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1. (WO2008051363) FORMULATIONS STABLES DE POLYPEPTIDE
Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

What is claimed is:

1. A formulation comprising a buffer having a pH from about 4.0 to less than 6.0, a divalent cation between about 5-150 mM, an excipient comprising a sugar or polyol and an effective amount of a therapeutic antibody having specific binding activity to human epidermal growth factor receptor (EGFR), wherein said therapeutic antibody retains at least about 80% stability for up to two months in solution.

2. The formulation of claim 1 , wherein said divalent cation is selected from CaCl2, ZnCl2, MnCl2 or MgCl2.

3. The formulation of claim 2, wherein said divalent cation is CaCl2.

4. The formulation of claim 1 , wherein said divalent cation concentration is selected from about 25 mM, 50 mM, 75 mM, 100 mM or 125 mM.

5. The formulation of claim 3, wherein said CaCl2 concentration is 75 mM.

6. The formulation of claim 1 , wherein said pH comprises between 4.8-5.2

7. The formulation of claim 1, wherein said buffer is selected from acetic acid, glutamic acid or succinic acid, or a salt thereof.

8. The formulation of claim 1, wherein said buffer comprises a concentration of about 1-5O mM.

9. The formulation of claim 1, wherein said sugar or polyol is selected from glycerol, sucrose, trehalose or sorbitol.

10. The formulation of claim 9, wherein said glycerol, sucrose, trehalose or sorbitol comprises a concentration of about 1-20%.

11. The formulation of claim 9, wherein said glycerol comprises a concentration of between about 1-3%.

12. The formulation of claim 1 , further comprising a surfactant.

13. The formulation of claim 12, wherein said surfactant comprises a polysorbate.

14. The formulation of claim 12, wherein said surfactant comprises a
concentration of about 0.001-0.10 % (w/v).

15. The formulation of claim 1, further comprising a second excipient.

16. The formulation of claim 15, wherein said second excipient is selected from a buffer, stabilizer, tonicity agent, bulking agent, surfactant, cryoprotectant, lyoprotectant, antioxidant, metal ion, chelating agent and preservative.

17. The formulation of claim 1 , wherein said therapeutic antibody having specific binding activity to human EGFR comprises an Asp or Asn residue susceptible to
isomerization to isoaspartic acid.

18. The formulation of claim 1 , wherein said therapeutic antibody having specific binding activity to human EGFR comprises a human antibody, a humanized antibody, a chimeric antibody, or a functional fragment thereof.

19. The formulation of claim 18, wherein said human antibody is panitumumab.

20. The formulation of claim 18, wherein said chimeric antibody is ErbituxTm (cetuximab).

21. The formulation of claim 18, wherein said human antibody is selected from IMC-11F8 or HUMAX-EGFR.

22. The formulation of claim 18, wherein said humanized antibody is selected from matuzumab (EMD-7200) or nimotuzumab (TheraCIM hR3).

23. The formulation of claim 18, wherein said functional fragment thereof comprises a Fd, Fv, Fab, F(ab'), F(ab)2, F(ab')2, single chain Fv (scFv) or chimeric antibody.

24. The formulation of claim 1, wherein said therapeutic antibody comprises a concentration selected from between about 10-200 mg/ml.

25. A method of stabilizing a polypeptide, comprising contacting a therapeutic antibody having specific binding activity to human epidermal growth factor receptor (EGFR) with a concentration of divalent cation between about 5-150 150 mM in a buffer having a pH from about 4.0 to less than 6.0 and an excipient comprising a sugar or polyol, wherein said therapeutic antibody retains at least about 80% stability for up to two months in solution.

26. The method of claim 25, wherein said divalent cation is selected from CaCl2, ZnCl2, MnCl2 or MgCl2.

27. The method of claim 26, wherein said divalent cation is CaCl2.

28. The method of claim 25, wherein said divalent cation concentration is selected from about 25 mM, 50 mM, 75 mM, 100 mM or 125 mM.

29. The method of claim 27, wherein said CaCl2 concentration is 75 mM.

30. The method of claim 25, wherein said pH comprises between 4.8-5.2

31. The method of claim 25, wherein said buffer is selected from acetic acid, glutamic acid or succinic acid, or a salt thereof.

32. The method of claim 25, wherein said buffer comprises a concentration of about 1-5O mM.

33. The method of claim 25, wherein said sugar or polyol is selected from glycerol, sucrose, trehalose or sorbitol.

34. The method of claim 33, wherein said glycerol, sucrose, trehalose or sorbitol comprises a concentration of about 1 -20%.

35. The method of claim 33, wherein said glycerol comprises a concentration of between about 1-3%.

36. The method of claim 25, further comprising a surfactant.

37. The method of claim 36, wherein said surfactant comprises a polysorbate.

38. The method of claim 36, wherein said surfactant comprises a concentration of about 0.001-0.10 % (w/v).

39. The method of claim 25, further comprising a second excipient.

40. The method of claim 39, wherein said second excipient is selected from a buffer, stabilizer, tonicity agent, bulking agent, surfactant, cryoprotectant, lyoprotectant, antioxidant, metal ion, chelating agent and preservative.

41. The method of claim 25, wherein said therapeutic antibody having specific binding activity to human EGFR comprises an Asp or Asn residue susceptible to
isomerization to isoaspartic acid.

42. The method of claim 25, wherein said therapeutic antibody having specific binding activity to human EGFR comprises a human antibody, a humanized antibody, a chimeric antibody, or a functional fragment thereof.

43. The method of claim 42, wherein said human antibody is panitumumab.

44. The method of claim 42, wherein said chimeric antibody is ErbituxTm
(cetuximab).

45. The method of claim 42, wherein said human antibody is selected from IMC-11F8 or HUMAX-EGFR.

46. The method of claim 42, wherein said humanized antibody is selected from matuzumab (EMD-7200) or nimotuzumab (TheraCIM hR3).

47. The method of claim 42, wherein said functional fragment thereof comprises a Fd, Fv, Fab, F(ab'), F(ab)2, F(ab')2, single chain Fv (scFv) or chimeric antibody.

48. The method of claim 25, wherein said therapeutic antibody comprises a concentration selected from between about 10-200 mg/ml.