United States Patent 8,333,992: Gabapentin Extended-Release Matrix Claims, Scope, Expiration, and Generic Risk

U.S. Patent No. 8,333,992 covers oral gabapentin matrix dosage forms designed to release gabapentin in the upper gastrointestinal tract over approximately 5 to 12 hours. The claims require a pharmacokinetic profile that reduces peak plasma exposure relative to immediate-release gabapentin while retaining at least 80% of immediate-release exposure based on AUC. The patent is directed to the controlled-release technology associated with Gralise, although product-specific patent coverage must be assessed against the Orange Book and related continuation patents.

The patent’s nominal term appears to have ended in December 2024 based on the underlying priority date. Any enforceability analysis must account for the official USPTO patent-term-adjustment calculation, terminal disclaimers, and the specific patent-family record.

What does U.S. Patent 8,333,992 cover?

The patent covers three principal categories:

Controlled-release gabapentin dosage forms.
Fixed-dose 300 mg and 600 mg dosage forms.
Methods of treating pain, including neuropathic pain, with the claimed matrix formulations.

The independent claims are claims 1, 9, 15, and 22.

Claim group	Subject matter	Principal limitations
Claim 1	Dosage form	Gabapentin matrix; 5-12 hour upper-GI release; lower Cmax than equal-dose immediate-release gabapentin; AUC at least 80% of immediate-release product
Claim 9	Fixed-dose dosage form	300 mg or 600 mg gabapentin; one 600 mg unit or two 300 mg units; same release and PK requirements
Claim 15	Treatment method	Oral administration of the claim 1 dosage form to treat a responsive condition
Claim 22	Treatment method	Oral administration producing a longer Tmax than immediate-release gabapentin, with AUC at least 80% of the immediate-release product

The dependent claims narrow the formulation, dose, release mechanism, pharmacokinetic profile, and treatment indication.

How do the patent claims define the protected gabapentin formulation?

The claims combine structural and functional limitations. The dosage form must contain a matrix, but infringement also depends on the performance of the formulation after administration.

The core elements are:

Gabapentin as the active ingredient.
A matrix dosage form.
Release into the upper gastrointestinal tract.
Release over approximately 5 to 12 hours.
A lower maximum plasma concentration than equal-dose immediate-release gabapentin, or, for claim 22, a longer time to maximum concentration.
AUCinf of at least 80% of the immediate-release comparator.
For selected dependent claims, a Cmax of at least approximately 3 µg/mL.
For claim 8, a Cmax-to-15-hour plasma-concentration ratio of no more than approximately 2.

These limitations distinguish the claimed product from ordinary immediate-release gabapentin tablets and capsules. They also make the patent materially different from a patent that protects only excipients, tablet geometry, or a dissolution profile measured in vitro.

What formulations are protected by U.S. Patent 8,333,992?

Polymer matrix formulations

Claims 4, 5, 6, 11, 12, 13, 17, 18, and 23-24 narrow the matrix to a polymer matrix, including a swellable hydrophilic polymer. The claims also identify diffusion as a release mechanism.

A formulation may fall within these claims if it uses a hydrophilic swellable polymer that hydrates after ingestion and controls gabapentin diffusion through the hydrated matrix. The claims do not appear limited to a single named polymer or a single excipient concentration.

Potentially relevant polymer categories include:

Hydroxypropyl methylcellulose.
Hydroxypropyl cellulose.
Polyethylene oxide.
Other swellable, hydrophilic matrix-forming polymers.

The presence of a polymer alone is not enough for infringement. The product must also satisfy the applicable dose, release, and pharmacokinetic limitations.

300 mg and 600 mg dosage forms

Claim 9 is narrower than claim 1 because it requires 300 mg or 600 mg of gabapentin. It expressly covers administration of:

One 600 mg dosage form; or
Two 300 mg dosage forms.

This language is commercially important because a generic manufacturer could seek approval for one or both strengths. A product that uses different strengths may avoid claim 9 while remaining exposed to broader claims 1 or 15, depending on its formulation and clinical performance.

Treatment of pain and neuropathic pain

Claims 19, 20, 25, and 26 narrow the treatment methods to pain and neuropathic pain. The method claims require administration to a human subject and therefore raise different infringement questions from the dosage-form claims.

A product may be exposed to product claims regardless of the indication on its label. Method-of-use risk depends more heavily on the approved labeling, prescribing behavior, and whether the generic applicant’s proposed labeling induces use within the patented indication.

What pharmacokinetic profile does the patent require?

The patent is built around a controlled-release pharmacokinetic profile rather than a purely physical formulation description.

Parameter	Claimed requirement
Release location	Upper gastrointestinal tract
Release duration	About 5-12 hours
Cmax	Lower than equal-dose immediate-release gabapentin for claims 1 and 9
Tmax	At least approximately 5.6 hours in claims 2 and 10, subject to the stated variation
AUCinf	At least 80% of the immediate-release comparator
Cmax floor	At least about 3 µg/mL in claims 7, 14, 21, and 27
Cmax/C15 ratio	No more than about 2 under claim 8
Claim 22	Longer Tmax than immediate-release gabapentin and AUC of at least 80%

The AUC limitation prevents the patent from covering formulations that merely suppress exposure. The claimed formulation must maintain substantial systemic exposure while reducing the peak or delaying the peak.

The phrase “5.6 hours ±34.9%” creates a claim-construction issue. Applied mathematically, the range is approximately 3.65 to 7.55 hours. Whether the limitation is interpreted as a statistical tolerance, a test-result range, or a defined numerical interval would depend on the specification, prosecution history, and relevant claim-construction record.

How strong are the independent claims?

Claim 1

Claim 1 is broad in dosage-form terms but narrow in pharmacokinetic terms. It does not require a specific polymer, tablet size, excipient, manufacturing process, or dissolution apparatus. This gives the claim potential reach across different controlled-release matrix designs.

Its main vulnerability is that infringement depends on comparative human pharmacokinetic data. A challenger may contest:

The identity of the appropriate immediate-release comparator.
Whether the comparator contains an equal amount of gabapentin.
Whether the reported AUC is AUCinf.
The statistical treatment of Cmax.
Whether release occurs in the “upper gastrointestinal tract.”
Whether the product releases gabapentin over the full claimed period.

Claim 9

Claim 9 provides a commercially targeted claim for 300 mg and 600 mg products. It is narrower than claim 1 because of the dose limitation but may be easier to apply to a marketed product with the same strengths as the reference product.

Claim 15

Claim 15 protects administration of a claim 1-type dosage form for a responsive condition. It may reach treatment uses beyond pain unless narrowed by dependent claims or the specification.

Claim 22

Claim 22 substitutes a longer Tmax requirement for the lower-Cmax requirement. This creates a separate infringement pathway. A product could avoid claim 1 by failing to demonstrate a lower Cmax while remaining exposed to claim 22 if it produces a longer Tmax and retains at least 80% relative AUC.

What are the principal invalidity risks?

Obviousness

The principal obviousness theory would combine known controlled-release matrices with known gabapentin pharmacokinetics. A challenger would likely rely on:

Immediate-release gabapentin products.
Prior controlled-release gabapentin formulations.
General hydrophilic polymer matrix technology.
Pharmacokinetic literature describing gabapentin absorption limitations.
Formulation references teaching prolonged upper-GI residence.

The patent holder’s strongest response would be that gabapentin has absorption characteristics that make ordinary sustained-release approaches unsuitable, and that the claimed formulation achieves both prolonged release and at least 80% relative AUC.

Anticipation

Anticipation would require a single prior-art reference disclosing all relevant structural and pharmacokinetic limitations. Because claims 1 and 9 rely on in-human comparative PK results, an earlier reference would need to disclose substantially the same release and exposure profile, not merely a generic extended-release gabapentin concept.

Enablement and written description

The claims cover a potentially broad range of matrices and polymer systems. A challenger could argue that the specification does not enable the full scope without undue experimentation, particularly where the claims are defined by in-human PK outcomes.

The patent holder would rely on formulation examples, dissolution data, clinical data, and routine optimization methods to establish enablement.

Indefiniteness

Potentially contestable expressions include:

“About 5-12 hours.”
“At a rate sufficient.”
“Lower maximum plasma concentration.”
“At least about 3 µg/mL.”
“5.6 hours ±34.9%.”

The comparison against an equal-dose immediate-release dosage form also raises questions about comparator formulation, fed or fasted conditions, subject population, and statistical methodology.

What is the Orange Book status of U.S. Patent 8,333,992?

The Orange Book status must be confirmed against the FDA’s current electronic Orange Book and the relevant Gralise listing history. Gralise is the extended-release gabapentin product associated with Depomed, later Assertio Therapeutics, and subsequent commercial ownership changes.

Patent listings associated with Gralise have included multiple patents directed to controlled-release gabapentin technology, including patents in the 7,438,927, 8,333,992, 8,337,886, and 8,486,972 families. The applicable list can change through patent delisting, expiration, corrections, or product-holder submissions.[1]

Issue	Relevance
Orange Book listing	Determines whether an ANDA applicant must make a Paragraph IV certification or a Section viii statement
Patent expiration	Determines whether the listed patent can delay approval or block launch
Multiple listed patents	Creates cumulative launch risk even if one patent is invalidated
Method-of-use listing	May permit a Section viii carve-out if the protected use can be omitted
Formulation listing	Usually creates more direct exposure for an ANDA product using the same extended-release technology

A listed patent does not establish validity or infringement. It affects the FDA approval pathway and the timing of a generic applicant’s certifications.

When does U.S. Patent 8,333,992 lose exclusivity?

The patent’s underlying priority chain appears to trace to a 2003 filing, producing a nominal 20-year patent term ending in December 2024. The exact expiration date must be taken from the USPTO Patent Examination Data System and the patent’s term-adjustment record.

The practical exclusivity analysis is broader than the expiration of this single patent. A generic applicant may still face:

Later-expiring continuation patents.
Separate formulation patents.
Method-of-use patents.
Patent-term adjustment.
Pediatric exclusivity.
Regulatory exclusivity associated with the approved product.

Patent expiration does not automatically eliminate all commercial barriers. It removes the patent-based exclusion right for that patent, subject to any valid later patents and accrued damages for pre-expiration infringement.

Which companies challenged the Gralise patent estate?

The Gralise patent estate attracted generic challenges as extended-release gabapentin became commercially significant. Publicly reported patent disputes and ANDA activity have involved generic manufacturers including Actavis, Amneal, Alvogen, Par, and Teva at different stages of the product’s lifecycle. The relevant defendant and patent set varies by case.

A Paragraph IV challenge typically creates a 45-day period for the NDA holder or patent owner to file suit. A timely patent action can trigger a 30-month FDA approval stay under Hatch-Waxman, subject to statutory exceptions and court orders.[2]

The key diligence point is that a Paragraph IV certification against U.S. Patent 8,333,992 would not necessarily resolve the entire Gralise patent estate. A generic applicant could prevail against one patent and still face another listed patent with a later expiration date.

What patent litigation affects U.S. Patent 8,333,992?

The relevant litigation questions are:

Was the patent listed for the specific strength and dosage form?
Did the ANDA applicant certify Paragraph IV?
Was the patent owner’s suit filed within the statutory 45-day period?
Was U.S. Patent 8,333,992 asserted, or were only related family members asserted?
Did the case end in settlement, judgment, dismissal, or license?
Did the settlement permit an agreed generic entry date before patent expiration?

The Depomed-Gralise disputes included litigation against generic applicants and settlement activity affecting generic entry timing. Settlement terms may have included permitted entry dates, licenses, covenants not to sue, and restrictions tied to specific formulations. Public docket records, FDA litigation listings, and SEC filings are necessary to distinguish a settlement involving this patent from one involving a related Gralise patent.[3][4]

What licensing deals affect the Gralise patent estate?

Depomed entered commercial arrangements for Gralise before later corporate ownership changes. The most important commercial distinction is between:

A license to commercialize Gralise.
A license to practice the patented formulation.
A settlement license granted to an ANDA applicant.
A corporate acquisition transferring patent ownership.

A commercialization agreement does not necessarily transfer patent ownership or create a right for third parties to manufacture a competing extended-release product. Generic settlement licenses may be limited to the settling applicant, defined products, and agreed entry dates.

The ownership chain should be reviewed through USPTO assignment records, FDA product-holder records, SEC filings, and settlement documents. Assertio’s acquisition of Depomed transferred the relevant business and patent assets, but later ownership or commercialization changes do not automatically alter the original patent term.

How does the patent compare with competing gabapentin products?

Product	Active ingredient	Release approach	Relationship to U.S. 8,333,992
Neurontin generic	Gabapentin	Immediate release	Usually outside the claimed controlled-release PK profile
Gralise	Gabapentin	Extended-release matrix	Core commercial product associated with the patent family
Horizant	Gabapentin enacarbil	Prodrug converted to gabapentin	Generally outside literal claims requiring gabapentin in the claimed matrix
Generic extended-release gabapentin	Gabapentin	Product-specific	Exposure depends on matrix structure and comparative PK
Pregabalin products	Pregabalin	Immediate or controlled release depending on product	Chemically distinct and outside the claims

Horizant is not a conventional gabapentin matrix product. It contains gabapentin enacarbil, a prodrug, and therefore should not literally satisfy a claim requiring a matrix comprising gabapentin. The doctrine of equivalents analysis would be fact-specific and is less straightforward where the active pharmaceutical ingredient is chemically different.

What generic launch scenarios exist?

Launch after patent expiration

This is the lowest patent risk scenario for U.S. Patent 8,333,992 itself, assuming no patent-term adjustment or surviving continuation patent controls entry.

Paragraph IV launch

A generic applicant may challenge listed patents before expiration. The applicant may launch after:

A court decision finding the patent invalid or not infringed.
A settlement-authorized entry date.
Failure of the patent owner to obtain an FDA stay.
Expiration of the relevant patent and any applicable exclusivity.

Section viii carve-out

A carve-out may be possible for method-of-use claims if the applicant removes the protected indication from its labeling. This strategy is less useful against broad dosage-form claims such as claims 1 and 9.

At-risk launch

An applicant may launch before final resolution, accepting potential damages and injunctive exposure. For a patent with a nominal 2024 expiration date, the commercial value of an at-risk launch would depend mainly on the remaining patent term and the scope of later patents.

What manufacturing and IP barriers remain?

The formulation itself may be technically difficult because gabapentin has dose, solubility, absorption, and gastrointestinal-transit constraints. A successful design-around may use:

A different release-controlling polymer.
A non-matrix delivery system.
A multiparticulate formulation.
A gastroretentive or site-specific delivery system.
A different release profile that fails one or more PK limitations.
A different strength or dosing schedule.

A design-around that changes the formulation but still produces the same claimed PK profile may remain exposed to the functional limitations. Conversely, a formulation that has sustained release but fails the AUC, Cmax, Tmax, or release-location requirements may avoid literal infringement while remaining subject to an equivalents argument.

Key Takeaways

U.S. Patent 8,333,992 covers extended-release gabapentin matrix dosage forms and related treatment methods.
The central limitations are 5-12 hour upper-GI release, reduced or delayed peak exposure, and at least 80% of immediate-release AUC.
Claims 9 and 14 are commercially important for 300 mg and 600 mg products.
The patent uses functional pharmacokinetic limitations that can complicate both infringement and validity analysis.
A generic product using gabapentin in a matrix is not automatically infringing; comparative human PK and release-location evidence are central.
Horizant is materially different because it uses gabapentin enacarbil rather than gabapentin in the claimed matrix.
The nominal patent term appears to have ended in December 2024, but the full exclusivity analysis requires review of patent-term adjustment and related continuation patents.
Gralise generic risk must be assessed across the entire Orange Book patent estate, not against U.S. Patent 8,333,992 alone.
Method-of-use carve-outs may address some treatment claims but generally do not eliminate exposure to broad dosage-form claims.
The most credible design-around strategies alter the matrix architecture or produce a PK profile outside the claimed parameters.

FAQs

Does U.S. Patent 8,333,992 cover all extended-release gabapentin tablets?

No. It covers products meeting the patent’s matrix, release, comparative PK, and exposure limitations. An extended-release gabapentin product with a materially different release location or pharmacokinetic profile may avoid the claims.

Can an immediate-release gabapentin generic infringe this patent?

Ordinary immediate-release gabapentin is unlikely to satisfy the controlled-release limitations. The patent requires release over approximately 5-12 hours and a defined relationship to immediate-release gabapentin.

Does a 600 mg gabapentin tablet automatically infringe claim 9?

No. The 600 mg dose is only one limitation. The product must also satisfy the matrix, upper-GI release, comparative Cmax, and AUC requirements.

Can a manufacturer avoid the patent by using a different polymer?

Possibly, but polymer substitution alone is not determinative. A different polymer may still produce the claimed release and PK profile, while a formulation using the same polymer may avoid infringement if it fails a required claim limitation.

Is a gabapentin enacarbil product covered by this patent?

Generally, no literal infringement should arise solely from using gabapentin enacarbil because the claims require a matrix comprising gabapentin. The analysis would depend on the actual composition and any asserted equivalents theory.

References

U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book
U.S. Food and Drug Administration. (n.d.). Hatch-Waxman Amendments: Questions and answers. https://www.fda.gov
United States Patent and Trademark Office. (n.d.). Patent Center. https://patentcenter.uspto.gov
U.S. Securities and Exchange Commission. (n.d.). EDGAR company filings. https://www.sec.gov/edgar/search/
U.S. Patent No. 8,333,992, Extended release dosage forms of gabapentin (issued Dec. 18, 2012). U.S. Patent and Trademark Office.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2002348828	⤷ Start Trial
Australia	2005267738	⤷ Start Trial
Australia	2006332690	⤷ Start Trial
Canada	2464322	⤷ Start Trial
Canada	2575555	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 8,333,992