Angiogenically effective unit dose of FGF-2 and method of use

Abstract

The present invention has multiple aspects. In particular, in one aspect, the present invention is directed to a unit dose composition comprising 0.2 μg/kg to 48 μg/kg of an FGF-2 of SEQ ID NO:2, or an angiogenically active fragment or mutein thereof in a pharmaceutically acceptable carrier. In another aspect, the present invention is directed to a method for treating a human patient for coronary artery disease, comprising administering into one or more coronary vessels or a peripheral vein of a human patient in need of treatment for coronary artery disease a safe and angiogenically effective dose of a recombinant FGF-2, or an angiogenically active fragment or mutein thereof. The single unit dose composition of the present invention provides an angiogenic effect in a human CAD patient that lasts six months before retreatment is required. In another aspect, the present invention is directed to a method of administration which optimizes patient's safety. In this embodiment, fluids, heparin and/or rate of infusion all play a role. In another aspect, the present invention is directed to a pharmaceutical composition comprising a therapeutically effective amount of FGF-2, alone or in combination with heparin, in a therapeutically effective carrier. The magnitude and duration of benefit were unexpected; in addition benefit with the IV route was unexpected.

What is claimed is:  
     
         1 . A unit dose composition for inducing angiogenesis in a human, comprising about 0.008 mg to about 7.2 mg of FGF-2 or an angiogenically active fragment or an angiogenically active mutein thereof in a pharmaceutically acceptable carrier.  
     
     
         2 . The unit dose composition of  claim 1 , comprising 0.3 mg to 3.5 mg of said FGF-2, or said angiogenically active fragment or said angiogenically active mutein thereof.  
     
     
         3 . The unit dose composition of  claim 1 , wherein said FGF-2 has the amino acid sequence of SEQ ID NO:2.  
     
     
         4 . The unit dose composition of  claim 3 , comprising 0.3 mg to 3.5 mg of said FGF-2 of SEQ ID NO:2 or said angiogenically active fragment or said angiogenically active mutein thereof in a pharmaceutically acceptable carrier.  
     
     
         5 . The unit dose composition of  claim 3 , comprising about 0.008 mg to about 7.2 mg of said angiogenically active mutein of said FGF-2 of SEQ ID NO:2 in a pharmaceutically acceptable carrier.  
     
     
         6 . The unit dose composition of  claim 5 , comprising 0.3 mg to 3.5 mg of said angiogenically active mutein of said FGF-2 of SEQ ID NO:2 in a pharmaceutically acceptable carrier.  
     
     
         7 . The unit dose composition of  claim 3 , comprising about 0.008 mg to about 7.2 mg of said angiogenically active fragment of said FGF-2 of SEQ ID NO:2 in a pharmaceutically acceptable carrier.  
     
     
         8 . The unit dose composition of  claim 7 , comprising 0.3 mg to 3.5 mg of said angiogenically active fragment of said FGF-2 of SEQ ID NO:2 in a pharmaceutically acceptable carrier.  
     
     
         9 . The unit dose composition of  claim 3 , comprising about 0.008 mg to about 7.2 mg of said FGF-2 of SEQ ID NO:2 in a pharmaceutically acceptable carrier.  
     
     
         10 . A unit dose composition for inducing angiogenesis in a human, comprising about 0.008 mg to about 7.2 mg of FGF-2 in a pharmaceutically acceptable carrier, wherein said FGF-2 has the sequence set forth in SEQ ID NO:2.  
     
     
         11 . The unit dose composition of  claim 11 , comprising 0.3 mg to 3.5 mg of said FGF-2 in a pharmaceutically acceptable carrier.  
     
     
         12 . A unit dose composition for inducing angiogenesis in a human, comprising about 0.008 mg to about 7.2 mg of an angiogenically active fragment of FGF-2 or an angiogenically active mutein of FGF-2, wherein said FGF-2 has the sequence set forth in SEQ ID NO:2.  
     
     
         13 . The unit dose composition of  claim 12 , comprising 0.3 mg to 3.5 mg of said angiogenically active fragment of said FGF-2 in a pharmaceutically acceptable carrier.  
     
     
         14 . The unit dose composition of  claim 12 , comprising 0.3 mg to 3.5 mg of said angiogenically active mutein of said FGF02 in a pharmaceutically acceptable carrier.