Pro-angiogenic peptides and uses thereof

Abstract

This present invention is directed to peptides, compositions, and methods for modulating endogenous cytokine expression in a subject. More specifically, the invention provides peptides useful in regulating the release of a specific pattern of cytokines that promote angiogenesis and / or can be used to modulate the immune system of a subject.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]More than one reissue application has been filed for the reissue of U.S. Pat. No. 8,460,697 B2. The reissue applications are application Ser. No. 14 / 734,785 (issued as U.S. Pat. No. RE46,425) and Ser. No. 15 / 278,016 (the present application), all of which are reissue divisional applications of U.S. Pat. No. 8,460,697 B2. The present application is a reissue divisional of application Ser. No. 14 / 734,785 (issued as U.S. Pat. No. RE46,425), which is an application for reissue of U.S. Pat. No. 8,460,697 B2, which is related to and claims the benefit of U.S. Provisional Application No. 61 / 221,021 filed Jun. 26, 2009, and; U.S. Pat. No. 8,460,697 B2 is also a continuation-in-part of U.S. patent application Ser. No. 11 / 955,143 filed Dec. 12, 2007, which in turn claims the benefit of U.S. Provisional Application No. 60 / 869,862 filed Dec. 13, 2006, the contents of each of which are incorporated herein by reference thereto.INCORPORATION-BY-REFERENC...

AI Technical Summary

Problems solved by technology

Chronic wounds affect more than 6.5 million patients each year and cause significant impairment of quality of life.

The consequence is a vicious cycle of recruitment of neutrophils in response to IL-8, damage to tissues, and more production of IL-8 leading to deleterious inflammation as a side effect.

Increased levels of certain types of clinically deleterious cytokines, such as IL-8 and ICAM-1, at a site of infection or injury can therefore cause deleterious side effects which can hinder the process of healing.

The use of such peptides for clinical applications has, however, been hampered by several problematic issues including deleterious side effects.

However, Substance P has also been shown to stimulate neurons to release factors that recruit inflammatory cytokines and neutrophils to the site of a wound, thereby causing pain and inflammation.

Therefore, the use of peptides or growth factors and their analogs as therapeutic agents for wound healing can be problematic for a number of reasons, including efficacy, cost, and deleterious side effects such as inflammation.

1. the requirement for expression of a polynucleotide containing the nucleotide sequence encoding the protein, which can complicate production and significantly increase costs;

2. the requirement for purification of expressed proteins from the other proteins of the host cell, which can complicate production and significantly increase costs;

3. administration of angiogenic growth factors without the further ability to activate phagocytes and thereby enhance efficacy or ameliorate infection or other concomitant disorders;

4. administration of angiogenic growth factors without the further ability to reduce inflammation, thereby reducing deleterious side effects; and

5. administration of a peptide which can stimulate the release of factors that recruit inflammatory cytokines and neutrophils to the site of a wound, causing pain and inflammation.

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