Angiogenically effective unit dose of fgf and method of administering

Abstract

The present invention provides a unit dose comprising 0.2 μg/kg to 36 μg/kg of a recombinant FGF or an angiogenically active fragment or mutein thereof. Also provided is a pharmaceutical composition comprising an angiogenically effective dose of an FGF or an angiogenically active fragment or mutein thereof, and a pharmaceutically acceptable carrier. Also provided is a method for treating a human patient for coronary artery disease, comprising administering into at least one coronary vessel of said patient a safe and angiogenically effective dose of a recombinant FGF of any of SEQ ID NOS:1-3, 5, 8-10, or 12-14, or an angiogenically active fragment or mutein thereof.

That which is claimed is: 
     
         1 . A method for treating a human patient for coronary artery disease, comprising administering into one or more coronary vessels in a human patient in need of treatment for coronary artery disease a therapeutically effective amount of an angiogenically active fragment or angiogenically active mutein of a recombinant fibroblast growth factor (FGF) having the sequence set forth in SEQ ID NO:3, SEQ ID NO:5, SEQ ID NO:8, SEQ ID NO:9, or SEQ ID NO:13. 
     
     
         2 . The method of  claim 1 , wherein said therapeutically effective amount administered to said patient is a unit dose of about 0.008 mg to about 6.1 mg of said angiogenically active fragment or angiogenically active mutein of said recombinant FGF. 
     
     
         3 . The method of  claim 2 , wherein said therapeutically effective amount administered to said patient is a unit dose of 0.3 mg to 3.5 mg of said angiogenically active fragment or angiogenically active mutein of said recombinant FGF. 
     
     
         4 . The method of  claim 1 , comprising administering into one or more coronary vessels of said patient about 0.2 μg/kg to about 36 μg/kg of said angiogenically active fragment or angiogenically active mutein of said recombinant FGF. 
     
     
         5 . The method of  claim 4 , comprising administering into one or more coronary vessels of said patient about 0.2 μg/kg to about 2 μg/kg of said angiogenically active fragment or angiogenically active mutein of said recombinant FGF. 
     
     
         6 . The method of  claim 4 , comprising administering into one or more coronary vessels of said patient about 2 μg/kg to about 20 μg/kg of said angiogenically active fragment or angiogenically active mutein of said recombinant FGF. 
     
     
         7 . The method of  claim 4 , comprising administering into one or more coronary vessels of said patient about 20 μg/kg to about 36 μg/kg of said angiogenically active fragment or angiogenically active mutein of said recombinant FGF. 
     
     
         8 . A method for treating a human patient for coronary artery disease, comprising administering into one or more coronary vessels in a human patient in need of treatment for coronary artery disease a therapeutically effective amount of a recombinant fibroblast growth factor (FGF) having the sequence set forth in SEQ ID NO:10, 12, or 14 or an angiogenically active fragment or an angiogenically active mutein thereof. 
     
     
         9 . The method of  claim 8 , wherein said therapeutically effective amount administered to said patient is a unit dose of about 0.008 mg to about 6.1 mg of said recombinant FGF or said angiogenically active fragment or said angiogenically active mutein thereof. 
     
     
         10 . The method of  claim 9 , wherein said therapeutically effective amount administered to said patient is a unit dose of 0.3 mg to 3.5 mg of said recombinant FGF or said angiogenically active fragment or said angiogenically active mutein thereof. 
     
     
         11 . The method of  claim 8 , comprising administering into one or more coronary vessels of said patient about 0.2 μg/kg to about 36 μg/kg of said recombinant FGF or said angiogenically active fragment or said angiogenically active mutein thereof. 
     
     
         12 . The method of  claim 11 , comprising administering into one or more coronary vessels of said patient about 0.2 μg/kg to about 2 μg/kg of said recombinant FGF or said angiogenically active fragment or said angiogenically active mutein thereof. 
     
     
         13 . The method of  claim 11 , comprising administering into one or more coronary vessels of said patient about 2 μg/kg to about 20 μg/kg of said recombinant FGF or said angiogenically active fragment or said angiogenically active mutein thereof. 
     
     
         14 . The method of  claim 11 , comprising administering into one or more coronary vessels of said patient about 20 μg/kg to about 36 μg/kg of said recombinant FGF or said angiogenically active fragment or said angiogenically active mutein thereof. 
     
     
         15 . A method for inducing angiogenesis in the heart of a patient, comprising administering into one or more coronary vessels of a human patient in need of coronary angiogenesis a therapeutically effective amount of a recombinant fibroblast growth factor (FGF) having the sequence set forth in SEQ ID NO:3, 5, 10, 12, or 14 or an angiogenically active fragment or an angiogenically active mutein thereof, or a therapeutically effective amount of an angiogenically active fragment or an angiogenically active mutein of a recombinant fibroblast growth factor (FGF) having the sequence set forth in SEQ ID NO:8, SEQ ID NO:9, or SEQ ID NO:13. 
     
     
         16 . The method of  claim 15 , wherein said therapeutically effective amount administered to said patient is a unit dose of about 0.008 mg to about 6.1 mg of said recombinant FGF or said angiogenically active fragment or said angiogenically active mutein thereof. 
     
     
         17 . The method of  claim 15 , wherein said unit dose is administered into two coronary vessels of said patient. 
     
     
         18 . The method of  claim 15 , further comprising the step of administering to said patient an effective amount of a glycosaminoglycan within 30 minutes of administering said recombinant FGF or said angiogenically active fragment or said angiogenically active mutein thereof. 
     
     
         19 . A unit dose of a fibroblast growth factor (FGF), comprising about 0.008 mg to about 6.1 mg of an FGF having the amino acid sequence of SEQ ID NO:1-3, 5, 8-10 or 12-14 or an angiogenically active fragment or an angiogenically active mutein thereof. 
     
     
         20 . A pharmaceutical composition comprising the unit dose of said FGF according to  claim 19 , and a pharmaceutically acceptable carrier, said composition being in a form and a size suitable for administration to a human patient. 
     
     
         21 . A pharmaceutical composition comprising (i) a therapeutically effective amount of a fibroblast growth factor (FGF) having the sequence of SEQ ID NO:1-3, 5, 8-10 or 12-14 or an angiogenically active fragment or an angiogenically active mutein thereof, and (ii) a pharmaceutically acceptable carrier, said composition being in a form and a size suitable for administration to a human patient, wherein said therapeutically effective amount comprises about 0.2 μg/kg to about 36 μg/kg of said FGF or said angiogenically active fragment or said angiogenically active mutein thereof.