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 further 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 - 2 . (canceled) 
     
     
         3 . A self-buffering protein formulation consisting of:
 water; and   adalimumab or epratuzumab at a concentration between 20 and 200 mg/ml, wherein the formulation is self-buffering by the concentration of adalimumab in the water.   
     
     
         4 . The self-buffering protein formulation of  claim 3 , wherein the self-buffering formulation consists of adalimumab and water. 
     
     
         5 . The self-buffering protein formulation of  claim 4 , wherein the self-buffering formulation is a pharmaceutical formulation. 
     
     
         6 . The self-buffering protein formulation of  claim 4 , wherein the pH of the self-buffering formulation is from 4 to 8. 
     
     
         7 . The self-buffering protein formulation of  claim 4 , wherein the pH of the formulation is from 5 to 6. 
     
     
         8 . The self-buffering protein formulation of  claim 4 , wherein the pH of the formulation is from 4 to 6. 
     
     
         9 . A formulation consisting of:
 water; and   adalimumab or epratuzumab at a concentration between 20 and 200 mg/ml, wherein the formulation has a pH of 4 to 6.   
     
     
         10 . The formulation of  claim 9 , wherein the formulation consists of water and adalimumab. 
     
     
         11 . The formulation of  claim 10 , wherein the formulation is a pharmaceutical formulation. 
     
     
         12 . The formulation of  claim 10 , wherein the pH of the self-buffering formulation is from 4 to 8. 
     
     
         13 . The formulation of  claim 10 , wherein the pH of the formulation is from 5 to 6. 
     
     
         14 . The formulation of  claim 10 , wherein the pH of the formulation is from 4 to 6. 
     
     
         15 . A formulation comprising:
 adalimumab or epratuzumab at concentration between 20 and 200 mg/ml; and   water, wherein, the formulation has less than 25 mM total salt.   
     
     
         16 . The formulation of  claim 15 , wherein the formulation comprises adalimumab. 
     
     
         17 . The formulation of  claim 16 , wherein the pH of the formulation is from 4 to 8. 
     
     
         18 . The formulation of  claim 16 , wherein the pH of the formulation is from 4 to 6. 
     
     
         19 . The formulation of  claim 16 , wherein the pH of the formulation is from 5 to 6. 
     
     
         20 . The formulation of  claim 16 , wherein the pH of the formulation is 5. 
     
     
         21 . The formulation of  claim 16 , wherein the formulation, exclusive of the buffer capacity of the antibody, has a buffer capacity per unit volume of the solution at the pH of the solution, 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere of no more than that of 2.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 at 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere. 
     
     
         22 . The formulation of  claim 16 , wherein, the formulation, exclusive of the buffer capacity of the antibody, has a buffer capacity per unit volume of the solution at the pH of the solution, 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere of no more than that of 2.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 at 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere, and wherein at the pH of the composition, 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere, the antibody has a buffer capacity per unit volume of at least that of 4.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 at 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere. 
     
     
         23 . The formulation of  claim 16 , wherein the formulation is substantially free of any buffering agent other than the pharmaceutical protein. 
     
     
         24 . A formulation comprising:
 adalimumab or epratuzumab at concentration between 20 and 200 mg/ml; and   water, wherein, the formulation lacks a tonicity agent.   
     
     
         25 . The formulation of  claim 24 , wherein the formulation comprises adalimumab. 
     
     
         26 . The formulation of  claim 25 , wherein a pH of the formulation is from 4 to 6. 
     
     
         27 . The formulation of  claim 25 , wherein a pH of the formulation is from 4 to 8. 
     
     
         28 . The formulation of  claim 25 , wherein a pH of the formulation is 5. 
     
     
         29 . The formulation of  claim 25 , wherein a pH of the formulation is from 5 to 6. 
     
     
         30 . The formulation of  claim 25 , wherein the formulation, exclusive of the buffer capacity of the antibody, has a buffer capacity per unit volume of the solution at the pH of the solution, 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere of no more than that of 2.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 at 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere. 
     
     
         31 . The formulation of  claim 25 , wherein, the formulation, exclusive of the buffer capacity of the antibody, has a buffer capacity per unit volume of the solution at the pH of the solution, 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere of no more than that of 2.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 at 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere, and wherein at the pH of the composition, 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere, the antibody has a buffer capacity per unit volume of at least that of 4.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 at 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere. 
     
     
         32 . The formulation of  claim 25 , wherein the formulation is substantially free of any buffering agent other than the pharmaceutical protein.