IP Library › Granted Patent US 12,414,985
Granted Patent B2
US 12,414,985 · App. 17/699,927 · Granted Sep 16, 2025

Augmented acid alpha-glucosidase for the treatment of Pompe disease

Inventors: Hung V. Do (New Hope, PA); Richie Khanna (Somerset, NJ); Russell Gotschall (Doylestown, PA)
Assignee: Amicus Therapeutics, Inc.
A61K38/47A61K31/445A61P3/00A61P21/00C12Y302/0102
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Quick Facts
Patent No.
US 12,414,985
App. No.
17/699,927
Granted
Sep 16, 2025
Kind
B2
Abstract

A method for treating Pompe disease including administration of recombinant human acid α-glucosidase having optimal glycosylation with mannose-6-phosphate residues in combination with an amount of miglustat effective to maximize tissue uptake of recombinant human acid α-glucosidase while minimizing inhibition of the enzymatic activity of the recombinant human acid α-glucosidase is provided.

Claims (33)

1. A method of treating Pompe disease in a patient in need thereof, the method comprising administering miglustat to the patient in combination with a recombinant human acid α-glucosidase, wherein the recombinant human acid α-glucosidase is expressed in Chinese hamster ovary (CHO) cells and comprises an increased content of N-glycan units bearing one or two mannose-6-phosphate residues when compared to a content of N-glycan units bearing one or two mannose-6-phosphate residues of alglucosidase alfa and wherein the recombinant human acid α-alglucosidase comprises a sequence at least 95% identical to SEQ ID NO: 1 or SEQ ID NO: 5, wherein the recombinant human acid α-glucosidase is administered intravenously at a dose of about 5 mg/kg to about 20 mg/kg every week or every other week and the miglustat is administered orally at a dose of about 200 mg to about 600 mg every week or every other week.

2. The method according to claim 1 wherein at least 30% of molecules of the recombinant human acid α-glucosidase comprise one or more N-glycan units bearing one or two mannose-6-phosphate residues.

3. The method according to claim 1 wherein the recombinant human acid α-glucosidase comprises on average from 0.5 to 7.0 moles of N-glycan units bearing one or two mannose-6-phosphate residues per mole of recombinant human acid α-glucosidase.

4. The method according to claim 1 wherein the recombinant human acid α-glucosidase comprises on average at least 2.5 moles of mannose-6-phosphate residues per mole of recombinant human acid α-glucosidase and at least 4 moles of sialic acid residues per mole of recombinant human acid α-glucosidase.

5. The method according to claim 1 wherein the recombinant human acid α-glucosidase comprises seven potential N-glycosylation sites, at least 50% of molecules of the recombinant human acid α-glucosidase comprise an N-glycan unit bearing two mannose-6-phosphate residues at the first site, at least 30% of molecules of the recombinant human acid α-glucosidase comprise an N-glycan unit bearing one mannose-6-phosphate residue at the second site, at least 30% of molecules of the recombinant human acid α-glucosidase comprise an N-glycan unit bearing two mannose-6-phosphate residue at the fourth site, and at least 20% of molecules of the recombinant human acid α-glucosidase comprise an N-glycan unit bearing one mannose-6-phosphate residue at the fourth site.

6. The method according to claim 1 wherein the miglustat is administered prior to administration of the recombinant human acid α-glucosidase.

7. The method according to claim 6 wherein the miglustat is administered about one hour prior to administration of the recombinant human acid α-glucosidase.

8. The method according to claim 1 wherein the recombinant human acid α-glucosidase is administered intravenously at a dose of about 5 mg/kg to about 20 mg/kg every other week and the miglustat is administered orally at a dose of about 233 mg to about 500 mg every other week.

9. The method according to claim 1 wherein the recombinant human acid α-glucosidase is administered intravenously at a dose of about 5 mg/kg to about 20 mg/kg every other week and the miglustat is administered orally at a dose of about 50 mg to about 200 mg every other week.

10. The method according to claim 1 wherein the recombinant human acid α-glucosidase is administered intravenously at a dose of about 20 mg/kg every other week and the miglustat is administered orally at a dose of about 260 mg every other week.

11. The method according to claim 10 wherein the miglustat is administered prior to administration of the recombinant human acid α-glucosidase.

12. The method according to claim 11 wherein the miglustat is administered about one hour prior to administration of the recombinant human acid α-glucosidase.

13. The method according to claim 1 wherein the recombinant human acid α-glucosidase has a shorter half-life than alglucosidase alfa in the plasma of the patient.

14. The method according to claim 13 wherein the half-life of recombinant human acid α-glucosidase is 20-30% shorter than alglucosidase alfa in the plasma of the patient.

15. The method according to claim 13 wherein the half-life of recombinant human acid α-glucosidase is about 25% shorter than alglucosidase alfa in the plasma of the patient.

16. The method according to claim 1 wherein the recombinant human acid α-glucosidase on average has at least one more mole of N-glycan units bearing two mannose-6-phosphate residues per compared to alglucosidase alfa.

17. The method according to claim 1 wherein the recombinant human acid α-glucosidase on average has about 1.2 more moles of N-glycan units bearing two mannose-6-phosphate residues per compared to alglucosidase alfa.

18. The method according to claim 1 wherein the recombinant human acid α-glucosidase induces a lower incidence of anti-drug antibodies than alglucosidase alfa in the patient.

19. The method according to claim 1 wherein the recombinant human acid α-glucosidase reduces glycogen in muscle tissues more effectively than alglucosidase alfa.

20. The method according to claim 19 wherein the recombinant human acid α-glucosidase is administered at a dose of 10-20 mg/kg every other week.

21. The method according to claim 1 wherein the recombinant human acid α-glucosidase reduces vacuoles in muscle fibers more effectively than alglucosidase alfa.

22. The method according to claim 1 wherein the recombinant human acid α-glucosidase clears lysosomal glycogen more effectively than alglucosidase alfa in the patient.

23. The method according to claim 1 wherein the recombinant human acid α-glucosidase increases muscle function more efficiently than alglucosidase alfa.

24. The method according to claim 1 wherein the recombinant human acid α-glucosidase internalizes into muscle fibroblasts more efficiently than alglucosidase alfa.

25. The method according to claim 1 wherein the recombinant human acid α-glucosidase reduces lysosomal proliferation more efficiently than alglucosidase alfa.

26. The method according to claim 1 wherein the recombinant human acid α-glucosidase binds cation-independent mannose-6-phosphate receptor to a greater degree than alglucosidase alfa.

27. The method according to claim 26 wherein at least about 43% more of the recombinant human acid α-glucosidase binds cation-independent mannose-6-phosphate receptor than alglucosidase alfa.

28. The method according to claim 1 , wherein at least 3% of the total glycans on the recombinant human acid α-glucosidase are bis-M6P glycans.

29. The method according to claim 1 wherein the recombinant human acid α-glucosidase comprises on average at least 1 mol bis-M6P per mol recombinant human acid α-glucosidase.

30. The method according to claim 1 wherein the recombinant human acid α-glucosidase comprises on average 1.3 mol bis-M6P per mol recombinant human acid α-glucosidase.

31. The method according to claim 1 wherein at least 17% of the total glycans on the recombinant human acid α-glucosidase are bis-M6P.

32. The method according to claim 1 wherein 3% to 25% of the total glycans on the recombinant human acid α-glucosidase are bis-M6P.

33. The method according to claim 1 wherein 17% to 25% of the total glycans on the recombinant human acid α-glucosidase are bis-M6P.

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 →
Continuity (10)
Continuation 17061691 · Oct 2, 2020
Continuation 15950347 · Apr 11, 2018
Continuation 15394135 · Dec 29, 2016
Provisional Application 62431791 · Dec 8, 2016
Provisional Application 62428867 · Dec 1, 2016
Provisional Application 62402454 · Sep 30, 2016
Provisional Application 62315412 · Mar 30, 2016
Provisional Application 62300479 · Feb 26, 2016
Provisional Application 62272890 · Dec 30, 2015
Related Publication 20220370571A1 · Nov 24, 2022
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