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 conductivity resulting from the low levels of ionic excipients. Also included in the invention are formulations comprising water and proteins having low osmolality.

What is claimed: 
     
         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 any one of  claims 1 - 4 , wherein the antibody, or antigen-binding fragment thereof, is an anti-TNFα antibody. 
     
     
         6 . The formulation of any one of  claims 1 - 4 , 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 any one of  claims 1 - 4   
     
     
         10 . A device comprising the formulation of any one of  claims 1 - 4 . 
     
     
         11 . An article of manufacture comprising the formulation of any one of  claims 1 - 4 . 
     
     
         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 .