Claims for Patent: 9,744,138

Summary for Patent: 9,744,138

Title:	Treatment method and product for uterine fibroids using purified collagenase
Abstract:	The invention relates to compositions and methods for treating uterine fibroids, wherein a uterine fibroid treatment agent comprising collagenase in an amount effective to cause shrinkage of uterine fibroids is injected or inserted into the uterine fibroid.
Inventor(s):	Leppert; Phyllis Carolyn (Salt Lake City, UT), Wegman; Thomas L. (N. Merrick, NY), Taylor; Darlene K. (Burlington, NC)
Assignee:	BioSpecifics Technologies Corp. (Lynbrook, NY) Duke University (Durham, NC) North Carolina Central University (Durham, NC)
Application Number:	14/213,910
Patent Claims:	1. A method for the treatment of uterine fibroids in a patient comprising: injecting or inserting into the uterine fibroid a composition comprising: (a) a thermally responsive polymer having a lower critical solution temperature (LCST) that is less than or equal to the body temperature of said patient; and (b) collagenase, wherein said composition is formulated such that the thermally responsive polymer entraps and maintains the stability of the collagenase and is non-toxic and biodegradable, wherein the collagenase is from Clostridium histolyticum, and wherein said composition is injected at a temperature that is less than said lower critical solution temperature (LCST) to provide about 0.06 to about 1 mg collagenase per 1 cm.sup.3 uterine fibroid tissue. 2. The method of claim 1, wherein the composition provides sustained release of an amount of said collagenase sufficient to treat said uterine fibroids. 3. The method of claim 1, wherein about 0.1 mg to about 0.8 mg collagenase is administered per cm.sup.3 of uterine fibroid to be treated. 4. The method of claim 3, wherein about 0.2 mg to about 0.6 mg collagenase is administered per cm.sup.3 of uterine fibroid to be treated. 5. The method of claim 1, wherein 100 .mu.L of said composition is injected or inserted into 1 cm.sup.3 uterine fibroid tissue. 6. A composition for treating uterine fibroids in a patient comprising: (a) a thermally responsive polymer having a lower critical solution temperature (LCST) that is less than or equal to the body temperature of said patient; and (b) collagenase, wherein said composition is formulated such that the thermally responsive polymer entraps and maintains the stability of the collagenase and is non-toxic and biodegradable, wherein the collagenase is from Clostridium histolyticum, and wherein said composition is formulated to provide about 0.06 to about 1 mg collagenase per dose administered to 1 cm.sup.3 of uterine fibroid tissue. 7. The composition of claim 6, wherein said polymer is a triblock polymer or a copolymer based on N-isopropylacrylamide (NIPAAm). 8. The composition of claim 7, wherein said triblock polymers comprise poly(lactic-co-glycolic acid) (PLGA) and polyethylene glycol (PEG). 9. The composition of claim 8, wherein said triblock polymers comprise a copolymer formed from PLGA and polyethylene glycol (PEG). 10. The composition of claim 9, wherein the PLGA and PEG copolymers are formed in repetitions of PLGA-PEG-PLGA or PEG-PLGA-PEG. 11. The composition of claim 7, wherein the NIPAAm based polymer is a copolymer based on N-isopropylacrylamide (NIPAAm) and one or more of polylactide-hydroxyethyl methacrylate (HEMAPLA), acrylic acid (AAc), and hyperbranched polyglycerol (HPG). 12. The composition of claim 11, comprising copolymers of poly-NIPAAm and hyperbranched polyglycerols (HPG). 13. The composition of claim 7, having a lower critical solution temperature (LCST) of 10-37.degree. C. 14. The composition of claim 6, wherein said composition is injectable, insertable or applied topically. 15. The composition of claim 6, which can be administered through a syringe fitted with a 10 gauge or smaller needle without pre-gelation in the needle on injection. 16. The composition of claim 6, wherein the composition exists as a liquid at temperatures below body temperature and as a gel at body temperature. 17. The composition of claim 6, wherein the collagenase is a mixture of collagenase I and collagenase II. 18. The composition of claim 6, wherein the polymer does not negatively affect enzymatic activity of the collagenase. 19. The composition of claim 6, wherein said composition is formulated to provide about 0.1 to about 0.8 mg collagenase per dose administered to 1 cm.sup.3 of uterine fibroid tissue. 20. The composition of claim 19, wherein said composition is formulated to provide about 0.2 to about 0.6 mg collagenase per dose administered to 1 cm.sup.3 of uterine fibroid tissue. 21. A composition for treating uterine fibroids in a patient comprising: (a) a thermally responsive polymer having a lower critical solution temperature (LCST) that is less than or equal to the body temperature of said patient; and (b) collagenase, wherein said composition comprises 0.25-2.0 mg/ml collagenase from Clostridium histolyticum. 22. The composition of claim 21, comprising 0.25 mg/mL collagenase from Clostridium histolyticum. 23. The composition of claim 21, comprising 0.5 mg/mL collagenase from Clostridium histolyticum. 24. The composition of claim 21, comprising 1.0 mg/mL collagenase from Clostridium histolyticum. 25. The composition of claim 21, comprising 2.0 mg/mL collagenase from Clostridium histolyticum. 26. A method for the treatment of uterine fibroids in a patient comprising: injecting or inserting into the uterine fibroid a composition comprising: (a) a thermally responsive polymer having a lower critical solution temperature (LCST) that is less than or equal to the body temperature of said patient; and (b) collagenase, wherein said composition is formulated such that the thermally responsive polymer entraps and maintains the stability of the collagenase and is non-toxic and biodegradable, wherein the composition comprises 0.25-2.0 mg/mL collagenase from Clostridium histolyticum, and wherein said composition is injected at a temperature that is less than said lower critical solution temperature (LCST). 27. The method of claim 26, wherein 100 .mu.L of said composition is injected or inserted into 1 cm.sup.3 uterine fibroid tissue. 28. The method of claim 26, wherein said composition comprises 0.25 mg/mL collagenase from Clostridium histolyticum. 29. The method of claim 26, wherein said composition comprises 0.5 mg/mL collagenase from Clostridium histolyticum. 30. The method of claim 26, wherein said composition comprises 1.0 mg/mL collagenase from Clostridium histolyticum. 31. The method of claim 26, wherein said composition comprises 2.0 mg/mL collagenase from Clostridium histolyticum.

Details for Patent 9,744,138

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Smith & Nephew, Inc.	SANTYL	collagenase	Ointment	101995	06/04/1965		2033-03-15
Auxilium Pharmaceuticals, Inc.	XIAFLEX	collagenase clostridium histolyticum	For Injection	125338	02/02/2010		2033-03-15