Claims
- 1. A composition comprising IFN-β or variant thereof and highly purified mannitol.
- 2. The composition of claim 1, wherein said composition is characterized by increased stability.
- 3. The composition of claim 1, wherein said composition is lyophilized.
- 4. The composition of claim 1, wherein said composition is a liquid.
- 5. The composition of claim 1, wherein said highly purified mannitol is present at a concentration of about 0.25% to about 5% by weight per volume.
- 6. The composition of claim 1, wherein said IFN-β or variant thereof is present at a concentration of 0.01 mg/ml to 15 mg/ml.
- 7. The composition of claim 1, wherein said formulation has a pH within a range of about pH 3.0 to about pH 9.0.
- 8. The composition of claim 1, also comprising human albumin.
- 9. The composition of claim 8, wherein said human albumin is present at a concentration of about 0.01% to about 15% by weight per volume.
- 10. A composition comprising IFN-β and highly purified mannitol, wherein said IFN-β is recombinant human IFN-β, said recombinant human IFN-β is present at a concentration of about 0.01 mg/ml to about 15 mg/ml, said highly purified mannitol is present at a concentration of about 0.25% to about 5% by weight per volume, the pH of the composition is about 3.0 to about 9.0, and the composition additionally comprises human albumin at a concentration of about 0.01% to about 15% by weight per volume.
- 11. The composition of claim 10, wherein said composition is lyophilized.
- 12. The composition of claim 10, wherein said composition is a liquid or is frozen.
- 13. A composition comprising IFN-β and highly purified mannitol, wherein said IFN-β is recombinant human IFN-β, said recombinant human IFN-β is present at a concentration of about 0.01 mg/ml to about 15 mg/ml, said highly purified mannitol is present at a concentration of about 0.25% to about 5% by weight per volume, the pH of the composition is about 3.0 to about 9.0, and the composition additionally comprises human albumin at a concentration of about 0.01% to about 15% by weight per volume and sufficient sodium chloride to render the composition isotonic.
- 14. The composition of claim 13, wherein said composition is lyophilized.
- 15. The composition of claim 13, wherein said composition is a liquid or frozen.
- 16. A composition comprising IFN-β and highly purified mannitol, wherein the IFN-β is recombinant human IFN-β, said recombinant human IFN-β is present at a concentration of about 0.05 mg/ml to about 1 mg/ml, said highly purified mannitol is present at a concentration of about 0.25% to about 2.5% by weight per volume, the pH of the composition is about 6.8 to about 8.2, and the composition additionally comprises human albumin at a concentration of about 0.25% to about 2.5% by weight per volume.
- 17. The composition of claim 16, further comprising sufficient sodium chloride to render the composition isotonic.
- 18. The composition of claim 16, wherein said composition is a liquid, wherein said liquid is frozen or lyophilized.
- 19. The composition of claim 17, wherein said composition is a liquid, wherein said liquid is frozen or lyophilized.
- 20. A composition comprising IFN-β and highly purified mannitol, wherein the IFN-β is recombinant human IFN-β, said recombinant human IFN-β is present at a concentration of about 0.25 mg/ml, said highly purified mannitol is present at a concentration of about 1.25% by weight per volume, the pH of the composition is about 7.3 to about 7.5, and the composition additionally comprises human albumin at a concentration of about 1.25% by weight per volume.
- 21. The composition of claim 20, further comprising sufficient sodium chloride to render the composition isotonic.
- 22. The composition of claim 20, wherein said composition is a liquid, wherein said liquid is frozen or lyophilized.
- 23. The composition of claim 21, wherein said composition is a liquid, wherein said liquid is frozen or lyophilized.
- 24. The composition of claim 1, wherein said IFN-β is the polypeptide with the amino acid sequence of mature native human IFN-β.
- 25. The composition of claim 24, wherein said IFN-β is glycosylated or unglycosylated.
- 26. The composition of claim 1, wherein said IFN-β is recombinantly produced.
- 27. A pre-filled syringe comprising the composition of claim 1.
- 28. The pre-filled syringe of claim 27, wherein said composition is frozen.
- 29. A composition comprising IFN-β or variant thereof and mannitol, wherein said mannitol has a reducing activity of less than 20 parts per million.
- 30. A composition comprising a pharmaceutical polypeptide and highly-purified mannitol.
- 31. The composition of claim 30, wherein said pharmaceutical polypeptide is selected from the group consisting of human growth hormone, interferon, interleukin, granulocyte-macrophage colony stimulating factor, granulocyte colony stimulating factor, macrophage colony stimulating factor, beta-glucocerebrosidase, thyrotropins, etanercept, monoclonal antibodies, factor VIIa, factor VIII, urokinase, asparginase, anistreplase, and alteplase.
- 32. A method of producing a formulation of IFN-β or a biologically active variant thereof characterized by improved stability, said method comprising producing a formulation comprising IFN-β or biologically active variant thereof and highly purified mannitol in an amount sufficient to stabilize said IFN-β or variant thereof.
- 33. A formulation made according to the method of claim 32.
- 34. A method of producing a formulation of IFN-β or a biologically active variant thereof, comprising the steps of:
a) removing sodium dodecyl sulfate and salts from the IFN-β by chromatography; b) combining said IFN-β with a solution of human albumin at a pH of about 11.5 to about 12.0; c) adjusting the pH of the solution to 7.5 with HCl; and d) adding a solution of highly purified mannitol.
- 35. A formulation produced according to the method of claim 34.
- 36. The method of claim 34, further comprising the step of lyophilizing the formulation.
- 37. A method for increasing the stability of IFN-β or variant thereof in a pharmaceutical composition, said method comprising incorporating into said composition highly purified mannitol in an amount sufficient to stabilize said IFN-β or variant thereof.
- 38. The method of claim 34, further comprising the step of adding sufficient sodium chloride to render the composition isotonic.
- 39. A formulation produced according to the method of claim 38.
- 40. The method of claim 38, further comprising the step of lyophilizing the formulation.
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional Application Serial No. 60/246,456, filed Nov. 7, 2000, and U.S. Provisional Application Serial No. 60/252,224, filed Nov. 21, 2000, each of which is hereby incorporated in its entirety by reference herein.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60246456 |
Nov 2000 |
US |
|
60252224 |
Nov 2000 |
US |