US Patent 10,016,372: Donepezil Transdermal Delivery Claims, Scope, Expiration, and Competitive Patent Landscape
US Patent No. 10,016,372 protects a transdermal donepezil method in which donepezil hydrochloride or another donepezil salt is converted into free-base donepezil inside the patch reservoir after application to the skin. The patent is directed to the formulation architecture and administration method used for a weekly donepezil patch, rather than to donepezil as a molecule.
The strongest claim combination is claim 8 and its dependents. It requires donepezil hydrochloride, sodium bicarbonate, glycerol, triethyl citrate, lauryl lactate, and sorbitan monolaurate in the reservoir or associated adhesive system. Claims 1 and 17-18 are broader because they cover a donepezil salt and alkaline salt generally, with dependent claims narrowing the formulation to donepezil hydrochloride and sodium bicarbonate.
ADLARITY, Corium's donepezil transdermal system, was approved by the FDA in September 2022 for the treatment of dementia of the Alzheimer’s type [2]. Patent No. 10,016,372 is relevant to the product’s formulation and method-of-use protection, but it does not prevent all transdermal donepezil products. A design-around product could attempt to avoid the in situ salt-to-base conversion requirement, the specified excipients, or the claimed concentration ranges.
What does US Patent 10,016,372 cover?
The patent covers a transdermal drug-delivery method with four central elements:
- A transdermal system containing a drug reservoir.
- A donepezil salt in the reservoir.
- An alkaline salt in the reservoir.
- In situ generation of donepezil base after the system is applied to the skin.
The claimed chemistry is a neutralization reaction. Donepezil hydrochloride reacts with sodium bicarbonate to generate free-base donepezil, with hydrochloride-derived acid neutralized by bicarbonate. The free base is the claimed permeating species delivered through the skin.
What is the inventive concept?
The patent’s central technical proposition is that a patch can store donepezil in salt form, then generate the more skin-permeable free base within the reservoir. This approach addresses formulation and stability problems associated with loading a patch directly with preformed donepezil base.
The claims therefore combine:
- Chemical conversion inside the patch.
- Transdermal administration.
- Reservoir-based drug delivery.
- Defined solvent and permeation-enhancing systems.
- Weekly or near-weekly dosing capability.
- Specific concentration windows for drug, alkaline salt, polymer, and excipients.
The claims are method claims. They do not broadly claim every donepezil patch, every donepezil formulation, or donepezil base as a chemical entity.
How do claims 1 and 8 differ?
Claims 1 and 8 are the two principal independent claims.
| Feature |
Claim 1 |
Claim 8 |
| Dosage form |
Transdermal delivery system |
Transdermal delivery system |
| Drug salt |
Donepezil salt |
Donepezil hydrochloride |
| Alkaline agent |
Alkaline salt |
Sodium bicarbonate |
| In situ conversion |
Required |
Required |
| Solvent composition |
Not specified |
Glycerol, triethyl citrate, lauryl lactate, and sorbitan monolaurate |
| Weekly dosing |
Not required |
Not required |
| Free-base delivery |
Required |
Required |
| Breadth |
Broader |
Narrower but more formulation-specific |
Claim 1 can cover a formulation using a donepezil salt other than hydrochloride and an alkaline salt other than sodium bicarbonate, provided the other limitations are met.
Claim 8 is narrower because it requires a particular formulation system. A competing product that uses donepezil hydrochloride and sodium bicarbonate but omits one of the four named solvent components may avoid literal infringement of claim 8, although it could remain exposed under claim 1 or another patent.
What do the dependent claims add?
Claims 2 and 14: Weekly administration
Claim 2 requires application once weekly. Claim 14 requires a reservoir containing enough donepezil hydrochloride to deliver 1-25 mg of donepezil base every 24 hours for at least approximately one week.
These claims tie the formulation to extended-duration administration. Claim 2 is a dosing-frequency limitation. Claim 14 adds a quantitative drug-loading and duration requirement.
A product administered every seven days could implicate these claims if it also meets the salt, alkaline-salt, conversion, and dose limitations. A product applied more frequently would not literally meet claim 2, but the weekly limitation does not restrict claim 1.
Claim 3: Dose delivered to the skin
Claim 3 requires an amount of donepezil salt sufficient to deliver 1-25 mg of donepezil base to the skin over 24 hours.
The phrase "deliver to the skin" is narrower than a claim requiring only drug loading. It focuses on delivery performance rather than the amount initially placed in the reservoir. The claim could raise factual issues concerning measurement methodology, including whether the relevant quantity is drug leaving the reservoir, entering the skin, or systemically absorbed.
Claims 4-5: Excipient combinations
Claim 4 covers a reservoir, contact adhesive, or both containing at least one of:
- Sorbitan monolaurate.
- Triethyl citrate.
- Lauryl lactate.
Claim 5 requires two of:
- Lauryl lactate.
- Triethyl citrate.
- Glycerol.
These are formulation limitations. They may be important in a patent dispute because many transdermal systems use permeation enhancers, plasticizers, solvents, and adhesive modifiers. The claim language can reach excipients located in either the reservoir or contact adhesive, depending on the claim.
Claims 6-7: Donepezil hydrochloride and sodium bicarbonate
Claim 6 requires donepezil hydrochloride and sodium bicarbonate in the reservoir. Claim 7 adds one or both of sorbitan monolaurate and lauryl lactate.
These claims are materially narrower than claim 1, but they align more closely with the commercial formulation disclosed for ADLARITY and therefore may have greater product relevance.
Claims 9-15: Detailed reservoir formulation
Claims 9-15 define a formulation window around claim 8:
| Claim |
Limitation |
| 9 |
25-65 wt% acrylate copolymer |
| 10 |
10-30 wt% donepezil hydrochloride and 0.5-10 wt% sodium bicarbonate |
| 11 |
5-15 wt% triethyl citrate |
| 12 |
1-10 wt% lauryl lactate |
| 13 |
Contact adhesive containing triethyl citrate, lauryl lactate, and sorbitan monolaurate |
| 14 |
Drug quantity sufficient for 1-25 mg/day for at least about one week |
| 15 |
2-20 wt% glycerol |
A competing patch may avoid the narrower claims by shifting one or more components outside the claimed ranges. That strategy does not necessarily avoid claim 1, claim 17, or claim 18, which contain fewer formulation limitations.
Claims 16-18: Concentration and ingredient narrowing
Claims 16 and 18 define:
- 10-30 wt% donepezil salt or donepezil hydrochloride.
- 0.5-10 wt% alkaline salt or sodium bicarbonate.
Claim 17 identifies donepezil hydrochloride and sodium bicarbonate without specifying concentrations.
These claims are important because they create intermediate fallback positions. A patent owner could assert a broad claim such as claim 1 and rely on claims 17-18 if the accused formulation uses the specific salt/base combination and concentration ranges.
What formulation is most exposed under US Patent 10,016,372?
The formulation with the highest apparent claim overlap is a reservoir containing:
- Donepezil hydrochloride.
- Sodium bicarbonate.
- Glycerol.
- Triethyl citrate.
- Lauryl lactate.
- Sorbitan monolaurate.
- Acrylate copolymer.
If the product generates donepezil base after application and delivers approximately 1-25 mg per day for at least one week, it could fall within claims 8-15 and claims 17-18, subject to claim construction and proof of the formulation’s actual composition.
The commercial product does not need to use every limitation in claim 8 to remain potentially exposed to the broader claims. For example, a product using donepezil hydrochloride and sodium bicarbonate without the complete solvent composition could still implicate claims 1, 6, 16, 17, or 18.
When does US Patent 10,016,372 expire?
The patent issued on July 10, 2018 [1]. Its term is generally calculated from the earliest effective nonprovisional filing date, not from the issue date. Public patent records associate the patent family with a January 2014 nonprovisional filing period, producing a nominal expiration in January 2034, subject to patent-term adjustment and any terminal disclaimer reflected in the official USPTO record.
| Event |
Date |
| Earliest relevant nonprovisional filing period |
January 2014 |
| Patent issued |
July 10, 2018 |
| Nominal 20-year term endpoint |
January 2034 |
| FDA approval of ADLARITY |
September 28, 2022 |
| FDA three-year exclusivity for new dosage form |
Generally September 2025, if applicable |
| Expected patent protection period after approval |
Approximately 11 years, subject to official term calculation |
The precise expiration date should be determined from the USPTO patent-term adjustment calculation. FDA regulatory exclusivity and patent term are separate rights. Approval of ADLARITY did not create new chemical entity exclusivity because donepezil was previously approved in oral products.
What is the Orange Book status of US Patent 10,016,372?
ADLARITY is an FDA-approved prescription transdermal system containing donepezil. The FDA Orange Book may list patents associated with the approved product, including method-of-use or formulation-related patents submitted by the NDA holder [3].
An Orange Book listing does not establish that every claim is valid or infringed. It does create a regulatory pathway for a generic applicant filing an ANDA with a Paragraph IV certification. The ANDA applicant would need to address each listed patent through a certification or statement, depending on the patent and the proposed label.
Because US Patent 10,016,372 contains method claims, a central regulatory issue is whether the approved label induces use of the product in a manner covered by the listed claims. A generic applicant could attempt a section viii label carve-out if the patented method is separable from the nonprotected use. That strategy is more difficult where the patented administration method corresponds to the product’s principal or only labeled use.
Which companies are challenging the patent?
No specific Paragraph IV challenger or final litigation outcome is established by the claim text supplied. Public litigation and Orange Book status change over time and must be matched to the current FDA listing and court docket.
A Paragraph IV challenge would likely attack one or more of the following:
- Lack of novelty over earlier donepezil transdermal systems.
- Obviousness of converting donepezil hydrochloride to donepezil base with an alkaline salt.
- Enablement of the broad genus covering different donepezil salts and alkaline salts.
- Written-description support for the full scope of the solvent and excipient combinations.
- Indefiniteness of terms such as "generating ... in situ," "sufficient to deliver," and "for at least about one week."
- Noninfringement based on preformed donepezil base, a different pH-modifying agent, or a separate-layer architecture.
How strong is the patent estate for ADLARITY?
US Patent 10,016,372 is potentially valuable because it claims the product architecture rather than only a single use or isolated formulation. Its strength is highest against a patch that uses the same chemical strategy:
- Donepezil hydrochloride is loaded into the reservoir.
- Sodium bicarbonate is co-located in the reservoir.
- Free-base donepezil is generated after application.
- The system uses the specified solvent and enhancer package.
- The patch delivers drug for approximately one week.
Its limitations are equally clear. A competitor could seek to design around:
- Preloading the reservoir with donepezil base.
- Using a non-alkaline pH modifier.
- Generating free base in a separate layer or during manufacture.
- Using an alternative solvent or permeation-enhancer system.
- Applying the patch at a dosing interval outside the claimed weekly limitation.
- Moving one or more excipients outside the recited weight ranges.
The broadest independent claim still creates risk where a design-around retains both a donepezil salt and an alkaline salt in the reservoir and generates the base after application.
What generic launch scenarios exist?
Scenario 1: Paragraph IV challenge
A generic applicant could file an ANDA with a Paragraph IV certification against listed ADLARITY patents. The filing would trigger notice to the patent holder and could produce a 30-month stay of approval if litigation is timely filed under the Hatch-Waxman Act.
Scenario 2: Carve-out or section viii statement
If a patent covers only a particular method of use, the applicant could attempt to omit the patented instructions from its labeling. This approach is less effective if the patent claims the product’s core approved transdermal administration method.
Scenario 3: Noninfringing patch formulation
A competing company could develop a transdermal donepezil product using preformed donepezil base or a different conversion mechanism. It would still need to assess separate patents covering patch construction, adhesive chemistry, permeation enhancement, stability, and manufacturing.
Scenario 4: Post-expiration entry
A generic or authorized generic could launch after the relevant patent and regulatory exclusivity periods expire, assuming no other listed patent or litigation order blocks approval.
Does biosimilar risk apply to donepezil transdermal products?
No. Donepezil is a small-molecule active ingredient, and ADLARITY is regulated as a new drug product rather than a biologic. The relevant competitive pathway is an ANDA for a generic drug, not a biosimilar application under the Public Health Service Act.
The competitive risks are therefore:
- ANDA Paragraph IV challenges.
- Generic transdermal formulation development.
- Product-by-process or manufacturing design-arounds.
- Authorized generic entry.
- Off-label or alternative dosage-form competition from oral donepezil.
What manufacturing and geographic IP barriers remain?
The patent has US territorial effect. It does not, by itself, establish protection in Europe, Japan, Canada, China, or other markets. Corresponding patent-family members would need separate review for claim scope, prosecution history, term, opposition status, and enforceability.
Manufacturing barriers may arise from:
- Uniform mixing of donepezil hydrochloride and sodium bicarbonate.
- Control of in-reservoir neutralization during storage.
- Maintaining adhesive cohesion over a seven-day wear period.
- Controlling crystallization or precipitation of generated donepezil base.
- Managing skin flux and dose uniformity.
- Maintaining stability across temperature and humidity conditions.
- Producing multilayer systems at commercial scale.
These technical barriers may support commercial protection even where a competitor avoids literal infringement of the patent.
What licensing deals affect the patent?
The patent record identifies the patent owner or assignee and its prosecution chain, but the claim text does not establish a license, assignment, co-development agreement, or royalty transaction. Corium is associated with ADLARITY commercialization and development. No licensing arrangement should be treated as affecting freedom to operate unless documented in an SEC filing, patent assignment record, transaction announcement, or court filing.
Key Takeaways
- US Patent 10,016,372 protects transdermal delivery of donepezil base generated in situ from a donepezil salt and an alkaline salt.
- Claim 1 is the principal broad method claim.
- Claim 8 is narrower and targets a formulation containing donepezil hydrochloride, sodium bicarbonate, glycerol, triethyl citrate, lauryl lactate, and sorbitan monolaurate.
- Claims 2 and 14 address weekly administration and sustained delivery.
- Claims 9-15 establish detailed excipient, polymer, concentration, and dose ranges.
- The patent is relevant to ADLARITY, approved by FDA in 2022.
- The expected patent term extends into approximately January 2034, subject to official USPTO term adjustment.
- Donepezil does not present biosimilar risk because it is a small molecule.
- The clearest design-around routes involve preformed donepezil base, a different alkaline system, alternative excipients, or a different reservoir architecture.
- Generic risk will depend on Orange Book listings, Paragraph IV certifications, any 30-month stay, and other ADLARITY patent-family members.
FAQs About US Patent 10,016,372
Does the patent cover an oral donepezil tablet?
No. The claims require a transdermal delivery system and transdermal administration.
Does a patch containing donepezil base automatically infringe?
No. The broad claims require a donepezil salt and an alkaline salt, with donepezil base generated in situ after application. A patch loaded only with preformed donepezil base may avoid these limitations, although other patents could apply.
Is weekly application required by every claim?
No. Weekly application is required by claim 2 and certain dose-duration limitations in claim 14. Claim 1 does not require weekly administration.
Can a product avoid claim 8 by omitting sorbitan monolaurate?
Potentially, but omission of sorbitan monolaurate would not necessarily avoid claims 1, 6, 16, 17, or 18. Infringement analysis must evaluate each claim independently.
Is US Patent 10,016,372 the only patent relevant to ADLARITY?
No. A complete freedom-to-operate review must evaluate the entire ADLARITY patent family, Orange Book listings, continuation patents, adhesive and reservoir patents, manufacturing patents, and any pending applications.
References
- United States Patent and Trademark Office. (2018). US Patent No. 10,016,372, transdermal delivery of donepezil.
- U.S. Food and Drug Administration. (2022, September 28). FDA approves new drug for Alzheimer’s disease.
- U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, Orange Book.
- U.S. Food and Drug Administration. (2022). ADLARITY prescribing information. Corium, Inc.
- Hatch, W. (1984). Drug Price Competition and Patent Term Restoration Act, Pub. L. No. 98-417, 98 Stat. 1585.
