Claims for Patent: 12,109,205

Summary for Patent: 12,109,205

Title:	Methods of treating Fabry patients having renal impairment
Abstract:	Provided are methods for treatment of Fabry disease in patients having HEK assay amenable mutations in α-galactosidase A. Certain methods comprise administering migalastat or a salt thereof every other day, such as administering about 150 mg of migalastat hydrochloride every other day.
Inventor(s):	Jeff Castelli, Elfrida Benjamin
Assignee:	Amicus Therapeutics Inc
Application Number:	US17/078,840
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 12,109,205
Patent Claims:	1. A method of treating Fabry disease, the method comprising administering migalastat to a patient in need thereof, wherein the patient has an α-galactosidase A protein comprising a HEK assay amenable mutation selected from the group consisting of: R4M/Y207S, A15T, A15G, F18C, W24G, N34D, G35V, M42I, E48Q, N53D, P60S, F69L, M721, G85S, G85N, G104V, L106F, A108T, D109G, R112G, G144D, L167V, L180W, G195V, R196G, V199A, E203D, P210S, P210L, P214S, R220P, Q221P, F229L, I242T, W245G, Q250H, p.V254del, G260E, G261S, G271S/D313Y, W277C, D299E, S304T, D313Y/G411D, I319F, F337S, P343L, G361A, P362T, K391T, G395E and p.T400_S401dup. 2. The method of claim 1, wherein the mutation is selected from the group consisting of: A15T, F18C, W24G, G35V, M42I, N53D, P60S, F69L, M72I, G104V, L106F, A108T, G144D, L167V, L180W, G195V, R196G, V199A, P210S, P210L, P214S, R220P, Q221P, F229L, I242T, W245G, Q250H, p.V254del, G260E, G261S, W277C, D299E, S304T, I319F, F337S, P343L, G361A, P362T and K391T. 3. The method of claim 1, wherein the mutation is selected from the group consisting of: N53D, P60S, L180W, R196G, P210S, P210L, P214S, R220P, Q221P, I242T, Q250H, p.V254del, G260E, G261S, D299E, S304T and P362T. 4. The method of claim 1, wherein the mutation is selected from the group consisting of: R4M/Y207S, A15T, A15G, W24G, G35V, M42I, E48Q, N53D, P60S, F69L, M72I, G85S, G85N, G104V, L106F, A108T, D109G, G144D, L167V, L180W, G195V, R196G, V199A, E203D, P210S, P210L, P214S, R220P, Q221P, F229L, I242T, W245G, Q250H, p.V254del, G260E, G261S, W277C, D299E, S304T, I319F, F337S, P343L, G361A, P362T, K391T, G395E and p.T400_S401dup. 5. The method of claim 1, wherein the mutation is selected from the group consisting of: R4M/Y207S, W24G, G35V, M421, E48Q, N53D, P60S, F69L, G85S, G85N, G104V, L106F, D109G, G144D, L180W, G195V, R196G, E203D, P210S, P210L, P214S, R220P, Q221P, F229L, I242T, Q250H, p.V254del, G260E, G261S, W277C, D299E, S304T, I319F, F337S, G361A, P362T, K391T, G395E and p.T400_S401dup. 6. The method of claim 1, wherein the mutation is selected from the group consisting of: G35V, M421, F69L and L180W. 7. The method of claim 1, wherein the mutation is selected from the group consisting of: A15T, W24G, G35V, M42I, N53D, P60S, F69L, M72I, G104V, L106F, A108T, G144D, L167V, L180W, G195V, R196G, V199A, P210S, P210L, P214S, R220P Q221P, F229L, I242T, W245G, Q250H, p.V254del, G260E, G261S, W277C, D299E, S304T, I319F, F337S, P343L, G361A, P362T and K391T. 8. The method of claim 1, wherein the mutation is selected from the group consisting of: W24G, G35V, M42I, N53D, P60S, F69L, G104V, L106F, G144D, L180W, G195V, R196G, P210S, P210L, P214S, R220P, Q221P, F229L, I242T, Q250H, p.V254del, G260E, G261S, W277C, D299E, S304T, I319F, F337S, G361A, P362T and K391T. 9. The method of claim 1, wherein the mutation is selected from the group consisting of: R4M/Y207S, A15T, A15G, F18C, W24G, N34D, G35V, M42I, E48Q, N53D, P60S, F69L, M72I, G85S, G85N, G104V, L106F, A108T, D109G, R112G, G144D, L167V, L180W, G195V, R196G, V199A, E203D, P210S, P210L, P214S, R220P, Q221P, F229L, I242T, W245G, Q250H, G260E, G261S, G271S/D313Y, W277C, D299E, S304T, D313Y/G411D, I319F, F337S, P343L, G361A, P362T, K391T and G395E. 10. The method of claim 1, wherein the mutation is selected from the group consisting of: R4M/Y207S, W24G, G35V, M42I, E48Q, N53D, P60S, F69L, G85S, G85N, G104V, L106F, D109G, G144D, L180W, G195V, R196G, E203D, P210S, P210L, P2145, R220P, Q221P, F229L, I242T, Q250H, G260E, G261S, W277C, D299E, S304T, I319F, F337S, G361A, P362T, K391T and G395E. 11. The method of claim 1, wherein the mutation is selected from the group consisting of: A15T, F18C, W24G, G35V, M42I, N53D, P60S, F69L, M72I, G104V, L106F, A108T, G144D, L167V, L180W, G195V, R196G, V199A, P210S, P210L, P214S, R220P, Q221P, F229L, I242T, W245G, Q250H, G260E, G261S, W277C, D299E, S304T, I319F, F337S, P343L, G361A, P362T and K391T. 12. The method of claim 1, wherein the mutation is selected from the group consisting of: N53D, P60S, L180W, R196G, P210S, P210L, P214S, R220P, Q221P, I242T, Q250H, G260E, G261S, D299E, S304T and P362T. 13. The method of claim 1, wherein the mutation is selected from the group consisting of: W24G, G35V, M42I, N53D, P60S, F69L, G104V, L106F, G144D, L180W, G195V, R196G, P210S, P210L, P214S, R220P, Q221P, F229L, I242T, Q250H, G260E, G261S, W277C, D299E, S304T, I319F, F337S, G361A, P362T and K391T. 14. The method of claim 1, wherein the patient has a Fabry disease-causing mutation. 15. The method of claim 1, wherein the migalastat or salt thereof is administered to the patient every other day. 16. The method of claim 1, wherein the patient is administered about 123 to about 300 mg of the migalastat or salt thereof every other day. 17. The method of claim 1, wherein the patient is administered about 150 mg of the migalastat or salt thereof every other day. 18. The method of claim 1, wherein the patient is administered about 150 mg of migalastat hydrochloride every other day. 19. The method of claim 1, wherein the patient is male. 20. The method of claim 1, wherein the patient is female. 21. The method of claim 1, wherein the patient has renal impairment. 22. The method of claim 21, wherein the patient has mild or moderate renal impairment. 23. The method of claim 1, wherein the patient is an enzyme replacement therapy (ERT)-experienced patient. 24. The method of claim 1, wherein the patient is an enzyme replacement therapy (ERT)-experienced patient with renal impairment. 25. The method of claim 1, wherein the patient is an enzyme replacement therapy (ERT)-naïve patient. 26. The method of claim 1, wherein the patient has a proteinuria level of less than 100 mg/24 hr prior to initiating the administration of the migalastat or salt thereof. 27. The method of claim 1, wherein the patient has a proteinuria level of 100 to 1,000 mg/24 hr prior to initiating the administration of the migalastat or salt thereof. 28. The method of claim 1, wherein the patient has a proteinuria level of greater than 1,000 mg/24 hr prior to initiating the administration of the migalastat or salt thereof. 29. The method of claim 1, wherein the migalastat or salt thereof is administered orally. 30. The method of claim 29, wherein the migalastat or salt thereof is in a solid dosage form. 31. The method of claim 30, wherein the solid dosage form comprises a capsule. 32. The method of claim 1, wherein the migalastat is administered as a pharmaceutically acceptable salt. 33. The method of claim 1, wherein the patient is orally administered a capsule comprising about 150 mg of migalastat hydrochloride every other day. 34. The method of claim 8, wherein the patient has a Fabry disease-causing mutation. 35. The method of claim 8, wherein the migalastat or salt thereof is administered to the patient every other day. 36. The method of claim 8, wherein the patient is administered about 123 to about 300 mg of the migalastat or salt thereof every other day. 37. The method of claim 8, wherein the patient is administered about 150 mg of the migalastat or salt thereof every other day. 38. The method of claim 8, wherein the patient is administered about 150 mg of migalastat hydrochloride every other day. 39. The method of claim 8, wherein the patient is male. 40. The method of claim 8, wherein the patient is female. 41. The method of claim 8, wherein the patient has renal impairment. 42. The method of claim 41, wherein the patient has mild or moderate renal impairment. 43. The method of claim 8, wherein the patient is an enzyme replacement therapy (ERT)-experienced patient. 44. The method of claim 8, wherein the patient is an enzyme replacement therapy (ERT)-experienced patient with renal impairment. 45. The method of claim 8, wherein the patient is an enzyme replacement therapy (ERT)-naïve patient. 46. The method of claim 8, wherein the patient has a proteinuria level of less than 100 mg/24 hr prior to initiating the administration of the migalastat or salt thereof. 47. The method of claim 8, wherein the patient has a proteinuria level of 100 to 1,000 mg/24 hr prior to initiating the administration of the migalastat or salt thereof. 48. The method of claim 8, wherein the patient has a proteinuria level of greater than 1,000 mg/24 hr prior to initiating the administration of the migalastat or salt thereof. 49. The method of claim 8, wherein the migalastat or salt thereof is administered orally. 50. The method of claim 49, wherein the migalastat or salt thereof is in a solid dosage form. 51. The method of claim 50, wherein the solid dosage form comprises a capsule. 52. The method of claim 8, wherein the migalastat is administered as a pharmaceutically acceptable salt. 53. The method of claim 8, wherein the patient is orally administered a capsule comprising about 150 mg of migalastat hydrochloride every other day. 54. The method of claim 1, wherein the administration is effective to reduce globotriaosylceramide (GL-3) accumulated in an organ of the patient. 55. The method of claim 1, wherein the administration is effective to reduce plasma globotriaosylsphingosine (lyso-Gb3) in the patient. 56. The method of claim 1, wherein the administration is effective to increase white blood cell (WBC) α-galactosidase A activity in the patient. 57. The method of claim 1, wherein the administration is effective to reduce left ventricular mass index (LVMi) in the patient. 58. The method of claim 1, wherein the administration is effective to stabilize renal function in the patient. 59. The method of claim 1, wherein the administration is effective to (i) reduce globotriaosylceramide (GL-3) accumulated in an organ of the patient, (ii) reduce plasma globotriaosylsphingosine (lyso-Gb3) in the patient, (iii) increase white blood cell (WBC) α-galactosidase A activity in the patient, (iv) reduce left ventricular mass index (LVMi) in the patient, or (v) stabilize renal function in the patient. 60. A molecule comprising migalastat bound to an a-galactosidase A protein comprising a HEK assay amenable mutation selected from the group consisting of: R4M/Y207S, A15T, A15G, F18C, W24G, N34D, G35V, M42I, E48Q, N53D, P60S, F69L, M721, G85S, G85N, G104V, L106F, A108T, D109G, R112G, G144D, L167V, L180W, G195V, R196G, V199A, E203D, P210S, P210L, P214S, R220P, Q221P, F229L, I242T, W245G, Q250H, p.V254del, G260E, G261S, G271S/D313Y, W277C, D299E, S304T, D313Y/G411D, I319F, F337S, P343L, G361A, P362T, K391T, G395E and p.T400_S401dup. 61. The molecule of claim 60, wherein the mutation is selected from the group consisting of: A15T, F18C, W24G, G35V, M42I, N53D, P60S, F69L, M72I, G104V, L106F, A108T, G144D, L167V, L180W, G195V, R196G, V199A, P210S, P210L, P214S, R220P, Q221P, F229L, I242T, W245G, Q250H, p.V254del, G260E, G261S, W277C, D299E, S304T, I319F, F337S, P343L, G361A, P362T and K391T. 62. The molecule of claim 60, wherein the mutation is selected from the group consisting of: N53D, P60S, L180W, R196G, P210S, P210L, P214S, R220P, Q221P, I242T, Q250H, p.V254del, G260E, G261S, D299E, S304T and P362T. 63. The molecule of claim 60, wherein the mutation is selected from the group consisting of: R4M/Y207S, A15T, A15G, W24G, G35V, M42I, E48Q, N53D, P60S, F69L, M72I, G85S, G85N, G104V, L106F, A108T, D109G, G144D, L167V, L180W, G195V, R196G, V199A, E203D, P210S, P210L, P214S, R220P, Q221P, F229L, I242T, W245G, Q250H, p.V254del, G260E, G261S, W277C, D299E, S304T, I319F, F337S, P343L, G361A, P362T, K391T, G395E and p.T400_S401dup. 64. The molecule of claim 60, wherein the mutation is selected from the group consisting of: R4M/Y207S, W24G, G35V, M421, E48Q, N53D, P60S, F69L, G85S, G85N, G104V, L106F, D109G, G144D, L180W, G195V, R196G, E203D, P210S, P210L, P214S, R220P, Q221P, F229L, I242T, Q250H, p.V254del, G260E, G261S, W277C, D299E, S304T, I319F, F337S, G361A, P362T, K391T, G395E and p.T400_S401dup. 65. The molecule of claim 60, wherein the mutation is selected from the group consisting of: G35V, M421, F69L and L180W. 66. The molecule of claim 60, wherein the mutation is selected from the group consisting of: A15T, W24G, G35V, M421, N53D, P60S, F69L, M721, G104V, L106F, A108T, G144D, L167V, L180W, G195V, R196G, V199A, P210S, P210L, P214S, R220P, Q221P, F229L, I242T, W245G, Q250H, p.V254del, G260E, G261S, W277C, D299E, S304T, I319F, F337S, P343L, G361A, P362T and K391T. 67. The molecule of claim 60, wherein the mutation is selected from the group consisting of: W24G, G35V, M421, N53D, P60S, F69L, G104V, L106F, G144D, L180W, G195V, R196G, P210S, P210L, P214S, R220P, Q221P, F229L, I242T, Q250H, p.V254del, G260E, G261S, W277C, D299E, S304T, I319F, F337S, G361A, P362T and K391T. 68. The molecule of claim 60, wherein the mutation is selected from the group consisting of: R4M/Y207S, A15T, A15G, F18C, W24G, N34D, G35V, M421, E48Q, N53D, P60S, F69L, M721, G85S, G85N, G104V, L106F, A108T, D109G, R112G, G144D, L167V, L180W, G195V, R196G, V199A, E203D, P210S, P210L, P214S, R220P, Q221P, F229L, I242T, W245G, Q250H, G260E, G261S, G271S/D313Y, W277C, D299E, S304T, D313Y/G411D, I319F, F337S, P343L, G361A, P362T, K391T and G395E. 69. The molecule of claim 60, wherein the mutation is selected from the group consisting of: R4M/Y207S, W24G, G35V, M421, E48Q, N53D, P60S, F69L, G85S, G85N, G104V, L106F, D109G, G144D, L180W, G195V, R196G, E203D, P210S, P210L, P214S, R220P, Q221P, F229L, I242T, Q250H, G260E, G261S, W277C, D299E, S304T, I319F, F337S, G361A, P362T, K391T and G395E. 70. The molecule of claim 60, wherein the mutation is selected from the group consisting of: A15T, F18C, W24G, G35V, M42I, N53D, P60S, F69L, M72I, G104V, L106F, A108T, G144D, L167V, L180W, G195V, R196G, V199A, P210S, P210L, P214S, R220P, Q221P, F229L, I242T, W245G, Q250H, G260E, G261S, W277C, D299E, S304T, I319F, F337S, P343L, G361A, P362T and K391T. 71. The molecule of claim 60, wherein the mutation is selected from the group consisting of: N53D, P60S, L180W, R196G, P210S, P210L, P214S, R220P, Q221P, I242T, Q250H, G260E, G261S, D299E, S304T and P362T. 72. The molecule of claim 60, wherein the mutation is selected from the group consisting of: W24G, G35V, M42I, N53D, P60S, F69L, G104V, L106F, G144D, L180W, G195V, R196G, P210S, P210L, P214S, R220P, Q221P, F229L, I242T, Q250H, G260E, G261S, W277C, D299E, S304T, I319F, F337S, G361A, P362T and K391T. 73. An α-galactosidase A protein having a HEK amenable mutation selected from the group consisting of: R4M/Y207S, A15T, A15G, F18C, W24G, N34D, G35V, M42I, E48Q, N53D, P60S, F69L, M72I, G85S, G85N, G104V, L106F, A108T, D109G, R112G, G144D, L167V, L180W, G195V, R196G, V199A, E203D, P210S, P210L, P214S, R220P Q221P, F229L, I242T, W245G, Q250H, p.V254del, G260E, G261S, G271S/D313Y, W277C, D299E, S304T, D313Y/G411D, I319F, F337S, P343L, G361A, P362T, K391T, G395E and p.T400_S401dup, wherein the protein is bound to migalastat and the protein has increased stability as compared to a naturally-occurring a-galactosidase A protein having the same mutation. 74. The α-galactosidase A protein of claim 73, wherein the mutation is selected from the group consisting of: A15T, F18C, W24G, G35V, M421, N53D, P60S, F69L, M721, G104V, L106F, A108T, G144D, L167V, L180W, G195V, R196G, V199A, P210S, P210L, P214S, R220P, Q221P, F229L, I242T, W245G, Q250H, p.V254del, G260E, G261S, W277C, D299E, S304T, I319F, F337S, P343L, G361A, P362T and K391T. 75. The α-galactosidase A protein of claim 73, wherein the mutation is selected from the group consisting of: N53D, P60S, L180W, R196G, P210S, P210L, P214S, R220P, Q221P, I242T, Q250H, p.V254del, G260E, G261S, D299E, S304T and P362T. 76. The α-galactosidase A protein of claim 73, wherein the mutation is selected from the group consisting of: R4M/Y207S, A15T, A15G, W24G, G35V, M421, E48Q, N53D, P60S, F69L, M721, G85S, G85N, G104V, L106F, A108T, D109G, G144D, L167V, L180W, G195V, R196G, V199A, E203D, P210S, P210L, P214S, R220P, Q221P, F229L, I242T, W245G, Q250H, p.V254del, G260E, G261S, W277C, D299E, S304T, I319F, F337S, P343L, G361A, P362T, K391T, G395E and p.T400_S401dup. 77. The α-galactosidase A protein of claim 73, wherein the mutation is selected from the group consisting of: R4M/Y207S, W24G, G35V, M421, E48Q, N53D, P60S, F69L, G85S, G85N, G104V, L106F, D109G, G144D, L180W, G195V, R196G, E203D, P210S, P210L, P214S, R220P, Q221P, F229L, I242T, Q250H, p.V254del, G260E, G261S, W277C, D299E, S304T, I319F, F337S, G361A, P362T, K391T, G395E and p.T400_S401dup. 78. The α-galactosidase A protein of claim 73, wherein the mutation is selected from the group consisting of: G35V, M421, F69L and L180W. 79. The α-galactosidase A protein of claim 73, wherein the mutation is selected from the group consisting of: A15T, W24G, G35V, M42I, N53D, P60S, F69L, M72I, G104V, L106F, A108T, G144D, L167V, L180W, G195V, R196G, V199A, P210S, P210L, P214S, R220P, Q221P, F229L, I242T, W245G, Q250H, p.V254del, G260E, G261S, W277C, D299E, S304T, I319F, F337S, P343L, G361A, P362T and K391T. 80. The α-galactosidase A protein of claim 73, wherein the mutation is selected from the group consisting of: W24G, G35V, M42I, N53D, P60S, F69L, G104V, L106F, G144D, L180W, G195V, R196G, P210S, P210L, P214S, R220P, Q221P, F229L, I242T, Q250H, p.V254del, G260E, G261S, W277C, D299E, S304T, I319F, F337S, G361A, P362T and K391T. 81. The α-galactosidase A protein of claim 73, wherein the mutation is selected from the group consisting of: R4M/Y207S, A15T, A15G, F18C, W24G, N34D, G35V, M42I, E48Q, N53D, P60S, F69L, M72I, G85S, G85N, G104V, L106F, A108T, D109G, R112G, G144D, L167V, L180W, G195V, R196G, V199A, E203D, P210S, P210L, P214S, R220P Q221P, F229L, I242T, W245G, Q250H, G260E, G261S, G271S/D313Y, W277C, D299E, S304T, D313Y/G411D, I319F, F337S, P343L, G361A, P362T, K391T and G395E. 82. The α-galactosidase A protein of claim 73, wherein the mutation is selected from the group consisting of: R4M/Y207S, W24G, G35V, M42I, E48Q, N53D, P60S, F69L, G85S, G85N, G104V, L106F, D109G, G144D, L180W, G195V, R196G, E203D, P210S, P210L, P214S, R220P, Q221P, F229L, I242T, Q250H, G260E, G261S, W277C, D299E, S304T, I319F, F337S, G361A, P362T, K391T and G395E. 83. The α-galactosidase A protein of claim 73, wherein the mutation is selected from the group consisting of: A15T, F18C, W24G, G35V, M42I, N53D, P60S, F69L, M72I, G104V, L106F, A108T, G144D, L167V, L180W, G195V, R196G, V199A, P210S, P210L, P214S, R220P, Q221P, F229L, I242T, W245G, Q250H, G260E, G261S, W277C, D299E, S304T, I319F, F337S, P343L, G361A, P362T and K391T. 84. The α-galactosidase A protein of claim 73, wherein the mutation is selected from the group consisting of: N53D, P60S, L180W, R196G, P210S, P210L, P214S, R220P, Q221P, I242T, Q250H, G260E, G261S, D299E, S304T and P362T. 85. The α-galactosidase A protein of claim 73, wherein the mutation is selected from the group consisting of: W24G, G35V, M42I, N53D, P60S, F69L, G104V, L106F, G144D, L180W, G195V, R196G, P210S, P210L, P214S, R220P, Q221P, F229L, I242T, Q250H, G260E, G261S, W277C, D299E, S304T, 1319F, F337S, G361A, P362T and K391T. 86. The method of claim 1, wherein the mutation is selected from the group consisting of: A15T, A15G, F18C, E48Q, F69L, G104V, L106F, A108T, D109G, L167V, G195V, R196G, P210S, P210L, Q221P, F229L, W245G, D299E, F337S, P343L and K391T. 87. The molecule of claim 60, wherein the mutation is selected from the group consisting of: A15T, A15G, F18C, E48Q, F69L, G104V, L106F, A108T, D109G, L167V, G195V, R196G, P210S, P210L, Q221P, F229L, W245G, D299E, F337S, P343L and K391T. 88. The α-galactosidase A protein of claim 73, wherein the mutation is selected from the group consisting of: A15T, A15G, F18C, E48Q, F69L, G104V, L106F, A108T, D109G, L167V, G195V, R196G, P210S, P210L, Q221P, F229L, W245G, D299E, F337S, P343L and K391T. 89. The method of claim 1, wherein the mutation is selected from the group consisting of: N34D, M42I, R196G, V199A, E203D, p. V254del and G260E. 90. The method of claim 1, wherein the mutation is N34D. 91. The method of claim 1 wherein the mutation is M42I. 92. The method of claim 1 wherein the mutation is R196G. 93. The method of claim 1 wherein the mutation is V199A. 94. The method of claim 1 wherein the mutation is E203D. 95. The method of claim 1 wherein the mutation is V254del. 96. The method of claim 1 wherein the mutation is G260E. 97. The method of claim 1, wherein the mutation is selected from the group consisting of: R196G, p. V254del and G260E.