Clostridium botlinum neurotoxin serotype a compositions and improved drying processes

Abstract

Provided herein are solid compositions comprising Clostridium botulinum neurotoxin serotype A (BoNT / A), human serum albumin (HSA) and sodium chloride (NaCl); wherein less than 34% of soluble HSA conta

Claims

1. A solid composition comprising a 900 kDa Clostridium botulinum neurotoxin serotype A (BoNT / A) complex, human serum albumin (HSA), and sodium chloride (NaCl), wherein the HSA comprises HSA monomer and HSA aggregates, wherein at least a portion of the HSA is in the form of soluble HSA when the solid composition is reconstituted in an aqueous medium, and wherein less than 34% of soluble HSA contained in the solid composition are HSA aggregates.

2. The solid composition of claim 1, wherein the HSA aggregates comprise HSA polymer, HSA oligomer, and HSA dimer.

3. The solid composition of claim 1 and claim 2, wherein less than 30% of the soluble HSA contained in the solid composition is HSA polymer.

4. The solid composition of claim 1 and claim 2, wherein less than 0.8% of soluble HSA contained in the solid composition is HSA oligomer.

5. The solid composition of claim 1 and claim 2, wherein less than 4.8% of soluble HSA contained in the solid composition is HSA dimer.

6. The solid composition of any one of claims 1 to 5, wherein the percentage of the HSA aggregates, the HSA polymer, the HSA oligomer, and / or the HSA dimer in the soluble HSA contained in the solid composition is determined using size exclusion chromatography (SEC) after at least a portion of the solid composition is reconstituted with water.

7. The solid composition of any one of claims 1 to 6, wherein the solid composition is a powdered pharmaceutical composition.

8. The solid composition of any one of claims 1 to 7, wherein the percentage of the HSA aggregates, the HSA polymer, the HSA oligomer, and / or the HSA dimer in the soluble HSAcontained in the solid composition is determined using size exclusion chromatography (SEC) by a 220 nm wavelength UV detector after at least a portion of the solid composition is reconstituted with water.

9. The solid composition of any one of claims 1 to 8, wherein the solid composition is animal product free.

10. The solid composition of any one of claims 1 to 9, wherein the HSA is recombinant HSA.

11. The solid composition of any one of claims 1 to 10, wherein the solid composition comprises about 0.5 mg of HSA per 100 units of BoNT / A.

12. The solid composition of any one of claims 1 to 11, wherein the solid composition comprises about 0.9 mg of NaCl per 100 units of BoNT / A.

13. The solid composition of any one of claims 1 to 12, wherein the BoNT / A is onabotulinumtoxinA.

14. The solid composition of any one of claims 1 to 13, where the BoNT / A is produced by a column chromatography purification process.

15. The solid composition of any one of claims 1 to 14, where the BoNT / A is produced by a column chromatography purification process, wherein the column chromatography purification process comprises hydrophobic interaction chromatography.

16. The solid composition of any one of claims 1 to 15, wherein the column chromatography purification process further comprises anion exchange chromatography.

17. The solid composition of any one of claims 1 to 16, wherein the column chromatography purification process further comprises cation exchange chromatography.

18. The solid composition of any one of claims 1 to 17, wherein the solid composition does not comprise a protease inhibitor.

19. The solid composition of any one of claims 1 to 18, wherein the solid composition does not comprise benzamidine hydrocholoride.

20. The solid composition of any one of claims 1 to 19, wherein the solid composition has a potency of about 1.5 x 107 units / mg to about 6.0 x 107 units / mg.

21. A method of producing a solid composition comprising a 900 kDa BoNT / A complex, HSA, and NaCl, said method comprising a step of drying a solution comprising BoNT / A, HSA, and NaCl to produce said solid composition, wherein the solution does not undergo freezing during the drying step.

22. The method of claim 21, wherein the step of drying is at least partially manually controlled.

23. The method of claim 21 or claim 22, wherein the step of drying is vacuum drying.

24. The method of claim 23, wherein the vacuum drying step comprises a stepwise evacuating step.

25. The method of any one of claims 21-24, wherein the method produces a solid composition according to any one of claims 1 -20.

26. A solid composition produced by the method of any one of claims 21 to 25.

27. A method of treating a patient in need thereof, comprising administering the solid composition of any one of claims 1-20 and 26.

28. A method substantially as described herein.

29. A composition substantially as described herein.

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