Freeze-dried formulations of fgf-18

Abstract

The invention relates to the field of pharmaceutical formulations. More particularly it is directed to freeze-dried formulations of Fibroblast Growth Factor 18 (FGF-18) compound and to methods of producing such formulations. The freeze-dried formulations according to the invention are stable upon storage for an appropriate period of time. They can be used, after reconstitution, for the treatment of cartilage disorders such as osteoarthritis or cartilage injury.

1 . (canceled) 
     
     
         2 . A freeze-dried formulation comprising fibroblast growth factor 18 (FGF-18), a buffer, a poloxamer surfactant and a sugar as stabilizing agent, wherein the buffer is a phosphate buffer maintaining the pH at or about 7.2. 
     
     
         3 . The freeze-dried formulation according to  claim 2 , wherein the concentration of the buffer is at or about 5 to 100 mM. 
     
     
         4 . The freeze-dried formulation according to  claim 2 , wherein the poloxamer surfactant is poloxamer 188. 
     
     
         5 . The freeze-dried formulation according to  claim 2 , wherein the concentration of the poloxamer surfactant is at or about 0.1 to 0.4 mg/vial. 
     
     
         6 . The freeze-dried formulation according to  claim 2 , wherein the stabilizing agent is sucrose. 
     
     
         7 . The freeze-dried formulation according to  claim 2 , wherein the concentration of the stabilizing agent is at or about 10 to 60 mg/vial. 
     
     
         8 . The freeze-dried formulation according to  claim 2 , wherein the concentration of FGF-18 is at or about 20 to 300 mcg/vial. 
     
     
         9 . The freeze-dried formulation according to  claim 2 , wherein the formulation comprises 20, 30, 60, 100, 200 or 300 mcg/vial of FGF-18, 10 mM phosphate buffer which keep the pH at or about 7.2, 30 mg/vial of sucrose and 0.2 mg/vial of poloxamer 188. 
     
     
         10 . The freeze-dried formulation according to  claim 8 , wherein the formulation further comprises a 5% overage of FGF-18. 
     
     
         11 . The freeze-dried formulation according to  claim 2 , wherein FGF-18 is selected from the group consisting of:
 a) a polypeptide comprising or consisting of the amino acid residues 28-207 of SEQ ID NO:1;   b) a polypeptide comprising or consisting of the amino acid residues 28-196 of SEQ ID NO:1; and   c) a polypeptide comprising or consisting of SEQ ID NO:2.   
     
     
         12 . The freeze-dried formulation according to  claim 2 , wherein the formulation retains at least 80% of the FGF-18 activity over a period of 12 months when stored at room temperature. 
     
     
         13 . An article of manufacture comprising a first container comprising the freeze-dried formulation according to  claim 2  and a second container comprising a solvent for reconstitution. 
     
     
         14 . The article of manufacture according to  claim 13 , wherein the container comprising the freeze-dried formulation and the one comprising a solvent for reconstitution are the two compartments of a dual-chamber system.