United States Patent 8,329,216: Oxymorphone Extended-Release Patent Scope, Expiration, and Patent Landscape

US Patent 8,329,216 covers controlled-release oral oxymorphone formulations, including Opana ER-type matrix tablets, defined by both formulation architecture and clinical or dissolution performance. Its broadest commercial relevance is concentrated in claims requiring a 12-hour release profile, hydrophilic or gelling matrix technology, food-effect pharmacokinetics, and characteristic oxymorphone plasma peaks.

The patent issued on December 11, 2012, to Endo Pharmaceuticals, Inc. The patent is no longer an active barrier to U.S. generic entry because its expected patent-term expiration occurred in 2023. The patent remains important as a historical reference for Opana ER formulation technology and for assessing validity, infringement, and settlement positions taken during the earlier genericization period.

What does US Patent 8,329,216 protect?

US 8,329,216 protects controlled-release oral dosage forms containing approximately 5 mg to 80 mg of oxymorphone or an oxymorphone salt as the sole active ingredient. The claims focus on four technical elements:

A hydrophilic controlled-release matrix.
Defined in vitro dissolution performance.
Defined in vivo pharmacokinetic behavior.
Sustained analgesia for at least approximately 12 hours.

The claims do not broadly cover all oxymorphone products. They target a formulation that combines oxymorphone with a release-controlling matrix and produces specified dissolution, plasma-concentration, or food-effect characteristics.

The principal claim categories are:

Claim category	Claims	Primary limitation
Oral formulation with pharmacokinetic profile	1-12	Oxymorphone, hydrophilic material, metabolite exposure, 12-hour analgesia and two or three plasma peaks
Direct-compression tablet	13-20	Controlled-release granules, direct compression, 15%-50% release at one hour
Tablet dissolution and analgesia	21-30	Specified dissolution milestones and 12-24-hour pain relief
Food-effect method claims	31-48	Fed-state Cmax at least 50% higher than fasted-state Cmax
Composition claims with food effect	49-54	Controlled release, dissolution, and fed/fasted pharmacokinetics
Composition claims with metabolite exposure	55-65	Oxymorphone and 6-hydroxy-oxymorphone levels and dissolution profile
Multiple-peak plasma claims	66-71	One, two, or three oxymorphone plasma peaks
Gelling-agent matrix claims	72-82	Matrix containing 10%-75% gelling agent and specified dissolution or food-effect behavior

What are the broadest independent claims in US 8,329,216?

The broadest practical claim groups are claims 1, 21, 31, 49, 55, 66, 72, 77, 81, and 82. Each claims a different combination of structural, performance, or method limitations.

Claim 1: pharmacokinetic formulation claim

Claim 1 requires:

An oral controlled-release oxymorphone formulation.
Approximately 5 mg to 80 mg of oxymorphone or a pharmaceutically acceptable salt.
A hydrophilic material.
Detectable oxymorphone and 6-hydroxy-oxymorphone plasma levels.
Peak plasma levels within approximately one to eight hours.
A metabolite-to-parent AUC ratio of approximately 0.5 to 1.5.
Analgesia lasting at least approximately 12 hours.
Two or three oxymorphone plasma peaks within approximately 12 hours.

This is a compound-performance claim rather than a simple excipient claim. A product could contain a hydrophilic matrix and still avoid literal infringement if its measured pharmacokinetic profile does not satisfy one or more of the plasma-level limitations. Conversely, a structurally different formulation could present risk if it produces all claimed pharmacokinetic characteristics.

Claims 21-30: dissolution-profile tablet claims

Claim 21 requires a tablet that:

Contains oxymorphone or an oxymorphone salt.
Uses one or more controlled-release excipients.
Releases approximately 15%-50% of drug at one hour in a USP Paddle Method test.
Provides 12-24-hour pain relief.

Claim 22 adds:

45%-80% release at four hours.
At least 80% release at 10 hours.

Claim 23 provides a more detailed release schedule:

Test time	Minimum cumulative release
1 hour	27%
2 hours	40%
3 hours	50%
5 hours	64%
6 hours	70%
8 hours	79%
10 hours	85%
12 hours	89%

The dependent claims from 24 through 30 isolate individual release thresholds. These claims create multiple potential infringement positions because a product may satisfy one or several individual dissolution limitations without satisfying the full profile in claim 23.

Claims 72 and 77: gelling-agent matrix claims

Claim 72 requires:

Oxymorphone as the sole active ingredient.
A controlled-release matrix.
Approximately 10%-75% gelling agent by total matrix weight.
The gelling agent must form a gel upon exposure to gastrointestinal fluid.
15%-50% oxymorphone release at approximately one hour.

Claim 77 adds a more complete release profile:

15%-50% release at one hour.
45%-80% release at four hours.
At least 80% release at 10 hours.
Fed-state Cmax at least 50% higher than fasted-state Cmax.
Fed-state AUC less than 20% higher than fasted-state AUC.

Claim 77 is commercially significant because it combines a formulation limitation, dissolution limitations, and a clinical food-effect limitation. The claim is narrower than a conventional matrix-tablet claim but potentially stronger against a product that reproduces the specific Opana ER performance characteristics.

What formulations are protected by US 8,329,216?

The patent protects a range of hydrophilic matrix systems. The claims expressly identify gums, cellulose ethers, acrylic resins, protein-derived materials, and mixtures.

Claimed hydrophilic materials

Claims 2-6 identify:

Xanthan gum.
Tragacanth.
Acacia.
Karaya.
Alginates.
Agar.
Guar and hydroxypropyl guar.
Carrageenan.
Locust bean gum.
Hydroxyethyl cellulose.
Hydroxypropyl cellulose.
Hydroxypropyl methylcellulose.
Carboxymethylcellulose.

Claims 7-10 focus on heteropolysaccharide systems, particularly xanthan-based matrices. The claims contemplate:

A heteropolysaccharide alone.
A heteropolysaccharide combined with a cross-linking agent.
A heteropolysaccharide, cross-linking agent, and polysaccharide gum mixture.
Xanthan, deacylated xanthan, carboxymethyl ether xanthan, or propylene glycol ester xanthan.
A homopolysaccharide gum as the cross-linking agent.

Claim 11 adds a hydrophobic polymer. That limitation can capture mixed hydrophilic-hydrophobic matrices rather than purely hydrophilic systems.

Gelling-agent concentration

Claims 72 and 77 require a gelling agent representing approximately 10%-75% of the total controlled-release matrix. This limitation is material to both infringement and validity analysis. The relevant calculation is based on the matrix, not necessarily the entire tablet weight. Excipients outside the matrix may therefore affect claim analysis differently from excipients included within the matrix.

How do the dissolution limitations affect infringement analysis?

The dissolution claims use a defined test:

USP Paddle Method.
50 revolutions per minute.
500 mL medium.
pH from 1.2 to 6.8.
Temperature of 37°C.

The language presents several claim-construction issues:

Whether the pH range describes alternative test conditions or a sequential test.
Whether "about" permits a technical tolerance around each percentage and time point.
Whether the dissolution result must be met at every pH within the range.
Whether release is measured as cumulative release of oxymorphone from the tablet.
Whether the test must use the exact medium volume and agitation conditions.

A generic applicant would normally evaluate the entire dissolution profile, not only the one-hour result. A product that releases too slowly at one hour could avoid a claim requiring 15%-50% release. A product that exceeds the upper limit at one hour could also avoid literal infringement of a claim with a closed numerical range, subject to claim construction and the doctrine of equivalents.

The detailed profile in claim 23 may create a narrower but more testable infringement theory. Laboratory reproducibility, assay variability, sampling intervals, and media preparation can become important in litigation.

What are the pharmacokinetic limitations?

The patent contains unusually extensive pharmacokinetic limitations for a formulation patent.

Oxymorphone and 6-hydroxy-oxymorphone exposure

Claims 1, 37, 42, 68, 76, and 78 require:

Detectable plasma oxymorphone.
Detectable plasma 6-hydroxy-oxymorphone.
Peak concentrations within approximately one to eight hours.
A 6-hydroxy-oxymorphone-to-oxymorphone AUC ratio of approximately 0.5 to 1.5.

These limitations seek to distinguish the claimed controlled-release product by its systemic exposure profile and metabolite relationship. They may be difficult to assess from an ANDA alone because the applicant may not disclose all clinical plasma data publicly. In an ANDA litigation setting, the applicant's bioequivalence studies, product samples, dissolution data, and expert pharmacokinetic analysis would be central.

Multiple plasma peaks

Claims 1, 66-71, 75, and 78 cover formulations producing two or three oxymorphone plasma peaks within approximately 12 hours. Claim 70 identifies:

A first peak at approximately three hours.
A second peak at approximately six to seven hours.

Multiple peaks can result from matrix erosion, delayed gastrointestinal transit, differential release from granules, or food-related changes in absorption. The claim language does not appear to require a particular mechanism. It focuses on the observed plasma profile.

Food-effect limitations

Claims 31-56 and 77-82 require a specific fed-versus-fasted relationship:

Oxymorphone Cmax at least 50% higher under fed conditions.
In certain dependent claims, approximately 58% higher Cmax.
AUC difference less than 20%.
Claim 36 identifies approximately 18% AUC difference.

These limitations are commercially relevant because a generic formulation with a materially different food effect could potentially avoid the claims while remaining bioequivalent under FDA standards. The limitations also raise questions about study design, meal composition, fasting period, dose strength, statistical treatment, and whether "at least 50% higher" is evaluated using mean values or individual-subject data.

When did US Patent 8,329,216 lose exclusivity?

US Patent 8,329,216 reached the end of its standard patent term in 2023. The patent term was tied to the relevant priority and continuation chain rather than to the 2012 issue date. The applicable expiration was approximately July 2023, subject to the official USPTO term calculation and any patent-term adjustment.

The patent's commercial exclusivity also depended on FDA regulatory exclusivity and Orange Book listings. Patent expiration and regulatory exclusivity are separate concepts. FDA approval of an ANDA may have been restricted before patent expiry by listed patent certifications, litigation, pediatric exclusivity, or settlement terms.

Event	Approximate date
Earliest relevant family filing	2003
US 8,329,216 issued	December 11, 2012
Expected standard patent-term expiry	July 2023
Opana ER U.S. marketing withdrawal	2017
Post-expiration patent barrier	None from US 8,329,216

What was the FDA and Orange Book status of the related oxymorphone product?

The principal commercial product associated with this technology was Opana ER, an extended-release oxymorphone hydrochloride tablet marketed by Endo Pharmaceuticals.

FDA requested withdrawal of reformulated Opana ER in 2017 after concluding that the benefits of the product no longer outweighed its risks because of concerns related to abuse by injection. FDA stated that the withdrawal was based on public-health considerations, not on a finding that the product lacked efficacy for its approved indication. FDA also determined that the product should not be withdrawn for reasons of safety or effectiveness in a manner that would permit ANDA applicants to rely on the withdrawal as a basis for approval.[1]

The practical consequences were:

Opana ER was no longer marketed in the United States.
The product remained relevant to historical Orange Book and ANDA litigation analysis.
Generic applicants could not treat the withdrawal as a simple product-discontinuation issue.
The product's controlled-release technology remained relevant to bioequivalence and patent disputes.

Orange Book listing information should be checked by product strength and historical edition because listed patents, delisting events, and marketing status can change over time. US 8,329,216 was one member of a larger Opana ER patent estate, and analysis of the product cannot rely on this patent alone.[2]

How many patents covered Opana ER and related oxymorphone formulations?

The Opana ER estate included multiple patent families covering different aspects of the product and its use. The relevant categories included:

Controlled-release formulation technology.
Matrix composition.
Oxymorphone dosage strengths.
Abuse-deterrent or tamper-resistant formulations.
Methods of treating pain.
Manufacturing and tablet-processing techniques.
Pharmacokinetic and dissolution performance.

US 8,329,216 appears to belong to the controlled-release formulation family rather than representing the entire Opana ER patent estate. Related continuation and divisional applications could have overlapping specifications but different claim scope. A family-level review is required to determine whether a generic product faces residual risk from continuation patents after expiration of this patent.

Known publicly associated Opana ER patent activity included Endo and related entities, with patent disputes involving generic applicants such as Actavis, Impax Laboratories, Sandoz, and other ANDA filers. The exact list of Orange Book-listed patents depended on the applicable product, strength, and date.[2][3]

Which companies challenged Opana ER patents?

Generic challenges to Opana ER involved multiple ANDA applicants. Public litigation and regulatory records identify disputes involving companies including:

Actavis.
Impax Laboratories.
Sandoz.
Endo Pharmaceuticals.
Endo Health Solutions and affiliated entities.

The disputes included Paragraph IV certifications directed to listed formulation and method-of-use patents. The central business issues were whether the generic formulation infringed the asserted claims, whether the claims were valid, and whether settlements delayed launch.

The most significant public antitrust and settlement-related proceeding was FTC litigation concerning Endo's agreements with generic applicants. In FTC v. Actavis, the Supreme Court held that certain reverse-payment settlements can violate antitrust law and must be evaluated under a rule-of-reason framework rather than treated as categorically lawful or unlawful.[4] The decision did not itself invalidate US 8,329,216, but it affected the legal environment for pharmaceutical patent settlements.

What patent litigation affected the oxymorphone market?

The Opana ER litigation landscape included three recurring issues.

Paragraph IV certification disputes

ANDA applicants could certify that listed patents were invalid, unenforceable, or not infringed. A Paragraph IV notice generally created the statutory pathway for patent litigation under 35 U.S.C. §271(e)(2), which treats submission of an ANDA with the required certification as an artificial act of infringement.[5]

Abuse-deterrent reformulation disputes

Endo's reformulated Opana ER used physical and chemical properties intended to make abuse more difficult. FDA's 2017 withdrawal decision affected the regulatory status of the product but did not automatically resolve all patent disputes involving the formulation.

Settlement agreements

Settlements could provide a negotiated generic entry date, licensing rights, or other commercial terms. Their value depended on:

Remaining patent life.
Probability of invalidity or noninfringement.
FDA approval timing.
Potential damages exposure.
Antitrust risk under FTC v. Actavis.

No current commercial exclusivity should be attributed to US 8,329,216 after its 2023 patent-term expiration.

How strong was the patent estate for US 8,329,216?

The patent had meaningful historical value because it claimed a combination of structural and performance parameters closely associated with a commercial extended-release oxymorphone product. Its strength varied by claim.

Claim type	Historical strength	Main vulnerability
Broad hydrophilic-matrix claims	Moderate	Prior art involving opioid hydrophilic matrices
Xanthan and polysaccharide claims	Moderate to strong	Known use of gums in controlled-release tablets
Dissolution-profile claims	Stronger for product-specific enforcement	Test variability and design-around release rates
Food-effect claims	Narrow but potentially useful	Reproducibility and clinical-study dependence
Multiple-peak claims	Narrow	Subject-to-subject pharmacokinetic variation
Gelling-agent claims	Moderate	Prior art on gel-forming matrices and numerical ranges
Method-of-treatment claims	Dependent on formulation limitations	Inducement and divided-infringement issues

The patent's validity risk would have centered on obviousness, written description, enablement, indefiniteness, and anticipation. The most exposed limitations were the use of known hydrophilic excipients and the predictable objective of achieving 12-hour opioid release. The more specific combinations of dissolution, food-effect, metabolite, and multiple-peak parameters could have provided stronger distinctions over generic controlled-release opioid prior art.

What generic entry risks exist after patent expiration?

After expiration of US 8,329,216, the patent itself presents no continuing U.S. patent infringement barrier. Residual risks could arise from:

Other unexpired Opana ER or oxymorphone patents.
Separate patents covering abuse-deterrent technology.
Regulatory exclusivity.
Product-specific labeling restrictions.
Controlled-substance manufacturing and distribution requirements.
FDA requirements for demonstrating bioequivalence to a discontinued or withdrawn reference product.
State and federal opioid-control rules.

A generic applicant would need to distinguish between:

Patent risk from this patent.
Patent risk from related family members.
FDA reference-product and bioequivalence risk.
Commercial risk from a small or declining oxymorphone market.

Because Opana ER was withdrawn and the branded product was no longer actively marketed, the commercial value of a generic launch is materially different from the value of a pre-expiration Paragraph IV launch. The market may be constrained by opioid prescribing trends, regulatory controls, payer restrictions, and limited demand.

How does US 8,329,216 compare with conventional extended-release opioid patents?

US 8,329,216 differs from a basic extended-release matrix patent in three ways:

Issue	Conventional matrix patent	US 8,329,216
Active ingredient	May cover broad drug classes	Oxymorphone or oxymorphone salt
Release definition	Often structural or dissolution-based	Dissolution plus pharmacokinetic and analgesic limitations
Clinical profile	Usually not required	Food effect, metabolite ratio, plasma peaks, and analgesia are central

The patent therefore sits between a formulation patent and a product-by-performance patent. Its claims are narrower than a broad opioid matrix claim but more closely aligned with the commercial product's observed behavior.

Key Takeaways

US 8,329,216 covers controlled-release oral oxymorphone formulations, particularly hydrophilic and gelling matrix tablets.
The claims cover approximately 5 mg to 80 mg oxymorphone, 12-hour analgesia, defined dissolution profiles, and specific pharmacokinetic behavior.
Xanthan gum, cellulose ethers, other polysaccharides, and mixed hydrophilic-hydrophobic systems are expressly identified.
The patent claims fed-state Cmax increases of at least 50%, in some claims approximately 58%, while limiting AUC differences to less than 20%.
Several claims target two or three oxymorphone plasma peaks and a 6-hydroxy-oxymorphone-to-oxymorphone AUC ratio of approximately 0.5 to 1.5.
The patent issued December 11, 2012, and reached its expected patent-term expiration in approximately July 2023.
US 8,329,216 is no longer a standalone U.S. exclusivity barrier.
Historical Opana ER generic litigation involved Endo, Actavis, Impax, Sandoz, and other ANDA participants.
Residual launch risk must be assessed against the broader Opana ER patent family, not this patent in isolation.
The commercial opportunity is limited by Opana ER's 2017 withdrawal, opioid-market contraction, and controlled-substance regulation.

FAQs

Does US 8,329,216 cover immediate-release oxymorphone?

No. The claims require controlled-release characteristics, a controlled-release delivery system, a matrix, or defined dissolution and pharmacokinetic behavior.

Does the patent cover oxymorphone combined with another active ingredient?

Generally no. Many claims expressly require oxymorphone to be the sole active ingredient.

Is a xanthan-gum oxymorphone tablet automatically infringing?

No. Xanthan gum is expressly identified, but infringement also depends on the applicable claim's dose, matrix structure, dissolution profile, pharmacokinetic behavior, and other limitations.

Are the food-effect claims relevant to FDA approval?

They can be relevant to patent infringement, but FDA bioequivalence standards and patent claim limitations are separate analyses. A product may satisfy FDA bioequivalence requirements without reproducing every claimed fed-versus-fasted characteristic.

Can a generic launch after 2023 still face Opana ER patent litigation?

Yes, but not from US 8,329,216 solely because it covered the same formulation concept. A launch could still face separate unexpired patents, continuation patents, regulatory disputes, or claims directed to other product features.

References

U.S. Food and Drug Administration. (2017, June 8). FDA requests removal of Opana ER for risks related to abuse. https://www.fda.gov/news-events/press-announcements/fda-requests-removal-opana-er-risks-related-abuse
U.S. Food and Drug Administration. (2023). Approved drug products with therapeutic equivalence evaluations: The Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book-data-files
United States Patent and Trademark Office. (2023). Patent Center and Patent Examination Data System. https://patentcenter.uspto.gov
Federal Trade Commission v. Actavis, Inc., 570 U.S. 136 (2013).
Hatch-Waxman Amendments, 21 U.S.C. §355(j); 35 U.S.C. §271(e)(2).
U.S. Patent No. 8,329,216. (2012). Controlled release oxymorphone formulations. U.S. Patent and Trademark Office.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	359077	⤷ Start Trial
Austria	376832	⤷ Start Trial
Australia	2002316582	⤷ Start Trial
Australia	2002318211	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 8,329,216

Summary for Patent: 8,329,216