US Patent 10,471,053: Migalastat Fabry Disease Claims, Scope, Expiration and Patent Landscape

US Patent 10,471,053 protects the use of migalastat, principally 150 mg migalastat hydrochloride administered every other day, for Fabry disease patients carrying specified HEK-assay amenable mutations in the GLA gene. The patent is a mutation-specific method-of-treatment patent, not a broad composition, formulation, manufacturing, or platform patent.

Its commercial relevance is tied to Galafold, Amicus Therapeutics’ oral migalastat product. The claims cover a large enumerated mutation set, but they require proof that the patient has one of the listed mutations and that the mutation is amenable under the applicable HEK assay.

What does US Patent 10,471,053 protect?

The patent protects a treatment method with four core elements:

A human patient has Fabry disease.
The patient has a specified mutation in alpha-galactosidase A, encoded by GLA.
The mutation is amenable in a HEK-cell assay.
The patient receives migalastat or a salt, generally at an every-other-day dose.

Independent claim 1 identifies the mutations directly. Independent claim 21 uses a reference-table formulation, while claim 22 requires the reference table to include the complete listed mutation set. The dependent claims narrow the therapy by dose, frequency, sex, renal function, and mechanism.

The claims do not cover every Fabry patient or every GLA mutation. They are limited to the listed mutations and to mutations satisfying the claimed HEK assay condition.

Patent profile

Item	Data
Patent	US 10,471,053 B2
Grant date	November 12, 2019
Technology	Migalastat treatment of Fabry disease
Patent holder/assignee	Amicus Therapeutics, Inc.
Drug	Migalastat, principally migalastat hydrochloride
Dosage form	Oral capsule
Core regimen	150 mg every other day
Disease	Fabry disease
Biomarker limitation	Specified HEK-assay amenable GLA mutation
Claim type	Method of treatment
Primary commercial product	Galafold
Regulatory pathway	New drug application, not biologic licensing application

The patent document and prosecution history should be read together. Claim scope can be affected by amendments, examiner interviews, terminal disclaimers, priority claims, and statements made during prosecution. The issued claims supplied for this analysis establish the operative claim limitations. (United States Patent No. 10,471,053, 2019.)

How broad is the mutation coverage?

The patent lists more than 200 mutation entries, including single substitutions, compound mutations, and a duplication variant. The list includes entries such as L3V, A13T, R112G, D165G, M187I, D313Y, G271S/D313Y, and M421V.

The mutation limitations are unusually specific. A potential infringement analysis would generally require:

Genetic confirmation of the patient’s GLA variant.
Determination that the variant corresponds to a listed mutation.
Evidence that the variant is amenable in the relevant HEK assay.
Evidence that the patient received migalastat or a covered salt.
Evidence that the administration occurred for Fabry disease treatment.

Mutation-list structure

Claim group	Scope
Claim 1	All listed mutations plus migalastat treatment and HEK assay amenability
Claims 2-5	Every-other-day administration and 123-300 mg, including 150 mg migalastat hydrochloride
Claim 6	Enhancement of alpha-galactosidase A activity
Claims 7-8	Male or female patients
Claims 9-10	Renal impairment, including mild or moderate impairment
Claims 11-20	Subsets of the mutation list
Claim 21	Mutation disclosed in a reference table
Claim 22	Complete mutation set in the reference table
Claims 23-31	Dose, frequency, sex, mechanism, and renal-impairment limitations tied to claim 21

Claims 11 through 20 are not independent treatment concepts. They divide the claim 1 mutation list into smaller groups. These dependent claims may be useful in litigation if a court narrows the scope of the broader list or if a specific mutation group has stronger written-description support.

What is the scope of the 150 mg every-other-day claims?

Claims 2 through 5 and claims 23 through 26 create a commercially important dosing cluster.

Claim 3 covers approximately 123 to approximately 300 mg every other day. Claim 4 narrows that range to approximately 150 mg every other day. Claim 5 is narrower still and specifies 150 mg of migalastat hydrochloride every other day.

The likely commercial target is the Galafold label, which directs administration of one 123 mg migalastat capsule every other day. The 123 mg capsule contains 150 mg of migalastat hydrochloride, equivalent to 123 mg of migalastat free base. This distinction matters when comparing the patent language with the FDA-approved labeling.

The claim’s “about” language gives some numerical flexibility, but it does not eliminate the need to analyze the actual strength, salt form, dosing interval, and prescribing instructions. A generic product using the same active moiety and equivalent dosing instructions would face a direct method-of-use risk if the product is labeled for patients with covered amenable mutations.

Does the patent cover Galafold’s formulation or manufacturing process?

No. The issued claims supplied here do not claim:

A composition comprising migalastat.
A capsule formulation.
A specific excipient system.
A manufacturing process.
A purification process.
A crystalline form.
A polymorph.
Packaging or drug-device technology.
A diagnostic test by itself.
A general alpha-galactosidase A chaperone platform.

The patent claims use of migalastat in a defined patient population. A competing manufacturer could therefore avoid this particular patent only by establishing that its product, labeling, conduct, or patient population does not satisfy one or more treatment-method limitations. Other patents could separately protect the active ingredient, solid form, formulation, manufacturing process, or clinical use.

What is the Orange Book status of US Patent 10,471,053?

The patent’s commercial significance depends on whether and how it is listed in the FDA Orange Book for Galafold. Orange Book listing is separate from patent validity and infringement. A listed patent can be challenged through an ANDA Paragraph IV certification, while an unlisted method-of-use patent may still create litigation risk under other statutory provisions.

For an approved small-molecule drug, the principal generic pathway is an abbreviated new drug application. An ANDA applicant must address patents listed for the reference-listed drug and may certify that a listed patent is invalid, unenforceable, or will not be infringed.

Paragraph IV implications

A generic applicant could challenge the patent by arguing that:

The listed mutation set lacks adequate written description.
The claims are indefinite because “HEK assay amenable” is not sufficiently defined.
The reference-table claims are indefinite or improperly incorporated.
The claimed treatment was anticipated or obvious.
The claims lack enablement across the full mutation list.
The patent is unenforceable because of inequitable conduct, if supported by evidence.
The proposed label does not induce infringement.

Amicus could respond by asserting that the mutation list is supported by experimental data, that the HEK assay is described in the specification, and that the claimed patient-selection method reflects a clinically meaningful genotype-treatment relationship.

A Paragraph IV notice does not itself establish invalidity or noninfringement. It normally creates a statutory litigation window for the patent holder and may delay final FDA approval under the Hatch-Waxman framework. (21 U.S.C. § 355(j); 35 U.S.C. § 271(e).)

When does US Patent 10,471,053 lose exclusivity?

The patent was granted on November 12, 2019. Its expiration depends on the earliest effective nonprovisional filing date, any patent-term adjustment, any patent-term extension, and any terminal disclaimer. The applicable term is generally 20 years from the earliest effective nonprovisional filing date under 35 U.S.C. § 154.

The grant date alone does not determine the expiration date. The relevant term calculation must account for the patent family’s priority and continuation structure. FDA regulatory exclusivity also runs independently from patent term.

Exclusivity categories

Exclusivity type	Relevance to migalastat
Patent exclusivity	Controlled by the patent family’s effective filing date and adjustments
FDA new-drug exclusivity	Separate statutory period tied to approval
Orphan-drug exclusivity	Potentially relevant because Fabry disease is rare, subject to FDA designation and approval details
Pediatric exclusivity	Adds six months if awarded
Data exclusivity	Distinct from patent protection
Market exclusivity	May restrict approval of certain competing applications even without patent infringement

The FDA approved Galafold in 2018 for adults with Fabry disease who have an amenable GLA variant. The FDA label defines the approved patient population and provides the dosing instructions. (U.S. Food and Drug Administration, 2018.)

Is biosimilar risk relevant to migalastat?

No. Migalastat is a chemically synthesized small molecule, not a biologic. Biosimilar approval under section 351(k) of the Public Health Service Act does not apply.

The relevant competitive threat is an ANDA generic, not a biosimilar. Generic companies could pursue:

A Paragraph IV challenge to listed patents.
A Section VIII statement carving out patented methods of use.
A label that omits protected mutation-specific language.
A noninfringing label limited to unprotected patient populations, if clinically and regulatorily acceptable.

A skinny-label strategy would be difficult if the approved use of the generic product necessarily corresponds to the patented mutation-selected population. The outcome would depend on the exact Orange Book listings, proposed label, prescribing information, and evidence of induced infringement.

How does this patent compare with competing Fabry therapies?

US 10,471,053 is strongest against oral migalastat products used in patients with covered amenable mutations. It is not directed to enzyme-replacement therapies.

Therapy	Active ingredient	Modality	Patient selection	Relationship to US 10,471,053
Galafold	Migalastat	Oral pharmacological chaperone	Amenable GLA mutation	Direct commercial target
Fabrazyme	Agalsidase beta	Intravenous enzyme replacement	Broad Fabry population	Outside the claim scope
Replagal	Agalsidase alfa	Intravenous enzyme replacement	Broad Fabry population	Outside the claim scope
Elfabrio	Pegunigalsidase alfa	Intravenous enzyme replacement	Broad Fabry population	Outside the claim scope
Investigational gene therapies	Various	Genetic replacement or editing	Program-specific	Not directly covered

The patent creates a genotype-defined barrier around migalastat treatment. Enzyme-replacement products do not practice the claimed administration of migalastat and therefore do not face ordinary infringement exposure under these claims.

How strong is the patent estate?

The patent is commercially meaningful but legally narrower than a composition patent. Its principal strengths are:

Direct alignment with the approved Galafold patient-selection concept.
A large enumerated mutation set.
Specific coverage of the 150 mg migalastat hydrochloride every-other-day regimen.
Separate claims covering renal impairment and both male and female patients.
Potential use against a generic label that identifies amenable GLA mutations.

Its principal vulnerabilities are:

Dependence on the definition and reproducibility of the HEK assay.
Potential enablement and written-description issues across a large mutation list.
Possible indefiniteness arguments concerning “amenable” and “reference table.”
The need to prove the patient’s mutation and treatment facts in an individual case.
Method-of-treatment limitations that may not reach all commercial activity associated with the product.
Potential overlap with other Amicus patents and terminal-disclaimer constraints.

The patent is stronger against a generic that copies Galafold’s labeled patient population and regimen than against an entrant using a materially different label or targeting non-amenable variants.

What litigation and settlement risks affect generic entry?

The key litigation trigger would be a Paragraph IV certification involving a listed Galafold patent. Potential case issues include claim construction of “HEK assay amenable mutation,” the meaning of “about 150 mg,” the scope of salt coverage, and whether a generic label induces use for the claimed mutation population.

A settlement could involve:

A delayed generic launch date.
A license to use the patent.
A label restriction.
A covenant not to sue.
A supply or commercialization arrangement.
An authorized generic structure.

No settlement terms can be inferred from the issued claims. Patent litigation status must be established from the relevant district-court docket, Federal Circuit decisions, FDA listing records, and Orange Book supplements.

What generic launch scenarios exist?

Scenario 1: Direct-label challenge

A generic applicant copies the amenable-mutation indication and every-other-day dosing. This creates the highest infringement exposure and makes a Paragraph IV challenge likely.

Scenario 2: Skinny-label launch

The applicant removes or narrows the mutation-specific use. This reduces labeled-use exposure but may not eliminate inducement risk if the remaining label, promotional activity, or prescribing environment encourages the patented use.

Scenario 3: Post-expiration launch

The applicant accepts the patent and launches after the relevant patent and regulatory exclusivities expire. This avoids patent litigation risk but may delay entry materially.

Scenario 4: License or authorized generic

Amicus could control entry through a license, settlement, or authorized-generic arrangement. The commercial value would depend on the remaining term of the broader Galafold estate, not this patent alone.

Key Takeaways

US 10,471,053 is a mutation-specific method patent for treating Fabry disease with migalastat.
The central regimen is 150 mg migalastat hydrochloride every other day.
The patent covers a large but closed list of HEK-assay amenable GLA mutations.
It does not claim Galafold’s composition, capsule formulation, manufacturing process, or general Fabry treatment.
Generic risk is primarily an ANDA and Paragraph IV issue, not a biosimilar issue.
The strongest infringement case would involve a generic label that expressly identifies the covered mutation population and dosing regimen.
The main validity issues are likely to involve enablement, written description, indefiniteness, assay definition, and prior art.
Patent expiration requires family-level review of the earliest effective filing date, patent-term adjustment, terminal disclaimers, and any extension.
Competing enzyme-replacement therapies do not practice the asserted migalastat treatment claims.

FAQs

Does US 10,471,053 cover all Fabry disease patients?

No. It covers patients with Fabry disease who have one of the listed GLA mutations and whose mutation is amenable in the relevant HEK assay.

Does the patent cover migalastat free base?

The claims recite migalastat or a salt thereof. Claim 5 specifically recites 150 mg of migalastat hydrochloride. The exact infringement analysis depends on the product’s chemical form and how the dose is measured.

Can a generic launch with a 150 mg capsule but without the mutation language?

Possibly, but the risk would depend on the full proposed label, physician instructions, promotional conduct, Orange Book status, and evidence of induced infringement. Removing express mutation language does not automatically eliminate all infringement risk.

Is a HEK assay required for every patient claim?

Yes. The independent claims require a HEK-assay amenable mutation. The assay limitation is central to both the patient-selection scope and potential validity disputes.

Are enzyme-replacement products blocked by this patent?

No. Fabrazyme, Replagal, and Elfabrio do not administer migalastat and therefore do not ordinarily satisfy the asserted treatment-method limitations.

References

United States Patent No. 10,471,053. (2019, November 12). Methods for treating Fabry disease. United States Patent and Trademark Office.
U.S. Food and Drug Administration. (2018). Galafold (migalastat) prescribing information. FDA.
U.S. Food and Drug Administration. (2025). Approved drug products with therapeutic equivalence evaluations. FDA.
21 U.S.C. § 355(j). Abbreviated new drug applications.
35 U.S.C. § 154. Contents and term of patent; provisional rights.
35 U.S.C. § 271(e). Infringement of patents in regulated drug development.
35 U.S.C. § 282. Presumption of validity; defenses.

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	10,471,053	⤷ Start Trial				THE TREATMENT OF FABRY PATIENTS	⤷ 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
Australia	2017268649	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 10,471,053

Which drugs does patent 10,471,053 protect, and when does it expire?

Summary for Patent: 10,471,053