IP Library › Granted Patent US 11,612,593
Granted Patent B2
US 11,612,593 · App. 17/076,340 · 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 11,612,593
App. No.
17/076,340
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 (27)

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, 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 molecule 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, W227G, W227C, M284V, R301L, I303F, S304N, 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: L54F, P60T, P60S, I133M, K140T, F145S, V199G, I219L, Q221P, Q250R, G261C, G271D, W277G, M284V, R301L and I303F.

4. The molecule 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 molecule 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, Q221, N224T, Q250R, G261C, G271D, W277G, W277C, M284V, R301L, I303F, G325R, E358Q, E358D, G361E, G375E and T412N.

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

7. The molecule 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, W227G, W277C, M284V, R301L, I303F, S304N, G325R, E358Q, E358D, G361E, G375E, T412N and M421V.

8. The molecule 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, I303R, G325R, E358Q, E358D, G361E, G375E and T412N.

9. The molecule 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 molecule 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 molecule of claim 1 , wherein the mutation is selected from the group consisting of: I133M, F145S, I219L, Q221P, Q250R, G261C, and I303.

12. An α-galactosidase A protein having a HEK 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,

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.

13. The α-galactosidase A protein of claim 12 , wherein the mutation is selected from the group consisting of: A13T, A15T, W24R, N34T, M42K, L54F, P60T, P60S, E87D, L89F, R112G, Y123C, H125L, I133M, K140T, F145S, P136R, 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. protein is bound to migalastat.

14. The α-galactosidase A protein of claim 12 , wherein the mutation is selected from the group consisting of: L54F, P60T, P60S, I133M, K140T, F145S, V199G, I219L, Q221P, Q250R, G261C, G271D, W227G, M284V, R301L and I303F.

15. The α-galactosidase A protein of claim 12 , wherein the mutation is selected from the group consisting of: A15T, N34T, M42K, L54F, P60T, P60S, L89F, R112G, Y123C, H125L, I133M, K_140T, 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.

16. The α-galactosidase A protein of claim 12 , wherein the mutation is selected from the group consisting of: N34T, M43K, 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.

17. The α-galactosidase A protein of claim 12 , wherein the mutation is selected from the group consisting of N34T, R112G, G271D, W287L, G325R and T412N.

18. The α- galactosidase A protein of claim 12 , 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.

19. The α-galactosidase A protein of claim 12 , 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.

20. The α-galactosidase A protein of claim 12 , 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.

21. The α-glactosidase A protein of claim 12 , 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.

22. The α- galactosidase A protein of claim 12 , wherein the mutation is selected from the group consisting of: I133M, F145S, I219L, Q221P, Q250R,G261C, and I303F.

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

24. The molecule 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, W227G, W277C, M284V, R301L, I303F, S304N, D322N, K326N, G334E, E358Q, E358D, G361E, G375E, T412N and M421V.

25. The α-galactosidase A protein of claim 13 , wherein the mutation is selected from the group consisting of: R112G and G325R.

26. The α-galactosidase A protein of claim 12 , 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.

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 →