IP Library › Granted Patent US 11,612,594
Granted Patent B2
US 11,612,594 · App. 17/077,389 · Granted Mar 28, 2023

Methods of treating Fabry patients having renal impairment

Inventors: Jeff Castelli (New Hope, PA); Elfrida Benjamin (Millstone Township, NJ)
Assignee: Amicus Therapeutics, Inc.
A61K31/445A61P13/12A61K9/48
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Quick Facts
Patent No.
US 11,612,594
App. No.
17/077,389
Granted
Mar 28, 2023
Kind
B2
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.

Claims (70)

1. A composition comprising migalastat bound to an α-galactosidase A protein comprising a HEK assay amenable mutation selected from the group consisting of: A13T, A15T, W24R, N34T, M42K, L54F, P60T, P60S, E87D, L89F, R112G, Y123C, H125L, I133M, K140T, F145S, P146R, Y152H, D165G, p.M187_S188dup, V199G, M208R, I219L, Q221P, N224T, Q250R, G261C, G271D, W277G, W277C, M284V, R301L, I303F, S304N, D322N, G325R, K326N, G334E, E358Q, E358D, G361E, G375E, T412N and M421V.

2. The composition of claim 1 , wherein the mutation is selected from the group consisting of: A13T, A15T, W24R, N34T, M42K, L54F, P60T, P60S, E87D, L89F, I133M, K140T, F145S, P146R, Y152H, D165G, V199G, M208R, I219L, Q221P, N224T, Q250R, G261C, G271D, W277G, W277C, M284V, R301L, I303F, S304N, D322N, G325R, K326N, G334E, E358Q, E358D, G361E, G375E, T412N and M421V.

3. The composition of claim 1 , wherein the mutation is selected from the group consisting of: L54F, P60T, P60S, I133M, K140T, F145S, V199G, I219L, Q221P, Q250R, G261C, G271D, W277G, M284V, R301L and I303F.

4. The composition of claim 1 , wherein the mutation is selected from the group consisting of: A15T, N34T, M42K, L54F, P60T, P60S, L89F, R112G, Y123C, H125L, I133M, K140T, F145S, P146R, D165G, p.M187_S188dup, V199G, M208R, I219L, Q221P, N224T, Q250R, G261C, G271D, W277G, W277C, M284V, R301L, I303F, S304N, G325R, E358Q, E358D, G361E, G375E, T412N and M421V.

5. The composition of claim 1 , wherein the mutation is selected from the group consisting of: N34T, M42K, L54F, P60T, P60S, L89F, R112G, Y123C, H125L, I133M, K140T, F145S, P146R, D165G, p.M187_S188dup, V199G, M208R, I219L, Q221P, N224T, Q250R, G261C, G271D, W277G, W277C, M284V, R301L, I303F, G325R, E358Q, E358D, G361E, G375E and T412N.

6. The composition of claim 1 , wherein the mutation is selected from the group consisting of: N34T, R112G, G271D, W287L, G325R and T412N.

7. The composition of claim 1 , wherein the mutation is selected from the group consisting of: A15T, N34T, M42K, L54F, P60T, P60S, L89F, I133M, K140T, F145S, P146R, D165G, V199G, M208R, I219L, Q221P, N224T, Q250R, G261C, G271D, W277G, W277C, M284V, R301L, I303F, S304N, G325R, E358Q, E358D, G361E, G375E, T412N and M421V.

8. The composition of claim 1 , wherein the mutation is selected from the group consisting of: N34T, M42K, L54F, P60T, P60S, L89F, I133M, K140T, F145S, P146R, D165G, V199G, M208R, I219L, Q221P, N224T, Q250R, G261C, G271D, W277G, W277C, M284V, R301L, I303F, G325R, E358Q, E358D, G361E, G375E and T412N.

9. The composition of claim 1 , wherein the mutation is selected from the group consisting of: N34T, E87D, I133M, F145S, P146R, Y152H, D165G, M208R, I219L, Q221P, N224T, Q250R, G261C, I303F, K326N, E358Q and G375E.

10. The composition of claim 1 , wherein the mutation is selected from the group consisting of: N34T, I133M, F145S, P146R, D165G, M208R, I219L, Q221P, N224T, Q250R, G261C, I303F, E358Q and G375E.

11. The composition of claim 1 , wherein the mutation is selected from the group consisting of: I133M, F145S, I219L, Q221P, Q250R, G261C, and I303F.

12. The composition of claim 1 , wherein the mutation is selected from the group consisting of: R112G and G325R.

13. The composition of claim 1 , wherein the mutation is selected from the group consisting of: A13T, A15T, W24R, N34T, M42K, L54F, P60T, P60S, E87D, L89F, Y123C, H125L, I133M, K140T, F145S, P146R, Y152H, D165G, p.M187_S188dup, V199G, M208R, I219L, Q221P, N224T, Q250R, G261C, G271D, W277G, W277C, M284V, R301L, I303F, S304N, D322N, K326N, G334E, E358Q, E358D, G361E, G375E, T412N and M421V.

14. The composition of claim 1 , wherein the migalastat stabilizes the α-galactosidase A protein.

15. The composition of claim 1 , wherein the composition further comprises globotriaosylceramide (GL-3).

16. The composition of claim 1 , wherein the composition comprises white blood cells containing the migalastat bound to the α-galactosidase A protein.

17. The composition of claim 1 , wherein the composition comprises plasma containing the migalastat bound to the α-galactosidase A protein.

18. The composition of claim 1 , wherein the plasma contains migalastat at a concentration in the range of about 1 ng/mL to about 2191 ng/mL.

19. The composition of claim 1 , wherein the plasma further comprises globotriaosylsphingosine (lyso-Gb 3 ).

20. The composition of claim 1 , wherein the plasma contains lyso-Gb 3 at a concentration in the range of about 9.3 to about 13.1 nM/L.

21. The composition of claim 1 , wherein the composition comprises an organ containing migalastat bound to the α-galactosidase A protein.

22. The composition of claim 21 , wherein the organ comprises a heart.

23. The composition of claim 21 , wherein the organ comprises a kidney.

24. The composition of claim 21 , wherein the organ comprises skin.

25. The composition of claim 1 , wherein the composition comprises tissue containing migalastat bound to the α-galactosidase A protein.

26. The composition of claim 1 , wherein the composition comprises cells containing migalastat bound to the α-galactosidase A protein.

27. The composition of claim 26 , wherein the migalastat is bound to the α-galactosidase A protein in the endoplasmic reticulum.

28. The composition of claim 27 , wherein the migalastat stabilizes the α-galactosidase A protein in the endoplasmic reticulum and facilitates the proper trafficking of the α-galactosidase A protein to lysosomes.

29. The composition of claim 1 , wherein the composition further comprises 4-MU-α-Gal.

30. The composition of claim 1 , wherein the composition contains migalastat at a concentration in the range of 17 nM to 1 mM.

31. The composition of claim 1 , wherein the composition contains migalastat at a concentration in the range of 10 μM.

32. The composition of claim 1 , wherein the mutation is a Fabry disease-causing mutation.

33. The composition of claim 8 , wherein the migalastat stabilizes the α-galactosidase A protein.

34. The composition of claim 8 , wherein the composition further comprises globotriaosylceramide (GL-3).

35. The composition of claim 8 , wherein the composition comprises white blood cells containing the migalastat bound to the α-galactosidase A protein.

36. The composition of claim 8 , wherein the composition comprises plasma containing the migalastat bound to the α-galactosidase A protein.

37. The composition of claim 36 , wherein the plasma contains migalastat at a concentration in the range of about 1 ng/mL to about 2191 ng/mL.

38. The composition of claim 36 , wherein the plasma further comprises globotriaosylsphingosine (lyso-Gb 3 ).

39. The composition of claim 36 , wherein the plasma contains lyso-Gb 3 at a concentration in the range of about 9.3 to about 13.1 nM/L.

40. The composition of claim 8 , wherein the composition comprises an organ containing migalastat bound to the α-galactosidase A protein.

41. The composition of claim 40 , wherein the organ comprises a heart.

42. The composition of claim 40 , wherein the organ comprises a kidney.

43. The composition of claim 40 , wherein the organ comprises skin.

44. The composition of claim 8 , wherein the composition comprises tissue containing migalastat bound to the α-galactosidase A protein.

45. The composition of claim 8 , wherein the composition comprises cells containing migalastat bound to the α-galactosidase A protein.

46. The composition of claim 45 , wherein the migalastat is bound to the α-galactosidase A protein in the endoplasmic reticulum.

47. The composition of claim 46 , wherein the migalastat stabilizes the α-galactosidase A protein in the endoplasmic reticulum and facilitates the proper trafficking of the α-galactosidase A protein to lysosomes.

48. The composition of claim 8 , wherein the composition further comprises 4-MU-α-Gal.

49. The composition of claim 8 , wherein the composition contains migalastat at a concentration in the range of 17 nM to 1 mM.

50. The composition of claim 8 , wherein the composition contains migalastat at a concentration in the range of 10 μM.

51. The composition of claim 8 , wherein the mutation is a Fabry disease-causing mutation.

52. The composition of claim 9 , wherein the migalastat stabilizes the α-galactosidase A protein.

53. The composition of claim 9 , wherein the composition further comprises globotriaosylceramide (GL-3).

54. The composition of claim 9 , wherein the composition comprises white blood cells containing the migalastat bound to the α-galactosidase A protein.

55. The composition of claim 9 , wherein the composition comprises plasma containing the migalastat bound to the a-galactosidase A protein.

56. The composition of claim 55 , wherein the plasma contains migalastat at a concentration in the range of about 1 ng/mL to about 2191 ng/mL.

57. The composition of claim 55 , wherein the plasma further comprises globotriaosylsphingosine (lyso-Gb 3 ).

58. The composition of claim 55 , wherein the plasma contains lyso-Gb 3 at a concentration in the range of about 9.3 to about 13.1 nM/L.

59. The composition of claim 9 , wherein the composition comprises an organ containing migalastat bound to the α-galactosidase A protein.

60. The composition of claim 59 , wherein the organ comprises a heart.

61. The composition of claim 59 , wherein the organ comprises a kidney.

62. The composition of claim 59 , wherein the organ comprises skin.

63. The composition of claim 9 , wherein the composition comprises tissue containing migalastat bound to the α-galactosidase A protein.

64. The composition of claim 9 , wherein the composition comprises cells containing migalastat bound to the α-galactosidase A protein.

65. The composition of claim 64 , wherein the migalastat is bound to the α-galactosidase A protein in the endoplasmic reticulum.

66. The composition of claim 65 , wherein the migalastat stabilizes the α-galactosidase A protein in the endoplasmic reticulum and facilitates the proper trafficking of the α-galactosidase A protein to lysosomes.

67. The composition of claim 9 , wherein the composition further comprises 4-MU-α-Gal.

68. The composition of claim 9 , wherein the composition contains migalastat at a concentration in the range of 17 nM to 1 mM.

69. The composition of claim 9 , wherein the composition contains migalastat at a concentration in the range of 10 μM.

70. The composition of claim 9 , wherein the mutation is a Fabry disease-causing mutation.

Assignments (4)
SECURITY INTEREST Recorded Apr 27, 2026
From: BIOMARIN PHARMACEUTICAL INC.; AMICUS THERAPEUTICS, INC.
To: CITIBANK, N.A., AS COLLATERAL AGENT
Reel/Frame 075493/0968 →
RELEASE OF SECURITY INTEREST Recorded Apr 27, 2026
From: WILMINGTON TRUST, NATIONAL ASSOCIATION
To: AMICUS THERAPEUTICS, INC.
Reel/Frame 075494/0030 →
SECURITY INTEREST Recorded Oct 6, 2023
From: AMICUS THERAPEUTICS, INC.
To: WILMINGTON TRUST, NATIONAL ASSOCIATION
Reel/Frame 065177/0196 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 5, 2022
From: CASTELLI, JEFF; BENJAMIN, ELFRIDA
To: AMICUS THERAPEUTICS, INC.
Reel/Frame 061099/0803 →
Cited By (1)
US 12,594,268