IP Library › Granted Patent US 12,042,489
Granted Patent B2
US 12,042,489 · App. 18/326,279 · Granted Jul 23, 2024

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 12,042,489
App. No.
18/326,279
Granted
Jul 23, 2024
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 (31)

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

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

3. The molecule of claim 1 , wherein the mutation is selected from the group consisting of: N34T, M42K, L54F, P60T, L89F, Y123C, H125L, I133M, K140T, F145S, P146R, D165G, p.M187_S188dup, V199G, M208R, I219L, N224T, Q250R, G261C, G271D, M284V, I303F, G325R, E358Q, E358D, G361E, G375E, T412N and M421V.

4. The molecule of claim 1 , wherein the mutation is selected from the group consisting of: N34T, M42K, L54F, P60T, L89F, I133M, K140T, F145S, P146R, D165G, V199G, M208R, I219L, N224T, Q250R, G261C, G271D, M284V, I303F, G325R, E358Q, E358D, G361E, G375E, T412N and M421V.

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

6. An α-galactosidase A protein having a HEK amenable mutation selected from the group consisting of: A13T, N34T, M42K, L54F, P60T, E87D, L89F, Y123C, H125L, I133M, K140T, F145S, P146R, Y152H, D165G, p.M187_S188dup, V199G, M208R, I219L, N224T, Q250R, G261C, G271D, M284V, I303F, D322N, G325R, K326N, G334E, E358Q, E358D, G361E, G375E, T412N and M421V, wherein the protein is bound to migalastat and the protein has increased stability as compared to a naturally-occurring α-galactosidase A protein having the same mutation.

7. The α-galactosidase A protein of claim 6 , wherein the mutation is selected from the group consisting of: A13T, N34T, M42K, L54F, P60T, E87D, L89F, Y123C, H125L, I133M, K140T, F145S, P146R, Y152H, D165G, p.M187_S188dup, V199G, M208R, I219L, N224T, Q250R, G261C, G271D, M284V, I303F, D322N, G325R, K326N, G334E, E358Q, E358D, G361E, G375E, T412N and M421V.

8. The α-galactosidase A protein of claim 6 , wherein the mutation is selected from the group consisting of: N34T, M42K, L54F, P60T, L89F, I133M, K140T, F145S, P146R, D165G, V199G, M208R, I219L, N224T, Q250R, G261C, G271D, M284V, I303F, G325R, E358Q, E358D, G361E, G375E, T412N and M421V.

9. The α-galactosidase A protein of claim 6 , wherein the mutation is selected from the group consisting of: N34T, M42K, L54F, P60T, L89F, I133M, K140T, F145S, P146R, D165G, V199G, M208R, I219L, N224T, Q250R, G261C, G271D, M284V, I303F, G325R, E358Q, E358D, G361E, G375E, T412N and M421V.

10. The α-galactosidase A protein of claim 6 , wherein the mutation is selected from the group consisting of: A13T, N34T, M42K, L54F, P60T, E87D, L89F, Y123C, H125L, I133M, K140T, F145S, P146R, Y152H, D165G, p.M187_S188dup, V199G, M208R, I219L, N224T, Q250R, G261C, G271D, M284V, I303F, D322N, K326N, G334E, E358Q, E358D, G361E, G375E, T412N and M421V.

11. 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 A13T, N34T, M42K, L54F, P60T, E87D, L89F, Y123C, H125L, I133M, K140T, F145S, P146R, Y152H, D165G, p.M187_S188dup, V199G, M208R, I219L, N224T, Q250R, G261C, G271D, M284V, I303F, D322N, G325R, K326N, G334E, E358Q, E358D, G361E, G375E, T412N and M421V.

12. The method of claim 11 , wherein the mutation is selected from the group consisting of: A13T, N34T, M42K, L54F, P60T, E87D, L89F, I133M, K140T, F145S, P146R, Y152H, D165G, V199G, M208R, I219L, N224T, Q250R, G261C, G271D, M284V, I303F, D322N, G325R, K326N, G334E, E358Q, E358D, G361E, G375E, T412N and M421V.

13. The method of claim 11 , wherein the mutation is selected from the group consisting of: N34T, M42K, L54F, P60T, L89F, Y123C, H125L, I133M, K140T, F145S, P146R, D165G, p.M187_S188dup, V199G, M208R, I219L, N224T, Q250R, G261C, G271D, M284V, I303F, G325R, E358Q, E358D, G361E, G375E, T412N and M421V.

14. The method of claim 11 , wherein the mutation is selected from the group consisting of: N34T, M42K, L54F, P60T, L89F, I133M, K140T, F145S, P146R, D165G, V199G, M208R, I219L, N224T, Q250R, G261C, G271D, M284V, I303F, G325R, E358Q, E358D, G361E, G375E, T412N and M421V.

15. The method of claim 11 , wherein the mutation is selected from the group consisting of: A13T, N34T, M42K, L54F, P60T, E87D, L89F, Y123C, H125L, I133M, K140T, F145S, P146R, Y152H, D165G, p.M187_S188dup, V199G, M208R, I219L, N224T, Q250R, G261C, G271D, M284V, I303F, D322N, K326N, G334E, E358Q, E358D, G361E, G375E, T412N and M421V.

16. The method of claim 11 , wherein the patient has a Fabry disease-causing mutation.

17. The method of claim 11 , wherein the patient is administered about 150 mg of migalastat hydrochloride every other day.

18. The method of claim 11 , wherein the patient is male.

19. The method of claim 11 , wherein the patient is female.

20. The method of claim 11 , 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.

21. The method of claim 11 , wherein the mutation is selected from the group consisting of: E87D, L89F, Y123C, H125L, I133M, K140T, F145S, M208R, K326N, G334E, G375E, T412N and M421V and wherein the patient is administered about 150 mg of migalastat hydrochloride every other day.

22. The method of claim 11 , wherein the mutation is selected from the group consisting of: L54F, L89F, K140T and G334E.

23. The method of claim 22 , wherein the patient is administered about 150 mg of migalastat hydrochloride every other day.

24. The method of claim 22 , wherein the mutation is L54F.

25. The method of claim 24 , wherein the patient is administered about 150 mg of migalastat hydrochloride every other day.

26. The method of claim 22 , wherein the mutation is L89F.

27. The method of claim 26 , wherein the patient is administered about 150 mg of migalastat hydrochloride every other day.

28. The method of claim 22 , wherein the mutation is K140T.

29. The method of claim 28 , wherein the patient is administered about 150 mg of migalastat hydrochloride every other day.

30. The method of claim 22 , wherein the mutation is G334E.

31. The method of claim 30 , wherein the patient is administered about 150 mg of migalastat hydrochloride every other day.

Assignments (3)
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 →