US Patent 10,512,677: Scope, Claims, Expiration, and Pompe Disease Patent Landscape

US Patent No. 10,512,677 protects methods of treating Pompe disease with a combination of acid alpha-glucosidase and an active-site-specific chaperone, principally miglustat or 1-deoxynojirimycin. The patent is assigned to Amicus Therapeutics and is strategically relevant to the Pombiliti and Opfolda regimen, which combines cipaglucosidase alfa with miglustat.

The patent does not claim acid alpha-glucosidase alone, miglustat alone, or a generic Pompe treatment. Its independent claim requires both components, specified concentration ranges, and administration to a Pompe disease patient. The patent’s reported expiration date is June 27, 2033, subject to any applicable patent-term adjustment or extension shown in the USPTO record.[1]

What does US Patent 10,512,677 claim?

The patent’s core claim is a combination-treatment method for Pompe disease.

Claim element	Scope
Disease	Pompe disease
Patient	A subject receiving treatment
First composition	1-deoxynojirimycin or a pharmaceutically acceptable salt, or n-butyl-deoxynojirimycin or a pharmaceutically acceptable salt
Chaperone concentration	About 20 mg/mL to about 200 mg/mL
Second composition	Acid alpha-glucosidase
Enzyme concentration	About 5 mg/mL to about 500 mg/mL
Administration	Required by claim 1, but route and sequencing are generally narrowed in dependent claims
Formulation	May be liquid and may contain specified excipients or buffers
Separate administration	Covered expressly by claims 12, 14 and 15

N-butyl-deoxynojirimycin is miglustat. The patent uses the broader chemical terminology, while the commercial Pompe regimen uses miglustat as the chaperone component.

Claim 1 is an open “comprising” claim. A competing regimen could therefore contain additional active ingredients, excipients, buffers, or other treatment steps and still fall within the claim if all required elements are present.

How broad is claim 1 of US 10,512,677?

Claim 1 is broad in the identity of the enzyme but narrow in its required combination and concentration parameters.

The claim does not limit acid alpha-glucosidase to cipaglucosidase alfa. On its face, the term can encompass acid alpha-glucosidase products meeting the claim’s method requirements, including potentially engineered or otherwise modified forms of the enzyme. The commercial relevance is highest for cipaglucosidase alfa because Pombiliti is an acid alpha-glucosidase administered with Opfolda, which contains miglustat.[2]

The claim requires:

A first composition containing DNJ or miglustat.
A second composition containing acid alpha-glucosidase.
Chaperone concentration of approximately 20-200 mg/mL.
Enzyme concentration of approximately 5-500 mg/mL.
Administration of the combination to treat Pompe disease.

A product containing miglustat at a different concentration may avoid literal infringement of claim 1, depending on how the concentration is measured and whether a dependent claim or doctrine-of-equivalents theory applies. The same analysis applies to an enzyme formulation outside the stated range.

The phrase “about” creates an infringement boundary around the numerical ranges rather than an absolute cutoff. The scope would depend on the patent specification, prosecution history, analytical method, formulation state, and the ordinary meaning of the term in the relevant technical field.

Which dependent claims add the most commercial protection?

Claims 2 through 4 narrow the acid alpha-glucosidase concentration. Claim 4 is particularly relevant to a commercial formulation containing approximately 25 mg/mL enzyme.

Claim	Added limitation	Commercial significance
2	Enzyme at about 5-250 mg/mL	Narrows the broad enzyme range
3	Enzyme at about 10-200 mg/mL	Further narrows the concentration
4	Enzyme at about 25 mg/mL	Targets a specific formulation concentration
5	At least one composition is liquid	Relevant to injectable or oral liquid products
6	At least one composition contains an excipient	Covers formulation implementation
7	PEG 400, arginine, glutamic acid, proline, gamma-cyclodextrin, or combinations	Provides excipient-specific fallback positions
8	At least one composition contains a buffer	Covers buffered formulations
9	Citrate, acetate, bicarbonate, phosphate, or combinations	Provides buffer-specific protection
10	Chaperone is miglustat	Directly targets the commercial chaperone
11	Chaperone is 1-deoxynojirimycin	Covers the alternative chaperone
12	Independent subcutaneous injections	Covers separate subcutaneous delivery
13	Separate subcutaneous injections of 1-10 mL	Adds injection-volume limitations
14	Separate intravenous injections	Relevant to enzyme infusion and separate administration
15	Chaperone orally; enzyme intravenously	Closely tracks the commercial route of administration

Claims 10 and 15 are commercially important. Claim 10 narrows the chaperone to miglustat. Claim 15 expressly covers oral administration of the chaperone with intravenous administration of the enzyme, the route used for the Pombiliti and Opfolda treatment protocol.[2]

Does the patent cover Pombiliti and Opfolda?

The patent is highly relevant to the Pombiliti and Opfolda combination.

Pombiliti is cipaglucosidase alfa-atga, an acid alpha-glucosidase enzyme replacement therapy. Opfolda is miglustat, an enzyme stabilizer used with cipaglucosidase alfa-atga. FDA labeling directs administration of Opfolda before Pombiliti, with the two products administered as part of the same Pompe treatment regimen.[2]

The strongest apparent claim overlap is:

Claim 1: miglustat plus acid alpha-glucosidase within the specified concentration ranges.
Claim 10: miglustat as the active-site-specific chaperone.
Claim 15: oral miglustat with intravenous enzyme administration.
Claims 5 through 9: liquid formulations, excipients and buffers, depending on the approved formulations.
Claims 2 through 4: dependent enzyme concentration ranges, if the commercial enzyme presentation falls within those ranges.

The patent does not necessarily cover every use of Pombiliti or Opfolda independently. A miglustat product used for a non-Pompe indication would not satisfy the disease-treatment limitation. Likewise, cipaglucosidase alfa administered without miglustat would not satisfy the combination requirement.

What formulations are protected by US 10,512,677?

The formulation claims are not composition claims directed to a vial or bottle standing alone. They are dependent method claims. The formulation must be used in the claimed Pompe treatment method.

The patent covers methods using liquid compositions and formulations containing particular excipients or buffers. The listed excipients include:

Polyethylene glycol 400
Arginine
Glutamic acid
Proline
Gamma-cyclodextrin

The listed buffers include:

Citrate
Acetate
Bicarbonate
Phosphate

A formulation claim is therefore strongest when the accused regimen uses the specified active ingredient, concentration, formulation component, and Pompe treatment method. The presence of an alternative excipient does not necessarily avoid claim 1 because claim 1 does not require any excipient. It may avoid a narrower claim such as claim 7.

Does the patent require separate administration?

Claim 1 does not expressly require separate injections, oral administration, or intravenous administration. Those limitations appear in later claims.

The dependent claims divide the administration scope into three principal routes:

Separate subcutaneous injections under claims 12 and 13.
Separate intravenous injections under claim 14.
Oral administration of the chaperone and intravenous administration of the enzyme under claim 15.

This structure gives the patent broader protection through claim 1 and more specific protection through route-based claims. A regimen using oral miglustat and intravenous acid alpha-glucosidase is the clearest commercial match to claim 15.

The term “independently” in claims 12 and 14 supports separate administration rather than a single combined injection. Claim 15 is more explicit about the route assigned to each component.

When does US Patent 10,512,677 expire?

The patent’s nominal expiration date is June 27, 2033, based on the published priority and filing history reflected in the US patent record.[1]

Event	Date
Earliest reported priority date	June 27, 2012
US patent grant	December 24, 2019
Nominal patent expiration	June 27, 2033
FDA approval of Pombiliti and Opfolda	September 28, 2023
Approximate remaining patent life at product approval	About 9 years and 6 months

The effective end date should be confirmed against the USPTO patent-term-adjustment record and any applicable patent-term extension. The patent’s expiration date is separate from FDA regulatory exclusivity and orphan-drug exclusivity.

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

Pombiliti is an enzyme biologic, while Opfolda is the miglustat component. Biologic patent information is not handled through the Orange Book in the same manner as patents for conventional small-molecule NDAs. The Purple Book and the relevant biologic licensing framework are more important for Pombiliti.[3]

Opfolda’s small-molecule regulatory status creates a separate Orange Book analysis. A patent directed to a treatment method involving both miglustat and acid alpha-glucosidase may be relevant to the approved miglustat regimen, but Orange Book listing depends on FDA listing rules and the product-specific patent submission.

The existence of a patent does not itself establish Orange Book listing, a regulatory block, or an automatic bar to approval of a competing product. The relevant commercial effect depends on:

Whether the patent is listed against the relevant FDA-approved product.
Whether the listed claims cover an approved method of use.
Whether the patent remains active.
Whether an applicant submits a Paragraph IV certification.
Whether the patent owner brings suit within the statutory period.

What FDA exclusivities protect Pombiliti and Opfolda?

FDA exclusivity and patent protection operate separately.

Pombiliti and Opfolda were approved by FDA on September 28, 2023 for use together in adults with late-onset Pompe disease.[2] The regulatory protection includes product-specific exclusivity periods that do not necessarily end when US Patent 10,512,677 expires.

The principal regulatory barriers are:

Protection	Product relevance	Approximate timing
Orphan-drug exclusivity	Pompe disease indication	Approximately seven years from approval, subject to statutory conditions
Biologic reference-product exclusivity	Pombiliti	Potentially 12 years from first licensure for the biologic
New clinical investigation exclusivity	Opfolda, depending on FDA designation	Potentially three years for qualifying changes
Patent protection	Combination treatment and formulations	Nominally through June 27, 2033 for US 10,512,677

A biosimilar applicant could face the biologic reference-product exclusivity period before a 351(k) application can be approved. Orphan exclusivity can also restrict approval for the same disease and indication, although its operation differs from patent enforcement.

What Paragraph IV challenges and generic entry risks exist?

A Paragraph IV challenge is more likely to target the miglustat component or an Orange Book-listed method-of-use patent than the biologic enzyme itself.

A generic applicant seeking approval for miglustat would need to assess whether its proposed label includes the patented Pompe combination method. Potential strategies include:

Excluding the Pompe indication through a section viii statement, if legally and regulatorily available.
Certifying that the patent is invalid, unenforceable or not infringed.
Challenging the patent’s written description, enablement, claim construction or numerical-range scope.
Designing around the claimed concentration ranges.
Avoiding a label that directs use with acid alpha-glucosidase.

A label carve-out does not eliminate all infringement risk if the generic is marketed with knowledge that its product will be used for the patented indication. Induced-infringement exposure would depend on the proposed labeling, promotional conduct and evidence of intent.

For a competing acid alpha-glucosidase, the principal route would more likely be a biosimilar or separate biologic approval pathway rather than a conventional ANDA. A competing enzyme could face:

Biologic data exclusivity.
Orphan-drug exclusivity.
Product, formulation and manufacturing patents.
The combination-method claims in US 10,512,677.
Manufacturing-process and cell-line claims in related patent families.

How strong is the patent estate for the Pombiliti and Opfolda regimen?

US 10,512,677 is strongest against a direct copy of the approved regimen.

Strengths

The patent has several commercially useful features:

It covers the combination of chaperone and enzyme rather than a narrow brand formulation alone.
Claim 10 directly identifies miglustat.
Claim 15 tracks oral chaperone and intravenous enzyme administration.
The claims include broad and narrower concentration ranges.
The patent provides fallback positions for liquid formulations, buffers and excipients.
Method claims can cover use of a competing enzyme if the competitor follows the claimed regimen.

Limitations

The patent also has material design-around and validity pressure points:

It is a method patent, not a composition-of-matter claim.
The enzyme is not limited to cipaglucosidase alfa, which may create claim-construction and enablement disputes at the outer boundaries.
Concentration ranges must be met.
The claims require treatment of Pompe disease.
A competitor may attempt a different chaperone concentration, enzyme concentration, formulation, route or label.
Patent expiration occurs before the full period of biologic regulatory exclusivity potentially available to Pombiliti.

The patent therefore has high relevance to direct commercial substitution but less control over non-Pompe uses, enzyme monotherapy, or substantially different treatment protocols.

Which companies are challenging the Pompe disease market?

The main commercial competitors are Sanofi and Amicus.

Company	Product	Modality	Competitive position
Amicus Therapeutics	Pombiliti plus Opfolda	Cipaglucosidase alfa plus miglustat	Chaperone-stabilized enzyme replacement regimen
Sanofi	Myozyme/Lumizyme	Alglucosidase alfa	Established recombinant acid alpha-glucosidase therapy
Sanofi	Nexviazyme	Avalglucosidase alfa	Next-generation enzyme replacement therapy
Potential biosimilar developers	Future acid alpha-glucosidase products	351(k) biologics	Long-term price and access risk

The most important competitive distinction is that Pombiliti and Opfolda use a pharmacological chaperone to stabilize the enzyme, while Myozyme, Lumizyme and Nexviazyme are enzyme-replacement products without the same commercial two-product regimen.

What patent litigation affects US Patent 10,512,677?

The patent’s practical value depends on whether Amicus has asserted it against a proposed generic, biosimilar or competing Pompe regimen. The supplied claim text does not identify a litigation docket, asserted claims, settlement agreement or Paragraph IV notice.

No litigation conclusion should be drawn from the patent number alone. A patent can be listed, active and commercially important without being the subject of a filed infringement action. The principal litigation issues likely to arise from these claims are:

Whether a competing product contains the required chaperone and enzyme combination.
Whether formulation concentrations fall within the “about” ranges.
Whether an approved label induces use for Pompe disease.
Whether acid alpha-glucosidase is construed broadly enough to cover a competitor’s enzyme.
Whether the claims are enabled across the full scope of the enzyme and formulation alternatives.
Whether claim 15 covers the precise sequencing and administration protocol in the accused label.

What generic launch scenarios are most likely?

Direct miglustat generic

A generic miglustat could launch with a non-Pompe label if FDA permits a lawful section viii carve-out and the marketing conduct avoids inducing use of the patented combination. This would not necessarily provide a substitute for Opfolda in the approved regimen.

Generic with Pompe labeling

A generic that includes Pompe treatment with acid alpha-glucosidase would face the highest risk under claims 1, 10 and 15, particularly if it uses the claimed concentration ranges and route.

Competing enzyme or biosimilar

A competing acid alpha-glucosidase could avoid this patent by not using miglustat. It would still face regulatory, manufacturing, clinical, formulation and separate patent barriers.

Alternative chaperone regimen

A regimen using a chaperone outside DNJ or miglustat could avoid literal infringement of claim 1, although related patents or doctrine-of-equivalents arguments could remain relevant.

What geographic coverage does the patent provide?

US Patent 10,512,677 provides territorial protection in the United States only. Parallel foreign applications may protect corresponding treatment methods in Europe, Japan, Canada and other markets, but foreign scope, validity and expiration must be assessed separately.

US patent rights can be implicated by:

Treatment performed in the United States.
Commercial marketing or instructions directed to US Pompe patients.
Importation of an accused product into the United States.
Manufacturing activity in the United States that contributes to an infringing treatment method.

Foreign patents do not automatically have the same claims or expiration date as the US patent.

What manufacturing and intellectual-property barriers remain after patent expiration?

Expiration of US 10,512,677 would remove one method-patent barrier but would not eliminate the broader entry burden.

A competing cipaglucosidase product would still need:

A validated recombinant production system.
A suitable cell line and expression construct.
Control of glycosylation and enzyme activity.
A stable injectable formulation.
Comparability or biosimilarity data.
Clinical and immunogenicity data.
Commercial-scale manufacturing capacity.
Freedom to operate around process, formulation and delivery patents.

For miglustat, the active ingredient is chemically simpler than the enzyme, but the approved Pombiliti regimen depends on coordinated dosing, labeling and supply of both components. The commercial barrier is therefore a combination of patent rights, regulatory exclusivity, clinical evidence and regimen-specific market access.

Key Takeaways

US 10,512,677 is a method patent assigned to Amicus Therapeutics.
The core claim requires treatment of Pompe disease with DNJ or miglustat plus acid alpha-glucosidase.
Claim 10 directly narrows the protection to miglustat.
Claim 15 is particularly relevant to the Pombiliti and Opfolda regimen because it covers oral chaperone administration with intravenous enzyme administration.
The patent includes concentration, liquid formulation, excipient, buffer and injection-route fallback claims.
The reported nominal expiration date is June 27, 2033.
The patent is a method-of-use barrier, not a standalone composition-of-matter patent.
Pombiliti’s biologic exclusivity and Pompe orphan exclusivity are separate from the patent and may extend beyond the patent’s nominal expiration.
The highest generic risk arises from a miglustat product labeled for use with acid alpha-glucosidase.
A competing enzyme could avoid this patent by omitting miglustat but would face biosimilar, manufacturing and separate patent barriers.

FAQs

Can a generic miglustat avoid US Patent 10,512,677?

Potentially, if the approved label excludes the patented Pompe combination use and the manufacturer does not induce that use. The risk depends on the final label and promotional conduct.

Does US 10,512,677 cover Nexviazyme?

The claim language is not limited to cipaglucosidase alfa. It requires acid alpha-glucosidase plus DNJ or miglustat at the claimed concentrations. Nexviazyme used without miglustat would not satisfy the complete combination required by claim 1.

Is US 10,512,677 a composition patent?

No. The provided claims are method claims. They cover administering specified compositions to treat Pompe disease rather than claiming the compositions as products independent of use.

Does the patent cover subcutaneous Pompe treatment?

Claims 12 and 13 expressly address separate subcutaneous injections. The broader commercial regimen is principally associated with oral miglustat and intravenous enzyme administration under claim 15.

Could the patent block a 351(k) biosimilar to cipaglucosidase alfa?

It could create method-of-use risk if the biosimilar is labeled or marketed for use with miglustat in a manner satisfying the claims. It would not necessarily block a biosimilar labeled for enzyme monotherapy or a different non-infringing regimen.

References

United States Patent and Trademark Office. (2019). US Patent No. 10,512,677, Methods of treating Pompe disease. https://patents.google.com/patent/US10512677B2/en
U.S. Food and Drug Administration. (2023, September 28). FDA approves new treatment for late-onset Pompe disease. https://www.fda.gov
U.S. Food and Drug Administration. (2024). Purple Book: Database of licensed biological products. https://purplebooksearch.fda.gov
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book
U.S. Food and Drug Administration. (2023). Pombiliti and Opfolda prescribing information. https://www.accessdata.fda.gov/drugsatfda/

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: 10,512,677

Which drugs does patent 10,512,677 protect, and when does it expire?

Summary for Patent: 10,512,677