Angiogenically effective unit dose of FGF and method of administering

Abstract

The present invention has multiple aspects. In particular, in one aspect, the present invention is directed to a unit dose comprising 0.2 μg/kg to 36 μg/kg of a recombinant FGF or an angiogenically active fragment or mutein thereof. In another aspect, the present invention is directed to a pharmaceutical composition comprising an angiogenically effective dose of an FGF or an angiogenically active fragment or mutein thereof, and a pharmaceutically acceptable carrier. Typically, the angiogenically effective dose comprises 0.2 μg/kg to 36 μg/kg of an FGF of any one of SEQ ID NOS: 1-3, 5, 8-10, or 12-14 or an angiogenically active fragment or mutein thereof. In yet another aspect, the present invention is directed to a method for treating a human patient for coronary artery disease, comprising administering into at least one coronary vessel of a human patient in need of treatment for coronary artery disease a safe and angiogenically effective dose of a recombinant FGF of any one 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 of a recombinant fibroblast growth factor (FGF) having the sequence set forth in SEQ ID NO: 3 or SEQ ID NO: 5.  
     
     
         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 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 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 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 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  82  g/kg of said angiogenically active fragment 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 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 an angiogenically active mutein of a recombinant fibroblast growth factor (FGF) having the sequence set forth in SEQ ID NO: 3 or SEQ ID NO: 5.  
     
     
         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 angiogenically active mutein of said recombinant FGF.  
     
     
         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 angiogenically active mutein of said recombinant FGF.  
     
     
         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 angiogenically active mutein of said recombinant FGF.  
     
     
         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 angiogenically active mutein of said recombinant FGF.  
     
     
         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 angiogenically active mutein of said recombinant FGF.  
     
     
         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 angiogenically active mutein of said recombinant FGF.  
     
     
         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 or SEQ ID NO: 5 or an angiogenically active fragment or an angiogenically active mutein thereof.  
     
     
         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: 3 or SEQ ID NO: 5 or an angiogenically active fragment or an angiogenically active mutein thereof.  
     
     
         20 . The unit dose of  claim 19 , comprising 0.3 mg to 3.5 mg of said FGF or said angiogenically active fragment or said angiogenically active mutein thereof.  
     
     
         21 . The unit dose of  claim 19 , wherein said FGF has the sequence of SEQ ID NO: 3 or SEQ ID NO: 5.  
     
     
         22 . A pharmaceutical composition comprising (i) a therapeutically effective amount of a fibroblast growth factor (FGF) having the sequence of SEQ ID NO: 3 or SEQ ID NO: 5 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.  
     
     
         23 . The pharmaceutical composition of  claim 22 , 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.  
     
     
         24 . The pharmaceutical composition of  claim 23 , wherein said therapeutically effective amount comprises about 0.2 μg/kg to about 2 μg/kg of said FGF or said angiogenically active fragment or said angiogenically active mutein thereof.  
     
     
         25 . The pharmaceutical composition of  claim 23 , wherein said therapeutically effective amount comprises about 2 μg/kg to about 20 μg/kg of said FGF or said angiogenically active fragment or said angiogenically active mutein thereof.  
     
     
         26 . The pharmaceutical composition of  claim 23 , wherein said therapeutically effective amount comprises about 20 μg/kg to about 36 μg/kg.  
     
     
         27 . The pharmaceutical composition of  claim 22 , wherein said therapeutically effective amount comprises about 008 mg to about 6.1 mg of said FGF or said angiogenically active fragment or said angiogenically active mutein thereof.  
     
     
         28 . The pharmaceutical composition of  claim 27 , wherein said therapeutically effective amount comprises 0.3 mg to 3.5 mg of said FGF or said angiogenically active fragment or said angiogenically active mutein thereof.