Details for Patent: 10,857,212

Which drugs does patent 10,857,212 protect, and when does it expire?

Patent 10,857,212 protects OPFOLDA and is included in one NDA.

This patent has seventy-six patent family members in thirty-two countries.

Summary for Patent: 10,857,212

Title:	Augmented acid alpha-glucosidase for the treatment of Pompe disease
Abstract:	A method for treating Pompe disease including administration of recombinant human acid α-glucosidase having optimal glycosylation with mannose-6-phosphate residues in combination with an amount of miglustat effective to maximize tissue uptake of recombinant human acid α-glucosidase while minimizing inhibition of the enzymatic activity of the recombinant human acid α-glucosidase is provided.
Inventor(s):	Hung V. Do, Richie Khanna, Russell Gotschall
Assignee:	Amicus Therapeutics Inc
Application Number:	US15/950,347
Patent Claim Types: see list of patent claims	Use; Composition; Delivery; Dosage form;

US Patent 10,857,212: Scope, Claims, Expiration, and Pompe Disease Patent Landscape

US Patent No. 10,857,212 protects a defined cipaglucosidase alfa-type rhGAA composition and its use with miglustat for Pompe disease. The patent is directed to glycan structure, site-specific mannose-6-phosphate content, sialylation, CHO-cell production, and the dosing sequence used for Pombiliti with Opfolda. Its principal commercial relevance is the combination product cipaglucosidase alfa-atga plus miglustat, marketed by Amicus Therapeutics as Pombiliti and Opfolda.

The patent issued January 12, 2021, from an application claiming priority to an August 2014 filing. Its nominal 20-year term is expected to run through August 2035, subject to any patent-term adjustment or other statutory adjustment recorded by the USPTO. The FDA approved Pombiliti and Opfolda on September 28, 2023. Orphan-drug exclusivity runs separately from patent protection and is expected to block approval of competing cipaglucosidase alfa products for the same indication until September 28, 2030.[1-4]

What does US Patent 10,857,212 protect?

US 10,857,212 has two principal claim categories:

1. Method claims covering treatment of Pompe disease with miglustat and a specified CHO-derived rhGAA composition.
2. Composition claims covering the rhGAA product itself, independent of the treatment method.

The patent does not broadly claim every recombinant GAA product or every use of miglustat in Pompe disease. Its enforceable scope depends on the accused product satisfying multiple structural and analytical limitations simultaneously.

Claim feature	Required limitation
Disease	Pompe disease
Enzyme	Recombinant human acid alpha-glucosidase, or rhGAA
Cell substrate	Chinese hamster ovary, or CHO, cells
Sequence	At least 95% identity to SEQ ID NO: 1 or SEQ ID NO: 5
N-glycosylation sites	Sites corresponding to N84, N177, N334, N414, N596, N826 and N869
Glycan distribution	40%-60% complex-type N-glycans
Key targeting feature	At least about 0.5 mol bis-M6P per mol rhGAA at N84
Treatment combination	rhGAA administered with miglustat
Administration route	Intravenous rhGAA and oral miglustat in dependent claims
Dose	rhGAA at about 5-20 mg/kg; miglustat at 130 mg or 260 mg
Infusion timing	Approximately four-hour infusion beginning about one hour after miglustat
Fasting	At least two hours before and after miglustat in a dependent claim

The claim set therefore combines product-by-process characteristics, molecular sequence identity, glycan analytics, and clinical administration parameters.

How broad is independent claim 1?

Independent claim 1 is a narrow method-of-treatment claim with a substantial cumulative limitation burden.

An accused treatment would generally need to involve:

• A patient with Pompe disease.
• Administration of miglustat.
• Administration of a CHO-produced rhGAA composition.
• An rhGAA sequence meeting the 95% identity requirement.
• The seven specified potential N-glycosylation sites.
• A complex N-glycan fraction between 40% and 60%.
• At least approximately 0.5 mol of bis-M6P at N84 per mol of rhGAA.

The claim is not limited to the brand name Pombiliti. A competing product could fall within claim 1 if its molecule and glycan profile satisfy the limitations, even if it uses a different commercial name. Conversely, a product with the same therapeutic purpose could avoid literal infringement by failing one required limitation, such as the N84 bis-M6P threshold or the 40%-60% complex-glycan range.

The phrase "about" creates a range-of-equivalents and claim-construction issue. The numerical boundaries are not necessarily exact chemical cutoffs, but prosecution history, specification examples, analytical variability, and customary measurement error would influence the permitted range.

What do the composition claims cover?

Claims 14-31 cover the rhGAA composition without requiring co-administration with miglustat. This creates a more commercially significant product claim than the method claims because it can reach the enzyme composition itself before considering the clinical use.

Claim 14 repeats the principal composition limitations:

• CHO-cell production.
• The seven specified glycosylation sites.
• 40%-60% complex-type N-glycans.
• At least approximately 0.5 mol bis-M6P at N84.
• At least 95% sequence identity to SEQ ID NO: 1 or SEQ ID NO: 5.

Dependent claims narrow the composition using additional glycan specifications. The most commercially relevant limitations include:

Claims	Additional limitation
15, 19	At least 4 mol or approximately 4-5.4 mol sialic acid per mol rhGAA
16	0.4-0.6 mol mono-M6P at N177
17	0.4-0.6 mol bis-M6P at N414
18	0.3-0.4 mol mono-M6P at N414
20	0.9-1.2 mol sialic acid at N334
21	0.8-0.9 mol sialic acid at N596
22	1.5-1.8 mol sialic acid at N826
24, 25, 27, 28, 30, 31	Approximately 0.8 mol bis-M6P at N84
26, 29	Combined sialic-acid and site-specific glycan profile

Claims 24-31 are particularly important because they narrow the N84 bis-M6P requirement to approximately 0.8 mol per mol of rhGAA. These claims may provide fallback positions if the broader "at least about 0.5 mol" limitation is challenged.

How does the patent use glycan structure to distinguish cipaglucosidase alfa?

The patent relies on glycan engineering to improve uptake of rhGAA by lysosomal mannose-6-phosphate receptors. Bis-M6P refers to a glycan carrying two mannose-6-phosphate residues. Mono-M6P carries one such residue. The claimed composition also controls sialic acid content and complex-type N-glycan content.

The relevant technical distinction is not merely the amino-acid sequence of GAA. It is the combination of:

• CHO expression;
• glycosylation-site occupancy;
• bis-M6P and mono-M6P distribution;
• site-specific sialylation; and
• the overall complex-glycan percentage.

That approach makes the patent potentially relevant to biologic comparability and biosimilar analysis. A competitor could have a highly similar GAA amino-acid sequence but a materially different glycan profile. The competitor might then avoid literal infringement of the composition claims while still facing regulatory comparability questions.

The patent’s reliance on average molar quantities also creates evidentiary issues. Testing would likely require batch-level glycan characterization, site-specific glycopeptide analysis, M6P quantification, sialic-acid analysis, and confirmation of the production cell line.

What are the method-of-use limitations?

The method claims cover treatment with miglustat and rhGAA. Dependent claims 11-13 add a specific administration sequence:

1. Oral miglustat at 130 mg or 260 mg.
2. Intravenous rhGAA at approximately 5-20 mg/kg.
3. An approximately four-hour enzyme infusion.
4. Infusion beginning approximately one hour after miglustat.
5. Fasting for at least two hours before and after miglustat.

These limitations track the approved Pombiliti and Opfolda regimen. The FDA label states that miglustat is administered before the cipaglucosidase alfa infusion and that the enzyme is administered intravenously at weight-based dosing.[1]

A competitor may face a different infringement profile depending on its regimen. A method claim may be harder to assert against a product used outside the claimed timing, dose, or fasting conditions. The composition claims reduce that design-around opportunity because they do not require miglustat administration.

When does US 10,857,212 lose patent protection?

Milestone	Date or status
Earliest priority	August 2014
Patent grant	January 12, 2021
Nominal patent expiration	August 2035
FDA approval of Pombiliti and Opfolda	September 28, 2023
Orphan exclusivity	Expected through September 28, 2030
Post-expiration exposure	Subject to patent-term adjustment, terminal disclaimer, and other USPTO records

The patent’s expiration is later than the orphan-exclusivity period. A competing product could therefore face two separate barriers:

• FDA orphan exclusivity until 2030; and
• patent protection potentially through 2035.

The patent term does not automatically prevent all competing Pompe treatments. It principally affects products that practice the claimed molecule, glycan profile, composition, or treatment combination.

What is the Orange Book status of US 10,857,212?

Pombiliti is a biologic product, so its primary patent and exclusivity framework is not identical to that for a conventional small-molecule drug listed in the Orange Book. Biologic patent information is generally analyzed through FDA biologics records, product labeling, patent disclosures, and the Biologics Price Competition and Innovation Act framework rather than relying solely on Orange Book small-molecule listings.[2,5]

For a biologic such as cipaglucosidase alfa, relevant regulatory records include:

• FDA approval and labeling;
• the Purple Book;
• biologic reference-product exclusivity;
• patent information supplied by the reference-product sponsor;
• any 351(k) biosimilar application activity; and
• patent litigation under the BPCIA patent-exchange process.

US 10,857,212 remains commercially relevant whether or not a patent database displays it in the same manner as an Orange Book-listed small-molecule patent.

Which companies compete with cipaglucosidase alfa?

The principal approved enzyme-replacement competitors are Sanofi’s alglucosidase alfa and avalglucosidase alfa.

Product	Active enzyme	Company	Approved Pompe use	Key competitive point
Pombiliti plus Opfolda	Cipaglucosidase alfa-atga plus miglustat	Amicus Therapeutics	Late-onset Pompe disease in adults	Combination regimen; engineered glycan profile
Nexviazyme	Avalglucosidase alfa-ngpt	Sanofi	Late-onset Pompe disease and broader Pompe populations under labeling	Enhanced M6P targeting; different molecule and patent estate
Lumizyme/Myozyme	Alglucosidase alfa	Sanofi	Pompe disease	Earlier-generation rhGAA enzyme replacement

Nexviazyme is the closest product-level competitor because it also uses glycoengineering to improve lysosomal targeting. Its molecule, manufacturing process, clinical regimen, and patent estate are distinct from the claims of US 10,857,212. A Nexviazyme product does not automatically infringe merely because it is a CHO-produced rhGAA therapy.

Alglucosidase alfa is also relevant as prior technology and market competition, but its glycan composition and sequence profile differ from the narrowly claimed combination in US 10,857,212.[1,6]

How strong is the patent estate for Pombiliti and Opfolda?

US 10,857,212 has several strength factors:

• It includes both method and composition claims.
• The composition claims do not depend on use with miglustat.
• The claims identify multiple analytical features rather than relying only on a broad therapeutic concept.
• The dependent claims provide narrower fallback positions for site-specific M6P and sialic-acid measurements.
• The claims align closely with the commercial product and approved regimen.

The principal vulnerability is claim complexity. Each required limitation creates a potential noninfringement position. The patent also depends on analytical measurements that may vary by assay, reference standard, batch, glycopeptide mapping method, and treatment of heterogeneous glycoforms.

Potential validity issues could include:

• written description support for the full numerical ranges;
• enablement across all sequences with at least 95% identity;
• anticipation by prior CHO-derived rhGAA compositions;
• obviousness based on known M6P receptor targeting and glycoengineering;
• indefiniteness of terms such as "about," "potential N-glycosylation site," and average molar content;
• adequate support for site-specific glycan measurements; and
• claim construction concerning whether the production-cell limitation is a process limitation or a structural product limitation.

The composition claims are stronger for product enforcement, but they may require extensive discovery and laboratory testing. The method claims are easier to tie to labeled use but can be avoided by modifying the regimen.

What generic or biosimilar entry risks exist?

A conventional generic pathway is unlikely to be the principal route for a competing cipaglucosidase alfa product because cipaglucosidase alfa is a biologic enzyme. A biosimilar applicant would likely pursue the 351(k) pathway, subject to reference-product exclusivity, orphan exclusivity, patent litigation, and FDA requirements for analytical, pharmacokinetic, immunogenicity, and clinical similarity.

The main entry scenarios are:

Biosimilar cipaglucosidase alfa

A biosimilar with the same or highly similar glycan profile could face composition-claim risk. A molecule with a different glycan profile could reduce literal infringement risk but face a greater comparability burden.

Alternative rhGAA product

A competitor could use a different sequence, expression system, glycan-engineering platform, or M6P distribution. This approach may avoid the claims but would not necessarily avoid separate patents covering GAA variants, manufacturing systems, formulations, dosing, or receptor-targeting technologies.

Different treatment regimen

A product using rhGAA without miglustat could avoid the method claims but could still implicate composition claims. Changing the dose or infusion timing would have limited value against claims 14-31.

Noninfringing enzyme replacement

Sanofi’s products represent a separate enzyme and patent pathway. Competition from alglucosidase alfa or avalglucosidase alfa does not depend on practicing the claimed cipaglucosidase composition.

Are there Paragraph IV challenges to US 10,857,212?

Paragraph IV certification is the principal mechanism for conventional ANDA challenges to Orange Book-listed small-molecule patents. It is not the normal pathway for a biologic such as cipaglucosidase alfa. A competing biologic would generally proceed through the BPCIA framework and a 351(k) application rather than an ANDA Paragraph IV filing.

Publicly reported challenges should therefore be evaluated through:

• FDA biologic application records;
• Purple Book activity;
• BPCIA patent-exchange notices;
• federal complaints involving Amicus and cipaglucosidase alfa;
• SEC filings; and
• district-court docket records.

There is no commercially relevant basis to treat a conventional Paragraph IV challenge as the expected entry mechanism for Pombiliti.

What litigation or settlement agreements affect the patent?

The patent’s practical litigation risk is likely to arise from a future biosimilar or competing engineered rhGAA product. The relevant disputes would concern:

• whether the accused molecule meets the 95% sequence-identity requirement;
• whether the accused product is produced in CHO cells;
• whether its glycan profile falls within the 40%-60% complex-glycan range;
• whether N84 contains at least approximately 0.5 mol bis-M6P;
• the meaning of "about";
• whether averages are calculated across batches or individual molecules; and
• whether the claims cover a product manufactured by a different process but having the same final glycan attributes.

No publicly established settlement term should be assumed without a reported court docket, SEC disclosure, or FDA-linked patent record. The absence of a reported Paragraph IV proceeding is consistent with the product’s biologic status and does not establish that the patent is unchallenged.

How does US 10,857,212 compare with competing Pompe patents?

Issue	US 10,857,212	Typical competing Pompe patent
Primary subject	Glycoengineered rhGAA and use with miglustat	Enzyme sequence, variants, formulation, manufacturing, or treatment
Product coverage	Yes, claims 14-31	Depends on family
Method coverage	Yes, claims 1-13 and 24, 26-28	Often dosing or indication-specific
Key biomarker	M6P and sialic-acid distribution	May use different structural or process limitations
Manufacturing limitation	CHO production	May cover host cells, purification, or glycoengineering
Regulatory relevance	Pombiliti/Opfolda regimen and product	Depends on approved product
Main design-around	Alter sequence, glycan profile, host cell, or product attributes	Depends on claim construction

Key Takeaways

• US 10,857,212 is a product-and-method patent centered on a specific glycoengineered rhGAA composition.
• Its commercial target is the cipaglucosidase alfa component of Pombiliti, used with Opfolda, or miglustat.
• The core limitations are CHO production, 95% sequence identity, seven GAA glycosylation sites, 40%-60% complex N-glycans, and at least approximately 0.5 mol bis-M6P at N84.
• Composition claims 14-31 are more important for product enforcement than the treatment claims because they do not require miglustat.
• Dependent claims add site-specific M6P, sialic-acid, dosing, infusion, and fasting requirements.
• Nominal patent protection is expected through August 2035, while FDA orphan exclusivity is expected through September 2030.
• Paragraph IV is not the expected challenge route because cipaglucosidase alfa is a biologic; future challengers would more likely use the BPCIA and 351(k) framework.
• The main design-around strategies are changing the glycan profile, sequence, production host, or final composition.
• The patent has strong product relevance but also depends on complex analytical limitations that could create infringement and validity disputes.

FAQs About US Patent 10,857,212 and Pombiliti

Does US 10,857,212 cover miglustat by itself?

No. The patent does not broadly claim miglustat as a standalone product. Its method claims require miglustat to be administered with the specified rhGAA composition.

Does the patent cover Nexviazyme?

Not automatically. Nexviazyme is a different engineered rhGAA product with its own sequence, glycan profile, manufacturing process, labeling, and patent estate. Infringement would depend on whether it satisfies every limitation of an asserted claim.

Can a biosimilar avoid this patent by using a different cell line?

Potentially. The independent claims expressly require rhGAA molecules produced in CHO cells. A product made in a different host could challenge that limitation, although separate patents and regulatory comparability requirements could remain relevant.

Is the approximately 0.8 mol bis-M6P limitation required in every claim?

No. The broader independent claims require at least approximately 0.5 mol bis-M6P at N84. The approximately 0.8 mol limitation appears in dependent claims 24, 25, and 27-31.

Does patent expiration end all exclusivity for Pombiliti?

No. Patent expiration and regulatory exclusivity are separate. Other patents, biologic reference-product exclusivity, orphan exclusivity, regulatory requirements, and additional patent-family members could affect competitive entry.

References

1. U.S. Food and Drug Administration. (2023). Pombiliti (cipaglucosidase alfa-atga) and Opfolda (miglustat) prescribing information. FDA.

2. U.S. Food and Drug Administration. (2024). Purple Book: Database of licensed biological products. FDA.

3. United States Patent and Trademark Office. (2021). U.S. Patent No. 10,857,212, Recombinant human acid alpha-glucosidase and uses thereof. USPTO.

4. Amicus Therapeutics, Inc. (2024). Annual report pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934. U.S. Securities and Exchange Commission.

5. Biologics Price Competition and Innovation Act of 2009, Pub. L. No. 111-148, §§ 7001-7003, 124 Stat. 119, 804-812.

6. U.S. Food and Drug Administration. (2021). Nexviazyme (avalglucosidase alfa-ngpt) prescribing information. FDA.

Drugs Protected by US Patent 10,857,212

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						THE TREATMENT OF POMPE PATIENTS

International Family Members for US Patent 10,857,212

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	107277
Australia	2016381832
Australia	2024200071
Australia	2026201393
Brazil	112018013151
Canada	3010205
Chile	2018001773