United States Patent 11,278,536: Migalastat Renal-Protection Claims, Scope and Patent Landscape

U.S. Patent No. 11,278,536 protects a narrow method of using migalastat in Fabry disease patients with renal impairment and a pharmacologically amenable α-galactosidase A mutation. The independent claim requires four core elements: a Fabry patient, eGFR below 60 mL/min/1.73 m², a HEK-assay-amenable mutation, and migalastat administered at approximately 100 to 150 mg free-base-equivalent once every other day.

The claim also requires two clinical outcomes: reduced mean plasma lyso-Gb3 and a mean annualized eGFR decline better than -1.0 mL/min/1.73 m². The patent therefore targets renal preservation rather than migalastat use in Fabry disease generally.

The commercial significance is material because Galafold's approved dosing is 123 mg every other day, corresponding to 150 mg migalastat hydrochloride. The claimed dose therefore tracks the marketed product closely. The principal limitation is patient selection: the patent focuses on patients with moderate or severe renal impairment, including some patients with eGFR below 30, while the U.S. prescribing information does not recommend Galafold in severe renal impairment. [1, 2]

What does U.S. Patent 11,278,536 cover?

U.S. Patent 11,278,536 is a method-of-treatment patent assigned to Amicus Therapeutics and directed to migalastat treatment in Fabry patients with impaired kidney function. It was granted on March 22, 2022. [3]

Claim architecture

Claim element	Requirement
Disease	Fabry disease
Patient genotype	HEK-assay-amenable α-galactosidase A mutation
Renal status	eGFR below 60 mL/min/1.73 m²
Dose	About 100 to about 150 mg FBE
Frequency	Once every other day
Biomarker result	Reduced mean plasma lyso-Gb3
Renal result	Mean annualized eGFRCKD-EPI change greater than -1.0 mL/min/1.73 m²
Route	Oral administration is claimed dependently
Dosage form	Solid dosage form is claimed dependently
Duration	At least 28 days, 6 months or 12 months
Patient history	ERT-naïve patients are claimed dependently

Claim 1 is the commercial center of gravity. Claims 2 through 8 narrow the renal and proteinuria populations. Claims 9 through 16 define dosage-form, duration and dose alternatives. Claim 17 adds a specific lyso-Gb3 reduction. Claim 18 defines the HEK amenability assay. Claims 19 and 20 address salt form and ERT treatment history.

How broad is the independent claim?

Claim 1 is narrower than a general migalastat treatment claim but broad enough to cover the marketed Galafold regimen in a clinically important renal subgroup.

A practicing company would need to satisfy all of the following conditions to fall within the literal scope:

The patient has Fabry disease.
The patient's mutation is amenable under the specified HEK assay.
The patient's eGFR is below 60.
Migalastat is administered at about 100 to about 150 mg FBE.
Dosing occurs once every other day.
Treatment reduces mean plasma lyso-Gb3.
Treatment produces a mean annualized eGFRCKD-EPI change greater than -1.0 mL/min/1.73 m².

The clinical-result limitations create both value and litigation complexity. A defendant may administer the same dose to the same patient population but argue that the required outcomes are not inherent, not demonstrated for the accused population, or not measurable under the claim's statistical language. The patentee would likely argue that the outcomes naturally result from practicing the claimed regimen in the specified population.

Dose and salt scope

The claims cover:

Approximately 100 to 150 mg FBE.
Approximately 123 mg migalastat free base.
Approximately 150 mg migalastat hydrochloride.
A pharmaceutically acceptable salt.

The distinction between free-base-equivalent dosing and salt weight is commercially important. Galafold capsules contain 150 mg migalastat hydrochloride, equivalent to 123 mg migalastat free base. [2] A generic product labeled as 150 mg migalastat hydrochloride would closely align with claims 14 through 16 if used for the claimed renal population and indication.

The "about" language introduces ordinary patent-construction flexibility around the stated quantities. It does not necessarily cover every dose outside the 100-to-150 mg FBE range. The practical scope will depend on the specification's dose definitions, prosecution history and expert evidence.

What renal impairment populations are protected?

The patent divides renal impairment into commercially meaningful subgroups.

Claim	Renal subgroup
Claim 1	eGFR below 60
Claim 2	eGFR 30 to 59
Claim 3	eGFR 35 to 59
Claim 4	eGFR below 30
Claim 5	eGFR 15 to 29
Claim 6	Proteinuria below 100 mg/24 hours
Claim 7	Proteinuria 100 to 1,000 mg/24 hours
Claim 8	Proteinuria above 1,000 mg/24 hours

Claims 2 and 3 cover moderate renal impairment. Claims 4 and 5 reach severe renal impairment, including eGFR of 15 to 29. These claims are potentially important because the U.S. Galafold label states that use is not recommended in patients with severe renal impairment, defined as eGFR below 30 mL/min/1.73 m². [2]

That creates a regulatory-patent mismatch:

The patent claims treatment below eGFR 30.
The U.S. label does not recommend that use.
A generic applicant could seek approval for a narrower, label-consistent indication and avoid the severe-impairment claims.
A branded or specialty prescriber could still create infringement exposure through off-label use, depending on the facts and applicable inducement theories.

The proteinuria claims increase the estate's reach across patients with different renal disease burdens. They also create potential evidentiary issues because proteinuria may vary by collection method, timing, concomitant renin-angiotensin system blockade and disease progression.

What does the HEK assay limitation require?

Claim 18 defines an amenable mutation using HEK-293 cells exposed to 10 μM migalastat. The mutation must produce both:

A relative increase of at least 20% in α-galactosidase A activity; and
An absolute increase of at least 3% of wild-type α-galactosidase A activity.

Both thresholds are required. Meeting only one threshold would not satisfy the express definition in claim 18.

This limitation ties infringement to genotype classification. It is narrower than a claim covering every mutation listed as amenable by FDA or by Amicus's commercial testing program. Relevant questions include whether:

The accused mutation was tested in the same HEK-293 system.
The assay used the same migalastat concentration.
Relative and absolute activity were calculated using the same controls.
The mutation was known to be amenable when the treatment occurred.
A later assay can establish infringement for an earlier treatment period.

The assay limitation also creates a potential prosecution and validity issue. If the patent specification supports only a defined set of mutations, a challenger may examine whether the full class of mutations satisfying the functional thresholds was enabled and adequately described. The narrower dependent claim may be stronger than a broader construction of claim 1 because it supplies explicit assay parameters.

What clinical outcomes are required?

eGFR outcome

Claim 1 requires a mean annualized rate of change in eGFRCKD-EPI greater than -1.0 mL/min/1.73 m². The claim does not require eGFR improvement. A stable result, a modest decline, or an increase would satisfy the numerical direction of the limitation if the mean annualized rate exceeds -1.0.

The endpoint is population-based. It may not require every individual patient to maintain eGFR above the threshold. The likely dispute would concern:

The defined patient cohort.
Baseline and follow-up windows.
Handling of treatment discontinuations.
Missing data and imputation.
Whether the result is measured over 28 days, 6 months, 12 months or another period.
The meaning of "mean" and "annualized rate of change."

Claims 11 through 13 provide minimum treatment durations of 28 days, 6 months and 12 months. Claim 13 is the most relevant to the annualized eGFR endpoint because a 12-month observation period reduces extrapolation.

Lyso-Gb3 outcome

Claim 1 requires reduced mean plasma lyso-Gb3. Claim 17 narrows the population to eGFR 30 to 59 and specifies a mean reduction of about 29.0 nmol/L.

Lyso-Gb3 is a disease-burden biomarker used in Fabry disease. It is not itself the renal endpoint, but the claim links biomarker reduction with preservation of kidney function. A competitor could challenge whether the claimed mean reduction is inherent in every covered patient cohort or only demonstrated in a defined clinical dataset.

What formulations and dosage forms are protected?

The patent does not claim a new migalastat molecule, a new salt composition or a novel capsule formulation in the supplied claims. It claims use of migalastat in a therapeutic regimen.

Claims 9, 10 and 19 add:

Solid dosage form.
Oral administration.
Pharmaceutically acceptable salt.

These limitations align with Galafold's oral capsule presentation. [2] They have limited standalone value against an oral generic if the generic product is sold for the same renal-impaired, amenable-mutation population. They do not appear to cover every formulation or delivery system independently of the treatment method.

The patent is therefore more accurately characterized as a renal-population and dosing-regimen patent than as a formulation patent.

When does U.S. Patent 11,278,536 lose exclusivity?

The patent's expiration date should be determined from the earliest effective nonprovisional filing date in the relevant family, adjusted for patent-term adjustment, patent-term extension and any terminal disclaimer. The March 22, 2022 grant date does not determine expiration. [3, 4]

The patent is subject to the standard U.S. utility-patent term framework under 35 U.S.C. §154. A precise expiration date requires the USPTO continuity and term records, including:

Earliest effective nonprovisional filing date.
Continuation or divisional status.
Patent-term adjustment.
Terminal disclaimers.
Any patent-term extension.

The practical exclusivity period is likely to extend well beyond the initial Galafold composition and formulation patents because this patent was granted on a later clinical-use family. It should be analyzed separately from FDA regulatory exclusivity and from other Galafold patents.

What is the FDA and Orange Book status of Galafold?

Galafold is the U.S. brand for migalastat hydrochloride and is approved under NDA 208623 for adults with Fabry disease and an amenable α-galactosidase A mutation. The approved regimen is 123 mg orally once every other day, taken on an empty stomach. [1, 2]

The key regulatory facts are:

Item	Status
Product	Galafold
Active ingredient	Migalastat hydrochloride
Sponsor	Amicus Therapeutics
FDA application	NDA 208623
Route	Oral
Dose	123 mg migalastat free base, equivalent to 150 mg hydrochloride
Mutation requirement	Amenable α-galactosidase A mutation
Severe renal impairment	Use not recommended below eGFR 30
Product type	Small-molecule drug

Orange Book listing analysis must distinguish patents listed for the approved NDA from later method-of-use patents that may or may not have been submitted and accepted for listing. The supplied claims alone do not establish that U.S. Patent 11,278,536 is listed in the Orange Book for NDA 208623. A patent can remain enforceable without being listed, although the listing can affect ANDA certification mechanics and notice timing. [5]

What Paragraph IV challenges and generic entry risks exist?

A generic applicant seeking approval for migalastat could face several pathways.

Full-label generic

A full-label ANDA referencing Galafold would likely confront any properly listed composition, formulation or method-of-use patents. If U.S. Patent 11,278,536 is listed and its claims read on the proposed labeling, a Paragraph IV certification could trigger patent litigation under the Hatch-Waxman framework. [5]

Carved-out renal indication

Because the patent focuses on eGFR below 60, a generic applicant could attempt a section viii carve-out for the renal-preservation method. The feasibility depends on:

The exact Orange Book-listed use code.
Whether the proposed label can omit the patented indication.
Whether the remaining label still encourages the patented use.
Whether the patent is listed for an indication that FDA regards as separable.

A carve-out would reduce direct label overlap but would not eliminate all litigation risk. The patentee could argue induced infringement based on product labeling, prescriber instructions, promotional activity or the unavoidable clinical use of the product in the patented population.

Narrow severe-impairment approval

The patent's claims covering eGFR below 30 create a less direct risk because the U.S. label does not recommend Galafold for that population. A generic that preserves the same renal warning may avoid an approved-label inducement theory for claim 4 or claim 5. Claims 2 and 3 remain more commercially important because they correspond to eGFR 30 to 59, a population consistent with the label's renal dosing information.

Which companies compete with migalastat?

Migalastat competes primarily with enzyme replacement therapies rather than with conventional small-molecule generics.

Product	Company	Modality	Relevance to this patent
Galafold	Amicus	Pharmacological chaperone	Directly covered subject matter
Fabrazyme	Sanofi	Agalsidase beta ERT	Not a migalastat product; alternative treatment
Replagal	Takeda	Agalsidase alfa ERT	Alternative ERT where available
Elfabrio	Chiesi/Protalix	Pegunigalsidase alfa ERT	Alternative ERT
Future generic migalastat	Potential ANDA sponsors	Small molecule	Main direct patent challenge

The patent's ERT-naïve limitation in claim 20 is narrow. It does not require every claim to involve an ERT-naïve patient. A patient previously treated with ERT could still fall within claim 1 or claims 2 through 19 if the other elements are met.

The commercial value of claims 2, 3 and 17 is likely greater than the value of claims directed exclusively to eGFR below 30 because the moderate-impairment population is more consistent with current U.S. product labeling.

How strong is the patent estate?

The estate is strongest when all of the following are documented:

The patient's mutation satisfies the specified HEK assay.
The patient has eGFR 30 to 59.
The product is 150 mg migalastat hydrochloride.
Dosing is once every other day.
Treatment continues for at least 6 or 12 months.
Clinical data show the claimed eGFR and lyso-Gb3 outcomes.

The estate is weaker in enforcement scenarios where:

The accused label omits the renal-preservation indication.
The patient has eGFR at or above 60.
The mutation's amenability is established by a different assay.
Dosing differs materially from the claimed range or frequency.
The clinical outcomes cannot be attributed to the accused regimen.
The product is used in an ERT-experienced population and claim 20 is the only asserted claim.

Potential validity pressure points include written description and enablement across all amenable mutations, indefiniteness of "about" and "mean" limitations, and whether the clinical outcome limitations are sufficiently supported and reproducible across the claimed renal populations. The patent's specific assay and numerical endpoints also give the patentee defined infringement theories and may narrow the range of viable prior-art attacks.

What patent litigation or settlement agreements affect this patent?

The supplied record establishes the issued claims but does not establish a reported Paragraph IV case, final judgment, license, covenant not to sue or settlement specifically involving U.S. Patent 11,278,536. The patent should not be treated as cleared merely because no litigation is identified in the claim text.

Any generic launch analysis should separate:

Litigation involving Galafold's earlier composition or formulation patents.
Litigation involving later method-of-use patents.
Unlisted-patent enforcement under ordinary patent law.
Regulatory exclusivity and FDA approval timing.
Private licenses or settlement agreements that may impose launch restrictions.

A Paragraph IV notice, if served, would be assessed against the patent claims, the listed use code and the applicant's proposed label. A settlement could permit an authorized generic, a delayed entry date, or a field-limited launch without invalidating the patent.

What generic launch scenarios exist?

Scenario	Commercial consequence
No challenge	Generic waits for relevant patent and regulatory barriers to expire
Paragraph IV with litigation	Launch risk depends on 30-month stay, claim construction and validity
Section viii carve-out	Potential approval with renal-use language removed
At-risk launch	Exposure to damages and injunction if claims survive
Authorized generic license	Earlier market entry under negotiated restrictions
Alternative Fabry therapy	ERT competition without direct infringement of migalastat claims

The most credible generic strategy would likely combine a Paragraph IV challenge against listed patents with a section viii carve-out directed to renal-preservation language. The patentee's strongest counterargument would be that the ordinary Galafold label, mutation testing process and once-every-other-day dose inherently encourage use in the claimed moderate renal-impairment population.

Key Takeaways

U.S. Patent 11,278,536 is a targeted method-of-use patent, not a basic migalastat composition patent.
Claim 1 requires eGFR below 60, a HEK-assay-amenable mutation, 100 to 150 mg FBE once every other day, reduced lyso-Gb3 and an annualized eGFR decline better than -1.0.
Claims 2, 3 and 17 are commercially significant because they cover eGFR 30 to 59, a population compatible with labeled Galafold use.
Claims 4 and 5 reach eGFR below 30 even though the U.S. label does not recommend Galafold in severe renal impairment.
Claims 14 through 16 closely track the marketed 123 mg free-base and 150 mg hydrochloride dosing.
The HEK assay limitation creates a genotype-specific infringement requirement and a potential enablement and written-description battleground.
Orange Book listing of this patent is not established by the supplied claims and must be distinguished from enforceability.
Generic risk depends heavily on label design, use-code scope, Paragraph IV strategy and the patent's verified expiration and continuity data.
No specific litigation or settlement involving this patent is established by the supplied record.

Frequently Asked Questions

Does Patent 11,278,536 cover all Galafold prescriptions?

No. It requires a patient with eGFR below 60 and a HEK-assay-amenable mutation, along with the claimed dose, frequency and clinical outcomes.

Does the patent cover migalastat use in patients with normal kidney function?

No. The independent claim requires eGFR below 60 mL/min/1.73 m².

Is 150 mg Galafold the same dose as 123 mg migalastat?

Yes. Galafold contains 150 mg migalastat hydrochloride, equivalent to approximately 123 mg migalastat free base. [2]

Can a generic avoid the patent by using a different assay for mutation amenability?

Possibly, but the answer depends on claim construction, whether the mutation independently satisfies the claim's functional test, and whether the generic label or use induces treatment of the claimed population.

Does the patent protect a new migalastat formulation?

The supplied claims do not claim a new formulation composition. They claim use of migalastat, including oral and solid dosage forms, in a specified renal-impaired population.

References

U.S. Food and Drug Administration. (2018). FDA approves Galafold for adults with Fabry disease.
U.S. Food and Drug Administration. (2023). Galafold (migalastat hydrochloride) prescribing information. Amicus Therapeutics, Inc.
United States Patent and Trademark Office. (2022). U.S. Patent No. 11,278,536.
35 U.S.C. §154. (2024). Contents and term of patent; provisional rights.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book.

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	11,278,536	⤷ 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
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 11,278,536

Which drugs does patent 11,278,536 protect, and when does it expire?

Summary for Patent: 11,278,536