Protein formulations and methods of making same

Abstract

The invention provides an aqueous formulation comprising water and a protein, and methods of making the same. The aqueous formulation of the invention may be a high protein formulation and/or may have low levels of conductity resulting from the low levels of ionic excipients. Also included in the invention are formulations comprising water and proteins having low osmolality.

1 . An aqueous formulation comprising an antibody, or antigen-binding fragment thereof, and water, wherein the formulation has a conductivity of less than about 2.5 mS/cm and the antibody, or antigen-binding fragment thereof, has a molecular weight (Mw) greater than about 47 kDa 
     
     
         2 . An aqueous formulation comprising an antibody, or antigen-binding fragment thereof, at a concentration of at least about 50 mg/mL and water, wherein the formulation has an osmolality of no more than about 30 mOsmol/kg. 
     
     
         3 . An aqueous formulation comprising water and a given concentration of an antibody, or antigen-binding fragment thereof, wherein the antibody, or antigen-binding fragment thereof, has a hydrodynamic diameter (Dh) which is at least about 50% less than the Dh of the antibody, or antigen-binding fragment thereof, in a buffered solution at the given concentration. 
     
     
         4 . An aqueous formulation comprising an antibody, or an antigen-binding fragment, at a concentration of at least about 10 mg/mL and water, wherein the antibody, or antigen-binding fragment, has a hydrodynamic diameter (Dh) of less than about 5 μm. 
     
     
         5 . The formulation of  claim 1 , wherein the antibody, or antigen-binding fragment thereof, is an anti-TNFα antibody. 
     
     
         6 . The formulation of  claim 1 , wherein the concentration of antibody, or antigen-binding fragment thereof, is 50 to 200 mg/ml. 
     
     
         7 . The formulation of  claim 1 , further comprising a non-ionizable excipient. 
     
     
         8 . The formulation of  claim 7 , wherein the non-ionizable excipient is selected from the group consisting of sugar alcohols and polyols such as mannitol or sorbitol, a non-ionic surfactant, sucrose, trehalose, raffinose, and maltose. 
     
     
         9 . A method of treating a subject having a disorder, comprising administering to the subject the formulation of  claim 1 . 
     
     
         10 . A device comprising the formulation of  claim 1 . 
     
     
         11 . An article of manufacture comprising the formulation of  claim 1 . 
     
     
         12 . A method of preparing an aqueous formulation comprising an antibody, or antigen-binding fragment thereof, and water, the method comprising:
 a) providing the antibody, or antigen-binding fragment thereof, in a first solution; and   b) subjecting the first solution to diafiltration using water as a diafiltration medium until at least a five-fold volume exchange with the water has been achieved to thereby prepare the aqueous formulation.   
     
     
         13 . An aqueous formulation prepared according to the method of  claim 12 . 
     
     
         14 . The formulation of  claim 2 , wherein the antibody, or antigen-binding fragment thereof, is an anti-TNFα antibody. 
     
     
         15 . The formulation of  claim 2 , wherein the concentration of antibody, or antigen-binding fragment thereof, is 50 to 200 mg/ml. 
     
     
         16 . A method of treating a subject having a disorder, comprising administering to the subject the formulation of  claim 2 . 
     
     
         17 . A device comprising the formulation of  claim 2 . 
     
     
         18 . An article of manufacture comprising the formulation of  claim 2 . 
     
     
         19 . The formulation of  claim 3 , wherein the antibody, or antigen-binding fragment thereof, is an anti-TNFα antibody. 
     
     
         20 . The formulation of  claim 3 , wherein the concentration of antibody, or antigen-binding fragment thereof, is 50 to 200 mg/ml. 
     
     
         21 . A method of treating a subject having a disorder, comprising administering to the subject the formulation of  claim 3 . 
     
     
         22 . A device comprising the formulation of  claim 3 . 
     
     
         23 . An article of manufacture comprising the formulation of  claim 3 . 
     
     
         24 . The formulation of  claim 4 , wherein the antibody, or antigen-binding fragment thereof, is an anti-TNFα antibody. 
     
     
         25 . The formulation of  claim 4 , wherein the concentration of antibody, or antigen-binding fragment thereof, is 50 to 200 mg/ml. 
     
     
         26 . A method of treating a subject having a disorder, comprising administering to the subject the formulation of  claim 4 . 
     
     
         27 . A device comprising the formulation of  claim 4 . 
     
     
         28 . An article of manufacture comprising the formulation of  claim 4 .