Claims for Patent: 11,446,260

Summary for Patent: 11,446,260

Title:	Pharmaceutical composition of S-ketamine hydrochloride
Abstract:	The present invention is directed to an aqueous formulation of S-ketamine hydrochloride, preferably for nasal administration, wherein the formulation does not contain an antimicrobial preservative.
Inventor(s):	Esther D. G. Basstanie, Johanna Bentz, Roger C. A Embrechts, Nico Rudolph Niemeijer
Assignee:	Janssen Pharmaceutica NV
Application Number:	US16/221,950
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 11,446,260
Patent Claims:	1. A method comprising: intranasally administering to a human patient a pharmaceutical composition comprising (S)-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride and water; wherein the (S)-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride is present in a concentration in the range of from about eq. 120 mg/mL to about eq. 250 mg/mL, based on the total volume of the pharmaceutical composition; wherein the pharmaceutical composition is administered as clusters of from 2 and up to 8 consecutive sprays within a time period of up to about 60 minutes, and wherein the patient is in need of treatment for depression, wherein the depression is major depressive disorder, and a therapeutically effective amount of the pharmaceutical composition is administered to alleviate one or more symptoms of the depression. 2. The method of claim 1, wherein the time period is from 1 to about 60 minutes. 3. The method of claim 1, wherein the major depressive disorder is treatment resistant depression. 4. The method of claim 1, wherein the pharmaceutical composition is administered once every couple of days. 5. The method of claim 3, wherein the pharmaceutical composition is administered once every couple of days. 6. The method of claim 1, wherein the (S)-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride is present in a concentration in the range of from about eq. 120 mg/mL to about eq. 175 mg/mL, based on the total volume of the pharmaceutical composition. 7. The method of claim 1, wherein the (S)-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride is present in a concentration in the range of from about eq. 125 mg/mL to about eq. 180 mg/mL, based on the total volume of the pharmaceutical composition. 8. The method of claim 1, wherein the (S)-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride is present in a concentration in the range of from about eq. 125 mg/mL to about eq. 150 mg/mL, based on the total volume of the pharmaceutical composition. 9. The method of claim 1, wherein the (S)-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride is present in a concentration in the range of from about eq. 140 mg/mL to about eq. 160 mg/mL, based on the total volume of the pharmaceutical composition. 10. The method of claim 1, wherein the (S)-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride is present in a concentration of about eq. 140 mg/mL, based on the total volume of the pharmaceutical composition. 11. The method of claim 1, wherein the water content of the pharmaceutical composition is in the range of from 75 to 99.99 wt %, based on the total weight of the pharmaceutical composition. 12. The method of claim 1, wherein the pharmaceutical composition (i) additionally comprises one or more buffers; or (ii) has a pH value in the range of from about 3.5 to about 6.5. 13. The method of claim 12, wherein the pharmaceutical composition comprises the one or more buffers and has a pH value in the range of from about 4.0 to about 6.0. 14. The method of claim 13, wherein the one or more buffers is selected from the group consisting of citric acid, sodium dihydrogen phosphate, disodium hydrogen phosphate, acetic acid, boric acid, sodium borate, succinic acid, tartaric acid, malic acid, lactic acid, furmaric acid, and sodium hydroxide. 15. The method of claim 14, wherein the one or more buffers is selected from the group consisting of sodium hydroxide, citric acid, sodium dihydrogen phosphate, and disodium hydrogen phosphate. 16. The method of claim 15, wherein the buffer comprises citric acid or sodium hydroxide. 17. The method of claim 16, wherein the buffer comprises sodium hydroxide. 18. The method of claim 16, wherein the pH of the pharmaceutical composition is in the range of from about 4.0 to about 5.5. 19. The method of claim 18, wherein the pH of the pharmaceutical composition is in the range of from about 4.5 to about 5.0. 20. The method of claim 1, wherein the pharmaceutical composition further comprises a preservative. 21. The method of claim 20, wherein the preservative is selected from the group consisting of benzalkonium chloride, benzethonium chloride, benzoic acid, sodium benzoate, benzyl alcohol, bronopol, cetrimide, cetylpyridinium chloride, chlorhexidine, chlorbutanol, chlorocresol, chloroxylenol, cresol, ethyl alcohol, glycerin, hexetidine, imidurea, phenol, phenoxyethanol, phenylethyl alcohol, phenylmercuric nitrate, propylene glycol, sodium propionate, thimerosal, methyl paraben, ethyl paraben, propyl paraben, butyl paraben, isobutyl paraben, benzyl paraben, sorbic acid, and potassium sorbate, and mixtures thereof. 22. The method of claim 1, wherein the pharmaceutical composition does not contain a preservative. 23. The method of claim 1, wherein the pharmaceutical composition further comprises a penetrating agent. 24. The method of claim 23, wherein the penetrating agent is selected from the group consisting of tetradecyl maltoside, sodium glycocholate, tauroursodeoxycholic acid (TUDCA), lecithines, chitosan, benzalkonium chloride, sodium dodecyl sulfate, sodium docusate, polysorbates, laureth-9, oxtoxynol, sodium deoxycholate, polyarginine, and mixtures thereof. 25. The method of claim 14, wherein the pharmaceutical composition further comprises one or more additional excipients selected from the group consisting of a wetting agent, a surfactant, a solubilizing agent, a thickening agent, an isotonizing agent, a suspending agent, a colorant agent, and an antioxidant. 26. The method of claim 25, wherein the additional excipient is an antioxidant selected from the group consisting of a sulfite; ascorbic acid; an ascorbate; fumaric acid; ethylene diamine tetraacetic acid (EDTA) or its sodium or calcium salt; tocopherol; a gallate; vitamin E; and mixtures thereof. 27. The method of claim 25, wherein the additional excipient is a solubilizing agent selected from the group consisting of polyethylene glycol, glycerin, D-mannitol, trehalose, benzyl benzoate, ethanol, trisaminomethane, cholesterol, triethanolamine, sodium carbonate, sodium citrate, sodium salicylate, sodium acetate, and mixtures thereof. 28. The method of claim 25, wherein the additional excipient is an isotonizing agent selected from the group consisting of sodium chloride, glycerin, D-mannitol, D-sorbitol, glucose, and mixtures thereof. 29. The method of claim 25, wherein the additional excipient is a suspending agent selected from the group consisting of hydroxypropyl methylcellulose, sodium carmellose, microcrystalline cellulose, carbomer, pectin, sodium alginate, chitosan salts, gellan gum, poloxamer, polyvinyl pyrrolidone, xanthan gum, and mixtures thereof. 30. The method of claim 1, wherein the pharmaceutical composition further comprises an emulsifying agent selected from the group consisting of gelatin, cholesterol, acacia, tragacanth, pectin, methyl cellulose, carbomer, and mixtures thereof. 31. The method of claim 1, wherein the pharmaceutical composition further comprises a chelating agent. 32. The method of claim 31, wherein the chelating agent is EDTA, or its sodium or calcium salt. 33. The method of claim 1, wherein the (S)-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride is present in a concentration in the range of from about eq. 140 mg/mL to about eq. 160 mg/mL, based on the total volume of the pharmaceutical composition, and the pharmaceutical composition further comprises citric acid, EDTA, and sodium hydroxide, wherein the pH of the pharmaceutical composition is in the range of from about 4.0 to about 5.5. 34. The method of claim 33, wherein the (S)-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride is present in a concentration of about eq. 140 mg/mL. 35. The method of claim 33, wherein the pH of the pharmaceutical composition is about 4.5. 36. The method of claim 34, wherein the pH of the pharmaceutical composition is about 4.5. 37. The method of claim 3, wherein the (S)-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride is present in a concentration in the range of from about eq. 140 mg/mL to about eq. 160 mg/mL, based on the total volume of the pharmaceutical composition, and the pharmaceutical composition further comprises citric acid, EDTA, and sodium hydroxide, wherein the pH of the pharmaceutical composition is about 4.0 to about 5.5. 38. The method of claim 37, wherein the (S)-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride is present in a concentration of about eq. 140 mg/mL. 39. The method of claim 37, wherein the pH of the pharmaceutical composition is about 4.5. 40. The method of claim 38, wherein the pH of the pharmaceutical composition is about 4.5. 41. A method comprising: intranasally administering to a human patient a pharmaceutical composition comprising (S)-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride and water; wherein the (S)-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride is present in a concentration in the range of from about 126 mg/mL to about 250 mg/mL, based on the total volume of the pharmaceutical composition; wherein the pharmaceutical composition is administered as clusters of from 2 and up to 8 consecutive sprays within a time period of up to about 60 minutes, and wherein the patient is in need of treatment for depression, wherein the depression is major depressive disorder, and a therapeutically effective amount of the pharmaceutical composition is administered to alleviate one or more symptoms of the depression. 42. The method of claim 41, wherein the time period is from 1 to about 60 minutes. 43. The method of claim 41, wherein the major depressive disorder is treatment resistant depression. 44. The method of claim 41, wherein the pharmaceutical composition is administered once every couple of days. 45. The method of claim 43, wherein the pharmaceutical composition is administered once every couple of days. 46. The method of claim 41, wherein the (S)-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride is present in a concentration in the range of from about 126 mg/mL to about 162 mg/mL, based on the total volume of the pharmaceutical composition. 47. The method of claim 41, wherein the (S)-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride is present in a concentration in the range of from about 150 mg/mL to about 200 mg/mL, based on the total volume of the pharmaceutical composition. 48. The method of claim 41, wherein the (S)-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride is present in a concentration in the range of from about 150 mg/mL to about 175 mg/mL, based on the total volume of the pharmaceutical composition. 49. The method of claim 41, wherein the (S)-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride is present in a concentration in the range of from about 160 mg/mL to about 163 mg/mL, based on the total volume of the pharmaceutical composition. 50. The method of claim 41, wherein the water content of the pharmaceutical composition is in the range of from 75 to 99.99 wt %, based on the total weight of the pharmaceutical composition. 51. The method of claim 41, wherein the pharmaceutical composition (i) additionally comprises one or more buffers; or (ii) has a pH value in the range of from about 3.5 to about 6.5. 52. The method of claim 51, wherein the pharmaceutical composition comprises the one or more buffers and has a pH value in the range of from about 4.0 to about 6.0. 53. The method of claim 52, wherein the one or more buffers is selected from the group consisting of citric acid, sodium dihydrogen phosphate, disodium hydrogen phosphate, acetic acid, boric acid, sodium borate, succinic acid, tartaric acid, malic acid, lactic acid, furmaric acid, and sodium hydroxide. 54. The method of claim 53, wherein the one or more buffers is selected from the group consisting of sodium hydroxide, citric acid, sodium dihydrogen phosphate, and disodium hydrogen phosphate. 55. The method of claim 54, wherein the buffer comprises citric acid or sodium hydroxide. 56. The method of claim 55, wherein the buffer comprises sodium hydroxide. 57. The method of claim 55, wherein the pH of the pharmaceutical composition is in the range of from about 4.0 to about 5.5. 58. The method of claim 57, wherein the pH of the pharmaceutical composition is in the range of from about 4.5 to about 5.0. 59. The method of claim 41, wherein the pharmaceutical composition further comprises a preservative. 60. The method of claim 59, wherein the preservative is selected from the group consisting of benzalkonium chloride, benzethonium chloride, benzoic acid, sodium benzoate, benzyl alcohol, bronopol, cetrimide, cetylpyridinium chloride, chlorhexidine, chlorbutanol, chlorocresol, chloroxylenol, cresol, ethyl alcohol, glycerin, hexetidine, imidurea, phenol, phenoxyethanol, phenylethyl alcohol, phenylmercuric nitrate, propylene glycol, sodium propionate, thimerosal, methyl paraben, ethyl paraben, propyl paraben, butyl paraben, isobutyl paraben, benzyl paraben, sorbic acid, and potassium sorbate, and mixtures thereof. 61. The method of claim 41, wherein the pharmaceutical composition does not contain a preservative. 62. The method of claim 41, wherein the pharmaceutical composition further comprises a penetrating agent. 63. The method of claim 62, wherein the penetrating agent is selected from the group consisting of tetradecyl maltoside, sodium glycocholate, tauroursodeoxycholic acid (TUDCA), lecithines, chitosan, benzalkonium chloride, sodium dodecyl sulfate, sodium docusate, polysorbates, laureth-9, oxtoxynol, sodium deoxycholate, polyarginine, and mixtures thereof. 64. The method of claim 53, wherein the pharmaceutical composition further comprises one or more additional excipients selected from the group consisting of a wetting agent, a surfactant, a solubilizing agent, a thickening agent, an isotonizing agent, a suspending agent, a colorant agent, and an antioxidant. 65. The method of claim 64, wherein the additional excipient is an antioxidant selected from the group consisting of a sulfite; ascorbic acid; an ascorbate; fumaric acid; ethylene diamine tetraacetic acid (EDTA) or its sodium or calcium salt; tocopherol; a gallate; vitamin E; and mixtures thereof. 66. The method of claim 64, wherein the additional excipient is a solubilizing agent selected from the group consisting of polyethylene glycol, glycerin, D-mannitol, trehalose, benzyl benzoate, ethanol, trisaminomethane, cholesterol, triethanolamine, sodium carbonate, sodium citrate, sodium salicylate, sodium acetate, and mixtures thereof. 67. The method of claim 64, wherein the additional excipient is an isotonizing agent selected from the group consisting of sodium chloride, glycerin, D-mannitol, D-sorbitol, glucose, and mixtures thereof. 68. The method of claim 64, wherein the additional excipient is a suspending agent selected from the group consisting of hydroxypropyl methylcellulose, sodium carmellose, microcrystalline cellulose, carbomer, pectin, sodium alginate, chitosan salts, gellan gum, poloxamer, polyvinyl pyrrolidone, xanthan gum, and mixtures thereof. 69. The method of claim 41, wherein the pharmaceutical composition further comprises an emulsifying agent selected from the group consisting of gelatin, cholesterol, acacia, tragacanth, pectin, methyl cellulose, carbomer, and mixtures thereof. 70. The method of claim 41, wherein the pharmaceutical composition further comprises a chelating agent. 71. The method of claim 70, wherein the chelating agent comprises EDTA, or its sodium or calcium salt. 72. The method of claim 41, wherein the (S)-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride is present in a concentration in the range of from about 160 mg/mL to about 163 mg/mL, based on the total volume of the pharmaceutical composition, and the pharmaceutical composition further comprises citric acid, EDTA, and sodium hydroxide, wherein the pH of the pharmaceutical composition is in the range of from about 4.0 to about 5.5. 73. The method of claim 72, wherein the pH of the pharmaceutical composition is about 4.5. 74. The method of claim 43, wherein the (S)-2-(2-chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride is present in a concentration in the range of from about 160 mg/mL to about 163 mg/mL, based on the total volume of the pharmaceutical composition, and the pharmaceutical composition further comprises citric acid, EDTA, and sodium hydroxide, wherein the pH of the pharmaceutical composition is in the range of from about 4.0 to about 5.5. 75. The method of claim 74, wherein the pH of the pharmaceutical composition is about 4.5.