Araim Pharmaceuticals, Inc.

The Kenneth S. Warren Institute, Inc.

Warren Pharmaceuticals, Inc.

Thomas Coleman

Anthony Cerami

Michael Brines

Osman Yilmaz

The present invention is directed to novel tissue protective peptides. The tissue protective peptides of the invention may bind to a tissue protective receptor complex. In particular, the present invention is drawn to tissue protective peptides derived from or sharing consensus sequences with portions of cytokine receptor ligands, including Erythropoietin (EPO), that are not involved in the binding of the ligand to the receptor complex, e.g., to the EPO receptor homodimer. Accordingly, the tissue protective peptides of the invention are derived from the amino acid sequences of regions of cytokine receptor ligands that are generally located on or within the region of the ligand protein that is opposite of the receptor complex, i.e., are generally derived from amino acid sequences of regions of the ligand protein that face away from the receptor complex while the ligand is bound to the receptor. The invention is further directed to the consensus sequences for use in engineering a synthetic tissue protective peptide. These tissue protective peptides also include fragments, chimeras, as well as peptides designed to mimic the spatial localization of key amino acid residues within the tissue protective receptor ligands, e.g., EPO. The invention further encompasses methods for treating or preventing a disease or disorder using tissue protective peptides of the current invention. The invention also encompasses methods for enhancing excitable tissue function using tissue protective peptides of the current invention.

Tissue protective peptides and uses thereof

Provided herein are tissue protective peptides derived from or sharing consensus sequences with portions of cytokine receptor ligands, including Erythropoietin (EPO), that are generally located on or within the region of the cytokine receptor ligand that faces away from a receptor complex while the ligand is bound to the receptor. Also provide herein are fragments, chimeras, as well as peptides designed to mimic the spatial localization of key amino acid residues within the tissue protective receptor ligands, e.g., EPO; methods for treating or preventing a disease or disorder using tissue protective peptides; and methods for enhancing excitable tissue function using tissue protective peptides.

The present invention is directed methods for identifying compounds that have a tissue protective activity using a heteromultimer receptor complex that mediates the tissue protective activities. The complex consists of at least one EPO-R in complex with at least one &#x3b2;Receptor. These compounds used in the assays to identify tissue protective compounds include, but are not limited to, small molecules and biologics. The compounds identified using these assays can be used to treat various conditions of the central and peripheral nervous systems as well as those of other erythropoietin-responsive or excitable cells, tissues, and organs.

Tissue protective cytokine receptor complex and assays for identifying tissue protective compounds

A method of treating, preventing, delaying the onset, and/or reducing the effects of proinflammatory cytokines in conditions including, but not limited to, sepsis, adhesion formation, wounds, organ failure, chronic disease, general inflammatory conditions resulting from infection, scarring resulting from injury and incisions, and combinations thereof.

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Mount Kisco, NY, United States of America

Thomas Coleman