Claims for Patent: 12,576,067

Summary for Patent: 12,576,067

Title:	Methods and compositions for treatment of mydriasis
Abstract:	The invention provides methods, compositions, and kits containing an alpha-adrenergic antagonist, such as phentolamine, for use in monotherapy or as part of a combination therapy to treat patients suffering from presbyopia, mydriasis, and/or other ocular disorders.
Inventor(s):	Mina Sooch, Alan R. Meyer, Konstantinos Charizanis, Bernhard Hoffmann, William H. Pitlick
Assignee:	Opus Genetics Inc
Application Number:	US19/029,592
Patent Claims:	1. A method of treating mydriasis in a human patient due to said patient having received tropicamide, phenylephrine, or a pharmaceutically acceptable salt thereof, or a combination of hydroxyamphetamine hydrobromide and tropicamide or a pharmaceutically acceptable salt thereof, comprising administering to an eye of the human patient in need thereof a dosage of phentolamine mesylate to thereby treat the mydriasis, wherein the dosage is topically administered to the patient's eye as two eye drops of a 1% (w/w) phentolamine mesylate solution. 2. The method of claim 1, wherein the mydriasis is due to the patient having received tropicamide or a pharmaceutically acceptable salt thereof. 3. The method of claim 1, wherein the mydriasis is due to the patient having received phenylephrine or a pharmaceutically acceptable salt thereof. 4. The method of claim 1, wherein the mydriasis is due to the patient having received a combination of hydroxyamphetamine hydrobromide and tropicamide or a pharmaceutically acceptable salt thereof. 5. The method of claim 1, wherein a therapeutic benefit is observed within 1 hour after administering the dosage of phentolamine mesylate. 6. The method of claim 2, wherein a therapeutic benefit is observed within 1 hour after administering the dosage of phentolamine mesylate. 7. The method of claim 3, wherein a therapeutic benefit is observed within 1 hour after administering the dosage of phentolamine mesylate. 8. The method of claim 1, wherein the eye drop is a liquid aqueous ophthalmic formulation. 9. The method of claim 2, wherein the eye drop is a liquid aqueous ophthalmic formulation. 10. The method of claim 3, wherein the eye drop is a liquid aqueous ophthalmic formulation. 11. The method of claim 1, wherein the patient experiences at least a 2 mm reduction in pupil diameter when measured under photopic conditions relative to the diameter of the patient's pupil under the same photopic conditions but not having received said dosage. 12. The method of claim 1, wherein at two hours after the dosage of phentolamine mesylate is administered to the patient's eye, the patient experiences at least a 1 mm reduction in pupil diameter when measured under photopic conditions relative to the diameter of the patient's pupil under the same photopic conditions but not having received said dosage. 13. The method of claim 2, wherein at two hours after the dosage of phentolamine mesylate is administered to the patient's eye, the patient experiences at least a 1 mm reduction in pupil diameter when measured under photopic conditions relative to the diameter of the patient's pupil under the same photopic conditions but not having received said dosage. 14. The method of claim 3, wherein at two hours after the dosage of phentolamine mesylate is administered to the patient's eye, the patient experiences at least a 1 mm reduction in pupil diameter when measured under photopic conditions relative to the diameter of the patient's pupil under the same photopic conditions but not having received said dosage. 15. The method of claim 1, wherein the patient experiences an increase in eye redness of no more than two grades measured using the CCLRU Redness Grading Scale compared to the patient's level of eye redness without receiving said dosage of phentolamine mesylate. 16. The method of claim 2, wherein the patient experiences an increase in eye redness of no more than two grades measured using the CCLRU Redness Grading Scale compared to the patient's level of eye redness without receiving said dosage of phentolamine mesylate. 17. The method of claim 3, wherein the patient experiences an increase in eye redness of no more than two grades measured using the CCLRU Redness Grading Scale compared to the patient's level of eye redness without receiving said dosage of phentolamine mesylate. 18. The method of claim 1, wherein human patient is an adult human patient. 19. The method of claim 2, wherein human patient is an adult human patient. 20. The method of claim 3, wherein human patient is an adult human patient. 21. A method of treating mydriasis in a human patient due to said patient having received tropicamide, phenylephrine, or a pharmaceutically acceptable salt thereof, or a combination of hydroxyamphetamine hydrobromide and tropicamide or a pharmaceutically acceptable salt thereof, comprising administering to an eye of the human patient in need thereof a dosage of phentolamine mesylate to thereby treat the mydriasis, wherein the dosage is topically administered to the patient's eye as two eye drops of a 1% (w/v) phentolamine mesylate aqueous solution. 22. The method of claim 21, wherein the mydriasis is due to the patient having received tropicamide or a pharmaceutically acceptable salt thereof. 23. The method of claim 21, wherein the mydriasis is due to the patient having received phenylephrine or a pharmaceutically acceptable salt thereof. 24. The method of claim 21, wherein the mydriasis is due to the patient having received a combination of hydroxyamphetamine hydrobromide and tropicamide or a pharmaceutically acceptable salt thereof. 25. The method of claim 21, wherein a therapeutic benefit is observed within 1 hour after administering the dosage of phentolamine mesylate. 26. The method of claim 21, wherein at two hours after the dosage of phentolamine mesylate is administered to the patient's eye there is at least a 30% reduction in pupil diameter in said eye of the patient measured under photopic conditions. 27. The method of claim 21, wherein the eye drop is a liquid aqueous ophthalmic formulation. 28. The method of claim 21, wherein at two hours after the dosage of phentolamine mesylate is administered to the patient's eye, the patient experiences at least a 1 mm reduction in pupil diameter when measured under photopic conditions relative to the diameter of the patient's pupil under the same photopic conditions but not having received said dosage. 29. The method of claim 21, wherein the patient experiences an increase in eye redness of no more than two grades measured using the CCLRU Redness Grading Scale compared to the patient's level of eye redness without receiving said dosage of phentolamine mesylate. 30. The method of claim 21, wherein human patient is an adult human patient. 31. A method of treating pharmacologically-induced mydriasis in a human patient due to said patient having received one or more of tropicamide, phenylephrine or a pharmaceutically acceptable salt thereof, or a combination of hydroxyamphetamine hydrobromide and tropicamide or a pharmaceutically acceptable salt thereof, where said patient does not have ocular inflammation, comprising administering to an eye of the human patient in need thereof a dosage of a phentolamine mesylate solution to thereby treat the mydriasis, wherein the dosage is topically administered to the patient's eye as two eye drops, where each eye drop contains from about 0.4 mg to about 0.6 mg of phentolamine mesylate. 32. The method of claim 31, wherein said ocular inflammation is iritis. 33. The method of claim 32, wherein at one hour after the dosage of phentolamine mesylate is administered to the patient's eye, the baseline in mean pupil diameters was statistically significant (p<0.01) for subjects treated the phentolamine mesylate solution relative to patients under the same photopic conditions but not having received said dosage. 34. The method of claim 31, wherein the patient experiences at least a 1 mm reduction in pupil diameter when measured under photopic conditions relative to the diameter of the patient's pupil under the same photopic conditions but not having received said dosage when measured two hours after the dosage. 35. The method of claim 32, wherein the patient experiences at least a 1 mm reduction in pupil diameter when measured under photopic conditions relative to the diameter of the patient's pupil under the same photopic conditions but not having received said dosage when measured two hours after the dosage. 36. The method of claim 33, wherein the patient experiences at least a 1 mm reduction in pupil diameter when measured under photopic conditions relative to the diameter of the patient's pupil under the same photopic conditions but not having received said dosage when measured two hours after the dosage. 37. The method of claim 31, wherein said phentolamine mesylate solution is administered to the eye of the patient once the patient has completed an eye examination in which the one or more of tropicamide, phenylephrine, or a pharmaceutically acceptable salt thereof was administered to the patient's eye. 38. The method of claim 32, wherein said patient received tropicamide or a pharmaceutically acceptable salt thereof. 39. The method of claim 32, wherein said patient received phenylephrine or a pharmaceutically acceptable salt thereof. 40. The method of claim 32, wherein said patient received a combination of hydroxyamphetamine hydrobromide and tropicamide or a pharmaceutically acceptable salt thereof. 41. The method of claim 32, wherein said phentolamine mesylate solution comprises: (a) about 0.1% (w/v) to about 2% (w/v) of phentolamine mesylate; (b) about 1% (w/v) to about 6% (w/v) of at least one polyol compound selected from the group consisting of mannitol, glycerol, and propylene glycol; (c) about 1 mM to about 6 mM of an alkali metal acetate; and (d) water; wherein the solution has a pH in the range of 4 to 6. 42. The method of claim 32, wherein said phentolamine mesylate solution comprises: (a) about 0.5% (w/v) to about 2% (w/v) of phentolamine mesylate; (b) about 1% (w/v) to about 6% (w/v) of at least one polyol compound selected from the group consisting of mannitol, glycerol, and propylene glycol; (c) about 1 mM to about 6 mM of an alkali metal acetate; and (d) water; wherein the solution has a pH in the range of 4.5 to 5.5. 43. The method of claim 32, wherein said phentolamine mesylate solution comprises: (a) about 0.25% (w/v) to about 2% (w/v) of phentolamine mesylate; (b) about 3% (w/v) to about 5% (w/v) of mannitol; (c) about 2 mM to about 4 mM of sodium acetate; and (d) water; wherein the solution has a pH in the range of 4.5 to 5.2. 44. The method of claim 32, wherein said phentolamine mesylate solution comprises: (a) about 0.5% (w/v) to about 2% (w/v) of phentolamine mesylate; (b) about 3% (w/v) to about 5% (w/v) of mannitol; (c) about 2 mM to about 4 mM of sodium acetate; and (d) water; wherein the solution has a pH in the range of 4.6 to 5.2. 45. The method of claim 32, wherein said phentolamine mesylate solution comprises: (a) about 0.5% (w/v) to about 1% (w/v) of phentolamine mesylate; (b) about 4% mannitol; (c) about 3 mM sodium acetate; and (d) water; wherein the solution has a pH in the range of 4.6 to 5.2. 46. The method of claim 32, wherein said phentolamine mesylate solution comprises: (a) about 0.25% (w/v) to about 2% (w/v) of phentolamine mesylate; (b) about 3% (w/v) to about 5% (w/v) of mannitol; (c) about 1 mM to about 6 mM of sodium acetate; and (d) water; wherein the solution has a pH in the range of 4.5 to 5.2. 47. The method of claim 32, wherein said phentolamine mesylate solution comprises: (a) about 1% (w/v) of phentolamine mesylate; (b) about 3% (w/v) to about 5% (w/v) of mannitol; (c) about 2 mM to about 4 mM of a buffer comprising sodium acetate; and (d) water; wherein the solution has a pH in the range of 4.5 to 5.2. 48. The method of claim 32, wherein said phentolamine mesylate solution comprises: (a) about 0.25% (w/v) to about 2% (w/v) of phentolamine mesylate; (b) about 3% (w/v) to about 5% (w/v) of mannitol; (c) about 2 mM to about 4 mM of sodium acetate; and (d) water; wherein the solution has a pH in the range of 4.5 to 5.2. 49. The method of claim 32, wherein said phentolamine mesylate solution comprises: (a) about 0.5% (w/v) to about 2% (w/v) of phentolamine mesylate; (b) about 3% (w/v) to about 5% (w/v) of mannitol; (c) about 2 mM to about 4 mM of a buffer comprising sodium acetate; and (d) water; wherein the solution has a pH in the range of 4.6 to 5.2 and does not contain any additional component that is a chelating agent. 50. The method of claim 32, wherein said phentolamine mesylate solution comprises: (a) about 0.5% (w/v) to about 1% (w/v) of phentolamine mesylate; (b) about 4% mannitol; (c) about 3 mM of a buffer comprising sodium acetate; and (d) water; wherein the solution has a pH in the range of 4.6 to 5.2 and does not contain any additional component that is a chelating agent. 51. The method of claim 31, wherein at twenty-four hours after the dosage of phentolamine mesylate is administered to the patient's eye there is a reduction in pupil diameter of said patient measured under photopic conditions relative to the patient under the same photopic conditions but not having received said dosage and said ocular inflammation is iritis. 52. The method of claim 1, wherein said phentolamine mesylate solution is characterized by less than 10% by weight of the phentolamine mesylate degrading upon storage at temperature in the range of 2-8° C. for 18 months, 24 months, or 36 months. 53. The method of claim 21, wherein said phentolamine mesylate aqueous solution is characterized by less than 10% by weight of the phentolamine mesylate degrading upon storage at temperature in the range of 2-8° C. for 18 months, 24 months, or 36 months. 54. The method of claim 31, wherein said phentolamine mesylate solution is characterized by less than 10% by weight of the phentolamine mesylate degrading upon storage at temperature in the range of 2-8° C. for 18 months, 24 months, or 36 months.