Method of treating myocardial infarction by administering a bi-specific fusion protein

Patent metadata

Field	Value
Publication number	US-9718892-B2
Application number	US-201514967980-A
Country	US
Kind code	B2
Filing date	Dec 14, 2015
Priority date	May 21, 2010
Publication date	Aug 1, 2017
Grant date	Aug 1, 2017

Abstract

Bi-specific fusion proteins with therapeutic uses are provided, as well as pharmaceutical compositions comprising such fusion proteins, and methods for using such fusion proteins to repair or regenerate damaged or diseased tissue. The bi-specific fusion proteins generally comprise: (a) a targeting polypeptide domain that binds to a target molecule; and (b) an activator domain that detectably modulates tissue regeneration.

First claim

The invention claimed is:

1. A method of treating myocardial infarction, the method comprising:
administering to a patient in need thereof a therapeutically effective amount of a fusion protein comprising annexin V and IGF-1,
wherein annexin V comprises an amino acid sequence recited in SEQ ID NO: 31 and wherein IGF-1 comprises an amino acid sequence having at least 98.5% identity with SEQ ID NO: 3,
wherein the fusion protein has the property to bind apoptotic cardiomyocytes and to stimulate Akt signaling in healthy cardiomyocytes.

2. The method of claim 1 , wherein the fusion protein further comprises a peptide.

3. The method of claim 2 , wherein the peptide extends the half-life of the fusion protein.

4. The method of claim 2 , wherein the peptide comprises a sequence from one of human serum albumin, alpha-fetoprotein, vitamin D- binding protein, transthyretin, single-chain of antibody Fc domain, proline-, alanine-, and/or serine-rich sequences, albumin-binding domain antibody, variants thereof, fragments thereof and combinations thereof.

5. The method of claim 2 , wherein the peptide comprises at least 100 consecutive amino acids that are at least 80% identical to a serum albumin amino acid sequence.

6. The method of claim 2 , wherein the peptide is a non-immunogenic peptide.

7. The method of claim 1 , wherein the annexin V and IGF-1 bind to different molecules on a same cell.

8. The method of claim 1 , wherein the annexin V and IGF-1 bind to different molecules on different cells.

9. The method of claim 2 , wherein the annexin V is joined via a peptide bond to the amino terminus of the peptide and the IGF-1 is joined via a peptide bond to the carboxy terminus of the peptide.

10. The method of claim 2 , wherein the annexin V is joined via a peptide bond to the carboxy terminus of the peptide and the IGF-1 is joined via a peptide bond to the amino terminus of the peptide.

Assignees

• Merrimack Pharmaceuticals Inc

Inventors

• Nielsen Ulrik
• Wickham Thomas
• Schoeberl Birgit
• Harms Brian
• Linggi Bryan
• Onsum Matthew
• Delabarre Byron
• Lippow Shaun M

Classifications

• A61P43/00

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

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title