Self-buffering protein formulations

Abstract

The invention herein described, provides, among other things, self-buffering protein formulations. Particularly, the invention provides self-buffering pharmaceutical protein formulations that are suitable for veterinary and human medical use. The self-buffering protein formulations are substantially free of other buffering agents, stably maintain pH for the extended time periods involved in the distribution and storage of pharmaceutical proteins for veterinary and human medical use. The invention farther provides methods for designing, making, and using the formulation. In addition to other advantages, the formulations avoid the disadvantages associated with the buffering agents conventionally used in current formulations of proteins for pharmaceutical use. The invention in these and other respects can be productively applied to a wide variety of proteins and is particularly useful for making and using self-buffering formulations of pharmaceutical proteins for veterinary and medical use, especially, in particular, for the treatment of diseases in human subjects.

1 . (canceled) 
     
     
         2 . An aqueous pharmaceutical formulation consisting essentially of:
 (a) a pharmaceutical protein that is either etanercept or a vascular endothelial growth factor (VEGF) binding protein, wherein the concentration of the pharmaceutical protein is 50 to 200 mg/ml; and   (b) water,   wherein the pH of the formulation is from 3.5 to 8.   
     
     
         3 . The formulation of  claim 2 , wherein the pharmaceutical protein is etanercept. 
     
     
         4 . The formulation of  claim 2 , wherein the pharmaceutical protein is the VEGF binding protein. 
     
     
         5 . The formulation of  claim 2 , wherein the pH of the formulation is from 4 to 6. 
     
     
         7 . The formulation of  claim 2 , wherein the pH of the formulation is about 6. 
     
     
         8 . The formulation of  claim 3 , wherein the pH of the formulation is about 6. 
     
     
         9 . The formulation of  claim 3 , further comprising arginine as a free amino acid. 
     
     
         10 . The formulation of  claim 9 , wherein the pH is from 4.5 to 7.5. 
     
     
         11 . The formulation of  claim 2 , wherein the formulation does not comprise an antibody. 
     
     
         12 . An aqueous pharmaceutical formulation comprising:
 (a) a pharmaceutical protein that is either etanercept or a vascular endothelial growth factor (VEGF) binding protein, wherein the concentration of the pharmaceutical protein is 50 to 200 mg/ml; and   (b) water,   wherein the formulation does not comprise a tonicity modifier and wherein the pH of the formulation is from 3.5 to 8.   
     
     
         13 . The formulation of  claim 12 , wherein the pharmaceutical protein is etanercept. 
     
     
         14 . The formulation of  claim 12 , wherein the antibody is the VEGF binding protein. 
     
     
         15 . The formulation of  claim 12 , wherein the pH of the formulation is from about 6. 
     
     
         16 . The formulation of  claim 12 , wherein the formulation does not comprise an antibody. 
     
     
         17 . An aqueous pharmaceutical formulation comprising:
 (a) a pharmaceutical protein that is either etanercept or a vascular endothelial growth factor (VEGF) binding protein, wherein the concentration of the pharmaceutical protein is 50 to 200 mg/ml; and   (b) water,   wherein the formulation does not comprise a buffering system other than the pharmaceutical protein, and wherein the pH of the formulation is from 3.5 to 8.   
     
     
         18 . The formulation of  claim 17 , wherein the pharmaceutical protein is etanercept. 
     
     
         19 . The formulation of  claim 17 , wherein the pharmaceutical protein is the VEGF binding protein. 
     
     
         20 . The formulation of  claim 17 , wherein the pH of the formulation is from 4 to 6. 
     
     
         21 . The formulation of  claim 17 , wherein the pH of the formulation is about 6. 
     
     
         22 . The formulation of  claim 18 , wherein the pH of the formulation is about 6. 
     
     
         23 . The formulation of  claim 18 , further comprising arginine as a free amino acid. 
     
     
         24 . The formulation of  claim 23 , wherein the pH is from 4.5 to 7.5. 
     
     
         25 . The formulation of  claim 24 , wherein the formulation does not comprise an antibody. 
     
     
         26 . The formulation of  claim 24 , wherein the formulation further comprises a non-ionizable excipient. 
     
     
         27 . The formulation of  claim 24 , wherein the formulation further comprises a polyol. 
     
     
         28 . The formulation of  claim 27 , wherein the polyol is selected from the group consisting of mannitol, sorbitol, and sucrose. 
     
     
         29 . The formulation of  claim 17 , wherein the formulation further comprises a surfactant. 
     
     
         30 . The formulation of  claim 29 , wherein the surfactant is selected from the group consisting of polysorbate 80 and polysorbate 20.