United States Patent 8,026,284: Scope, Claims, Expiration, and Cysteamine Patent Landscape
U.S. Patent No. 8,026,284 protects administration of enterically delivered cysteamine or cystamine, principally through twice-daily dosing, delivery to the small intestine, delayed release above approximately pH 4.5, and treatment of cystinosis and selected neurodegenerative or metabolic conditions. The patent issued September 27, 2011, and has a nominal expiration date of November 30, 2026, subject to any applicable patent-term adjustment.
The patent is directed to the product concept later commercialized in delayed-release cysteamine products such as Procysbi. Its strongest practical coverage is method-of-treatment coverage tied to an enteric or delayed-release cysteamine formulation. It does not claim every cysteamine product. Its enforceability depends on whether an accused product satisfies the delivery, dosing, timing, and therapeutic-use limitations recited in the asserted claim.
What does U.S. Patent 8,026,284 cover?
The patent covers methods of administering cysteamine, cystamine, or pharmaceutically acceptable salts using a formulation that increases delivery to the small intestine. The claims combine four principal concepts:
- Reduced dosing frequency, particularly twice-daily administration.
- Enteric or pH-dependent delivery.
- Specific dosing levels, including approximately 1.35 g/m²/day.
- Treatment of cystinosis and other specified diseases.
The patent is primarily a method patent. The claims do not broadly claim a composition consisting solely of cysteamine and an enteric coating. Instead, they claim administering such a composition for specified purposes or under specified pharmacokinetic conditions.
Patent identification and timeline
| Item |
Data |
| Patent |
U.S. Patent No. 8,026,284 |
| Title |
Methods and compositions for treating cystinosis |
| Issue date |
September 27, 2011 |
| Patent family technology |
Enteric or delayed-release cysteamine |
| Principal therapeutic area |
Cystinosis; neurodegenerative and metabolic disorders |
| Earliest priority |
November 30, 2006 |
| Nominal expiration |
November 30, 2026 |
| Likely commercial product relevance |
Delayed-release cysteamine, including Procysbi |
| Claim type |
Method of treatment and administration |
| FDA relevance |
Potentially listed for delayed-release cysteamine products |
The expiration date should be distinguished from regulatory exclusivity. Patent expiration is governed by the Patent Act and any patent-term adjustment. FDA orphan-drug exclusivity and other regulatory exclusivities are separate rights and do not extend the patent term.
How are the 27 claims structured?
Claims 1 through 3 establish the principal twice-daily administration concept. Claims 4 through 9 focus on enteric coatings and disease treatment. Claims 10 through 15 address reduced dosing frequency, delayed pharmacokinetics, and gastrointestinal delivery. Claims 16 through 23 add disease and combination-treatment limitations. Claims 24 through 27 narrow the twice-daily or reduced-frequency methods by adding coating, gastric-acid, or leukocyte-cystine effects.
Independent claim analysis
| Claim |
Core limitation |
Commercial significance |
| 1 |
Cysteamine or cystamine administered twice daily using a composition that increases small-intestinal delivery |
Core dosing and delivery claim |
| 4 |
Enteric-coated cysteamine or cystamine providing increased small-intestinal delivery |
Core formulation-use claim |
| 7 |
Enterically coated cysteamine for cystinosis |
Disease-specific claim |
| 8 |
Enterically coated cysteamine for neurodegenerative disease |
Broad but potentially vulnerable disease-use claim |
| 9 |
Enterically coated cysteamine as a hepatoprotective agent |
Broad therapeutic-use claim |
| 10 |
Small-intestinal delivery with administration less than four times daily |
Captures twice-daily and some three-times-daily regimens |
| 11 |
Enteric formulation producing increased time to Cmax |
Pharmacokinetic claim |
| 12 |
Total daily dose of approximately 1.35 g/m²/day |
Dose-specific limitation |
Claims 1 through 3: Twice-daily dosing
Claim 1 requires:
- cysteamine, cystamine, or a pharmaceutically acceptable salt;
- administration to a patient in need;
- a pharmaceutical composition;
- twice-daily administration; and
- increased delivery to the small intestine.
Claims 2 and 3 narrow the dose to approximately 0.5 to 1.0 g/m² per dose and, more narrowly, approximately 0.7 to 0.8 g/m² per dose.
A product administered twice daily would not infringe claim 1 solely because it contains cysteamine. The formulation must also increase delivery to the small intestine. The dosing frequency and delivery profile are cumulative limitations.
Claims 4 through 6: Enteric coating and pH-dependent release
Claim 4 requires an enteric coating that increases delivery of cysteamine or cystamine to the small intestine. Claim 5 lists coating materials, including:
- shellac;
- cellulose acetate phthalate;
- polyvinyl acetate phthalate;
- hydroxypropyl methylcellulose phthalate;
- hydroxypropyl methylcellulose acetate succinate;
- cellulose-based phthalates and succinates; and
- acrylic and methacrylic acid polymers and copolymers.
Claim 6 requires release in the small intestine or another gastrointestinal region with a pH greater than 4.5.
The claim language creates two potential infringement routes. A formulation may fall within the claim because it uses one of the expressly listed coatings. It may also fall within the broader functional language if the coating increases intestinal delivery and releases the active ingredient above the specified pH threshold.
Claims 7 through 9: Disease-use coverage
Claim 7 covers treatment of cystinosis. This is the most commercially relevant disease claim because cysteamine is an established treatment for nephropathic cystinosis.
Claim 8 covers neurodegenerative diseases, including the Huntington's disease and Parkinson's disease embodiments in claim 18. Claim 9 covers use as a hepatoprotective agent.
The neurodegenerative and hepatoprotective claims are broader in therapeutic scope but may face greater validity and enforcement risks. A patentee would need to establish that the accused use falls within the claimed therapeutic category and that the specification adequately supports the relevant disease or therapeutic effect.
Claims 10 through 15: Reduced frequency and gastrointestinal location
Claim 10 covers administration less than four times daily. This language reaches twice-daily and three-times-daily administration, provided the formulation increases small-intestinal delivery.
Claims 13 and 14 identify the target regions as the proximal or mid-small intestine, including the duodenum, jejunum, and mid-ileum. Claim 15 uses a functional pH limitation of greater than 4.5.
These claims are important for product differentiation. An immediate-release cysteamine product administered four or more times daily would be less likely to satisfy the central delivery and frequency limitations. A delayed-release product administered twice daily presents a closer infringement risk.
Claim 11: Increased time to Cmax
Claim 11 requires an enteric formulation that provides an increased time to maximum plasma concentration compared with non-enteric cysteamine or cystamine.
This claim depends on a comparative pharmacokinetic analysis. The relevant comparison is not simply whether the product has a measurable Cmax. The question is whether the enteric formulation delays the time at which Cmax occurs relative to an appropriate non-enteric comparator.
Potential disputes include:
- the identity of the comparator;
- dose normalization;
- fed versus fasted conditions;
- patient population;
- sampling schedule; and
- statistical significance.
Claims 24 through 27: Narrowed performance limitations
Claim 24 adds an enteric coating to claims 1 through 3 or claim 10. Claim 25 identifies the coating materials listed in claim 5.
Claim 26 requires decreased gastric acid levels compared with non-coated cysteamine. Claim 27 requires a significant reduction in leukocyte cystine levels compared with non-coated cysteamine.
These claims may provide stronger factual infringement theories but also create proof burdens. The patentee would likely need clinical or pharmacodynamic data showing the claimed comparative effects.
What formulations are protected by Patent 8,026,284?
The patent does not require one particular enteric polymer. It lists multiple coating classes and also uses functional language directed to intestinal delivery and release above pH 4.5.
Potentially covered formulation categories include:
| Formulation type |
Relevance |
| Enteric-coated capsules |
Directly aligned with claims 4, 5, and 24 |
| Enteric-coated tablets |
Potentially covered if the delivery and release limitations are met |
| Multiparticulates with enteric polymer coating |
Potentially covered under functional delivery language |
| Cysteamine bitartrate with delayed release |
Commercially important product category |
| pH-sensitive acrylic polymer systems |
Expressly identified in claim 5 |
| Cellulose-phthalate systems |
Expressly identified in claim 5 |
| HPMCAS systems |
Expressly identified in claim 5 |
| Shellac-coated systems |
Expressly identified in claim 5 |
A formulation that uses a different polymer may still raise infringement issues if it increases small-intestinal delivery, releases above pH 4.5, delays Cmax, or supports the claimed reduced-frequency regimen.
How strong is the patent estate for delayed-release cysteamine?
Patent 8,026,284 is commercially meaningful but not comprehensive. Its principal strengths are:
- direct coverage of twice-daily cysteamine administration;
- alignment with delayed-release cysteamine product design;
- specific coverage of small-intestinal delivery;
- support from dose and gastrointestinal-location dependent claims; and
- disease-specific cystinosis claims.
Its principal vulnerabilities are:
- functional terms such as "increases delivery";
- the comparative term "increased time to Cmax";
- the term "significant reduction" in claim 27;
- broad claims covering multiple diseases and therapeutic effects;
- potential prior art involving enteric cysteamine or cystamine formulations; and
- the requirement to prove the accused product's delivery profile, not merely its label or ingredient list.
The patent is stronger against a labeled delayed-release cysteamine product that uses twice-daily dosing for cystinosis than against an unapproved or off-label product whose intestinal delivery and pharmacokinetic profile are not established.
When does cysteamine patent protection expire?
The nominal expiration date for Patent 8,026,284 is November 30, 2026, based on the earliest effective priority date. The patent does not provide perpetual protection for delayed-release cysteamine. After expiration, a generic manufacturer could potentially market a product that practices the claimed method, subject to other unexpired patents, FDA approval requirements, and regulatory exclusivity.
The relevant exclusivity framework is:
| Right |
Approximate status |
| Patent 8,026,284 |
Nominally expires November 30, 2026 |
| Procysbi orphan exclusivity |
Began with FDA approval in April 2013 and generally ran for seven years |
| FDA approval |
Procysbi approved April 30, 2013 |
| Generic approval pathway |
ANDA or other applicable pathway, depending on product and labeling |
| Post-expiration risk |
Other formulation, method, or manufacturing patents may remain relevant |
A generic launch before November 2026 would require avoiding, invalidating, or otherwise resolving the patent rights asserted against the product.
What is the Orange Book status of Patent 8,026,284?
Patent 8,026,284 has been associated with the delayed-release cysteamine product Procysbi and is relevant to Orange Book patent analysis for that product. Orange Book listing does not establish validity or infringement. It identifies patents that the NDA holder or FDA recognizes for the approved product under the Hatch-Waxman framework.
An ANDA applicant seeking approval for a product with a listed patent may submit:
- a Paragraph III certification accepting approval after patent expiration;
- a Paragraph IV certification asserting that the patent is invalid, unenforceable, or not infringed; or
- another certification where legally applicable.
A Paragraph IV notice can trigger patent litigation and a potential 30-month stay of approval under the Hatch-Waxman Act. The stay does not automatically prevent litigation-based settlement or an earlier launch arrangement.
Which companies are challenging delayed-release cysteamine patents?
Generic competition is likely to focus on manufacturers seeking approval for delayed-release cysteamine bitartrate or therapeutically equivalent products. Public patent disputes involving Procysbi have included ANDA litigation concerning later Raptor and Horizon patent rights, including patents directed to delayed-release cysteamine formulations and pharmacokinetic performance.
The relevant competitive groups are:
- The branded product sponsor and its successors or licensees.
- Generic companies filing ANDAs for delayed-release cysteamine.
- Suppliers of cysteamine salts and enteric-release technologies.
- Companies developing alternative cystinosis treatments or delivery systems.
A complete current list of Paragraph IV filers and live district-court dockets is not established by the claim text alone. Patent 8,026,284 should therefore be analyzed together with the current FDA Orange Book, ANDA notices, USPTO maintenance records, and federal court dockets before making a launch or litigation decision.
How does Patent 8,026,284 compare with immediate-release cysteamine?
| Issue |
Immediate-release cysteamine |
Delayed-release cysteamine under Patent 8,026,284 |
| Typical administration |
More frequent dosing |
Twice daily or less than four times daily |
| Release location |
May begin in stomach or upper gastrointestinal tract |
Designed for small-intestinal release |
| Enteric coating |
Generally absent |
Central claim feature |
| Gastric exposure |
Greater potential exposure |
Reduced gastric exposure is contemplated |
| Cmax timing |
Earlier relative to delayed-release product |
Increased time to Cmax |
| Commercial example |
Cystagon-type therapy |
Procysbi-type therapy |
| Patent risk under 8,026,284 |
Lower if no enteric delivery or reduced frequency |
Higher if all claim limitations are met |
An immediate-release product may still create risk under a broad method claim if it is used in the claimed dosing regimen and demonstrably increases small-intestinal delivery. In practice, the enteric and pharmacokinetic limitations materially distinguish the patented product concept.
What generic launch risks exist after patent expiration?
Patent expiration will remove one barrier but will not guarantee immediate generic entry. Remaining issues may include:
- other unexpired formulation patents;
- manufacturing-process patents;
- salt or particle-size patents;
- FDA requirements for demonstrating bioequivalence;
- labeling restrictions for patented indications;
- pediatric or orphan-disease requirements;
- supply of pharmaceutical-grade cysteamine;
- enteric-coating reproducibility; and
- commercial difficulty competing in a small cystinosis market.
The most likely launch scenarios are:
| Scenario |
Timing and risk |
| Paragraph III filing |
Approval delayed until patent expiration |
| Paragraph IV filing |
Earlier approval possible, but litigation and 30-month-stay risk apply |
| Label carve-out |
Possible only if patented use can be removed while preserving an approvable label |
| Post-expiration launch |
Lower risk from Patent 8,026,284, but other patents must be cleared |
| Reformulated product |
May avoid certain coating or pharmacokinetic limitations while creating new regulatory work |
Key Takeaways
- Patent 8,026,284 protects methods using enterically delivered cysteamine or cystamine, especially twice-daily administration.
- The strongest claims require increased delivery to the small intestine, release above pH 4.5, or delayed time to Cmax.
- Claims 7 and 16 are particularly relevant to cystinosis treatment.
- Claims 8, 9, 17, and 18 extend the patent to neurodegenerative disease and hepatoprotective uses but may present greater validity and proof issues.
- The patent lists numerous coating materials, including CAP, PVAP, HPMCAS, shellac, and acrylic or methacrylic polymers.
- The nominal patent expiration date is November 30, 2026.
- FDA orphan-drug exclusivity for Procysbi was separate from patent protection and generally expired seven years after the April 30, 2013 approval.
- Generic risk depends on the full Procysbi patent estate, not Patent 8,026,284 alone.
- A delayed-release cysteamine product administered twice daily for cystinosis presents the highest infringement exposure under the patent.
FAQs About U.S. Patent 8,026,284
Does Patent 8,026,284 claim cysteamine itself?
No. The claims primarily cover methods of administering cysteamine, cystamine, or their pharmaceutically acceptable salts using specific dosing, enteric-delivery, pharmacokinetic, or therapeutic-use conditions.
Does an enteric coating automatically infringe Patent 8,026,284?
No. The accused product must satisfy the applicable claim limitations, such as increased small-intestinal delivery, release above pH 4.5, dosing frequency, disease treatment, or delayed time to Cmax.
Can a generic use a different enteric polymer?
Possibly. A different polymer may avoid a specific composition limitation, but the product could still implicate broader functional limitations concerning intestinal delivery, release location, dosing frequency, or pharmacokinetic performance.
Is a twice-daily cysteamine product outside the patent if it is used for a disease other than cystinosis?
Not necessarily. Claims 1 and 10 do not require cystinosis. Claims 16 through 18 add disease-specific limitations, but the broader administration claims may apply if the delivery and dosing requirements are met.
What patent should be reviewed with Patent 8,026,284 for a Procysbi launch analysis?
The analysis should include the complete Orange Book listing for Procysbi, continuation and divisional patents, later formulation and pharmacokinetic patents, current maintenance status, and any active Hatch-Waxman litigation or settlement agreements.
References
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U.S. Patent No. 8,026,284. (2011). Methods and compositions for treating cystinosis. United States Patent and Trademark Office.
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U.S. Food and Drug Administration. (2013). Procysbi (cysteamine bitartrate) delayed-release capsules: Prescribing information. FDA.
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U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, Orange Book. FDA.
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U.S. Code, 21 U.S.C. § 355. (2024). Applications for FDA approval of new drugs.
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U.S. Code, 35 U.S.C. §§ 154, 271, and 282. (2024). Patent term, infringement, and defenses.
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United States Patent and Trademark Office. (n.d.). Patent Center and Patent Examination Data System. USPTO.
