Buffering agents for biopharmaceutical formulations

• US 20080003220A1
• Filed: 04/19/2007
• Published: 01/03/2008
• Est. Priority Date: 04/21/2006
• Status: Abandoned Application

• Current Assignee: Amgen Inc.
• Original Assignee: Amgen Inc.
• Inventors: Gokarn, Yatin
• Application Number:
  US11/788,770
• Publication Number:
  US 20080003220A1
• Time in Patent Office: Days
• US Class Current: 424/135.1
• CPC Class Codes: A61K 39/39591 Stabilisation, fragmentation
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• 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: A61P 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily

Abstract

The invention provides a biopharmaceutical formulation including an aqueous solution having a propionate buffer with a pH from about 4.0 to about 6.0, at least one excipient and an effective amount of a therapeutic polypeptide. The propionate buffer can include a concentration selected from between about 1-50 mM, 2-30 mM, 3-20 mM, 4-10 mM and 5-8 mM. The therapeutic polypeptide included in a biopharmaceutical formulation of the invention can include an antibody, Fd, Fv, Fab, F(ab′), F(ab)₂, F(ab′)₂, single chain Fv (scFv), chimeric antibodies, diabodies, triabodies, tetrabodies, minibody, peptibody, hormone, growth factor or cell signaling molecule. The invention also provides a method of preparing a biopharmaceutical formulation. The method includes combining an aqueous solution having a propionate buffer with a pH from about 4.0 to about 6.0 and at least one excipient with an effective amount of a therapeutic polypeptide.

Claims

1. A biopharmaceutical formulation comprising an aqueous solution having a propionate buffer with a pH from about 4.0 to about 6.0, at least one excipient and an effective amount of a therapeutic polypeptide.

2. The biopharmaceutical formulation of claim 1, wherein said propionate buffer comprises sodium propionate or propionic acid.

3. The biopharmaceutical formulation of claim 1, wherein said propionate comprises a concentration selected from between about 1-50 mM, 2-30 mM, 3-20 mM, 4-10 mM and 5-8 mM.

4. The biopharmaceutical formulation of claim 1, wherein said propionate comprises a concentration of about 10 mM.

5. The biopharmaceutical formulation of claim 1, having an isotonic concentration of solutes.

6. The biopharmaceutical formulation of claim 1, where in said excipient comprises a sugar or polyols

7. The biopharmaceutical formulation of claim 6, wherein said polyols comprises a concentration selected from between about 1-10%, 2-9%, 3-8%, 4-7% and 5-6%.

8. The biopharmaceutical formulation of claim 6, wherein said polyol comprises sorbitol.

9. The biopharmaceutical formulation of claim 6, wherein said sugar comprises a concentration selected from between about 1-20% (w/v), 2-18% (w/v), 4-16% (w/v), 6-14% (w/v) and 8-12% (w/v).

10. The biopharmaceutical formulation of claim 6, wherein said sugar comprises a non-reducing sugar.

11. The biopharmaceutical formulation of claim 1, wherein said at least one excipient comprises a surfactant.

12. The biopharmaceutical formulation of claim 11, wherein said surfactant comprises a non-ionic surfactant.

13. The biopharmaceutical formulation of claim 11, wherein said non-ionic surfactant comprises a concentration selected from between about 0.001-0.10% (w/v), 0.002-0.05% (w/v), 0.003-0.01% (w/v), 0.004-0.008% (w/v) and 0.005-0.006% (w/v).

14. The biopharmaceutical formulation of claim 12, wherein said non-ionic surfactant comprises polysorbate 20.

15. The biopharmaceutical formulation of claim 1, wherein said at least one excipient further comprises two or more excipients.

16. The biopharmaceutical formulation of claim 15, wherein said two or more excipients are selected from a buffer, stabilizer, tonicity agent, bulking agent, surfactant, cryoprotectant, lyoprotectant, anti-oxidant, metal ion, chelating agent and preservative.

17. The biopharmaceutical formulation of claim 1, wherein said therapeutic polypeptide comprises an antibody, a functional fragment of an antibody, a hormone, a growth factor or a cell signaling molecule.

18. A biopharmaceutical formulation comprising an aqueous solution having between about 1-50 mM propionate with a pH from about 4.0 to about 6.0, sorbitol between about 1-20% (w/v), polysorbate 20 between about 0.001-0.10% and an effective amount of a therapeutic polypeptide.

19. The biopharmaceutical formulation of claim 18, wherein said propionate comprises a concentration of about 10 mM of sodium propionate.

20. The biopharmaceutical formulation of claim 18, wherein said pH is about 5.0.

21. The biopharmaceutical formulation of claim 18, wherein said sorbitol is about 5% (w/v).

22. The biopharmaceutical formulation of claim 18, wherein said polysorbate 20 is about 0.005% (w/v).

23. The biopharmaceutical formulation of claim 18, wherein said therapeutic polypeptide comprises an antibody, Fd, Fv, Fab, F(ab′

), F(ab)₂, F(ab′

)₂, single chain Fv (scFv), chimeric antibodies, diabodies, triabodies, tetrabodies, minibody, peptibody, hormone, growth factor or cell signaling molecule.

24. The biopharmaceutical formulation of claim 18, wherein said therapeutic polypeptide comprises a concentration selected from between about 10-200 mg/ml, 20-180 mg/ml, 30-160 mg/ml, 40-120 mg/ml, 50-100 mg/ml and 60-80 mg/ml.

25. A method of preparing a biopharmaceutical formulation comprising combining an aqueous solution having a propionate buffer with a pH from about 4.0 to about 6.0 and at least one excipient with an effective amount of a therapeutic polypeptide.

26. The method of claim 25, wherein said aqueous solution comprises between about 1-50 mM propionate with a pH from about 4.0 to about 6.0 and sorbitol between about 1-20% (w/v).

27. The method of claim 25, wherein said propionate comprises a concentration of about 10 mM of sodium propionate.

28. The method of claim 25, wherein said pH is about 5.0.

29. The method of claim 25, wherein said sorbitol is about 5% (w/v).

30. The method of claim 25, wherein said at least one excipient further comprises a surfactant.

31. The method of claim 30, wherein said surfactant comprises polysorbate 20 between about 0.001-0.10% (w/v).

32. The method of claim 31, wherein said polysorbate 20 is about 0.005% (w/v).

33. The method of claim 25, wherein said at least one excipient further comprises two or more excipients.

34. The method of claim 33, wherein said two or more excipients are selected from a buffer, stabilizer, tonicity agent, bulking agent, surfactant, cryoprotectant, lyoprotectant, anti-oxidant, metal ion, chelating agent and preservative.

35. The method of claim 25, wherein said therapeutic polypeptide comprises an antibody, Fd, Fv, Fab, F(ab′

), F(ab)₂, F(ab′

)₂, single chain Fv (scFv), chimeric antibodies, diabodies, triabodies, tetrabodies, minibody, peptibody, hormone, growth factor or cell signaling molecule.

36. The method of claim 25, wherein said therapeutic polypeptide comprises a concentration selected from between about 10-200 mg/ml, 20-180 mg/ml, 30-160 mg/ml, 40-120 mg/ml, 50-100 mg/ml and 60-80 mg/ml.

37. A container containing a biopharmaceutical formulation comprising an aqueous solution having between about 3-20 mM propionate with a pH from about 4.0 to about 6.0, sorbitol between about 1-10% (w/v), polysorbate 20 between about 0.001-0.10% (w/v) and an effective amount of a therapeutic polypeptide.