PROTEIN FORMULATIONS AND METHODS OF MAKING SAME
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.
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 .