METHODS OF PREPARING STABLE LIQUID THERAPEUTIC PROTEIN COMPOSITIONS
The invention relates to a method of preparing a stable liquid therapeutic protein pharmaceutical (biopharmaceutical) comprising: a) obtaining an open-ended container comprising a sample, wherein the sample is a therapeutic protein in a solution; b) freezing the sample; c) applying a vacuum while the sample is frozen and; d) sealing the open end of the container while the sample is frozen and while the vacuum is applied to obtain the liquid therapeutic protein composition.
1 . A method of preparing a liquid therapeutic protein composition comprising:
a. Obtaining an open-ended container comprising a sample, wherein the sample is a therapeutic protein in a solution;
b. Freezing the sample;
c. Applying a vacuum while the sample is frozen; and
d. Sealing the open end of the container while the sample is frozen and while the vacuum is applied to obtain the liquid therapeutic protein composition.
2 . The method of claim 1 , wherein the therapeutic protein is selected from the group consisting of antigen binding proteins, antibodies, recombinant proteins, fusion proteins, protein domains, enzymes, polypeptides, and protein-drug conjugates.
3 . The method of claim 1 , wherein the therapeutic protein is a recombinant protein.
4 . The method of claim 3 , wherein the recombinant protein is a fusion protein.
5 . The method of claim 1 , wherein the therapeutic protein is a monoclonal antibody.
6 . The method of claim 1 , wherein the solution is a pharmaceutical formulation.
7 . The method of claim 6 , wherein the pharmaceutical formulation consists of at least one buffer.
8 . The method of claim 6 , wherein the pharmaceutical formulation does not comprise an excipient.
9 . The method of claim 1 , wherein the container is a vial.
10 . The method of claim 1 , wherein the freezing temperature is below the glass transition temperature of the solution.
11 . The method of claim 1 , wherein the vacuum is applied until an internal pressure of less than or equal to 150 mM Ton is achieved.
12 . The method of claim 1 , wherein the container comprises a headspace between the sample and the open end of the container; and wherein after sealing the container the headspace lacks air or is not filled with a gas.
13 . The method of claim 1 , wherein the container is sealed with a stopper.
14 . The method of claim 1 , wherein the obtained liquid therapeutic protein composition has reduced aggregation under stress.
15 . The method of claim 14 , wherein the aggregation is reduced to about 5% to about 20%.
16 . The method of claim 1 wherein the obtained liquid therapeutic protein composition has reduced color change under stress.
17 . The method of claim 16 , wherein the color change is reduced about 2-fold to about 10-fold.
18 . The method of claim 1 , wherein the obtained liquid therapeutic protein composition has reduced oxidation under stress.
19 . The method of claim 18 , wherein the oxidation is reduced to about 5% to about 20%.
20 . The method of claim 14 , wherein the stress is at least one selected from the group consisting of photo stress, thermal stress, and mechanical stress.