Protease resistant mutants of stromal cell derived factor-1 in the repair of tissue damage

Patent metadata

Field	Value
Publication number	US-9631005-B2
Application number	US-201314039580-A
Country	US
Kind code	B2
Filing date	Sep 27, 2013
Priority date	Oct 23, 2006
Publication date	Apr 25, 2017
Grant date	Apr 25, 2017

Abstract

The present invention is directed stromal cell derived factor-1 peptides that have been mutated to make them resistant to digestion by the proteases dipeptidyl peptidase IV (DPPIV) and matrix metalloproteinase-2 (MMP-2) but which maintain the ability of native SDF-1 to attract T cells. The mutants may be attached to membranes formed by self-assembling peptides and then implanted at sites of tissue damage to help promote repair.

First claim

What is claimed is:

1. A method of treating a patient to promote the repair of damaged tissue, the method comprising administering locally to the damaged tissue an isolated mutant form of stromal cell derived factor-1 (SDF-1) peptide consisting of SEQ ID NO:54; and
wherein said mutant form of the SDF-1 peptide consisting of SEQ ID NO:54 has chemoattractant activity for T cells and is inactivated by matrix metalloproteinase-2 (MMP-2) at a rate that is less than one-half of the rate at which native SDF-1 peptide is inactivated, and said mutant form of the SDF-1 peptide consisting of SEQ ID NO:54 has chemoattractant activity for T cells and is inactivated by dipeptidyl peptidase IV (DPPIV) at a rate that is less than one-half of the rate at which native SDF-1 peptide is inactivated.

2. The method of claim 1 , wherein the mutant form of the SDP-1 peptide consisting of SEQ ID NO:54 maintains chemoattractant activity for T cells of at least 10% that of native SDF-1 peptide and is inactivated by MMP-2 at a rate that is less than one- fourth of the rate of inactivation of native SDF-1 peptide.

3. The method of claim 1 , wherein the damaged tissue is a wound.

4. The method of claim 3 , wherein the wound is from a diabetic ulcer.

5. The method of claim 1 , wherein the patient has had a stroke or limb ischemia or is at risk of having a stroke or limb ischemia.

6. The method of claim 1 , wherein the isolated mutant form of SDF-1 peptide is attached to a biologically compatible membrane or is attached to a self-assembling peptide that forms a biologically compatible membrane after administration locally to said damaged tissue.

Assignees

• Brigham & Womens Hospital Inc

Inventors

• Lee Richard T
• Segers Vincent

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P25/08

  Antiepileptics; Anticonvulsants · CPC title