Patent EA-001616-B1 (EA)
Title: Method for treating a heart disease, method for treating a peripheral deficient vascular disease and method of limiting transgene delivery and expression to a single organ or structure
Inventor: HAMMOND H KIRK
IPC: A61P9/08
Filed: 1996-02-27
Abstract: 1. The method for treating a heart disease using stimulating coronary collateral vessel development in a patient having myocardial ischemia, comprising delivering a replication-deficient adenovirus vector to the myocardium of the patient by intracoronary injection directly into one or both coronary arteries, said vector comprising a transgene coding for an angiogenic protein or peptide, and capable of expressing said protein or peptide in the myocardium, thereby promoting coronary collateral vessel development. 2. The method of Claim 1, wherein a single injection of said vector is delivered. 3. The method of Claim 1, wherein about 10<7> to about 10<13> vector particles are delivered in the injection. 4. The method of Claim 1, wherein about 10<9> to about 10<12> vector particles are delivered in the injection. 5. The method of Claim 1, wherein about 10<11> vector particles are delivered in the injection. 6. The method according to Claim 1, wherein said angiogenic protein or peptide expression is driven by a CMV promoter which is contained in the vector. 7. The method according to Claim 1, wherein said angiogenic protein or peptide expression is driven by a ventricular myocyte-specific promoter which is contained in the vector. 8. The method according to Claim 7, wherein said ventricular myocyte-specific promoter has the sequences of ventricular myosin light chain-2. 9. The method according to Claim 7, wherein said ventricular myocyte-specific promoter has the sequences of myosin heavy chain promoter. 10. The method according to Claim 1, wherein said angiogneic protein or peptide is selected from the group consisting of aFGF, bFGF, FGF-5, and VEGF. 11. The method of Claim 1, wherein said angiogenic protein is FGF-5. 12. The method of Claim 1, wherein said angiogenic protein is aFGF. 13. The method of Claim 1, wherein said angiogenic protein is bFGF. 14. The method of Claim 1, wherein said angiogenic peptide is VEGF. 15. The method according to Claim 1, wherein said intracoronary injection is conducted about 1 cm into the lumens of the left and right coronary arteries. 16. The method according to Claim 1, wherein said intracoronary injection is conducted about 1 cm into the lumens of a saphenous vein graft and/or an internal mammary artery graft in addition to a intracoronary injection. 17. A method for treating a patient having peripheral-deficient vascular disease by stimulating vessel development, comprising delivering a replication-deficient adenovirus vector to the peripheral vascular system of the patient by intra-femoral artery injection directly into one or both femoral arteries, said vector comprising a transgene coding for angiogenic protein or peptide, and capable of expressing said protein or peptide in the peripheral vascular system, thereby promoting peripheral vascular development. 18. The method of Claim 17, wherein a single injection of said vector is delivered. 19. The method of Claim 17, wherein about 10<7> to about 10<13> vector particles are delivered in the injection. 20. The method of Claim 17, wherein about 10<9> to about 10<12> vector particles are delivered in the injection. 21. The method of Claim 17, wherein about 10<11> vector particles are delivered in the injection. 22. The method according to Claim 17, wherein said angiogneic protein or peptide is selected from the group consisting of aFGF, bFGF, FGF-5, and VEGF. 23. A method of limiting transgene delivery and expression to a single organ or structure by injecting the recombinant a replication-deficient adenovirus vector, said vector comprising said structure, through a catheter inserted not less than about 1 cm into the arterial vascular supply system of said organ or structure; said vector being capable of transgene expression in said organ or structure. 24. The method according to Claim 23, wherein said transgene structure encodes angiogneic protein or peptide.