Details for Patent: 8,741,343

Which drugs does patent 8,741,343 protect, and when does it expire?

Patent 8,741,343 protects GOCOVRI and is included in one NDA.

This patent has nineteen patent family members in eight countries.

Summary for Patent: 8,741,343

Title:	Method of administering amantadine prior to a sleep period
Abstract:	Methods of nighttime administration of amantadine to reduce sleep disturbances in patient undergoing treatment with amantadine are described, as well as compositions of extended release amantadine that are suitable for nighttime administration.
Inventor(s):	Gregory T. Went, Gayatri Sathyan, Kavita Vermani, Gangadhara Ganapati, Michael Coffee, Efraim Shek, Ashok Katdare
Assignee:	Adamas Pharma LLC
Application Number:	US12/959,321
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,741,343
Patent Claim Types: see list of patent claims	Use; Composition; Formulation; Dosage form;

US Patent 8,741,343: Amantadine Extended-Release Patent Scope, Validity, and Generic Entry Risk

US Patent 8,741,343 is a method-of-treatment patent directed to once-daily, bedtime administration of extended-release amantadine. Its core commercial relevance is the Gocovri product, an extended-release amantadine capsule approved for levodopa-induced dyskinesia in patients with Parkinson's disease and for off episodes in Parkinson's disease. The patent does not broadly claim every amantadine extended-release formulation. It claims administration methods tied to defined dose ranges, pharmacokinetic results, and bedtime dosing.

The strongest independent claims require a combination of four elements:

1. An extended-release amantadine composition.
2. A total amantadine dose of 220 mg to 445 mg.
3. Defined human pharmacokinetic parameters.
4. Once-daily oral administration 0 to 4 hours before bedtime.

The patent's principal commercial risk is therefore concentrated on products that reproduce the Gocovri dosing pattern and pharmacokinetic profile, rather than on immediate-release amantadine or all extended-release amantadine products.

What does US Patent 8,741,343 protect?

US 8,741,343 protects methods of administering extended-release amantadine to a human subject. The claims are not composition claims and do not require a particular tablet, capsule, polymer, coating, manufacturing process, or release-modifying excipient.

Core claim architecture

Claim group	Independent or parent claim	Required pharmacokinetic limitation	Main therapeutic or dosing limitations
Group 1	Claim 1	Median amantadine Tmax of 8 to 18 hours	220-445 mg, once daily, 0-4 hours before bedtime
Group 2	Claim 10	Mean Cmax of 1.0-2.8 ng/mL/mg and AUC0-inf of 40-75 ng·hr/mL/mg	220-445 mg, once daily, 0-4 hours before bedtime
Group 3	Claim 20	Mean Cmax of 1.0-2.4 ng/mL/mg	Depends on claim 10 and its limitations

The dependent claims add:

• Reduction of sleep disturbance.
• Treatment of levodopa-induced dyskinesia.
• Narrower administration windows of 0-3 hours or 0-2 hours before bedtime.
• Administration as one, two, or three dosage units.
• Unit doses containing 110-210 mg of extended-release amantadine.
• Specific unit-dose configurations based on 130 mg, 140 mg, or 170 mg of amantadine.

The claims use both pharmacokinetic and regimen limitations. A competing product could avoid literal infringement by failing one required element, but the commercial practicality of that strategy depends on whether the product still produces substantially equivalent pharmacokinetics and is promoted or prescribed for the claimed bedtime regimen.

How broad are the independent claims?

Claim 1 is the broadest practical claim because it requires only the Tmax range among the expressly stated pharmacokinetic parameters. It covers an extended-release composition with:

• 220-445 mg of amantadine or a pharmaceutically acceptable salt;
• At least one release-modifying excipient;
• Median Tmax of 8-18 hours in a single-dose, fasting human pharmacokinetic study; and
• Once-daily administration 0-4 hours before bedtime.

Claim 10 is narrower in one respect and potentially more demanding in another. It requires both Cmax and AUC values normalized per milligram of amantadine. It also requires the same total dose and bedtime schedule.

Claim 20 is narrower than claim 10 because it limits mean Cmax to 1.0-2.4 ng/mL/mg. It does not independently create a new product category. It depends on the claim 10 framework.

Literal infringement requirements

A product and regimen would generally need to satisfy all limitations of at least one asserted claim. For claim 1, the principal questions would be:

1. Does the product contain extended-release amantadine?
2. Is the total dose within 220-445 mg?
3. Does the product have a release-modifying excipient?
4. Does a qualifying fasting human study show median Tmax of 8-18 hours?
5. Is it administered once daily?
6. Is administration recommended or performed 0-4 hours before bedtime?

The claim does not require that the composition be branded, encapsulated, or marketed for Parkinson's disease. Claims 2 and 3 add therapeutic results or indications, but the independent claim can reach a regimen without those added limitations.

What formulations are protected by US 8,741,343?

The patent protects use of an extended-release composition, not a specific formulation design. The phrase "at least one release modifying excipient" is broad. It can encompass polymers, matrix-forming agents, coatings, diffusion-control materials, or other excipients that alter amantadine release.

The claims do not expressly require:

• A capsule rather than a tablet.
• A multiparticulate system.
• A specific polymer.
• A particular dissolution profile.
• A specified salt, provided the salt is pharmaceutically acceptable.
• A particular manufacturing process.
• A particular coating thickness or coating composition.

This creates a broad formulation interface but a narrower infringement test. A competing formulation would need to be evaluated against the claimed pharmacokinetic ranges and dosing schedule. A formulation with a different excipient system can still fall within the patent if it produces the claimed PK profile and is used under the claimed regimen.

Dose-unit limitations

The dependent claims are directed to unit-dose structures, including:

Dependent claim configuration	Claimed unit strength
Claims 6 and 16	One, two, or three units containing 110-210 mg each, within a 220-445 mg total
Claims 7 and 17	Two or three units containing 130 mg each
Claims 8 and 18	Two or three units containing 140 mg each
Claims 9 and 19	Two units containing 170 mg each
Claims 26-29	Corresponding configurations tied to claim 20

These claims may be commercially relevant to a two-capsule bedtime dose. They do not necessarily map directly to labeled strength nomenclature because drug labels may express strength as amantadine hydrochloride rather than free-base amantadine. Salt-equivalence analysis is required when comparing a product label with the claim's stated amount of amantadine.

How does the patent relate to Gocovri?

Gocovri is an extended-release amantadine product marketed by Supernus Pharmaceuticals following its acquisition of Adamas Pharmaceuticals. The FDA approved Gocovri in August 2017 for levodopa-induced dyskinesia in patients with Parkinson's disease receiving levodopa-based therapy, with or without concomitant dopaminergic medications. The FDA later approved an indication for treatment of "off" episodes in Parkinson's disease. [1]

Gocovri's label uses bedtime administration and an extended-release capsule design. The labeled dosage is generally initiated at 137 mg once daily at bedtime and may be increased to 274 mg once daily at bedtime, subject to renal-function considerations. [1]

That regimen closely corresponds to the patent's commercial center of gravity:

• Once-daily dosing.
• Administration at bedtime.
• Extended-release amantadine.
• Total daily exposure near 274 mg for the maintenance regimen.
• Use in Parkinson's disease.
• Treatment of levodopa-induced dyskinesia.

The patent claims, however, use numeric dose ranges and pharmacokinetic parameters that do not depend solely on the FDA-approved label. A generic applicant could therefore face infringement risk even if its proposed labeling uses different commercial language, if the approved or promoted regimen still falls within the claimed limitations.

What is the Orange Book status of US 8,741,343?

US 8,741,343 has been associated with the Gocovri regulatory patent estate and should be evaluated against the current FDA Orange Book patent listing for the applicable NDA. The Orange Book is the controlling source for current listed-patent status, expiration dates, and use codes. [2]

The patent is a drug-use patent rather than a composition-of-matter patent. Its regulatory importance depends on:

• Whether it remains listed against the relevant Gocovri NDA.
• The applicable use code.
• Whether the listed use code covers dyskinesia, Parkinson's disease, bedtime dosing, or another approved use.
• Whether later-issued continuation patents provide additional protection after this patent's nominal expiration.

A listed method-of-use patent can support a Paragraph IV challenge. It does not necessarily block approval of a generic for every use if the applicant uses a valid section viii skinny-label strategy that omits the patented indication or regimen. That strategy becomes more difficult when the patent claims the dosing method itself and the proposed label retains bedtime administration.

When does US Patent 8,741,343 lose exclusivity?

The patent's nominal expiration is generally calculated from the earliest effective nonprovisional filing date in its priority chain, subject to patent-term adjustment and any applicable regulatory patent-term extension. The patent term should be confirmed against the USPTO patent record and the FDA Orange Book because the operative date can differ from a simple 20-year calculation. [2,3]

The patent was issued June 3, 2014. Its issuance date does not determine expiration. The relevant term is tied primarily to the earliest effective nonprovisional filing date, with possible adjustment for USPTO examination delays.

The practical exclusivity analysis must distinguish:

Exclusivity type	Relevance to Gocovri
New chemical entity exclusivity	Applies to the active ingredient only if the FDA granted it under the applicable NDA framework; it is separate from the patent term
Orphan-drug exclusivity	Depends on the approved indication and designation status
Patent exclusivity	Determined by the patent term and listed patent claims
Pediatric exclusivity	Adds six months if granted
Later continuation patents	May extend protection for different claim categories after US 8,741,343 expires

US 8,741,343 should therefore be treated as one component of a broader patent estate rather than as the sole Gocovri exclusivity barrier.

Which patents compete with or extend the 8,741,343 patent estate?

The commercially relevant estate includes continuation and related patents covering various combinations of:

• Extended-release amantadine formulations.
• Pharmacokinetic profiles.
• Bedtime dosing.
• Parkinson's disease treatment.
• Dyskinesia treatment.
• Off-episode treatment.
• Formulation and release-control technology.

The relevant family must be reconstructed through USPTO continuity data, Patent Center, Google Patents, and Orange Book listings. Patent numbers that appear in regulatory records for Gocovri may not all claim the same subject matter. Some can cover formulation characteristics, some treatment methods, and others later-approved indications.

A patent-by-patent freedom-to-operate review should classify each family member by:

1. Independent claim type.
2. Active ingredient and salt definition.
3. Dose range.
4. Release profile.
5. Required indication.
6. Required dosing time.
7. PK limitation.
8. Current legal status.
9. Orange Book listing and use code.
10. Terminal disclaimer or continuation relationship.

What Paragraph IV challenges and litigation affect the patent?

A generic applicant seeking approval before expiration of an Orange Book-listed patent may file a Paragraph IV certification alleging that the patent is invalid, unenforceable, or not infringed. The NDA holder can file an infringement action within 45 days, triggering a statutory stay of FDA approval for up to 30 months under the Hatch-Waxman framework. [4]

For US 8,741,343, the principal litigation issues would likely include:

• Whether the proposed generic's label requires administration at bedtime.
• Whether the proposed product meets the claimed Tmax or Cmax ranges.
• Whether the PK data are measured under the claimed single-dose, fasting human study conditions.
• Whether the claimed amount of amantadine is calculated as free base or salt.
• Whether the patent claims are enabled across the full PK ranges.
• Whether the PK limitations are definite and reproducible.
• Whether the claims are invalid as obvious over immediate-release amantadine, other extended-release products, or known Parkinson's treatment regimens.
• Whether the generic applicant induces infringement through labeling or promotional materials.

Because the claims are method claims, the litigation record would be highly dependent on the proposed label, ANDA formulation, bioequivalence data, and dosing instructions. A composition-only noninfringement argument would not address the central claim structure.

How strong is the patent estate for generic entry?

Strengths

The patent has several features that increase generic-entry risk:

• It combines formulation, PK, dose, and timing limitations.
• The claims map closely to the commercially important bedtime regimen.
• Claims 2 and 3 cover clinically relevant Parkinson's uses.
• The dose ranges are broad enough to encompass common high-dose extended-release regimens.
• The PK limitations can make design-around difficult if therapeutic performance requires similar exposure.

Weaknesses

The patent also has potential attack points:

• It is a method patent, not a composition-of-matter patent.
• Literal infringement requires proof of multiple factual limitations.
• PK ranges can create claim-construction, reproducibility, and enablement disputes.
• A generic may pursue a skinny label excluding a patented indication.
• A product with a materially different Tmax or Cmax profile may avoid literal infringement.
• The claims depend on a specified fasting human PK methodology, which may not align with every regulatory bioequivalence study.
• Earlier amantadine products and known controlled-release technologies may support obviousness arguments.

The estate is strongest against a generic that copies the product's extended-release performance and retains once-daily bedtime dosing. It is weaker against a product with a different release profile, different timing instructions, or a legally effective label carve-out.

How does US 8,741,343 compare with immediate-release amantadine?

Issue	US 8,741,343 regimen	Immediate-release amantadine
Release type	Extended release	Immediate release
Dosing timing	0-4 hours before bedtime	Generally not defined by this patent
Daily dose	220-445 mg	Commonly lower divided-dose regimens
PK requirement	Defined Tmax, Cmax, and/or AUC	Does not inherently meet the claimed ER PK ranges
Main use	Dyskinesia and Parkinson's disease treatment	Broader historical amantadine uses
Patent exposure	High if all claim limitations are met	Lower under these claims

Immediate-release amantadine does not automatically infringe because the claims require an extended-release composition with specified pharmacokinetics and bedtime administration.

What generic launch scenarios exist?

Scenario 1: Direct Gocovri-style launch

A generic using a substantially similar extended-release formulation, a 274 mg maintenance dose, and bedtime administration would face the highest risk. It would likely need to challenge listed patents through Paragraph IV certifications or wait for relevant patent expiry.

Scenario 2: Skinny-label launch

A generic could seek approval for an unpatented indication while excluding patented uses from its labeling. The viability of this route depends on the Orange Book use codes and whether the remaining label still instructs the claimed bedtime regimen.

Scenario 3: Pharmacokinetic design-around

A manufacturer could develop an extended-release product that falls outside the claimed Tmax or normalized Cmax ranges. This approach could reduce literal infringement risk but may create bioequivalence, efficacy, or regulatory problems.

Scenario 4: Different dosing schedule

A product administered outside the 0-4-hour pre-bedtime window could avoid the express timing limitation. The commercial value of that design-around would depend on whether the alternative schedule preserves efficacy and tolerability.

Scenario 5: Salt or strength redesign

Changing the salt or unit strength alone is unlikely to provide a reliable design-around because the claims expressly cover pharmaceutically acceptable salts and broad total-dose ranges.

What licensing and ownership issues affect the patent?

Adamas Pharmaceuticals developed Gocovri and was later acquired by Supernus Pharmaceuticals. Supernus reported the acquisition in 2021 and obtained Adamas' commercial products and related intellectual-property assets. [5]

The ownership chain matters for:

• Patent enforcement.
• Orange Book certifications.
• Settlement negotiations.
• Authorized-generic strategy.
• Licensing or co-commercialization rights.
• Revenue exposure from Parkinson's disease products.

No license should be assumed merely because multiple companies appear in the patent family or product history. Assignment records and transaction documents control ownership and enforcement rights.

Key Takeaways

• US 8,741,343 is a method-of-use patent for extended-release amantadine administered once daily before bedtime.
• The key independent claims require a 220-445 mg total dose, release-modifying excipient, defined human PK results, and 0-4-hour pre-bedtime administration.
• The patent is closely aligned with the Gocovri commercial regimen, particularly the 274 mg bedtime dose.
• It does not broadly claim every amantadine extended-release composition.
• Immediate-release amantadine is outside the claim scope unless it somehow satisfies the extended-release and PK limitations.
• A generic copying the Gocovri regimen faces the greatest Paragraph IV and induced-infringement risk.
• Potential design-arounds include different PK exposure, different dosing time, and a valid skinny label, but each creates regulatory and commercial constraints.
• The patent must be analyzed together with continuation patents and the current Orange Book listings.
• Expiration should be determined from USPTO term data and Orange Book records, not from the 2014 issue date alone.
• Supernus is the relevant successor commercial owner following its acquisition of Adamas Pharmaceuticals.

FAQs

Does US 8,741,343 cover a 274 mg Gocovri dose?

It can cover a 274 mg dose when the product is extended release, meets the claimed PK limitations, and is administered once daily 0-4 hours before bedtime.

Can a generic sell immediate-release amantadine without infringing this patent?

Yes, these claims require an extended-release composition with specified pharmacokinetic characteristics. Immediate-release amantadine does not inherently satisfy those limitations.

Does changing Gocovri from capsules to tablets avoid US 8,741,343?

No. The claims do not require a capsule. A tablet can infringe if it satisfies the composition, dose, PK, and administration limitations.

Can a generic avoid the patent by using a different amantadine salt?

Not necessarily. The claims expressly cover amantadine and pharmaceutically acceptable salts. Salt selection alone is unlikely to create a dependable design-around.

Is a Paragraph IV challenge required for every Gocovri-related patent?

No. The required certification depends on the patents listed for the relevant NDA, their expiration dates, and the scope of the generic applicant's proposed label and product.

References

1. U.S. Food and Drug Administration. (2023). Gocovri (amantadine) extended-release capsules prescribing information. FDA.
2. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.
3. United States Patent and Trademark Office. (2014). U.S. Patent No. 8,741,343: Methods of treating. USPTO.
4. U.S. Food and Drug Administration. (2024). Hatch-Waxman amendments and abbreviated new drug applications. FDA.
5. Supernus Pharmaceuticals, Inc. (2021). Supernus Pharmaceuticals completes acquisition of Adamas Pharmaceuticals. Supernus Pharmaceuticals.

Drugs Protected by US Patent 8,741,343

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Supernus Pharms	GOCOVRI	amantadine hydrochloride	CAPSULE, EXTENDED RELEASE;ORAL	208944-001	Aug 24, 2017		RX	Yes	No						TREATMENT OF DYSKINESIA IN PATIENTS WITH PARKINSON'S DISEASE RECEIVING LEVODOPA-BASED THERAPY, WITH OR WITHOUT CONCOMITANT DOPAMINERGIC MEDICATIONS
Supernus Pharms	GOCOVRI	amantadine hydrochloride	CAPSULE, EXTENDED RELEASE;ORAL	208944-002	Aug 24, 2017		RX	Yes	Yes						TREATMENT OF DYSKINESIA IN PATIENTS WITH PARKINSON'S DISEASE RECEIVING LEVODOPA-BASED THERAPY, WITH OR WITHOUT CONCOMITANT DOPAMINERGIC MEDICATIONS

International Family Members for US Patent 8,741,343

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2010325960
Australia	2015202356
Brazil	112012013487