Claims for Patent: 12,521,390

Summary for Patent: 12,521,390

Title:	Dosage forms for Tyk2 inhibitors
Abstract:	Stable and bioavailable formulations and dosage forms comprising a dispersion (e.g., spray-dried dispersion) of solid amorphous 6-(cyclopropancamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-N-(methyl-d3)pyridazine-3-carboxamide (Formula (I): BMS-986165) in a solid polymer matrix are provided for the treatment of auto-immune and auto-inflammatory diseases such as an inflammatory bowel disease (IBD) and psoriasis.
Inventor(s):	Sherif Ibrahim Farag Badawy, Jonathan R. Brown, Candice Y. Choi, Christoph Gesenberg, Vivienne Gray, John Wynne Jones, Umesh Kestur, Balvinder S. Vig, Xiaotian S. Yin, Christopher A. Zordan, Corey Bloom, Ian Yates
Assignee:	Bristol Myers Squibb Co
Application Number:	US17/639,481
Patent Claims:	1. A dosage form of 6-(cyclopropaneamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-N-(methyl-d3)pyridazine-3-carboxamide (BMS-986165), the dosage form comprising a dispersion of amorphous BMS-986165 dispersed in a polymer matrix; wherein the polymer matrix comprises hydroxypropyl methylcellulose acetate succinate (HPMCAS); and wherein the proportion of amorphous BMS-986165 to HPMCAS in the dispersion is 4%-50% w/w amorphous BMS-986165 to 96%-50% w/w HPMCAS. 2. The dosage form according to claim 1, wherein the HPMCAS is HPMCAS H-grade. 3. The dosage form according to claim 1, wherein the proportion of amorphous BMS-986165 to HPMCAS in the dispersion is 5%-25% w/w amorphous BMS-986165 to 95%-75% w/w HPMCAS. 4. The dosage form according to claim 3, wherein the HPMCAS is HPMCAS H-grade. 5. The dosage form according to claim 4, further comprising a crystallization inhibitor. 6. The dosage form according to claim 5, wherein the crystallization inhibitor is hydroxypropyl methylcellulose acetate succinate (HPMCAS). 7. The dosage form according to claim 3, wherein the dispersion is a spray-dried dispersion. 8. The dosage form according to claim 4, wherein the dispersion is a spray-dried dispersion. 9. The dosage form according to claim 3, wherein the proportion of amorphous BMS-986165 to HPMCAS in the dispersion is 10%-20% w/w amorphous BMS-986165 to 90%-80% w/w HPMCAS. 10. The dosage form according to claim 4, wherein the proportion of amorphous BMS-986165 to HPMCAS in the dispersion is 10%-20% w/w amorphous BMS-986165 to 90%-80% w/w HPMCAS. 11. The dosage form according to claim 10, wherein the dispersion is a spray-dried dispersion. 12. The dosage form according to claim 3, wherein the proportion of amorphous BMS-986165 to HPMCAS in the dispersion is 25% w/w amorphous BMS-986165 to 75% w/w HPMCAS. 13. The dosage form according to claim 3, wherein the proportion of amorphous BMS-986165 to HPMCAS in the dispersion is 20% w/w amorphous BMS-986165 to 80% w/w HPMCAS. 14. The dosage form according to claim 3, wherein the proportion of amorphous BMS-986165 to HPMCAS in the dispersion is 15% w/w amorphous BMS-986165 to 85% w/w HPMCAS. 15. The dosage form according to claim 3, wherein the proportion of amorphous BMS-986165 to HPMCAS in the dispersion is 10% w/w amorphous BMS-986165 to 90% w/w HPMCAS. 16. The dosage form according to claim 14, wherein the dispersion is a spray-dried dispersion. 17. The dosage form according to claim 14, wherein the dosage form is free of crystalline BMS-986165 following storage at 40° C./75% Relative Humidity for at least three months. 18. The dosage form according to claim 14, wherein the dosage form is free of crystalline BMS-986165 following storage at 40° C./75% Relative Humidity for at least six months. 19. The dosage form according to claim 14, wherein the amorphous BMS-986165 in the dosage form exhibits less than 5% degradation when the dosage form is stored at 40° C./75% Relative Humidity for at least six months. 20. The dosage form according to claim 14, wherein at least 80% of the amorphous BMS-986165 in the dosage form is released by 30 minutes after the dosage form is placed in a medium having a pH of from 1 to 2. 21. The dosage form according to claim 14, wherein at least 80% of the amorphous BMS-986165 within the dosage form is released by 30 minutes after the dosage form is placed in a medium having a pH of from 6 to 7. 22. The dosage form according to claim 9, wherein the amount of amorphous BMS-986165 in the dosage form is from 1 to 12 mg. 23. The dosage form according to claim 10, wherein the amount of amorphous BMS-986165 in the dosage form is from 1 to 12 mg. 24. The dosage form according to claim 16, wherein the amount of amorphous BMS-986165 in the dosage form is from 1 to 12 mg. 25. The dosage form according to claim 11, wherein the amount of amorphous BMS-986165 in the dosage form is 12 mg. 26. The dosage form according to claim 25, wherein the dosage form is a tablet having a tablet weight that is 400 mg. 27. The dosage form according to claim 11, wherein the amount of amorphous BMS-986165 in the dosage form is 6 mg. 28. The dosage form according to claim 27, wherein the dosage form is a tablet having a tablet weight that is 200 mg. 29. The dosage form according to claim 10, wherein the amount of amorphous BMS-986165 in the dosage form is 3 mg. 30. The dosage form according to claim 11, wherein the amount of amorphous BMS-986165 in the dosage form is 3 mg. 31. The dosage form according to claim 10, further comprising microcrystalline cellulose, lactose, croscarmellose, magnesium stearate, and silicon dioxide. 32. The dosage form according to claim 1, wherein the dosage form comprises: said dispersion, in an amount of 20% w/w of the dosage form, wherein the proportion of amorphous BMS-986165 to HPMCAS in said dispersion is 15% w/w amorphous BMS-986165: 85% HPMCAS; microcrystalline cellulose in an amount of 51.25% w/w of the dosage form; lactose anhydrous in an amount of 22% w/w of the dosage form; croscarmellose sodium in an amount of 5% w/w of the dosage form; magnesium stearate in an amount of 0.75% w/w of the dosage form; and silicon dioxide in an amount of 1% w/w of the dosage form. 33. The dosage form according to claim 32, wherein the dosage form is made by a process comprising granulation, and wherein the 5% w/w croscarmellose sodium is 1:1 intragranular: extragranular, and wherein the 0.75% w/w magnesium stearate is 1:2 intragranular: extragranular. 34. The dosage form according to claim 9, wherein the dosage form is made by a process comprising direct compression. 35. The dosage form according to claim 16, wherein the amount of amorphous BMS-986165 in the dosage form is 6 mg. 36. The dosage form according to claim 9, wherein the amount of amorphous BMS-986165 in the dosage form is 6 mg. 37. The dosage form according to claim 9, wherein the amount of amorphous BMS-986165 in the dosage form is 3 mg. 38. The dosage form according to claim 16, wherein the dosage form is a tablet for oral administration. 39. The dosage form according to claim 16, wherein the dosage form is an oral dosage form, and bioavailability of BMS-986165 from the oral dosage form is measured by area under the curve of a plasma-concentration-versus-time curve, wherein the bioavailability of BMS-986165 from the oral dosage form administered to a subject concurrently with a proton pump inhibitor differs by no more than 25% from the bioavailability of BMS-986165 from the oral dosage form administered to the subject without concurrent administration of a proton pump inhibitor. 40. The oral dosage form according to claim 39, wherein the subject is a human subject. 41. A method of treating an inflammatory bowel disease in a human subject, the method comprising administering to the human subject the dosage form according to claim 9. 42. The method according to claim 41, wherein the inflammatory bowel disease is ulcerative colitis. 43. The method according to claim 41, wherein the inflammatory bowel disease is Crohn's disease. 44. A method of treating psoriasis in a human subject, the method comprising administering to the human subject the dosage form according to claim 9. 45. The method according to claim 44, wherein the psoriasis is plaque psoriasis. 46. A method of treating psoriatic arthritis in a human subject, the method comprising administering to the human subject the dosage form according to claim 9. 47. A method of treating an inflammatory bowel disease in a human subject, the method comprising administering to the human subject the dosage form according to claim 11. 48. The method according to claim 47, wherein the inflammatory bowel disease is ulcerative colitis. 49. The method according to claim 47, wherein the inflammatory bowel disease is Crohn's disease. 50. A method of treating psoriasis in a human subject, the method comprising administering to the human subject the dosage form according to claim 11. 51. The method according to claim 50, wherein the psoriasis is plaque psoriasis. 52. A method of treating psoriatic arthritis in a human subject, the method comprising administering to the human subject the dosage form according to claim 11. 53. A dosage form of 6-(cyclopropaneamido)-4-((2-methoxy-3-(1-methyl-1H-1,2,4-triazol-3-yl)phenyl)amino)-N-(methyl-d3)pyridazine-3-carboxamide (BMS-986165), the dosage form comprising a dispersion of amorphous BMS-986165 dispersed in a polymer matrix; wherein the polymer matrix comprises hydroxypropyl methylcellulose acetate succinate (HPMCAS); and wherein the dispersion comprises the amorphous BMS-986165 in an amount that is at least 10% w/w and no greater than 25% w/w of the dispersion. 54. The dosage form according to claim 53, wherein the HPMCAS is HPMCAS H-grade. 55. The dosage form according to claim 53, wherein the dispersion is a spray-dried dispersion. 56. The dosage form according to claim 54, wherein the dispersion is a spray-dried dispersion. 57. A method of treating psoriasis in a human subject, the method comprising administering to the human subject the dosage form according to claim 54. 58. The method according to claim 57, wherein the psoriasis is plaque psoriasis. 59. A method of treating psoriatic arthritis in a human subject, the method comprising administering to the human subject the dosage form according to claim 54. 60. The method according to claim 57, wherein the amount of amorphous BMS-986165 in the dosage form is 6 mg. 61. The method according to claim 57, wherein the amount of amorphous BMS-986165 in the dosage form is 3 mg. 62. The method according to claim 59, wherein the amount of amorphous BMS-986165 in the dosage form is 6 mg. 63. The method according to claim 59, wherein the amount of amorphous BMS-986165 in the dosage form is 3 mg. 64. A method of treating psoriasis in a human subject, the method comprising administering to the human subject the dosage form according to claim 53. 65. The method according to claim 64, wherein the psoriasis is plaque psoriasis. 66. A method of treating psoriatic arthritis in a human subject, the method comprising administering to the human subject the dosage form according to claim 53. 67. The method according to claim 64, wherein the amount of amorphous BMS-986165 in the dosage form is 6 mg. 68. The method according to claim 64, wherein the amount of amorphous BMS-986165 in the dosage form is 3 mg. 69. The method according to claim 66, wherein the amount of amorphous BMS-986165 in the dosage form is 6 mg. 70. The method according to claim 66, wherein the amount of amorphous BMS-986165 in the dosage form is 3 mg.