US Patent 11,278,599: Scope, Claims, Expiration, and Pompe Disease Patent Landscape

US Patent 11,278,599 protects combination treatment of Pompe disease using an acid alpha-glucosidase enzyme replacement therapy with an active-site-specific chaperone, particularly miglustat or migalastat, at specified concentration and dose ranges. The most commercially relevant embodiment is an oral chaperone combined with intravenous cipaglucosidase alfa at approximately 20 mg/kg, with the enzyme formulated at approximately 15 mg/mL. The patent is directed to a treatment method rather than composition-of-matter protection for either active ingredient.

The patent has potential relevance to Amicus Therapeutics' Pombiliti, a cipaglucosidase alfa-atga and miglustat regimen approved by the FDA in 2023. Because Pombiliti is regulated as a biologic combination regimen, generic-drug Paragraph IV litigation is not the principal entry mechanism. Biosimilar and interchangeable-biologic pathways, patent litigation, and labeling restrictions are more relevant.

What does US Patent 11,278,599 claim?

The patent has 20 claims. Claims 1 and 13 are the independent claims.

Claim element	Independent claim 1	Independent claim 13
Disease	Pompe disease	Pompe disease
First therapy	1-deoxynojirimycin or N-butyldeoxynojirimycin, or salt	N-butyldeoxynojirimycin, or salt
Second therapy	Acid alpha-glucosidase	Acid alpha-glucosidase
Enzyme concentration	About 5 to about 80 mg/mL	About 15 mg/mL
Chaperone dose	About 1 to about 10 mg/kg	About 1 to about 10 mg/kg
Enzyme dose	Effective amount	About 5 to about 50 mg/kg
Administration route	Not required in claim 1	Not required in claim 13
Dependent route limitation	Oral chaperone and intravenous enzyme in claim 12	Oral chaperone and intravenous enzyme in claim 20

Claim 1 is the broader independent claim because it covers either 1-deoxynojirimycin or N-butyldeoxynojirimycin and permits an enzyme concentration from about 5 mg/mL to about 80 mg/mL.

Claim 13 is narrower but more directly aligned with the commercial Pombiliti regimen. It requires N-butyldeoxynojirimycin, an enzyme concentration of about 15 mg/mL, and an acid alpha-glucosidase dose from about 5 mg/kg to about 50 mg/kg.

What compounds fall within the chaperone limitation?

1-Deoxynojirimycin is the core chemical structure associated with migalastat. N-butyldeoxynojirimycin is miglustat. The claims cover pharmaceutically acceptable salts, which would include the salt form used in an approved product where the active pharmaceutical ingredient is administered as a salt.

The claims do not require the chaperone to be marketed under a particular brand name. They focus on the chemical identity and administration in combination with acid alpha-glucosidase.

What enzyme products may fall within the claims?

The claims recite acid alpha-glucosidase generically. They do not expressly limit the enzyme to cipaglucosidase alfa, alglucosidase alfa, or avalglucosidase alfa.

Potentially relevant enzyme products include:

Enzyme	Commercial product	Sponsor	Relevance to claim language
Cipaglucosidase alfa-atga	Pombiliti	Amicus Therapeutics	Directly relevant to the commercial chaperone-enzyme regimen
Alglucosidase alfa	Myozyme, Lumizyme	Sanofi	Falls within the generic enzyme wording if all claim limitations are met
Avalglucosidase alfa-ngpt	Nexviazyme	Sanofi	Falls within the generic enzyme wording if all claim limitations are met
Other recombinant acid alpha-glucosidases	Development-stage products	Various developers	Potentially covered if used with the claimed chaperone and parameters

The patent does not require a particular glycosylation pattern, amino-acid sequence, cell line, or manufacturing process for the enzyme. Those limitations may arise from other patents or regulatory descriptions, but they are not apparent from the asserted claims supplied.

How narrow are the dose and concentration ranges?

The practical scope is materially narrower than the broad phrase "combination treatment."

The claims require all of the following:

Treatment of a subject with Pompe disease.
Administration of a specified chaperone.
Administration of acid alpha-glucosidase.
Chaperone dosing at about 1 to about 10 mg/kg.
Enzyme formulation at about 5 to about 80 mg/mL, or about 15 mg/mL under claim 13.
Enzyme dosing within the applicable dependent or independent claim range.
Administration of both compositions, although claim 1 does not itself require separate routes.

The dependent claims progressively narrow the enzyme dose:

Claim	Enzyme dose limitation
1	Effective amount
2	About 5 to about 50 mg/kg
3	About 10 to about 40 mg/kg
4	About 15 to about 25 mg/kg
5	About 20 mg/kg
13	About 5 to about 50 mg/kg
14	About 15 to about 25 mg/kg
15	About 20 mg/kg
18	About 10 to about 40 mg/kg

The 20 mg/kg claims are commercially significant because Pombiliti's FDA-approved dosing uses cipaglucosidase alfa-atga at 20 mg/kg by intravenous infusion every two weeks in combination with oral miglustat. The label identifies miglustat as the pharmacologic chaperone used with cipaglucosidase alfa-atga (FDA, 2023a).

What formulations are protected by US Patent 11,278,599?

The formulation limitations are functional and concentration-based rather than formulation-composition claims.

Claim 1 covers an acid alpha-glucosidase composition formulated at about 5 to about 80 mg/mL. Claim 8 narrows the formulation to about 15 mg/mL. Claims 6 and 7 require or specify a buffer, including:

Citrate buffer
Acetate buffer
Bicarbonate buffer
Phosphate buffer
Combinations of those buffers

Claim 9 covers an excipient in either the first or second composition.

The claims do not identify a required stabilizer, surfactant, tonicity agent, lyoprotectant, preservative, container, vial, reconstitution medium, or infusion device. A competing product could therefore avoid a particular dependent claim by changing the buffer or excipient while remaining within the broader enzyme concentration range of claim 1.

The formulation limitations are more useful against a product using the same or substantially similar enzyme concentration than against a development program using a different concentration, separate formulation, or modified administration protocol.

What is the strongest claim against Pombiliti?

Claim 13 is the most commercially targeted claim.

A Pombiliti regimen appears to correspond closely to the following limitations:

Claim 13 limitation	Pombiliti regimen
N-butyldeoxynojirimycin or salt	Miglustat
Acid alpha-glucosidase	Cipaglucosidase alfa-atga
Enzyme concentration about 15 mg/mL	Relevant product formulation limitation
Chaperone dose about 1 to about 10 mg/kg	Requires analysis of the applicable dosing expression and product presentation
Enzyme dose about 5 to about 50 mg/kg	20 mg/kg approved dose
Combined use for Pompe disease	Approved indication
Oral chaperone and IV enzyme	Approved administration pattern under claim 20

Claim 20 adds oral administration of the chaperone and intravenous administration of the enzyme. It may be the most direct method-of-use claim for a marketed regimen, assuming the dose and concentration limitations are met as construed.

The main claim-construction issue is whether the commercial miglustat dose can be expressed in the claimed 1 to 10 mg/kg range for the treated subject. An infringement analysis would require the actual patient-weight relationship, dosing instructions, and interpretation of "about." A fixed oral dose may fall within or outside a weight-based range depending on the patient and the applicable claim construction.

When does US Patent 11,278,599 expire?

The patent issued on March 29, 2022. Its effective expiration date depends on the earliest claimed priority date, patent-term adjustment, terminal disclaimers, and any patent-term extension.

A patent term generally runs 20 years from the earliest effective nonprovisional U.S. filing date, subject to adjustment under 35 U.S.C. § 154 and extension under 35 U.S.C. § 156. The patent's expiration should therefore be taken from the USPTO Patent Center term data rather than calculated solely from the issue date (USPTO, 2024).

Public patent-family records associate the patent with an earlier Pompe disease combination-treatment priority chain. On that basis, the nominal term is expected to extend into the mid-2030s, subject to the official USPTO term calculation. The patent should be treated as potentially relevant through at least the early-to-mid 2030s unless a court invalidates claims, a terminal disclaimer shortens the term, or the official register shows a different expiration date.

What is the FDA and Orange Book status of the patent?

Pombiliti is approved under a biologics license application, BLA 761262, rather than as a conventional small-molecule NDA. FDA approved Pombiliti in September 2023 in combination with miglustat for adults with late-onset Pompe disease (FDA, 2023a).

The principal regulatory implications are:

Pombiliti is a biologic product.
A competing product would generally use the biosimilar pathway under section 351(k) of the Public Health Service Act.
A biosimilar applicant does not rely on the conventional ANDA Paragraph IV framework used for small-molecule generics.
Biologic patent disclosures and reference-product exclusivity are handled through the biologics framework, including Purple Book-related procedures and the patent-exchange process.
Miglustat itself is a small-molecule drug, but the combination regimen's commercial protection depends on product, method-of-use, formulation, and biologic patent rights.

The 12-year reference-product exclusivity period for a newly licensed biologic is distinct from patent expiration. It does not establish the expiration date of US Patent 11,278,599 (FDA, 2023b).

Are Paragraph IV challenges available against this patent?

A conventional Paragraph IV certification is generally not the expected route for a biosimilar version of Pombiliti because cipaglucosidase alfa-atga is licensed as a biologic.

A small-molecule applicant seeking approval of miglustat alone could face different patent issues, but miglustat monotherapy would not practice the full combination claims. The claims require both a chaperone and acid alpha-glucosidase for treating Pompe disease.

A biosimilar applicant could challenge the patent through:

Patent-invalidity defenses in infringement litigation.
A declaratory judgment action in an appropriate case.
The biologics patent-dispute procedures.
A non-infringement position based on enzyme concentration, dosing, chaperone identity, route, or label.
A proposed label that excludes the patented method where legally and commercially feasible.

A product with a label that directs use of miglustat with cipaglucosidase alfa at 20 mg/kg would present greater method-of-use exposure than a product labeled for a different enzyme, dose, concentration, or treatment population.

Which companies are most exposed to this patent?

Amicus Therapeutics

Amicus is the company most directly associated with the claimed regimen because Pombiliti combines cipaglucosidase alfa-atga with miglustat. The patent is commercially relevant to the product's combination-treatment positioning.

Sanofi

Sanofi markets Myozyme, Lumizyme, and Nexviazyme for Pompe disease. Those products use acid alpha-glucosidase enzymes but are not, based on the supplied claims alone, required to be administered with miglustat or migalastat.

Sanofi could face claim exposure if it or a partner promotes use of one of those enzymes with a claimed chaperone at the specified doses and concentration. Enzyme monotherapy would not satisfy the combination limitation.

Biosimilar developers

A biosimilar developer targeting cipaglucosidase alfa-atga would face the greatest risk if its proposed labeling mirrors the Pombiliti regimen. A biosimilar of an enzyme used without the claimed chaperone would present a different infringement profile.

How strong is the patent estate?

The patent has moderate-to-strong commercial relevance for the specific combination regimen, but its legal strength depends on prior art and claim construction.

Strengths

Claims the combination of two pharmacologically distinct therapies.
Includes a commercially relevant 20 mg/kg enzyme dose.
Includes the approximately 15 mg/mL enzyme concentration associated with the narrower independent claim.
Covers oral chaperone and intravenous enzyme administration.
Uses generic enzyme language that may reach multiple acid alpha-glucosidase products.
Provides fallback positions through dependent claims.

Vulnerabilities

Combination use of enzyme replacement therapy and pharmacologic chaperones may have substantial prior-art exposure.
Overlapping dose ranges can create obviousness arguments where prior art teaches adjacent or overlapping ranges.
"About" may create claim-construction disputes around concentration and dose boundaries.
The claims may face written-description or enablement challenges if the specification does not adequately support the full range of acid alpha-glucosidases from 5 to 80 mg/mL.
A defendant may argue that the claimed regimen lacks a demonstrated unexpected result across the full genus of enzymes and chaperones.
The broad claim does not expressly identify cipaglucosidase alfa, which can create both breadth and support issues.

The strongest surviving position would likely be the narrower product-aligned claims covering miglustat, approximately 15 mg/mL enzyme formulation, 20 mg/kg enzyme dosing, and oral-plus-intravenous administration.

What generic or biosimilar launch scenarios exist?

Launch scenario	Likely patent exposure
Miglustat alone	Does not satisfy the combination claims
Acid alpha-glucosidase alone	Does not satisfy the chaperone limitation
Cipaglucosidase alfa biosimilar with the same combination label	High exposure
Cipaglucosidase alfa biosimilar without miglustat coadministration	Lower exposure under these claims
Enzyme at a materially different concentration	May avoid concentration-limited claims
Enzyme dose outside the claimed ranges	May avoid dependent claims, but claim 1 may remain relevant
Oral chaperone with IV enzyme at claimed parameters	Direct exposure to claims 12 and 20
Different chaperone outside DNJ and N-butyldeoxynojirimycin classes	Potential non-infringement
Modified enzyme or alternative formulation	Requires separate analysis under the generic acid alpha-glucosidase language

A launch strategy that removes miglustat from the label may reduce method-of-use exposure but could also undermine the clinical and commercial basis of a Pombiliti-like product. A biosimilar applicant must assess both patent infringement and regulatory substitutability.

What patent litigation and settlement risks affect the product?

No litigation outcome or settlement term is established by the supplied claim text. The likely dispute centers on whether a biosimilar or competing enzyme product practices the claimed combination regimen.

Potential litigation issues include:

Whether the product formulation is approximately 15 mg/mL.
Whether the enzyme dose is approximately 20 mg/kg.
Whether the chaperone dose falls within approximately 1 to 10 mg/kg.
Whether a product label induces administration of the two compositions together.
Whether "acid alpha-glucosidase" covers the accused enzyme.
Whether the patent claims are anticipated or obvious.
Whether the claims adequately support the full concentration and enzyme genus.
Whether a carve-out label can avoid induced infringement.

Settlement agreements could delay launch, permit entry on a negotiated date, restrict the use of a combination label, or define an authorized formulation. Such agreements would require review of the actual court docket and agreement terms.

How does this patent compare with competing Pompe disease patent positions?

Product	Chaperone combination	Main patent risk from US 11,278,599
Pombiliti	Yes, miglustat	Direct commercial relevance
Myozyme/Lumizyme	No approved chaperone combination	Limited unless combined use is promoted
Nexviazyme	No approved miglustat combination in the cited FDA approval	Limited under these claims
Experimental ERT plus migalastat	Potentially significant	Depends on dose, concentration, and route
Migalastat or miglustat monotherapy	No enzyme combination	Outside the supplied claims

The patent does not block all Pompe enzyme replacement therapy. It targets a defined combination method. Its commercial value is therefore highest where a competitor seeks to reproduce the same chaperone-enabled enzyme regimen.

Key Takeaways

US Patent 11,278,599 is a Pompe disease method-of-treatment patent.
It requires both a deoxynojirimycin-type chaperone and acid alpha-glucosidase.
The key chaperones are miglustat and migalastat.
Claim 13 is closely aligned with a miglustat-plus-enzyme regimen using an approximately 15 mg/mL enzyme formulation.
Claims 5 and 15 specifically reach an approximately 20 mg/kg enzyme dose.
Claims 12 and 20 require oral chaperone administration with intravenous enzyme administration.
Pombiliti is the product most directly implicated by the claim structure.
Pombiliti is a biologic, so biosimilar procedures are more relevant than conventional Paragraph IV litigation.
The patent does not cover acid alpha-glucosidase monotherapy or chaperone monotherapy.
Key validity risks include obviousness, overlapping dose ranges, written description, enablement, and construction of "about."
The patent's nominal term is expected to extend into the mid-2030s, subject to the official USPTO term calculation.

FAQs About US Patent 11,278,599

Does US Patent 11,278,599 cover Pombiliti?

It is potentially highly relevant to Pombiliti because the claims cover acid alpha-glucosidase administered with N-butyldeoxynojirimycin, the chemical class associated with miglustat. A definitive infringement conclusion requires comparison of the approved formulation, dosing instructions, patient-weight calculation, and patent construction.

Does the patent cover Nexviazyme?

The claims could reach Nexviazyme if it is administered with miglustat or migalastat at the claimed dose and formulation parameters. Nexviazyme monotherapy does not satisfy the combination requirement.

Does the patent cover migalastat?

Yes. Claim 1 expressly covers 1-deoxynojirimycin or a pharmaceutically acceptable salt. Migalastat is a 1-deoxynojirimycin derivative used as a pharmacologic chaperone. Product-specific chemical and salt-form analysis remains relevant.

Can a competitor avoid the patent by changing the enzyme dose?

Changing the dose may avoid narrower claims such as claims 5, 15, and 18, but it may not avoid claim 1 if the dose remains an effective amount and all other limitations are met.

Is the patent a composition-of-matter patent?

No. The supplied claims are method claims. They protect administering the specified chaperone and acid alpha-glucosidase combination for Pompe disease under defined formulation, dose, and route conditions.

References

Amicus Therapeutics, Inc. (2022). United States Patent No. 11,278,599, Methods of treating Pompe disease. U.S. Patent and Trademark Office.
U.S. Food and Drug Administration. (2023a). Pombiliti (cipaglucosidase alfa-atga) prescribing information. FDA.
U.S. Food and Drug Administration. (2023b). Purple Book: Database of licensed biological products. FDA.
U.S. Patent and Trademark Office. (2024). Patent term adjustment and patent term extension information. USPTO.
U.S. Food and Drug Administration. (2021). Nexviazyme (avalglucosidase alfa-ngpt) prescribing information. FDA.

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	OPFOLDA	miglustat	CAPSULE;ORAL	215211-001	Sep 28, 2023		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial				THE TREATMENT OF POMPE 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
Canada	2866683	⤷ Start Trial
European Patent Office	2823043	⤷ Start Trial
Japan	2015509542	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 11,278,599

Which drugs does patent 11,278,599 protect, and when does it expire?

Summary for Patent: 11,278,599