Formulation of human antibodies for treating tnf-alpha associated disorders

Abstract

A liquid aqueous pharmaceutical formulation is described which has a high protein concentration, a pH of between about 4 and about 8, and enhanced stability.

What is claimed is: 
     
         1 . A stable liquid aqueous pharmaceutical formulation comprising
 (a) a human IgG1 anti-human Tumor Necrosis Factor alpha (TNFα) antibody, at a concentration of 45 to 105 mg/ml,   (b) a polyol that is a sugar or sugar alcohol,   (c) a polysorbate, which is polysorbate 20 or polysorbate 80, at a concentration of 0.1 to 10 mg/ml, and   (d) a buffer system comprising acetate and having a pH of 4.5 to 7.0,   wherein the antibody is D2E7.   
     
     
         2 . The formulation of  claim 1 , wherein the concentration of the antibody is 50 to 100 mg/ml. 
     
     
         3 . The formulation of  claim 1 , wherein the formulation has a shelf life of at least 18 months. 
     
     
         4 . The formulation of  claim 1 , wherein the polyol is a sugar alcohol. 
     
     
         5 . The formulation of  claim 4 , wherein the sugar alcohol is mannitol, xylitol, erythritol, threitol, sorbitol, or glycerol. 
     
     
         6 . The formulation of  claim 5 , wherein the sugar alcohol is mannitol. 
     
     
         7 . The formulation of  claim 1 , wherein the polyol is a sugar. 
     
     
         8 . The formulation of  claim 7 , wherein the sugar is a nonreducing sugar. 
     
     
         9 . The formulation of  claim 8 , wherein the nonreducing sugar is sucrose. 
     
     
         10 . The formulation of  claim 8 , wherein the nonreducing sugar is trehalose. 
     
     
         11 . The formulation of  claim 1 , wherein the polysorbate is polysorbate 20. 
     
     
         12 . The formulation of  claim 11 , wherein the polysorbate 20 concentration is from 0.5 to 5 mg/ml. 
     
     
         13 . The formulation of  claim 12 , wherein the polysorbate 20 concentration is 1 mg/ml. 
     
     
         14 . The formulation of  claim 1 , wherein the polysorbate is polysorbate 80. 
     
     
         15 . The formulation of  claim 14 , wherein the polysorbate 80 concentration is from 0.5 to 5 mg/ml. 
     
     
         16 . The formulation of  claim 15 , wherein the polysorbate 80 concentration is 1 mg/ml. 
     
     
         17 . The formulation of  claim 1 , wherein the pH is from 4.5 to 6.0. 
     
     
         18 . The formulation of  claim 17 , wherein the pH is from 4.8 to 5.5. 
     
     
         19 . The formulation of  claim 1 , which is suitable for single use subcutaneous injection. 
     
     
         20 . The formulation of  claim 6 , wherein the polysorbate is polysorbate 20. 
     
     
         21 . The formulation of  claim 6 , wherein the polysorbate is polysorbate 80. 
     
     
         22 . The formulation of  claim 9 , wherein the polysorbate is polysorbate 20. 
     
     
         23 . The formulation of  claim 9 , wherein the polysorbate is polysorbate 80. 
     
     
         24 . The formulation of  claim 10 , wherein the polysorbate is polysorbate 20. 
     
     
         25 . The formulation of  claim 10 , wherein the polysorbate is polysorbate 80. 
     
     
         26 . The formulation of  claim 1 , comprising:
 (a) 50 to 100 mg/ml of the antibody,   (b) trehalose, and   (c) a polysorbate, which is polysorbate 20 or polysorbate 80,   wherein said buffer system has a pH of 5.0 to 6.5.   
     
     
         27 . The formulation of  claim 26 , wherein the polysorbate is polysorbate 20. 
     
     
         28 . The formulation of  claim 1 , comprising
 (a) 50 to 100 mg/ml of the antibody,   (b) sucrose, and   (c) a polysorbate, which is polysorbate 20 or polysorbate 80,   wherein said buffer system has a pH of 5.0 to 6.5.   
     
     
         29 . The formulation of  claim 28 , wherein the polysorbate is polysorbate 20.