IP Library › Granted Patent US 11,622,962
Granted Patent B2
US 11,622,962 · App. 17/077,402 · Granted Apr 11, 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 11,622,962
App. No.
17/077,402
Granted
Apr 11, 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: R4M/Y207S, A15G, F18C, W24G, N34D, G35V, M42I, E48Q, N53D, F69L, M72I, G85S, G85N, G104V, L106F, A108T, D109G, G144D, L167V, G171S, L180W, G195V, R196G, V199A, E203D, P210S, P210L, P214S, R220P, F229L, I242T, W245G, Q250H, p.V254del, G260E, G261S, G271S/D313Y, M290T, D299E, S304T, D313Y/G411D, I319F, D322H, F337S, P343L, R356G, G361A, P362T, K391T, G395E and p.T400_S401dup.

2. The molecule of claim 1 , wherein the mutation is selected from the group consisting of: F18C, W24G, G35V, M42I, N53D, F69L, M72I, G104V, L106F, A108T, G144D, L167V, G171S, L180W, G195V, R196G, V199A, P210S, P210L, P214S, R220P, F229L, I242T, W245G, Q250H, p.V254del, G260E, G261S, M290T, D299E, S304T, I319F, D322H, F337S, P343L, R356G, G361A, P362T and K391T.

3. The molecule of claim 1 , wherein the mutation is selected from the group consisting of: N53D, L180W, R196G, P210S, P210L, P214S, R220P, I242T, Q250H, p.V254del, G260E, G261S, M290T, D299E, S304T and P362T.

4. The molecule of claim 1 , wherein the mutation is selected from the group consisting of: R4M/Y207S, A15G, W24G, G35V, M42I, E48Q, N53D, F69L, M72I, G85S, G85N, G104V, L106F, A108T, D109G, G144D, L167V, G171S, L180W, G195V, R196G, V199A, E203D, P210S, P210L, P214S, R220P, F229L, I242T, W245G, Q250H, p.V254del, G260E, G261S, M290T, D299E, S304T, I319F, D322H, F337S, P343L, R356G, G361A, P362T, K391T, G395E and p.T400_S401dup.

5. The molecule of claim 1 , wherein the mutation is selected from the group consisting of: R4M/Y207S, W24G, G35V, M42I, E48Q, N53D, F69L, G85S, G85N, G104V, L106F, D109G, G144D, G171S, L180W, G195V, R196G, E203D, P210S, P210L, P214S, R220P, F229L, I242T, Q250H, p.V254del, G260E, G261S, M290T, D299E, S304T, I319F, D322H, F337S, R356G, G361A, P362T, K391T, G395E and p.T400_S401dup.

6. The molecule of claim 1 , wherein the mutation is selected from the group consisting of: G35V, M42I, F69L and L180W.

7. The molecule of claim 1 , wherein the mutation is selected from the group consisting of: W24G, G35V, M42I, N53D, F69L, M72I, G104V, L106F, A108T, G144D, L167V, G171S, L180W, G195V, R196G, V199A, P210S, P210L, P214S, R220P, F229L, I242T, W245G, Q250H, p.V254del, G260E, G261S, M290T, D299E, S304T, I319F, D322H, F337S, P343L, R356G, G361A, P362T and K391T.

8. The molecule of claim 1 , wherein the mutation is selected from the group consisting of: W24G, G35V, M42I, N53D, F69L, G104V, L106F, G144D, G171S, L180W, G195V, R196G, P210S, P210L, P214S, R220P, F229L, I242T, Q250H, p.V254del, G260E, G261S, M290T, D299E, S304T, I319F, D322H, F337S, R356G, G361A, P362T and K391T.

9. The molecule of claim 1 , wherein the mutation is selected from the group consisting of: R4M/Y207S, A15G, F18C, W24G, N34D, G35V, M42I, E48Q, N53D, F69L, M72I, G85S, G85N, G104V, L106F, A108T, D109G, G144D, L167V, L180W, G195V, R196G, V199A, E203D, P210S, P210L, P214S, R220P, F229L, I242T, W245G, Q250H, G260E, G261S, G271S/D313Y, D299E, S304T, D313Y/G411D, I319F, F337S, P343L, R356G, G361A, P362T, K391T and G395E.

10. The molecule of claim 1 , wherein the mutation is selected from the group consisting of: R4M/Y207S, W24G, G35V, M42I, E48Q, N53D, F69L, G85S, G85N, G104V, L106F, D109G, G144D, L180W, G195V, R196G, E203D, P210S, P210L, P214S, R220P, F229L, I242T, Q250H, G260E, G261S, D299E, S304T, I319F, F337S, R356G, G361A, P362T, K391T and G395E.

11. The molecule of claim 1 , wherein the mutation is selected from the group consisting of: F18C, W24G, G35V, M42I, N53D, F69L, M72I, G104V, L106F, A108T, G144D, L167V, L180W, G195V, R196G, V199A, P210S, P210L, P214S, R220P, F229L, I242T, W245G, Q250H, G260E, G261S, D299E, S304T, I319F, F337S, P343L, R356G, G361A, P362T and K391T.

12. The molecule of claim 1 , wherein the mutation is selected from the group consisting of: N53D, L180W, R196G, P210S, P210L, P214S, R220P, I242T, Q250H, G260E, G261S, D299E, S304T and P362T.

13. The molecule of claim 1 , wherein the mutation is selected from the group consisting of: W24G, G35V, M42I, N53D, F69L, G104V, L106F, G144D, L180W, G195V, R196G, P210S, P210L, P214S, R220P, F229L, I242T, Q250H, G260E, G261S, D299E, S304T, I319F, F337S, R356G, G361A, P362T and K391T.

14. An α-galactosidase A protein having a HEK amenable mutation selected from the group consisting of: R4M/Y207S, A15G, F18C, W24G, N34D, G35V, M42I, E48Q, N53D, F69L, M72I, G85S, G85N, G104V, L106F, A108T, D109G, G144D, L167V, G171S, L180W, G195V, R196G, V199A, E203D, P210S, P210L, P214S, R220P, F229L, I242T, W245G, Q250H, p.V254del, G260E, G261S, G271S/D313Y, M290T, D299E, S304T, D313Y/G411D, I319F, D322H, F337S, P343L, R356G, 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.

15. The α-galactosidase A protein of claim 14 , wherein the mutation is selected from the group consisting of: F18C, W24G, G35V, M42I, N53D, F69L, M72I, G104V, L106F, A108T, G144D, L167V, G171S, L180W, G195V, R196G, V199A, P210S, P210L, P214S, R220P, F229L, I242T, W245G, Q250H, p.V254del, G260E, G261S, M290T, D299E, S304T, I319F, D322H, F337S, P343L, R356G, G361A, P362T and K391T.

16. The α-galactosidase A protein of claim 14 , wherein the mutation is selected from the group consisting of: N53D, L180W, R196G, P210S, P210L, P214S, R220P, I242T, Q250H, p.V254del, G260E, G261S, M290T, D299E, S304T and P362T.

17. The α-galactosidase A protein of claim 14 , wherein the mutation is selected from the group consisting of: R4M/Y207S, A15G, W24G, G35V, M42I, E48Q, N53D, F69L, M72I, G85S, G85N, G104V, L106F, A108T, D109G, G144D, L167V, G171S, L180W, G195V, R196G, V199A, E203D, P210S, P210L, P214S, R220P, F229L, I242T, W245G, Q250H, p.V254del, G260E, G261S, M290T, D299E, S304T, I319F, D322H, F337S, P343L, R356G, G361A, P362T, K391T, G395E and p.T400_S401dup.

18. The α-galactosidase A protein of claim 14 , wherein the mutation is selected from the group consisting of: R4M/Y207S, W24G, G35V, M42I, E48Q, N53D, F69L, G85S, G85N, G104V, L106F, D109G, G144D, G171S, L180W, G195V, R196G, E203D, P210S, P210L, P214S, R220P, F229L, I242T, Q250H, p.V254del, G260E, G261S, M290T, D299E, S304T, I319F, D322H, F337S, R356G, G361A, P362T, K391T, G395E and p.T400_S401dup.

19. The α-galactosidase A protein of claim 14 , wherein the mutation is selected from the group consisting of: G35V, M42I, F69L and L180W.

20. The α-galactosidase A protein of claim 14 , wherein the mutation is selected from the group consisting of: W24G, G35V, M42I, N53D, F69L, M72I, G104V, L106F, A108T, G144D, L167V, G171S, L180W, G195V, R196G, V199A, P210S, P210L, P214S, R220P, F229L, I242T, W245G, Q250H, p.V254del, G260E, G261S, M290T, D299E, S304T, I319F, D322H, F337S, P343L, R356G, G361A, P362T and K391T.

21. The α-galactosidase A protein of claim 14 , wherein the mutation is selected from the group consisting of: W24G, G35V, M42I, N53D, F69L, G104V, L106F, G144D, G171S, L180W, G195V, R196G, P210S, P210L, P214S, R220P, F229L, I242T, Q250H, p.V254del, G260E, G261S, M290T, D299E, S304T, I319F, D322H, F337S, R356G, G361A, P362T and K391T.

22. The α-galactosidase A protein of claim 14 , wherein the mutation is selected from the group consisting of: R4M/Y207S, A15G, F18C, W24G, N34D, G35V, M42I, E48Q, N53D, F69L, M72I, G85S, G85N, G104V, L106F, A108T, D109G, G144D, L167V, L180W, G195V, R196G, V199A, E203D, P210S, P210L, P214S, R220P, F229L, I242T, W245G, Q250H, G260E, G261S, G271S/D313Y, D299E, S304T, D313Y/G411D, I319F, F337S, P343L, R356G, G361A, P362T, K391T and G395E.

23. The α-galactosidase A protein of claim 14 , wherein the mutation is selected from the group consisting of: R4M/Y207S, W24G, G35V, M42I, E48Q, N53D, F69L, G85S, G85N, G104V, L106F, D109G, G144D, L180W, G195V, R196G, E203D, P210S, P210L, P214S, R220P, F229L, I242T, Q250H, G260E, G261S, D299E, S304T, I319F, F337S, R356G, G361A, P362T, K391T and G395E.

24. The α-galactosidase A protein of claim 14 , wherein the mutation is selected from the group consisting of: F18C, W24G, G35V, M42I, N53D, F69L, M72I, G104V, L106F, A108T, G144D, L167V, L180W, G195V, R196G, V199A, P210S, P210L, P214S, R220P, F229L, I242T, W245G, Q250H, G260E, G261S, D299E, S304T, I319F, F337S, P343L, R356G, G361A, P362T and K391T.

25. The α-galactosidase A protein of claim 14 , wherein the mutation is selected from the group consisting of: N53D, L180W, R196G, P210S, P210L, P214S, R220P, I242T, Q250H, G260E, G261S, D299E, S304T and P362T.

26. The α-galactosidase A protein of claim 14 , wherein the mutation is selected from the group consisting of: W24G, G35V, M42I, N53D, F69L, G104V, L106F, G144D, L180W, G195V, R196G, P210S, P210L, P214S, R220P, F229L, I242T, Q250H, G260E, G261S, D299E, S304T, I319F, F337S, R356G, G361A, P362T and K391T.

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 →