Claims for Patent: 10,335,391

Summary for Patent: 10,335,391

Title:	Stabilized oxymetazoline formulations and their uses
Abstract:	The present invention provides stabilized cream formulations of oxymetazoline and uses thereof. The present invention also provides a method of treating facial erythema associated with rosacea in a patient in need of such treatment, comprising topically administering once or twice daily to the site of erythema on the face of the patient a pharmaceutical composition comprising 0.5%, 1.0% or 1.5% oxymetazoline or a pharmaceutically acceptable salt thereof as the sole active ingredient.
Inventor(s):	Sarpotdar; Pramod (Rhonert Park, CA), Warner; Kevin (Anaheim, CA), Zhang; Steven (Newton, MA), Ahluwalia; Gurpreet (Tustin, CA), Kuang; Amy (Irvine, CA)
Assignee:	ACLARIS THERAPEUTICS, INC. (Wayne, PA)
Application Number:	15/984,918
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,335,391
Patent Claims:	1. A method of treating facial erythema associated with rosacea in a patient in need of such treatment, comprising topically administering once daily to the site of erythema on the face of the patient a pharmaceutical composition comprising 1.0% w/w oxymetazoline hydrochloride thereof as the sole active ingredient, wherein the patient experiences no rebound or worsening of facial erythema post-treatment. 2. The method of claim 1, wherein the pharmaceutical composition is in a form selected from the group consisting of solutions, gels, lotions, creams, ointments, foams, emulsions, microemulsions, milks, serums, aerosols, sprays, dispersions, microcapsules, vesicles and microparticles thereof. 3. The method of claim 2, wherein the pharmaceutical composition is in the form of a cream. 4. The method of claim 3, wherein the topical administration is well tolerated by the patient and results in limited systemic exposure of the oxymetazoline hydrochloride. 5. The method of claim 3, wherein the pharmaceutical formulation further comprises methylparaben, propylparaben, phenoxyethanol, sodium citrate, citric acid, disodium edetate, butylated hydroxytoluene, lanolin, medium chain triglycerides, diisopropyl adipate, oleyl alcohol, polyethylene glycol PEG-300, polyethylene glycol PEG-6, polyethylene glycol PEG-32, glycol stearate, cetostearyl alcohol, ceteareth-6, stearyl alcohol, ceteareth-25, and purified water. 6. The method of claim 3, wherein the pharmaceutical formulation comprises about 1.0% w/w oxymetazoline HCl, about 0.2% w/w methylparaben, about 0.05% w/w propylparaben, about 0 8% w/w phenoxyethanol, about 0.3% w/w sodium citrate dihydrate, about 0.219% w/w anhydrous citric acid, about 0.01% w/w disodium edetate, about 0.05% w/w butylated hydroxytoluene, about 2% w/w anhydrous lanolin, about 7% w/w medium chain triglycerides, about 7% w/w diisopropyl adipate, about 7% w/w oleyl alcohol, about 4% w/w polyethylene glycol PEG-300, about 8% w/w polyethylene glycol PEG-6/polyethylene glycol PEG-32/glycol stearate (Tefose-63), about 8% w/w cetostearyl alcohol, about 2% w/w ceteareth-6/stearyl alcohol (Cremophor A6), about 2% w/w ceteareth-25, and purified water (q.s.). 7. The method of claim 6, wherein the topical administration is well tolerated by the patient and results in limited systemic exposure of the oxymetazoline hydrochloride. 8. The method of claim 1, wherein the treatment results in an at least 2-grade improvement from baseline on Clinician's Erythema Assessment (CEA) scale, Subject Self-Assessment of Erythema (SSA), or both. 9. The method of claim 1, wherein the treatment results in an at least 1-grade improvement from baseline on Clinician's Erythema Assessment (CEA) scale, Subject Self-Assessment of Erythema (SSA), or both. 10. The method of claim 1, wherein a median T.sub.max after 28 days of topical administration is about 10 hours to about 12 hours. 11. The method of claim 1, wherein a mean C.sub.max after 28 days of topical administration is less than about 133.5 pg/mL. 12. The method of claim 1, wherein the patient has a mean C.sub.max after 28 days of topical administration is less than about 66 pg/mL. 13. The method of claim 1, wherein the patient has an AUC.sub.0-24 post administration of less than about 2042 pghr/mL. 14. The method of claim 1, wherein the patient has an AUC.sub.0-24 post administration of less than about 1050 pghr/mL. 15. The method of claim 1, wherein the facial erythema is persistent facial erythema. 16. The method of claim 1, wherein the patient is an adult. 17. The method of claim 1, wherein the once daily administration is a pea sized amount of the pharmaceutical composition. 18. A method of treating facial erythema associated with rosacea in a patient in need of such treatment, comprising topically administering once daily on the face of the patient a pharmaceutical composition comprising 1.0% w/w oxymetazoline hydrochloride thereof as the sole active ingredient, wherein the patient experiences no rebound or worsening of facial erythema post-treatment. 19. The method of claim 18, wherein the pharmaceutical composition is topically administered in a thin layer to cover the entire face avoiding the eyes and lips. 20. The method of claim 18, wherein the pharmaceutical composition is a cream further comprising methylparaben, propylparaben, phenoxyethanol, sodium citrate, citric acid, disodium edetate, butylated hydroxytoluene, lanolin, medium chain triglycerides, diisopropyl adipate, oleyl alcohol, polyethylene glycol PEG-300, polyethylene glycol PEG-6, polyethylene glycol PEG-32, glycol stearate, cetostearyl alcohol, ceteareth-6, stearyl alcohol, ceteareth-25, and purified water. 21. The method of claim 20, wherein the cream comprises about 1.0% w/w oxymetazoline HCl, about 0.2% w/w methylparaben, about 0.05% w/w propylparaben, about 0 8% w/w phenoxyethanol, about 0.3% w/w sodium citrate dihydrate, about 0.219% w/w anhydrous citric acid, about 0.01% w/w disodium edetate, about 0.05% w/w butylated hydroxytoluene, about 2% w/w anhydrous lanolin, about 7% w/w medium chain triglycerides, about 7% w/w diisopropyl adipate, about 7% w/w oleyl alcohol, about 4% w/w polyethylene glycol PEG-300, about 8% w/w polyethylene glycol PEG-6/polyethylene glycol PEG-32/glycol stearate (Tefose-63), about 8% w/w cetostearyl alcohol, about 2% w/w ceteareth-6/stearyl alcohol (Cremophor A6), about 2% w/w ceteareth-25, and purified water (q.s.). 22. The method of claim 18, wherein the treatment results in an at least 2-grade improvement from baseline on Clinician's Erythema Assessment (CEA) scale, Subject Self-Assessment of Erythema (SSA), or both. 23. The method of claim 18, wherein a median T.sub.max after 28 days of topical administration is about 10 hours to about 12 hours. 24. The method of claim 18, wherein a mean C.sub.max after 28 days of topical administration is less than about 133.5 pg/mL. 25. The method of claim 18, wherein the patient has an AUC.sub.0-24 post administration of less than about 2042 pghr/mL. 26. The method of claim 18, wherein the facial erythema is persistent facial erythema. 27. The method of claim 18, wherein the patient is an adult. 28. A method of treating facial erythema associated with rosacea in a patient in need of such treatment, comprising topically administering once daily on the face of the patient a pharmaceutical composition comprising 1.0% w/w oxymetazoline hydrochloride thereof as the sole active ingredient. 29. The method of claim 28, wherein the pharmaceutical composition is topically administered in a thin layer to cover the entire face avoiding the eyes and lips. 30. The method of claim 28, wherein the pharmaceutical composition is a cream further comprising methylparaben, propylparaben, phenoxyethanol, sodium citrate, citric acid, disodium edetate, butylated hydroxytoluene, lanolin, medium chain triglycerides, diisopropyl adipate, oleyl alcohol, polyethylene glycol PEG-300, polyethylene glycol PEG-6, polyethylene glycol PEG-32, glycol stearate, cetostearyl alcohol, ceteareth-6, stearyl alcohol, ceteareth-25, and purified water. 31. The method of claim 30, wherein the cream comprises about 1.0% w/w oxymetazoline HCl, about 0.2% w/w methylparaben, about 0.05% w/w propylparaben, about 0 8% w/w phenoxyethanol, about 0.3% w/w sodium citrate dihydrate, about 0.219% w/w anhydrous citric acid, about 0.01% w/w disodium edetate, about 0.05% w/w butylated hydroxytoluene, about 2% w/w anhydrous lanolin, about 7% w/w medium chain triglycerides, about 7% w/w diisopropyl adipate, about 7% w/w oleyl alcohol, about 4% w/w polyethylene glycol PEG-300, about 8% w/w polyethylene glycol PEG-6/polyethylene glycol PEG-32/glycol stearate (Tefose-63), about 8% w/w cetostearyl alcohol, about 2% w/w ceteareth-6/stearyl alcohol (Cremophor A6), about 2% w/w ceteareth-25, and purified water (q.s.). 32. The method of claim 28, wherein the treatment results in an at least 2-grade improvement from baseline on Clinician's Erythema Assessment (CEA) scale, Subject Self-Assessment of Erythema (SSA), or both. 33. The method of claim 28, wherein a median T.sub.max after 28 days of topical administration is about 10 hours to about 12 hours. 34. The method of claim 28, wherein a mean C.sub.max after 28 days of topical administration is less than about 133.5 pg/mL. 35. The method of claim 28, wherein the patient has an AUC.sub.0-24 post administration of less than about 2042 pghr/mL. 36. The method of claim 28, wherein the facial erythema is persistent facial erythema. 37. The method of claim 28, wherein the patient is an adult.