Pharmaceutical composition comprising FGF18 and IL-1 antagonist and method of use

Abstract

FGF18 is known to stimulate the proliferation of chondrocytes, bone, and nervous tissue, resulting in repair of diseased tissue. When an IL-1 antagonist is administered in addition to FGF18, the effects on the IL-1 mediated disease and also, the effect on cartilage, bone, and nervous cell proliferation, are found to be greater than administration of FGF18 or the IL-1 antagonist alone. The present invention encompasses a pharmaceutical composition that combines FGF18 with IL-1 antagonist and methods of treating IL-1 mediated disease using this pharmaceutical composition.

1 . A pharmaceutical composition for the treatment of interleukin-1 mediated disease in a patient in need of such treatment comprising FGF18 and an IL-1 antagonist.  
     
     
         2 . The composition of  claim 1  wherein the FGF18 comprises residue 28 to residue 207 of SEQ ID NO:2.  
     
     
         3 . The composition of  claim 1  wherein the FGF18 comprises residue 28 to residue 196 of SEQ ID NO:2.  
     
     
         4 . The composition of  claim 1  wherein the IL-1 antagonist is selected from the group consisting of IL-1ra and recombinantly engineered formulations of IL-1ra.  
     
     
         5 . The composition of  claim 4  wherein the recombinantly engineered formulation of IL-1ra is Kineret™.  
     
     
         6 . The composition of  claim 1  wherein the IL-1 antagonist is an anti-IL-IR I  antibody.  
     
     
         7 . The composition of  claim 1  wherein the IL-1 antagonist is a fusion protein of IL-1ra comprising SEQ ID NO: X or an IL-1 inhibitory fragment with a constant domain of a heavy or light chain of human immunoglobulin at the amino-terminus of said IL-1ra.  
     
     
         8 . The composition of  claim 7  wherein the constant domain is a heavy chain.  
     
     
         9 . The composition of  claim 1  further comprising a negatively charged carrier selected from the group consisting of low molecular weight hyaluronans, high molecular weight hyaluronans, sulfated proteoglycans, polylactide matrices or polylactide-co-glycolide, B-cyclodextrin tetradecasulphate, hydroxyapatite, alginate microspheres, chitosans, and methylcellulose.  
     
     
         10 . The composition of  claim 1  wherein said composition is a time-release formulation.  
     
     
         11 . The composition of  claim 10  wherein said time-release formulation comprises a matrix selected from the group consisting of a solution, a gel, a paste, or a putty.  
     
     
         12 . The composition of  claim 10  wherein said time-release formulation comprises a reservoir system.  
     
     
         13 . The composition of  claim 1  further comprising an anti-inflammatory drug.  
     
     
         14 . A method for treatment of an interleukin-1 mediated disease in a patient in need of such treatment comprising the step of administering a pharmaceutical composition comprising FGF18 and an IL-1 antagonist.  
     
     
         15 . The method of  claim 14  wherein said administration comprises intraarticular injection.  
     
     
         16 . The method of  claim 14  wherein said administration comprises surgical implantation.  
     
     
         17 . The method of  claim 14  wherein said pharmaceutical composition further comprises a negatively-charged carrier selected from the group consisting of low molecular weight hyaluronans, high molecular weight hyaluronans, sulfated proteoglycans, B-cyclodextrin tetradecasulphate, hydroxyapatite, alginate microspheres, chitosans, and methylcellulose.  
     
     
         18 . The method of  claim 14  where said pharmaceutical composition is a time-release formulation.  
     
     
         19 . The method of  claim 18  wherein said time-release formulation comprises a matrix selected from the group consisting of a solution, a gel, a paste, or a putty.  
     
     
         20 . The method of  claim 19  wherein said time-release formulation comprises a reservoir system.  
     
     
         21 . The method of  claim 14  wherein said composition further comprises an anti-inflammatory drug.  
     
     
         22 . The method of  claim 14  further comprising the steps of allowing growth of new cartilage, bone, or nervous tissue and surgically contouring the new cartilage, bone or nervous surface.  
     
     
         23 . The method of  claim 14  wherein said interleukin-1 mediated disease is rheumatoid arthritis.  
     
     
         24 . The method of  claim 14  wherein said interleukin-1 mediated disease is osteoarthritis.