Details for Patent: 8,796,337
Summary for Patent: 8,796,337
| Title: | Composition and method for treating neurological disease | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Abstract: | A method of administering amantadine is provided. The method comprises orally administering to a subject a pharmaceutical composition comprising amantadine, or a pharmaceutically acceptable salt thereof, and one or more excipients, wherein at least one of the excipients modifies release of the amantadine. A dose of the composition provides a mean change in amantadine plasma concentration as a function of time (dC/dT) that is less than 40% of the change in amantadine plasma concentration provided by a dose of the same quantity of an immediate release form of amantadine. The change in plasma concentration over time (dC/dT) is measured in a single dose human pharmacokinetic study in a defined time period of 0 to 4 hours after administration. The amantadine, or pharmaceutically acceptable salt thereof, is administered once daily at a dose of 300 to 500 mg per day. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inventor(s): | Gregory T. Went, Timothy J. Fultz, Seth Porter, Laurence R. Meyerson, Timothy S. Burkoth | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Assignee: | Adamas Pharma LLC | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Application Number: | US13/958,153 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Patent Litigation and PTAB cases: | See patent lawsuits and PTAB cases for patent 8,796,337 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Patent Claim Types: see list of patent claims | Use; Composition; Formulation; | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Patent landscape, scope, and claims: | United States Patent 8,796,337: Claim Scope, Expiration, Orange Book Position, and Amantadine Patent LandscapeUS Patent 8,796,337 protects a high-dose, once-daily, modified-release amantadine treatment method. Its central limitations are cumulative: oral administration to a human, a controlled-release formulation, a 300-to-500 mg daily dose, and a pharmacokinetic release rate below 40% of immediate-release amantadine during the first four hours. The patent is method-of-treatment focused rather than a broad composition patent. The claims are potentially relevant to extended-release amantadine products used for Parkinson's disease and related central nervous system conditions. They do not cover every once-daily amantadine product. A competing product must satisfy all limitations of an asserted claim, including the dose range and pharmacokinetic limitation. What does US Patent 8,796,337 protect?US 8,796,337 protects methods for administering controlled-release amantadine at relatively high once-daily doses while reducing the early post-dose plasma concentration rise. The independent claims are claims 1 and 7:
Claims 2-6 and 8-12 narrow the independent claims by adding Parkinson's disease, dissolution requirements, extended-release content, or narrower dose ranges. Claims 13 and 14 expand the Parkinson's disease indication to specified associated conditions. The patent does not claim:
How should claim 1 be construed?Claim 1 has seven material elements. An accused product or regimen must be assessed against each element. 1. Human treatment methodThe claim requires administration to a human subject. Animal studies, in vitro testing, and formulation sales without use by a human do not satisfy this limitation by themselves. The claim is directed to a treatment method, so infringement analysis generally focuses on the product labeling, intended dosing instructions, actual administration, and evidence that the claimed method is practiced. 2. Amantadine or a pharmaceutically acceptable saltThe active ingredient may be amantadine itself or a pharmaceutically acceptable salt. Amantadine hydrochloride is the commercially dominant form. The salt language broadens the active-ingredient limitation but does not eliminate the dose, release-rate, dissolution, or administration requirements. 3. Oral pharmaceutical compositionThe composition must be administered orally. Injectable, transdermal, implantable, or other nonoral delivery systems fall outside the literal oral-administration limitation. The claim also requires one or more excipients. At least one excipient must modify amantadine release. This language targets a modified-release dosage form, not merely a formulation containing an inactive ingredient. 4. Modified releaseThe claim does not require a particular formulation technology. A matrix tablet, coated multiparticulate capsule, polymeric barrier system, osmotic system, or other release-modifying design could potentially meet the limitation if it produces the claimed pharmacokinetic result. The formulation must cause release behavior materially different from the immediate-release comparator. A product described as "extended release" would not automatically infringe if it fails the required dC/dT comparison. 5. Pharmacokinetic limitationThe central technical limitation requires:
This is a relative, performance-based limitation. The relevant comparison is not simply the absolute plasma concentration or the terminal half-life. It is the early plasma concentration change rate relative to an immediate-release dose containing the same quantity of amantadine. A generic developer would likely need to evaluate:
The pharmacokinetic limitation creates an important design-around opportunity. A product may use extended-release technology yet avoid the claim if its measured early dC/dT is 40% or higher, or if its labeled dose falls outside the claimed range. 6. Once-daily administrationClaim 1 requires once-daily dosing. Twice-daily administration is not a literal match to this limitation, even if the total daily dose is within the claimed range. A product that is physically capable of once-daily administration but is labeled only for divided dosing presents a different analysis from a product expressly labeled for once-daily use. 7. 300-to-500 mg per dayThe dose range is a major claim boundary. Claims 5 and 6 divide the range into:
The ordinary claim interpretation issue is whether the endpoints are inclusive. The claim language uses "300 to 500 mg" and dependent claims use similar ranges. Unless prosecution history establishes a different meaning, the endpoints would generally be treated as included. A regimen below 300 mg/day does not literally meet this limitation. That distinction matters because marketed extended-release amantadine products may use lower labeled doses than the claimed 300-to-500 mg range. What does claim 7 add?Claim 7 covers a related method directed to reducing treatment-induced debilitating side effects in a patient being treated for a CNS-related condition. Its key differences from claim 1 are:
"Consists essentially of" is narrower than "comprising." It generally permits additional components that do not materially affect the basic and novel characteristics of the claimed composition. Ingredients that materially alter the claimed release behavior or treatment result could create claim-construction disputes. Claim 7 is not limited expressly to Parkinson's disease, but claim 8 adds Parkinson's disease. The CNS-related condition could include other neurological disorders if the accused regimen satisfies the remaining limitations. What conditions are covered by claims 13 and 14?Claims 13 and 14 cover Parkinson's disease-associated conditions selected from:
These claims require the underlying Parkinson's disease limitation through claim 1 or claim 8. They do not create independent protection for treating those conditions in patients without Parkinson's disease. The term "other neuropsychiatric complications" may raise scope and definiteness issues depending on the asserted condition and the patent specification. A defendant could challenge whether a particular condition falls within the defined Parkinson's disease-associated category. What formulation is required by the dissolution claims?Claims 3 and 9 require the following in vitro dissolution profile in water:
The test conditions are:
Claims 3 and 9 are narrower than claims 1 and 7 because they add a defined laboratory release profile. A formulation can meet claim 1 without meeting claim 3 if its pharmacokinetic performance satisfies the dC/dT limitation but its in vitro dissolution results fall outside the listed ranges. Claims 4 and 10 further require that at least 95% of the amantadine or salt be in extended-release form. These claims are directed to the composition's extended-release fraction, not merely the release profile of the overall dosage form. What is the patent's legal and commercial scope?The patent's commercial value depends on whether a marketed or proposed product satisfies the combined dose and pharmacokinetic limitations.
The claims are therefore narrower than a conventional "all extended-release amantadine" patent. Their strongest position is against a high-dose, once-daily product engineered to produce a low early plasma concentration rise. When does US Patent 8,796,337 lose exclusivity?The patent issued on August 5, 2014. Its underlying nonprovisional filing date is the relevant starting point for the ordinary 20-year patent term, subject to patent-term adjustment, terminal disclaimers, or other statutory modifications. Public patent records associate the family with a 2010 filing chronology, producing a base term around 2030 rather than 2034, the grant date. [1] A practical term assessment is:
The relevant freedom-to-operate date is the enforceable expiration date after any patent-term adjustment or disclaimer. A patent does not lose enforceability merely because the branded product's regulatory exclusivity expires. What is the Orange Book status of US 8,796,337?US 8,796,337 has been associated with the U.S. patent estate for extended-release amantadine products, including products marketed for Parkinson's disease-related dyskinesia. The FDA Orange Book identifies patents submitted by NDA holders, but an Orange Book listing does not independently determine claim validity, infringement, or enforceability. [2] For a current product-specific analysis, the relevant NDA entry is the one covering the applicable extended-release amantadine product. The listing should be reviewed for:
Because US 8,796,337 is a method patent, its Orange Book relevance depends heavily on the listed use code and the proposed generic's labeling. A generic applicant can avoid an asserted method patent through a Paragraph IV certification, a section viii statement omitting the patented use, or a label that does not instruct the claimed regimen, depending on the listed use and applicable FDA rules. [3] How do Paragraph IV challenges affect this patent?A generic applicant submitting an ANDA may certify that the listed patent is invalid, unenforceable, or will not be infringed. That is a Paragraph IV certification under the Hatch-Waxman Act. [4] For US 8,796,337, likely challenge theories include: NoninfringementA generic applicant could argue that its product:
InvalidityPotential invalidity theories could include:
The dC/dT limitation may be central to both sides. The patent owner would likely rely on the specification's study methods and examples to establish a reproducible test. A challenger would focus on ambiguity in the mathematical definition, comparator selection, sampling design, and whether the limitation can be determined consistently. What patent litigation affects US 8,796,337?The principal litigation risk is an ANDA action under 35 U.S.C. ยง 271(e)(2), usually filed after receipt of a Paragraph IV notice. Such an action can trigger a 30-month stay of FDA approval under the Hatch-Waxman framework, subject to statutory exceptions. [4] The litigation analysis should distinguish:
A settlement involving a related amantadine patent does not necessarily resolve US 8,796,337. Each patent's claims, listing status, certification, and asserted use must be analyzed separately. A court judgment on a formulation patent also does not automatically invalidate this method patent. How strong is the patent estate for extended-release amantadine?The estate is stronger when several patent categories overlap:
US 8,796,337 is most important as a pharmacokinetic and treatment-method asset. It is less effective against a product that uses a materially different dose, administration schedule, or early exposure profile. The broader commercial protection for products such as Gocovri has historically depended on a portfolio rather than one patent. Related U.S. patents associated with extended-release amantadine products include US 9,675,587, US 9,919,014, US 10,034,938, and US 10,543,187. Each must be analyzed independently for priority, claims, Orange Book listing, expiration, and litigation history. [2,5] What is the biosimilar risk for this patent?There is no biosimilar pathway for amantadine. Amantadine is a small-molecule active ingredient regulated through the ANDA pathway rather than the biologic biosimilar pathway. The relevant competitive threats are:
The principal barrier for a generic extended-release product is not biosimilar comparability. It is the combination of bioequivalence, labeling, patent certification, formulation development, and potential Paragraph IV litigation. What generic launch scenarios exist?Scenario 1: Launch after patent expirationThis is the lowest litigation-risk pathway if all listed patents covering the proposed product have expired or become unenforceable. Scenario 2: Paragraph IV challengeA generic applicant challenges validity or infringement and seeks approval before patent expiration. The NDA holder may file suit, potentially triggering the statutory approval stay. Scenario 3: Section viii carve-outIf the listed patent covers only a method of use, the applicant may attempt to omit that use from its labeling. The strategy is more difficult if the proposed label still encourages the patented dose, schedule, or condition. Scenario 4: Dose-based design-aroundA product using less than 300 mg/day could avoid the express dose limitation in the provided claims. That strategy must be assessed against other patents and against induced-infringement theories based on labeling. Scenario 5: Pharmacokinetic design-aroundA formulation could be developed with a dC/dT at or above the claimed 40% threshold. That approach may reduce literal infringement risk but could create bioequivalence or tolerability issues. How does US 8,796,337 compare with formulation patents?US 8,796,337 primarily protects what the product does in the patient: it produces a reduced early plasma concentration change at a defined dose and schedule. A formulation patent typically protects what the product is, such as:
The distinction matters in litigation. A generic product may avoid a formulation claim while still meeting the pharmacokinetic method claim. Conversely, a product may use the same broad therapeutic concept but avoid US 8,796,337 by failing the dose or dC/dT limitation. What are the geographic coverage and manufacturing barriers?US 8,796,337 provides protection only in the United States. Corresponding foreign-family patents, if granted, require separate analysis in Europe, Canada, Japan, and other markets. Claim scope, patent term, supplementary protection certificates, prosecution history, and enforcement standards vary by jurisdiction. Manufacturing barriers may remain even if this patent is avoided. A generic developer may need to reproduce:
Those technical barriers are commercial rather than automatically legal. They become legal barriers only when covered by enforceable composition, formulation, manufacturing, or method claims. Key Takeaways
Frequently Asked QuestionsDoes US 8,796,337 cover all Gocovri or extended-release amantadine products?No. The claims require specific dose, schedule, pharmacokinetic, and, for narrower claims, dissolution limitations. A product must satisfy all required limitations. Can a 274 mg once-daily amantadine product infringe these claims?Not literally under the provided claims if 274 mg is the relevant amantadine dose, because the independent claims require 300-500 mg/day. Other patents or infringement theories could still apply. Is US 8,796,337 a formulation patent?No. It includes formulation and dissolution limitations in dependent claims, but its independent claims primarily protect treatment methods defined by dosing and pharmacokinetic performance. Can a generic omit the patented Parkinson's disease use?Potentially. A section viii carve-out may be available for a listed method-of-use patent, but the proposed labeling must not instruct or encourage the patented use. FDA and litigation treatment depend on the exact Orange Book use code and label language. Does the patent block generic immediate-release amantadine?No. The provided claims require modified-release behavior and a reduced early dC/dT relative to immediate-release amantadine. Immediate-release products are outside the literal scope of those limitations. References
More… ↓ |
Drugs Protected by US Patent 8,796,337
| Applicant | Tradename | Generic Name | Dosage | NDA | Approval Date | TE | Type | RLD | RS | Patent No. | Patent Expiration | Product | Substance | Delist Req. | Patented / Exclusive Use | Submissiondate |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| >Applicant | >Tradename | >Generic Name | >Dosage | >NDA | >Approval Date | >TE | >Type | >RLD | >RS | >Patent No. | >Patent Expiration | >Product | >Substance | >Delist Req. | >Patented / Exclusive Use | >Submissiondate |
International Family Members for US Patent 8,796,337
| Country | Patent Number | Estimated Expiration | Supplementary Protection Certificate | SPC Country | SPC Expiration |
|---|---|---|---|---|---|
| Canada | 2588296 | ⤷ Start Trial | |||
| European Patent Office | 1845968 | ⤷ Start Trial | |||
| European Patent Office | 2623099 | ⤷ Start Trial | |||
| World Intellectual Property Organization (WIPO) | 2006058236 | ⤷ Start Trial | |||
| >Country | >Patent Number | >Estimated Expiration | >Supplementary Protection Certificate | >SPC Country | >SPC Expiration |
