FORMULATIONS THAT STABILIZE PROTEINS

• US 20140242182A1
• Filed: 07/06/2012
• Published: 08/28/2014
• Est. Priority Date: 07/07/2011
• Status: Abandoned Application

• Current Assignee: LFB USA, Inc. (Agence des Participations de l’Etat)
• Original Assignee: rEVO Biologics, Inc. (Agence des Participations de l’Etat)
• Inventors: Allard, Greg J., Masiello, Nicholas C., Evans, Sean A.
• Application Number:
  US14/131,289
• Publication Number:
  US 20140242182A1
• Time in Patent Office: Days
• US Class Current: 424/535
• CPC Class Codes: A61K 38/57 from animals; from humans A61K38/553, A61K38/556 take precedence
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors

Abstract

In one aspect, the disclosure provides formulations that stabilize proteins, wherein the formulations comprise a buffer. In some embodiments, the buffer comprises potassium mono-hydrogen-phosphate and potassium di-hydrogen-phosphate, or the buffer comprises sodium mono-hydrogen-phosphate and sodium di-hydrogen-phosphate. In some embodiments, the protein is a therapeutic protein. In some embodiments, the therapeutic protein is antithrombin.

Claims

1. A formulation comprising a therapeutic protein and a buffer,

wherein the buffer comprises potassium mono-hydrogen-phosphate and potassium di-hydrogen-phosphate, or

wherein the buffer comprises sodium mono-hydrogen-phosphate and sodium di-hydrogen-phosphate.

2. The formulation of claim 1, wherein the buffer has a concentration of between 10 mM and 100 mM.

3. The formulation of claim 2, wherein the buffer has a concentration of 50 mM.

4. The formulation of claim 1, further comprising potassium chloride.

5. The formulation of claim 4, wherein the potassium chloride has a concentration of between 100 and 150 mM.

6. The formulation of claim 4, wherein the potassium chloride has a concentration of 120 mM.

7. The formulation of claim 1, wherein the pH of the formulation is between 7.5 and 8.5.

8. The formulation of claim 7, wherein the pH of the formulation is 8.

9. The formulation of claim 1, wherein the therapeutic protein is antithrombin.

10. The formulation of claim 1, wherein the formulation comprises a clarified milk product.

11. The formulation of claim 1, wherein the formulation includes additional proteins.

12. The formulation of claim 9, wherein the antithrombin maintains at least 90% of heparin binding functionality after storage at 2-8°

C. for three months as compared to heparin binding functionality prior to storage.

13. The formulation of claim 12, wherein the increase in the amount of antithrombin (by weight) that is in an aggregated form after storage at 2-8°

C. for three months is less than 3-fold as compared to the amount of antithrombin (by weight) that is in an aggregated form prior to storage.

14. The formulation of claim 12, wherein the increase in the amount of oxidation of antithrombin after storage at 2-8°

C. for three months is less than 2-fold compared to the amount of oxidation of antithrombin prior to storage.

15. A method for generating a formulation that stabilizes a therapeutic protein, the method comprising:

providing a solution comprising a buffer,

wherein the buffer comprises potassium mono-hydrogen-phosphate and potassium di-hydrogen-phosphate, or

wherein the buffer comprises sodium mono-hydrogen-phosphate and sodium di-hydrogen-phosphate, and

adding the therapeutic protein to the solution resulting in a formulation that stabilizes the therapeutic protein.

17. The method of claim 15, wherein the resulting concentration of the buffer is 50 mM.

18. The method of claim 15, wherein the formulation further comprises potassium chloride.

19. The method of claim 15, wherein the resulting pH of the solution is a pH of 8.

20. The method of claim 15, wherein the therapeutic protein is antithrombin.

16. A method for generating a formulation that stabilizes a therapeutic protein, the method comprising:

providing a solution comprising the therapeutic protein, and adding a buffer to the solution resulting in a formulation that stabilizes the therapeutic protein,

wherein the buffer comprises potassium mono-hydrogen-phosphate and potassium di-hydrogen-phosphate, or

wherein the buffer comprises sodium mono-hydrogen-phosphate and sodium di-hydrogen-phosphate.

21. A method for generating a formulation that stabilizes antithrombin, the method comprising:

separating antithrombin from a milk composition comprising antithrombin resulting in a solution comprising antithrombin,

pasteurizing the solution comprising antithrombin,

exchanging the solution comprising antithrombin for a buffer,

wherein the buffer comprises potassium mono-hydrogen-phosphate and potassium di-hydrogen-phosphate, or

wherein the buffer comprises sodium mono-hydrogen-phosphate and sodium di-hydrogen-phosphate,

thereby generating a formulation that stabilizes antithrombin.