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 . A method of preparing an aqueous formulation comprising a protein and water, the method comprising:
a) providing the protein 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.
2 . The method of claim 1 , wherein the diafiltration medium consists of water.
3 . The method of claim 1 , wherein the first solution is subjected to diafiltration with water until at least about a six-fold volume exchange is achieved.
4 . The method of claim 1 , wherein the aqueous formulation has a final concentration of excipients which is at least about 95% less than the first solution.
5 . The method of claim 1 , wherein the protein has a M w greater than about 150 kDa.
6 . The method of claim 1 , further comprising adding an excipient to the aqueous formulation.
7 . The method of claim 1 , wherein the aqueous formulation is a pharmaceutical formulation.
8 . The method of claim 1 , wherein the protein is an antibody, or an antigen-binding fragment thereof.
9 . The method of claim 8 , wherein the antibody, or antigen-binding fragment thereof, is selected from the group consisting of a chimeric antibody, a human antibody, a humanized antibody, and a domain antibody (dAb).
10 . The method of claim 8 , wherein the antibody, or antigen-binding fragment thereof, is an anti-TNRα antibody.
11 . The method of claim 8 , wherein the antibody, or antigen-binding fragment thereof, is adalimumab.
12 . A method of preparing an aqueous formulation of a protein, the method comprising:
a) providing the protein in a first solution;
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 a diafiltered protein solution; and
c) concentrating the diafiltered protein solution to thereby prepare the aqueous formulation of the protein.
13 . The method of claim 12 , wherein the diafiltration medium consists of water.
14 . The method of claim 12 , wherein the first solution is subjected to diafiltration with water until at least about a six-fold volume exchange is achieved.
15 . The method of claim 12 , wherein the aqueous formulation has a final concentration of excipients which is at least about 95% less than the first solution.
16 . The method of claim 12 , wherein the protein has a M w greater than about 150 kDa.
17 . The method of claim 12 , wherein the aqueous formulation is a pharmaceutical formulation.
18 . The method of claim 12 , further comprising adding an excipient to the aqueous formulation.
19 . The method of claim 12 , wherein the protein is an antibody, or an antigen-binding fragment thereof.
20 . The method of claim 19 , wherein the antibody, or antigen-binding fragment thereof, is selected from the group consisting of a chimeric antibody, a human antibody, a humanized antibody, and a domain antibody (dAb).
21 . The method of claim 19 , wherein the antibody, or antigen-binding fragment thereof, is an anti-TNRα antibody.
22 . The method of claim 19 , wherein the antibody, or antigen-binding fragment thereof, is adalimumab.