Claims for Patent: 7,491,403

Summary for Patent: 7,491,403

Title:	Pharmaceutical botulinum toxin compositions
Abstract:	Botulinum toxin, a well know systemic poison, produces favorable therapeutic effect by virtue of regionally attaching to nerves within the myoneural junction and possibly other tissues in a target region of a particular tissue. The present invention provides compositions of botulinum toxin and a sequestration agent that increase sequestration and delivery of the botulinum toxin to neural and associated tissues, as compared with available formulations of botulinum toxins, and thereby produce a beneficial clinical effect. The sequestration agents of the present invention include proteins, lipids and carbohydrates. A preferred composition of the present invention comprises a botulinum toxin and an albumin. The present invention also provides methods of treating neuromuscular diseases and pain using the disclosed compositions and methods of making the disclosed compositions.
Inventor(s):	Borodic; Gary (Canton, MA)
Assignee:	Botulinum Toxin Research Associates (Quincy, MA)
Application Number:	10/740,755
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 7,491,403
Patent Claims:	1. A composition comprising a therapeutically effective amount of a botulinum toxin, and a human serum albumin, wherein the human serum albumin is present in an amount between 13,000 and 550,000 .mu.g human serum albumin per 100 LD.sub.50 units botulinum toxin. 2. The composition of claim 1, wherein the botulinum toxin is selected from the group consisting of: botulinum toxin types A, B, C, D, E, F and G. 3. The composition of claim 2, wherein the botulinum toxin is botulinum toxin type A from Hall strain Clostridium botulinum. 4. The composition of claim 1, wherein the botulinum toxin comprises fractionated-light-chain botulinum toxin. 5. The composition of claim 1, wherein the botulinum toxin consists essentially of fractionated light chain botulinum toxin. 6. The composition of claim 1, wherein the botulinum toxin consists essentially of a mixture of hybrid and chain-translocated forms of botulinum toxin. 7. The composition of claim 1, wherein the botulinum toxin consists essentially of chimeric forms of botulinum toxin. 8. The composition of claim 1, wherein the botulinum toxin has a specific activity greater than or equal to 20 LD.sub.50 units per nanogram botulinum toxin. 9. The composition of claim 1 further comprising a pharmaceutically acceptable carrier. 10. The composition of claim 1, wherein the botulinum toxin is noncovalently bound to the human serum albumin. 11. The composition of claim 1, wherein the botulinum toxin is covalently bound to the human serum albumin. 12. A composition of claim 1 further comprising zinc or a zinc salt. 13. The composition of claim 1, wherein the human serum albumin is present in an amount between 13,000 and 50,500 .mu.g human serum albumin per 100 LD.sub.50 units botulinum toxin. 14. The composition of claim 1, wherein the human serum albumin is present in an amount between 50,500 and 505,000 .mu.g human serum albumin per 100 LD.sub.50 units botulinum toxin. 15. The composition of claim 1, wherein the human serum albumin is formulated as encapsulated microspheres in an amount between 50,500 and 90,500 .mu.g human serum albumin per 100 LD.sub.50 units botulinum toxin. 16. The composition of claim 1, wherein the human serum albumin is formulated as a solid human serum albumin particle. 17. The composition of claim 1, wherein the human serum albumin is recombinantly produced. 18. The composition of claim 1 further comprising one or more additional sequestration agents. 19. A pharmaceutical composition comprising a therapeutically effective amount of a botulinum toxin, a human serum albumin and a pharmaceutically acceptable carrier, wherein the human serum albumin is present in an amount between 13,000 and 550,000 .mu.g human serum albumin per 100 LD.sub.50 units botulinum toxin. 20. The pharmaceutical composition of claim 19, wherein the human serum albumin is present in an amount between 13,000 and 50,500 .mu.g human serum albumin per 100 LD.sub.50 units botulinum toxin. 21. The pharmaceutical composition of claim 19, wherein the human serum albumin is present in an amount between 50,500 and 505,000 .mu.g human serum albumin per 100 LD.sub.50 units botulinum toxin. 22. The pharmaceutical composition of claim 19, wherein the human serum albumin is present in an amount between 50,500 and 90,500 .mu.g human serum albumin per 100 LD.sub.50 units botulinum toxin. 23. A composition comprising a therapeutically effective amount of a botulinum toxin and a human serum albumin, wherein the human serum albumin is present in an amount between 13,000 and 50,500, between 50,500 and 505,000, or between 50,500 and 90,500, .mu.g human serum albumin per 100 LD.sub.50 units botulinum toxin. 24. A lyophilized pharmaceutical composition comprising a therapeutically effective amount of a botulinum toxin, a human serum albumin and a pharmaceutically acceptable carrier, wherein the human serum albumin is present in an amount between 13,000 and 550,000 .mu.g human serum albumin per 100 LD.sub.50 units botulinum toxin. 25. The lyophilized pharmaceutical composition of claim 24, wherein the human serum albumin is present in an amount between 13,000 and 50,500 .mu.g human serum albumin per 100 LD.sub.50 units botulinum toxin. 26. The lyophilized pharmaceutical composition of claim 24, wherein the human serum albumin is present in an amount between 50,500 and 505,000 .mu.g human serum albumin per 100 LD.sub.50 units botulinum toxin. 27. The lyophilized pharmaceutical composition of claim 24, wherein the human serum albumin is present in an amount between 50,500 and 90,500 .mu.g human serum albumin per 100 LD.sub.50 units botulinum toxin. 28. A lyophilized composition comprising a therapeutically effective amount of a botulinum toxin and a human serum albumin, wherein the human serum albumin is present in an amount between 13,000 and 50,500, between 50,500 and 505,000, or between 50,500 and 90,500 .mu.g human serum albumin per 100 LD.sub.50 units botulinum toxin. 29. A method of localized denervation in a subject in need thereof, comprising administering a therapeutically effective amount of the composition of claim 1 to the subject to produce localized denervation. 30. The method of claim 29, wherein the subject suffers from a neuromuscular disease associated with increased muscle tone or involuntary movement. 31. The method of claim 30, wherein the neuromuscular disease associated with increased muscle tone with involuntary movement is blepharospasm or torticollis. 32. The method of claim 31, wherein the neuromuscular disease associated with increased muscle tone with involuntary movement is blepharospasm. 33. The method of claim 32, wherein the effective amount is between 10-200 LD.sub.50 units. 34. The method of claim 31, wherein the neuromuscular disease associated with increased muscle tone with involuntary movement is torticollis. 35. The method of claim 34, wherein the effective amount is between 10 and 3000 LD.sub.50 units. 36. A method of treating a condition selected from the group consisting of facial wrinkles, rhytides and cosmetic alteration of lip and brow, in a subject in need thereof, comprising administering a therapeutically effective amount of the composition of claim 1 to the subject in order to alleviate at least one symptom of said condition. 37. The method of claim 36, wherein the effective amount is between 2.5 and 400 LD.sub.50 units. 38. A method of treating human headache disorders in a subject in need thereof, comprising administering a therapeutically effective amount of the composition of claim 1 to the subject in order to alleviate at least one symptom of said human headache disorder. 39. The method of claim 38, wherein the effective amount is between 5 and 1,000 LD.sub.50 units. 40. A method of treating human migraine headache disorders in a subject in need thereof, comprising administering a therapeutically effective amount of the composition of claim 1 to the subject in order to alleviate at least one symptom of said human migraine headache disorders. 41. The method of claim 40, wherein the effective amount is between 5 and 1,000 LD.sub.50 units. 42. A method of treating human inflammatory conditions in a subject in need thereof, comprising administering a therapeutically effective amount of the composition of claim 1 to the subject in order to alleviate at least one symptom of said human inflammatory conditions. 43. The method of claim 42, wherein the effective amount is between 5 and 4,000 LD.sub.50 units. 44. A method of treating myopathic or neuropathic pain in a subject in need thereof, comprising administering a therapeutically effective amount of the composition of claim 1 to the subject in order to alleviate at least one symptom of said myopathic or neuropathic pain. 45. The method of claim 44, wherein the effective amount is between 5 and 4,000 LD.sub.50 units. 46. A method of treating back pain or arthritic pain in a subject in need thereof, comprising administering a therapeutically effective amount of the composition of claim 1 to the subject in order to alleviate at least one symptom of said back pain or arthritic pain. 47. The method of claim 46, wherein the effective amount is between 5 and 4,000 LD.sub.50 units. 48. A method of treating gastrointestinal spasm and strictures in a subject in need thereof, comprising administering a therapeutically effective amount of the composition of claim 1 to the subject in order to alleviate at least one symptom of said gastrointestinal spasm and strictures. 49. The method of claim 48, wherein the effective amount is between 5 and 4,000 LD.sub.50 units. 50. A method of treating a hyperhydrosis syndrome in a subject in need thereof, comprising administering a therapeutically effective amount of the composition of claim 1 to the subject in order to alleviate at least one symptom of said hyperhydrosis syndrome. 51. The method of claim 50, wherein the effective amount is between 5 and 4,000 LD.sub.50 units. 52. A method of producing the composition of claim 1, comprising mixing human serum albumin and botulinum toxin in an amount between 13,000 and 550,000 .mu.g human serum albumin per 100 LD.sub.50 units botulinum toxin. 53. A method of producing the composition of claim 1, comprising freeze drying or flash drying a mixture of a botulinum toxin and human serum albumin in an amount between 13,000 and 550,000 .mu.g human serum albumin per 100 LD.sub.50 units botulinum toxin. 54. A method of producing the composition of claim 1, comprising lyophilizing a mixture of a botulinum toxin and human serum albumin in an amount between 13,000 and 550,000 .mu.g human serum albumin per 100 LD.sub.50 units botulinum toxin. 55. A composition comprising a therapeutically effective amount of a botulinum toxin and a human serum albumin, wherein the human serum albumin is present in an amount between about 13,000 and 25,000 .mu.g human serum albumin per 100 LD.sub.50 units botulinum toxin.

Details for Patent 7,491,403

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Grifols Therapeutics Llc	ALBUKED, PLASBUMIN-20, PLASBUMIN-25, PLASBUMIN-5	albumin (human)	For Injection	101138	10/21/1942		2022-12-20
Baxalta Us Inc.	BUMINATE, FLEXBUMIN	albumin (human)	Injection	101452	03/03/1954		2022-12-20
Csl Behring Ag	ALBURX	albumin (human)	Injection	102366	07/23/1976		2022-12-20
Grifols Biologicals Llc	ALBUTEIN	albumin (human)	Injection	102478	08/15/1978		2022-12-20
Instituto Grifols, S.a.	HUMAN ALBUMIN GRIFOLS	albumin (human)	Injection	103352	02/17/1995		2022-12-20
Instituto Grifols, S.a.	HUMAN ALBUMIN GRIFOLS	albumin (human)	Injection	103352	06/11/2003		2022-12-20