Compositions of pegylated soluble tumor necrosis factor receptors and methods of preparing

Abstract

The present invention provides for improved compositions comprising a PEGsTNF-R1 which, in addition to having useful higher concentrations, demonstrate decreased viscosity (<400 cP) and improved stability.

1 . A method for decreasing the viscosity of a pharmaceutical formulation comprising including a tonicity modifier selected from the group consisting of glycine, sorbitol, and sucrose,
 wherein the pharmaceutical formulation comprises a surfactant,   wherein the pharmaceutical formulation comprises a TNF inhibitor at a concentration of at least 45 mg/ml,   wherein the pharmaceutical formulation is between pH 4.0 and 5.5, and   wherein the viscosity of the pharmaceutical formulation including the tonicity modifier is less than 400 cP.   
     
     
         2 . The method of  claim 1 , wherein the surfactant is a polysorbate. 
     
     
         3 . The method of  claim 2 , wherein the polysorbate is polysorbate 20. 
     
     
         4 . The method of  claim 2 , wherein the polysorbate is polysorbate 80. 
     
     
         5 . The method of  claim 2 , wherein the tonicity modifier is sucrose. 
     
     
         6 . The method of  claim 4 , wherein the tonicity modifier is sorbitol. 
     
     
         7 . The method of  claim 6 , wherein the pharmaceutical formulation further comprises histidine and the pharmaceutical formulation comprises the TNF inhibitor at a concentration of at least 57 mg/ml. 
     
     
         8 . The method of  claim 2 , wherein the tonicity modifier is glycine. 
     
     
         9 - 10 . (canceled) 
     
     
         11 . The method of  claim 5 , wherein the TNF inhibitor comprises polyethylene glycol (PEG) and wherein the pharmaceutical formulation comprises the TNF inhibitor at concentration of at least 57 mg/ml. 
     
     
         12 . The method of  claim 11 , wherein the PEG has a molecular weight between about 5 kilodaltons and about 50 kilodaltons. 
     
     
         13 . A method for decreasing the viscosity of a pharmaceutical formulation comprising including mannitol in the pharmaceutical formulation,
 wherein the pharmaceutical formulation comprises polysorbate 80, sodium chloride, sodium phosphate, citric acid, and sodium citrate   wherein the pharmaceutical formulation comprises a TNF inhibitor at a concentration of at least 45 mg/ml,   and   wherein the viscosity of the pharmaceutical formulation including the mannitol is less than 400 cP.   
     
     
         14 . A method for decreasing the viscosity of a pharmaceutical formulation comprising including sorbitol in the pharmaceutical formulation,
 wherein the pharmaceutical formulation comprises polysorbate 80, histidine, and a TNF inhibitor,   wherein the concentration of the TNF inhibitor is at least 57 mg/ml,   and   wherein the viscosity of the pharmaceutical formulation including sorbitol is less than 400 cP.   
     
     
         15 . The method of  claim 14 , wherein the pH of the pharmaceutical formulation is between pH 4.0 and 5.5. 
     
     
         16 . A method for decreasing the viscosity of a pharmaceutical formulation comprising including sucrose in the formulation,
 wherein the pharmaceutical formulation comprises sodium chloride, sodium phosphate, and a TNF inhibitor,   wherein the TNF inhibitor is at a concentration of at least 45 mg/ml,   wherein the TNF inhibitor comprises the 40 kD TNF inhibitor, and   wherein the viscosity of the pharmaceutical formulation including the sucrose is less than 400 cP.   
     
     
         17 . The method of  claim 12 , wherein the pharmaceutical composition has been stored in a lyophilized form prior to reconstitution. 
     
     
         18 . A pharmaceutical formulation comprising
 (a) tonicity modifier selected from the group consisting of sorbitol and sucrose,   (b) a polysorbate, and   (c) a TNF inhibitor at a concentration of at least 57 mg/ml,   wherein the viscosity of the pharmaceutical formulation including the tonicity modifier is less than 400 cP.   
     
     
         19 . The pharmaceutical formulation of  claim 18 , wherein
 the tonicity modifier is sucrose,   the TNF inhibitor comprises PEG, which has a molecular weight between about 5 kilodaltons and about 50 kilodaltons, and   the pH of the pharmaceutical formulation is between pH 4.0 and 5.5.   
     
     
         20 . The pharmaceutical formulation of  claim 18 , wherein
 the tonicity modifier is sorbitol,   the polysorbate is polysorbate 80, and   the pharmaceutical composition further comprises histidine.   
     
     
         21 . The pharmaceutical formulation of  claim 20 , wherein the pH of the pharmaceutical formulation is between pH 4.0 and 5.5. 
     
     
         22 . A pharmaceutical formulation comprising mannitol, sodium chloride, sodium phosphate, sodium citrate, citric acid, polysorbate 80, and a TNF inhibitor,
 wherein the TNF inhibitor is at a concentration of at least 45 mg/ml, and   wherein the viscosity of the formulation is less than 400 cP.   
     
     
         23 . A pharmaceutical formulation comprising sucrose, sodium chloride, sodium phosphate, and a TNF inhibitor comprising the 40 kD TNF inhibitor,
 wherein the TNF inhibitor is at a concentration of at least 45 mg/ml, and   wherein the viscosity of the formulation is less than 400 cP.