Formulations

• US 20080213282A1
• Filed: 12/19/2007
• Published: 09/04/2008
• Est. Priority Date: 12/21/2006
• Status: Abandoned Application

• Current Assignee: Amgen Inc.
• Original Assignee: Amgen Inc.
• Inventors: Matsumura, Masazumi, Gokarn, Yatin, Brems, David, Jacob, Jaby
• Application Number:
  US12/004,114
• Publication Number:
  US 20080213282A1
• Time in Patent Office: Days
• US Class Current: 424/158.1
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• 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 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/22 against growth factors ; against growth regulators
• CPC Class Codes: C07K 2317/94 Stability, e.g. half-life, pH, temperature or enzyme-resistance

Abstract

The invention provides a formulation comprising a buffer with a pH from about 4.0 to about 6.0, proline and an effective amount of a polypeptide. The polypeptide can be an antibody. The specification also provides methods of preparing the formulation, a kit containing the formulation and methods of using the formulation.

Claims

1. A formulation comprising a glutamic acid or aspartic acid buffer having a pH from about 4.0 to about 6.0, proline at a concentration of about 2% to about 10%, and an antibody or antigen-binding fragment.

2. The formulation of claim 1, wherein the glutamic acid or aspartic acid buffer comprises a concentration from about 5 mM to about 50 mM.

3. The formulation of claim 1, wherein the glutamic acid buffer or aspartic acid buffer comprises a concentration of about 10 mM, about 30 mM or about 50 mM and a pH of about 5.

4. The formulation of claim 1 having an isotonic concentration.

5. The formulation of claim 1, wherein the antibody or antigen-binding fragment binds a growth factor.

6. The formulation of claim 5, wherein the growth factor is a nerve growth factor.

7. The formulation of claim 1, wherein the antibody or antigen-binding fragment has a concentration from about 10 to about 50 mg/ml.

8. The formulation of claim 1, wherein the formulation comprises between about 1-50 mM glutamic acid or aspartic acid with a pH from about 4.0 to about 6.0, about 2% to about 10% proline and a therapeutically effective amount an antibody or antigen-binding fragment to nerve growth factor.

9. The formulation of claim 1, wherein the glutamic acid buffer or the aspartic acid buffer is prepared from sodium glutamate or sodium aspartate.

10. The formulation of claim 1, wherein the pH is about 5.0.

11. The formulation of claim 5, wherein the antibody or antigen-binding fragment comprises about 10 to about 50 mg/ml.

46. The formulation of any one of claims 1, 18 or 35 wherein the antibody or antigen-binding fragment has a concentration greater than 50 mg/ml.

47. The formulation of claim 46 wherein the antibody or antigen-binding fragment has a concentration of about 50 mg/ml to about 100 mg/ml.

48. The formulation of claim 46 wherein the antibody or antigen-binding fragment concentration is greater than about 100 mg/ml.

49. The formulation of any one of claims 1, 18 or 35 wherein the antibody or antigen-binding fragment concentration is about 2 mg/ml to about 10 mg/ml.

12. A method of preparing a formulation comprising combining a glutamic acid or aspartic acid buffer having a pH from about 4.0 to about 6.0, proline and an effective amount of an antibody or antigen-binding fragment.

13. A container containing a formulation comprising an aqueous solution having between about 3 to about 50 mM glutamic acid or aspartic acid with a pH from about 4.0 to about 6.0, proline from about 2% to about 10% and an antibody or antigen-binding fragment.

14. The container of claim 13, wherein the antibody or antigen-binding fragment concentration is from about 10 to about 50 mg/ml.

15. The container of claim 13, wherein the container is a vial or a pre-filled syringe.

50. The container of claim 13, wherein the antibody or antigen-binding fragment concentration is from about 2 mg/ml to about 10 mg/ml. or about 50 mg/ml to about 100 mg/ml.

16. A method of treating a condition caused by increased expression of nerve growth factor or increased sensitivity to nerve growth factor in a patient, comprising administering to a patient a pharmaceutically effective amount of a formulation comprising a glutamic acid buffer or aspartic acid buffer having a pH from about 4.0 to about 6.0, proline at a concentration of about 2% to about 10%, and an effective amount of an antibody or antigen-binding fragment to nerve-growth factor.

17. The method of claim 16 wherein the condition is pain or neuropathic pain.

18. A formulation comprising an acetic buffer having a pH from about 4.0 to about 6.0, proline at a concentration of about 2% to about 10%, and an antibody or antigen-binding fragment, wherein the formulation does not further comprise both a polyol and a surfactant.

19. The formulation of claim 18, wherein the acetic acid buffer comprises a concentration from about 5 mM to about 50 mM.

20. The formulation of claim 18, wherein the acetic acid buffer comprises a concentration of about 10 mM, 30 mM or 50 mM and a pH of about 5.

21. The formulation of claim 18 having an isotonic concentration.

22. The formulation of claim 18, wherein the antibody or antigen-binding fragment binds a growth factor.

23. The formulation of claim 22, wherein the growth factor is a nerve growth factor.

24. The formulation of claim 18, wherein the antibody or antigen-binding fragment has a concentration from between about 10 mg/ml to about 50 mg/ml.

25. The formulation of claim 18, wherein the formulation comprises between about 1-50 acetic acid buffer with a pH from about 4.0 to about 6.0, about 2% to about 10% proline and a therapeutically effective amount of an antibody or antigen-binding fragment to nerve growth factor.

26. The formulation of claim 18, wherein the acetic acid buffer is prepared from sodium acetate.

27. The formulation of claim 18 wherein the pH is about 5.0.

28. The formulation of claim 22, wherein the antibody or antigen-binding fragment comprises about 10 to about 50 mg/ml.

29. A method of preparing a formulation comprising combining a acetic acid buffer having a pH from about 4.0 to about 6.0, proline and an effective amount of an antibody or antigen-binding fragment, wherein the formulation does not further comprise both a polyol and a surfactant.

30. A container containing a formulation comprising an aqueous solution having between about 3 to about 50 mM acetic acid with a pH from about 4.0 to about 6.0, proline from about 2% to about 10% and an antibody or antigen-binding fragment, wherein the aqueous solution does not further comprise both a polyol and a surfactant.

31. The container of claim 30, wherein the therapeutic polypeptide concentration is from about 3 to about 70 mg/ml, about 5 to about 60 mgl/ml, about 10 to about 50 mg/ml, about 20 to about 40 mg/ml, about 30 to about 100 mg/ml, or about 40 to about 200 mg/ml.

32. The container of claim 30, wherein the container is a vial or a pre-filled syringe.

33. A method of treating a condition caused by increased expression of nerve growth factor or increased sensitivity to nerve growth factor in a patient, comprising administering to a patient a pharmaceutically effective amount of a formulation comprising an acetic acid buffer having a pH from about 4.0 to about 6.0, proline at a concentration of about 2% to about 10%, and an effective amount of an antibody or antigen-binding fragment to nerve-growth factor, wherein the formulation does not further comprise both a polyol and a surfactant.

34. The method of claim 33, wherein the condition is pain or neuropathic pain.

35. A formulation consisting essentially of proline and an antibody or antigen-binding fragment at a concentration wherein the formulation maintains a selected pH during storage.

36. The formulation of claim 35 wherein the proline is at a concentration of about 2% to about 10%.

37. The formulation of claim 35, wherein the pH is maintained at a pH of about pH 4 to about pH 6 during storage.

38. The formulation of claim 37, wherein the pH is maintained at a pH of about pH 5.0

39. The formulation of claim 35, wherein the antibody or antigen-binding fragment binds to nerve growth factor.

40. A method of treating a condition caused by increased expression of nerve growth factor or increased sensitivity to nerve growth factor in a patient, comprising administering to a patient a pharmaceutically effective amount of a formulation consisting essentially of proline and an antibody or antigen-binding fragment at a concentration wherein the formulation maintains a selected pH during storage.

41. The method of claim 40, wherein the condition is pain or neuropathic pain.

42. A formulation comprising an acetic acid buffer having a pH from about 4.0 to about 6.0, proline at a concentration of about 2% to about 10%, and an antibody or antigen-binding fragment.

43. A kit comprising in one or more containers a glutamic acid or aspartic acid buffer having a pH from about 4.0 to about 6.0 or an appropriate glutamate or aspartate salt to prepare such a buffer, proline at a concentration of about 2% to about 10%, and an antibody or antigen-binding fragment, and instructions regarding the use thereof.

44. A kit comprising in one or more containers proline at a concentration of about 2% to about 10% and an antibody or antigen-binding fragment at a concentration wherein when mixed together, the proline and antibody or antigen-binding fragment maintain a selected pH during storage of the mixture, and instructions regarding the use thereof.

45. A kit comprising in one or more containers an acetic buffer having a pH from about 4.0 to about 6.0 or an appropriate acetate salt to prepare such a buffer, proline at a concentration of about 2% to about 10%, and an antibody or antigen-binding fragment, wherein the kit does not further comprise both a polyol and a surfactant, and instructions regarding the use thereof.