United States Patent 11,376,244: Scope, Claims, Expiration Risk, and Patent Landscape for Migalastat-Bound Alpha-Galactosidase A

US 11,376,244 protects two related subject matters: migalastat bound to specified alpha-galactosidase A, or GLA, variants, and the specified GLA variants themselves when they show increased stability relative to the corresponding naturally occurring mutant proteins. The patent is directed to pharmacological-chaperone technology for Fabry disease and is closely aligned with the mechanism of migalastat, marketed as Galafold.

The strongest claim coverage is composition-based. The claims do not require a particular dosage, capsule, treatment schedule, route of administration, formulation excipient, or manufacturing process. A competing product could therefore avoid these claims only by omitting migalastat, using a GLA sequence outside the listed mutation set, or demonstrating that the relevant protein does not satisfy the functional stability limitation in claim 16.

What does US Patent 11,376,244 claim?

The patent has two independent claims.

Claim	Protected subject matter	Core limitation
1	Migalastat-bound GLA molecule	GLA contains at least one listed HEK-assay-amenable mutation
16	GLA protein	GLA contains at least one listed mutation and has increased stability versus the naturally occurring GLA protein with the same mutation

Claims 2 through 14 narrow claim 1 to individual mutations or mutation combinations. Claims 17 through 30 narrow claim 16, primarily by specifying individual substitutions or binding to migalastat.

The listed mutations are:

Mutation or combination	Dependent claims
D33G	2, 18
L36W	3, 19
Q57L	4, 20
M96I	5, 21
R112G	6, 22
C174R	7, 23
M187I	8, 24
I253S	9, 25
G258R	10, 26
G271S/D313Y	11, 27
D313Y	11, 27
D322E	12, 28
G325R	13, 29
R356Q	14, 30

The claim set covers 14 principal sequence variants, although G271S/D313Y is a double-mutant designation and D313Y is separately claimed.

How broad is claim 1 for migalastat-bound GLA?

Claim 1 is broad in subject matter but narrow in sequence.

It requires a “molecule comprising migalastat bound to” a GLA protein containing one of the listed mutations. The claim does not expressly require:

A recombinant protein;
A particular cell line;
A defined amino-acid sequence outside the listed mutation;
A specific binding ratio between migalastat and GLA;
A particular conformation;
A specified pharmacological activity;
Increased stability;
A particular disease-causing genotype;
A particular pharmaceutical formulation; or
Administration to a patient.

The phrase “comprising” generally leaves room for additional molecular components. A complex containing migalastat, a covered GLA variant, and other components could fall within the claim if the migalastat is bound to the covered protein.

The central infringement question is whether migalastat is physically or functionally bound to the GLA variant. Mere co-formulation or co-administration would not necessarily satisfy the claim. A product containing migalastat and an unrelated enzyme would not satisfy claim 1 because the required bound complex would be absent.

Claim 1 also does not expressly impose the increased-stability limitation that appears in claim 16. That distinction gives claim 1 potentially broader coverage for the bound complex, subject to claim construction and the patent specification’s definitions.

Which mutations are covered by the patent?

The patent covers the following GLA variants:

D33G, L36W, Q57L, and M96I

These substitutions are individually claimed in claims 2 through 5 and claims 18 through 21. A protein carrying one of these mutations falls within the corresponding dependent claim if all parent-claim limitations are met.

R112G, C174R, and M187I

These variants are separately claimed in claims 6 through 8 and claims 22 through 24. C174R is particularly relevant to protein structure because cysteine substitution can affect disulfide-bonding behavior, folding, or intracellular processing, depending on the surrounding sequence and expression system.

I253S and G258R

These substitutions are covered by claims 9, 10, 25, and 26. Their coverage is sequence-specific and does not extend automatically to conservative substitutions at the same positions.

G271S/D313Y and D313Y

Claim 11 covers either the double-mutant designation G271S/D313Y or D313Y alone. The same alternatives appear in claim 27. The double-mutant language should be read carefully in an infringement analysis because G271S/D313Y is materially different from either G271S alone or D313Y alone.

D322E, G325R, and R356Q

These are covered by claims 12 through 14 and claims 28 through 30. D322E is a conservative substitution, but conservative biochemical character does not remove it from the literal scope of a sequence claim.

What does claim 16 add to the patent scope?

Claim 16 covers a GLA protein having one of the listed mutations and “increased stability as compared to a naturally-occurring alpha-galactosidase A protein having the same mutation.”

This creates a functional limitation that is absent from the basic mutation list. The claim is not satisfied merely because a protein contains D33G, L36W, or another listed substitution. The accused protein must also be more stable than the corresponding naturally occurring mutant protein.

The comparison is important. Claim 16 does not compare the engineered protein with wild-type GLA. It compares the engineered protein with a naturally occurring GLA protein containing the same mutation. The relevant control is therefore mutation-matched.

Potential stability measurements could include, depending on the specification and prosecution history:

Thermal stability;
Retained enzymatic activity after stress;
Intracellular half-life;
Proteolytic resistance;
Aggregation resistance;
Expression or secretion stability; or
Stability in the presence or absence of migalastat.

The enforceability of claim 16 will depend heavily on how the patent specification and prosecution record define “increased stability.” A stability comparison that lacks a defined assay, temperature, incubation period, endpoint, or control condition could create claim-construction and enablement disputes.

Does claim 15 cover disease-causing GLA mutations?

Claim 15 depends on claim 1 and requires that the mutation be a disease-causing mutation. It does not create an independent disease-treatment claim.

The claim therefore requires:

Migalastat;
Binding to a GLA protein;
At least one mutation from the listed group; and
The mutation being disease-causing.

Claim 15 is narrower than claim 1. It would not cover every listed variant if a particular variant is not established as disease-causing under the applicable evidentiary standard.

The claim also does not require treatment of a patient with Fabry disease. It remains a composition claim. A product can infringe without being marketed with a disease-treatment indication if the claimed composition is made, used, or sold within the relevant jurisdiction.

What products and activities could create infringement risk?

The highest-risk activities are the manufacture, importation, sale, or use of a complex containing migalastat bound to a GLA protein carrying one of the listed substitutions.

Activity	Likely relevance
Producing recombinant covered GLA and combining it with migalastat	High risk under claim 1 if binding is established
Selling a covered GLA-migalastat complex	High risk under claim 1
Producing a covered GLA variant without migalastat	Potential risk under claim 16 if increased stability is proven
Administering migalastat with an unrelated GLA variant	Depends on sequence and binding evidence
Administering migalastat alone	Not enough, by itself, to satisfy the claimed protein-complex limitation
Using a listed GLA mutation in research	Depends on statutory research-use protection and commercial purpose
Using a nonlisted mutation	Outside the literal sequence list, subject to equivalents analysis
Using wild-type GLA with migalastat	Outside the listed-mutant limitation, unless another claim applies
Using a listed mutant that is not more stable than the naturally occurring counterpart	Potentially outside claim 16, but claim 1 may remain relevant if the complex is claimed

The patent does not appear, from the supplied claims, to cover all forms of migalastat therapy. Its principal risk is directed to engineered or naturally occurring GLA variants and their interaction with migalastat.

What formulations are protected by US 11,376,244?

The supplied claims do not expressly claim a formulation.

They do not recite:

Tablets;
Capsules;
Liquid formulations;
Excipients;
Particle size;
Salt forms;
Polymorphs;
Release profiles;
Enteric coatings; or
Specific migalastat concentrations.

A formulation could still infringe if it contains the claimed migalastat-bound GLA molecule. The formulation itself would not be the source of infringement; the relevant issue would be whether the formulation contains the claimed molecular complex.

Separate formulation patents could create additional barriers for generic or follow-on products. Those rights must be assessed independently from US 11,376,244.

Does the patent claim a method of treating Fabry disease?

The supplied claims do not include a method-of-treatment claim.

There is no claim reciting:

Selecting a patient with Fabry disease;
Identifying a GLA mutation;
Administering migalastat;
Administering a GLA replacement product;
Improving alpha-galactosidase A activity; or
Reducing globotriaosylceramide levels.

The patent may contain treatment disclosures in its specification, but the enforceable claim set provided is directed to molecules and proteins. Method-of-use protection for migalastat would be a separate patent-landscape issue.

What is the FDA and Orange Book relevance?

Migalastat is an FDA-approved small-molecule therapy for eligible patients with Fabry disease who have amenable GLA variants. The FDA-approved product is Galafold, marketed by Amicus Therapeutics. The product’s pharmacology involves stabilization of amenable mutant GLA, allowing improved trafficking and lysosomal activity in appropriate patients [2].

US 11,376,244 is not, based on the supplied claims, a conventional small-molecule composition patent covering migalastat itself. It claims a protein-migalastat complex and engineered GLA variants. That distinction matters for Orange Book analysis.

The Orange Book generally identifies patents submitted for approved drug products and associated approved uses. A protein-variant patent may be relevant to product freedom to operate without being the principal composition-of-matter patent for the approved small molecule. The patent’s actual Orange Book listing status requires confirmation from the FDA’s current Orange Book data and the sponsor’s patent submissions [3].

The patent should therefore be analyzed alongside, not substituted for:

Migalastat active-ingredient patents;
Crystal-form or salt patents;
Tablet and formulation patents;
Method-of-use patents;
Label-related patents; and
Any pediatric-exclusivity or regulatory-exclusivity periods.

When does US 11,376,244 lose exclusivity?

The supplied claim text does not establish the patent’s expiration date, terminal disclaimer, patent-term adjustment, patent-term extension, or priority chain. Those facts control the enforceable expiration date.

For a US patent, the ordinary term is generally measured from the earliest effective nonprovisional filing date, subject to statutory adjustments and disclaimers. A reliable expiration analysis must review the front page, continuity data, priority applications, terminal disclaimers, and USPTO Patent Examination Data System records [1].

The grant date alone cannot be used to calculate the expiration date. The relevant commercial question is the earliest effective priority or nonprovisional filing date, not the date on which US 11,376,244 issued.

Are Paragraph IV challenges or generic-entry risks disclosed?

The supplied information does not identify an Abbreviated New Drug Application, Paragraph IV notice, Hatch-Waxman litigation, or settlement involving US 11,376,244.

A conventional generic challenge to Galafold would ordinarily focus on patents listed for the approved small-molecule product. US 11,376,244 presents a different risk profile because its claims require a GLA protein variant or a migalastat-bound GLA complex.

A generic migalastat tablet containing only the small molecule would not appear to practice the protein-complex claims on the supplied claim language. A biosimilar or follow-on biologic containing a covered GLA variant would face a more direct risk.

What biosimilar and follow-on biologic risks exist?

The patent is more relevant to enzyme-replacement or engineered-GLA programs than to ordinary small-molecule generic migalastat.

A follow-on GLA product could face claim risk if it:

Uses one of the listed mutations;
Produces the protein in a recombinant host;
Demonstrates increased stability relative to the naturally occurring mutant;
Combines the protein with migalastat; or
Uses migalastat as a pharmacological chaperone during production or administration.

A product using wild-type GLA, a different mutation, or a different chaperone may have a stronger noninfringement position. Equivalents risk remains relevant if the substituted residue performs substantially the same function in substantially the same way with substantially the same result, although prosecution-history estoppel and sequence-specific claim language can limit that theory.

How strong is the patent estate based on the claims?

The estate has meaningful technical specificity but limited breadth outside the listed variants.

Strengths

Two independent composition claims;
Direct coverage of migalastat-bound GLA;
Individual dependent claims for each listed substitution;
Coverage of the GLA protein independently from migalastat binding;
Potential protection for engineered proteins with improved stability;
Relevance to pharmacological-chaperone and enzyme-replacement programs.

Limitations

No express coverage of migalastat alone;
No formulation claim in the supplied set;
No treatment-method claim;
No dosage or regimen claim;
No general coverage of all GLA variants;
Claim 16 contains a potentially contestable comparative stability limitation;
Claim 15 depends on disease-causing status;
The claims do not identify a single universal assay in the text supplied.

The estate is strongest against a product deliberately using one of the specified GLA variants in combination with migalastat. It is weaker against a conventional generic tablet containing migalastat alone.

How does US 11,376,244 compare with competing technology?

Technology	Relationship to US 11,376,244	Primary patent risk
Generic migalastat tablet	Usually outside the supplied protein-complex claims	Migalastat composition, formulation, and use patents
Recombinant wild-type GLA	Outside the listed mutation requirement	Separate enzyme-replacement patents
Recombinant GLA with listed mutation	Directly relevant	Claims 16 through 30
Listed mutant GLA bound to migalastat	Highest overlap	Claims 1 through 14 and 17
GLA with nonlisted mutation	Usually outside literal scope	Equivalents and separate sequence patents
Gene therapy for Fabry disease	Technically adjacent	Vector, promoter, transgene, and delivery patents
Small-molecule pharmacological chaperone other than migalastat	Generally outside claim 1	Chaperone-specific patent estate

What geographic coverage applies?

US 11,376,244 provides rights in the United States only. Commercial programs using the same variants in Europe, Japan, China, or other markets require review of corresponding foreign applications and granted patents.

The international landscape may differ because:

Foreign claims may have been amended;
Some jurisdictions may reject functional stability language;
Patent-term calculations vary;
Opposition or invalidity proceedings may affect scope;
National-phase applications may not have issued; and
Continuation and divisional strategies may differ by country.

A global freedom-to-operate analysis should not assume that US claim scope maps directly to European or Asian claim scope.

Key Takeaways

US 11,376,244 targets specified GLA variants and their interaction with migalastat.
Claim 1 covers a molecule comprising migalastat bound to a GLA protein containing one of the listed mutations.
Claim 16 separately covers the GLA protein when it has increased stability relative to the corresponding naturally occurring mutant.
The patent does not, from the supplied claims, cover migalastat alone, a generic tablet, a dosage regimen, or a method of treating Fabry disease.
The principal commercial risk is for recombinant GLA products or engineered pharmacological-chaperone complexes using one of the listed substitutions.
The actual expiration date requires the patent’s priority chain, terminal-disclaimer information, and USPTO term data.
Current Orange Book listing, Paragraph IV activity, litigation, and settlement status are not established by the supplied claim text.
The patent has narrow sequence scope but potentially strong blocking value for programs that intentionally use the claimed variants.

FAQs

Does US 11,376,244 cover Galafold by itself?

Not based on the supplied claims. Galafold contains migalastat, while the claims require either a migalastat-bound GLA protein or a specified GLA protein variant.

Can a company avoid the patent by using a different GLA mutation?

A different mutation would generally fall outside the literal listed-mutation language. Equivalents risk and other patent families would still require separate analysis.

Does the patent cover enzyme replacement therapy for Fabry disease?

It can affect enzyme-replacement products using the listed GLA variants. The supplied claims do not broadly cover all alpha-galactosidase A replacement therapies.

Is D313Y covered separately from G271S/D313Y?

Yes. Claim 11 and claim 27 identify D313Y separately from the G271S/D313Y combination.

Is increased stability required for every claim?

No. The supplied language expressly imposes increased stability in claim 16 and its dependent claims. Claim 1 and its dependent claims focus on the migalastat-bound molecule and do not expressly recite that limitation.

References

United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term calculation resources. https://www.uspto.gov
U.S. Food and Drug Administration. (n.d.). Galafold (migalastat) prescribing information. https://www.accessdata.fda.gov
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. https://www.accessdata.fda.gov/scripts/cder/ob/index.cfm
United States Patent and Trademark Office. (n.d.). US Patent No. 11,376,244. Patent Center. https://patentcenter.uspto.gov

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Amicus Therap Us	GALAFOLD	migalastat hydrochloride	CAPSULE;ORAL	208623-001	Aug 10, 2018		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial		Y			⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	111971	⤷ Start Trial
Argentina	131106	⤷ Start Trial
Argentina	131107	⤷ Start Trial
Australia	2009214648	⤷ Start Trial
Australia	2014221321	⤷ Start Trial
Australia	2016206297	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 11,376,244

Which drugs does patent 11,376,244 protect, and when does it expire?

Summary for Patent: 11,376,244