Bi-specific fusion proteins
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 damaged tissue. The bi-specific fusion proteins generally comprise: (a) a targeting polypeptide domain that binds to an ischemia-associated molecule; and (b) an activator domain that that detectably modulates the activity of a cellular network.
1. A bi-specific fusion protein comprising:
(a) an anti-phosphatidylserine scFv comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 30; and
(b) an insulin-like growth factor 1 (IGF-1) comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 5.
2. A pharmaceutical composition comprising a physiologically acceptable carrier and a therapeutically effective amount of the bi-specific fusion protein of claim 1 .
3. A bi-specific fusion protein comprising:
(a) an anti-phosphatidylserine scFv comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 30;
(b) an insulin-like growth factor 1 (IGF-1) comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 5; and
(c) a human serum albumin comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 49.
4. The bi-specific fusion protein of claim 3 , wherein the human serum albumin extends the half-life of the bi-specific fusion protein.
5. A pharmaceutical composition comprising a physiologically acceptable carrier and a therapeutically effective amount of the bi-specific fusion protein of claim 3 .
6. A method of treating a tissue damage in a subject in need thereof, the method comprising:
administering to the subject a pharmaceutical composition comprising a physiologically acceptable carrier and a therapeutically effective amount of a bi-specific fusion protein, the bi-specific fusion protein comprising (a) an anti-phosphatidylserine scFv comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 30; (b) an insulin-like growth factor 1 (IGF-1) comprising an amino acid sequence having at least 90% identity with SEQ ID NO: 5;
wherein administration results in tissue regeneration and improvement of tissue function in the subject.
7. The method of claim 6 , wherein the bi-specific fusion protein further comprises a human serum albumin comprising an amino acid sequence having at least 80% identity with SEQ ID NO: 49.