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