 is a synthetic peptide comprising the amino acid sequence RRANAALKAGELYKSILY (SEQ ID NO: 1) or a conservatively modified variant sequence having at least 80% sequence identity with the amino acid sequence RRANAALKAGELYKSILY (SEQ ID NO: 1); and one or more P2 subunits, wherein P2 is cGRGDdvc (LXW7), or peg2V.

2 . The method of claim 1 , wherein P 1 is a synthetic peptide comprising the amino acid sequence RRANAALKAGELYKSILY (SEQ ID NO: 1).

3 . The method of claim 1 , wherein P 1 is a synthetic peptide of up to 40 amino acids comprising the amino acid sequence RRANAALKAGELYKSILY (SEQ ID NO: 1).

4 . The method of claim 1 , wherein P2 is LXW7.

5 . The method of claim 1 , wherein P2 is peg2V.

6 . The method of claim 1 , wherein the method further comprises administering to the subject a second compound comprising:
one or more P1 subunits; one or more P2 subunits; and a glycan, wherein each P1 subunit and each P2 subunit is linked to the glycan.

7 . The method of claim 6 , wherein the glycan is a glycosaminoglycan or polysaccharide.

8 . The method of claim 7 , wherein the glycan is alginate, agarose, dextran, chondroitin, dermatan, dermatan sulfate, heparan, heparin, keratin, or hyaluronan.

9 . The method of claim 8 , wherein the glycan is dermatan sulfate, dextran, or heparin.

10 . The method of claim 1 , wherein the composition comprises one or more pharmaceutically acceptable excipients, diluents, or a combination thereof.

11 . The method of claim 1 , wherein the subject is a patient suffering from a disease associated with endothelial dysfunction.

12 . The method of claim 11 , wherein the disease is an ulcer.

13 . The method of claim 1 , wherein the subject is in need of coronary stenting.

Assignees

• Univ California
• Purdue Research Foundation

Inventors

• Panitch Alyssa
• Misnick Emily Michelle
• Lin Jenny B
• Lam Kit S
• Liu Ruiwu
• Hao Dake
• Wang Aijun

Classifications

• C07K7/08

  having 12 to 20 amino acids (gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68) · CPC title

• C07K7/06

  having 5 to 11 amino acids · 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

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61K47/60

  the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol · CPC title