United States Patent 6,696,066: Claim Scope, Expiration, Orange Book Relevance, and Opioid Abuse-Deterrent Patent Landscape

US Patent 6,696,066 covers sustained-release oral opioid products that combine an opioid agonist with an opioid antagonist, principally hydrocodone or oxycodone with naltrexone. The claims require an analgesically effective oral product that is aversive to physically dependent users at therapeutic or higher doses and does not increase opioid analgesic efficacy. The patent also claims once-daily or twice-daily administration, 12-to-24-hour release, matrix formulations, antagonist-to-opioid ratios, and a method of deterring oral abuse.

The patent was issued on February 24, 2004. Its enforceable patent term expired in 2019 based on the patent’s underlying filing chronology. It therefore does not create a current blocking right against generic or branded products. Its commercial importance is historical and analytical: it established an early claim architecture for opioid-antagonist abuse-deterrent combinations later pursued in products such as Embeda and other extended-release opioid formulations.

What invention does US Patent 6,696,066 cover?

The patent covers a sustained-release oral dosage form containing four principal elements:

An opioid agonist.
An opioid antagonist.
A sustained-release carrier.
A dose and ratio that preserve analgesia while producing an aversive effect in physically dependent users.

The independent dosage-form claims are claims 1 and 58. The independent method claim is claim 30.

Claim group	Core subject matter	Principal limitations
Claims 1-29	Sustained-release oral dosage form	Opioid agonist, antagonist, sustained-release carrier, analgesic effect, aversive effect at higher or therapeutic dose
Claims 30-57	Method of treating oral abuse	Preparing a sustained-release opioid-antagonist dosage form with specified functional effects
Claims 58-63	Once-daily dosage form	Same general combination, with maintained or decreased analgesic efficacy and once-daily administration

The claims are not limited to one commercial product. They cover a platform concept involving several opioids, several antagonists, multiple ratios, and different matrix or coating arrangements.

What opioids and antagonists are covered by the patent claims?

The listed opioid agonists are:

Morphine
Hydromorphone
Hydrocodone
Oxycodone
Codeine
Levorphanol
Meperidine
Methadone
Mixtures of those opioids

The listed antagonists are:

Naltrexone
Naloxone
Nalmefene
Cyclazocine
Levallorphan
Mixtures of those antagonists

Hydrocodone/naltrexone is specifically claimed in claims 3-5 and 32-34. Oxycodone/naltrexone is specifically claimed in claims 11, 18, 36 and 37. The remaining opioid-specific claims primarily identify naltrexone as the antagonist.

Opioid agonist	Antagonist specified in claims	Representative ratio ranges
Hydrocodone	Naltrexone	0.03:1 to 0.27:1; 0.05:1 to 0.20:1
Oxycodone	Naltrexone	0.037:1 to 0.296:1; 0.056:1 to 0.222:1
Codeine	Naltrexone	0.005:1 to 0.044:1; 0.0083:1 to 0.033:1
Hydromorphone	Naltrexone	0.148:1 to 1.185:1; 0.222:1 to 0.889:1
Levorphanol	Naltrexone	0.278:1 to 2.222:1; 0.417:1 to 1.667:1
Meperidine	Naltrexone	0.0037:1 to 0.0296:1; 0.0056:1 to 0.022:1
Methadone	Naltrexone	0.056:1 to 0.444:1; 0.083:1 to 0.333:1
Morphine	Naltrexone	0.018:1 to 0.148:1; 0.028:1 to 0.111:1

The ratios are calculated as antagonist mass divided by opioid agonist mass. The claims do not state that every ratio is suitable for every opioid. Each opioid-specific dependent claim ties a particular range to a particular agonist.

Claims 13 and 23 as reproduced contain apparent drafting or transcription defects. Claim 13 recites a hydromorphone ratio of "0.148:2 to about 1.185:1," and claim 23 recites "0.083: to about 0.333:1." The patent’s issued text and prosecution record control the legally operative wording.

How broad is claim 1 of US Patent 6,696,066?

Claim 1 is broad in chemical scope but narrow in functional and formulation requirements.

A product would need to satisfy all of the following limitations:

It is a sustained-release oral dosage form.
It contains an orally therapeutically effective dose of an opioid agonist.
It contains an opioid antagonist.
It contains a sustained-release carrier.
The antagonist-to-agonist ratio preserves oral analgesic activity.
The combination is aversive in physically dependent human subjects when taken at the therapeutic dose or a higher dose.
The antagonist does not increase analgesic efficacy relative to the opioid alone.
The product is administrable once or twice daily.

The claim does not require:

A particular tablet shape.
A particular excipient.
A particular manufacturing process.
A particular antagonist, unless a dependent claim is being assessed.
A particular matrix polymer.
A particular release-dissolution profile beyond the once- or twice-daily limitation.
Physical sequestration of the antagonist inside a separate compartment.

The principal legal vulnerability of claim 1 is its functional language. Terms such as "aversive," "analgesically effective," and "does not increase analgesic efficacy" require factual interpretation. In an infringement dispute, the claimant would need to establish that the accused product meets those limitations, either through clinical evidence, human abuse-potential data, pharmacodynamic data, or an applicable claim-construction framework.

What formulations are protected by US Patent 6,696,066?

Claims 25-29 and 51-55 address formulation architecture.

The patent claims:

Opioid release for approximately 12 to 24 hours.
Incorporation of agonist and antagonist in a matrix.
Incorporation of the sustained-release carrier into the matrix.
Coating of the sustained-release carrier onto the matrix.
A hybrid formulation in which the carrier is incorporated with the opioid agonist and coated onto the matrix.

The formulation claims therefore reach both matrix-controlled and coated-matrix systems. They do not require a specific polymer. A sustained-release carrier could include hydrophilic polymers, hydrophobic materials, waxes, ion-exchange materials, or other pharmaceutically acceptable release-control systems disclosed or enabled by the patent.

Claim 29 is commercially significant because it covers a combined architecture in which release control is achieved through both matrix incorporation and coating. A later product using a different polymer could still face a claim if it satisfies the functional limitations and the structural requirements.

The claims also permit additional non-opioid drugs, including:

Acetaminophen
Aspirin
NSAIDs
COX-2 inhibitors
NMDA receptor antagonists
Antitussives
Expectorants
Decongestants
Antihistamines

Those additions are claimed in a dependent manner and do not independently define the central invention.

What is the difference between claims 1, 30, and 58?

Claims 1, 30, and 58 cover related but legally distinct subject matter.

Claim	Claim type	Distinguishing feature
Claim 1	Composition	Sustained-release oral product administered once or twice daily
Claim 30	Method	Preparing a sustained-release opioid product with an antagonist to treat oral abuse
Claim 58	Composition	Once-daily product that maintains or decreases analgesic efficacy

Claim 58 is broader in one respect because it permits the combination to "maintain or decrease" analgesic efficacy. Claim 1 requires that the combination maintain analgesic effect without increasing efficacy. Claims 56 and 57 reinforce the possibility that the antagonist ratio may decrease analgesia, based on direct or surrogate human measurements.

Claims 30-57 are method claims. They require conduct directed to preparing the dosage form, rather than merely making or selling the product. A method claim may present different infringement questions from a composition claim, particularly where a third party purchases a finished dosage form from another manufacturer.

When did US Patent 6,696,066 expire?

US Patent 6,696,066 issued on February 24, 2004. Its ordinary patent term expired in 2019, calculated from the relevant US nonprovisional filing date and subject to any applicable patent-term adjustment or terminal-disclaimer information recorded by the USPTO.

Event	Date or period
Patent issued	February 24, 2004
Patent term	20 years from the applicable nonprovisional filing date
Expected expiration period	2019
Current enforceability	Expired
Current Paragraph IV significance	None as an enforceable patent right

The expiration of the patent does not eliminate its value as prior art. The patent can remain relevant to novelty, obviousness, written-description, enablement, and double-patenting analyses involving later opioid abuse-deterrent patents.

What is the Orange Book status of US Patent 6,696,066?

The patent should not be treated as a current Orange Book barrier solely because it historically covered opioid-antagonist formulations. Orange Book relevance depends on whether a patent was submitted for a specific approved drug and whether the FDA accepted it for listing under the applicable statutory category.

The patent itself is not a current basis for an FDA approval delay because it has expired. A generic applicant would not need to provide a Paragraph IV certification against an expired patent as a basis for avoiding infringement. The more relevant Orange Book patents for abuse-deterrent opioids are later patents tied to specific approved products and product-specific formulations.

FDA Orange Book patent categories generally focus on:

Drug substance patents.
Drug product or formulation patents.
Method-of-use patents.

A broad, expired platform patent such as US 6,696,066 may have influenced later product development without remaining a live listed patent obstacle.

Which later products and patent estates are most relevant?

The principal commercial comparison is with later extended-release opioid products that use either antagonist combinations or physical abuse-deterrent technology.

Product or technology	Opioid	Abuse-deterrent approach	Relationship to US 6,696,066
Embeda	Morphine sulfate/naltrexone	Sequestered naltrexone in an extended-release formulation	Closest commercial concept to the claimed agonist-antagonist platform
Targiniq ER	Oxycodone/naloxone	Oxycodone combined with naloxone	Same general pharmacologic strategy, but different antagonist and later patent estate
OxyContin OP	Oxycodone	Physical and chemical abuse-deterrent formulation	Does not depend on the naltrexone platform
Hysingla ER	Hydrocodone	Abuse-deterrent extended-release formulation	Hydrocodone product, but not necessarily a naltrexone combination
Xtampza ER	Oxycodone	Microsphere-in-capsule, abuse-deterrent delivery technology	Formulation and manufacturing barriers rather than opioid-antagonist ratios
Vantrela ER	Hydrocodone	Abuse-deterrent extended-release tablet	Competes in hydrocodone extended-release delivery

Embeda is the closest product comparison because it combines morphine with naltrexone. Its relevant patent estate was developed after the issuance of US 6,696,066 and includes later patents directed to specific formulation and sequestration technology. Targiniq ER uses naloxone rather than naltrexone and therefore falls outside the naltrexone-specific dependent claims, although the broad independent claims must be analyzed separately based on the exact claim scope and expiration status.

How strong was the patent estate for commercial enforcement?

The patent had meaningful historical breadth but limited present-day value.

Historical strengths

It covered multiple opioid agonists.
It identified multiple opioid antagonists.
It claimed both composition and method categories.
It included once-daily and twice-daily administration.
It covered specific ratio windows.
It addressed both matrix and coating technologies.
It captured the functional objective of aversion without loss of analgesia.

Structural limitations

The claims depend heavily on human-response and pharmacodynamic limitations.
Some dependent claims repeat overlapping ratio ranges.
The patent claims a broad set of opioid-antagonist combinations without assigning a commercial product to each.
Infringement would require product-specific analysis of release behavior, dose, ratio, and clinical effect.
The patent’s expiration removes its ability to block current market entry.

The broad independent claims could have supported enforcement against a product using the same therapeutic and abuse-deterrent concept during the patent term. Later entrants could design around the patent by using physical sequestration, a different abuse-deterrent mechanism, different release architecture, different antagonist ratios, or a different therapeutic configuration.

What Paragraph IV challenges and litigation affected this patent?

Because US Patent 6,696,066 expired in 2019, it is not a current Paragraph IV litigation risk. Historical ANDA applicants could have challenged the patent if it was listed for an approved reference product, but the practical relevance of any such challenge ended with patent expiration.

The more important litigation and settlement questions concern later patents covering:

Embeda’s morphine/naltrexone formulation.
Targiniq ER’s oxycodone/naloxone formulation.
Abuse-deterrent oxycodone products.
Hydrocodone extended-release formulations.
Manufacturing processes and controlled-release excipients.

A Paragraph IV certification against an unexpired formulation or method-of-use patent can trigger a 30-month FDA approval stay under the Hatch-Waxman framework if the statutory requirements are met. That mechanism does not revive an expired platform patent.

No current generic launch restriction should be attributed to US 6,696,066 alone.

What manufacturing and intellectual-property barriers remain?

The patent’s expiration does not eliminate technical barriers to commercialization. A competing product still must solve:

Uniform distribution of the antagonist.
Compatibility between opioid and antagonist during storage.
Controlled release over 12 to 24 hours.
Prevention of dose dumping.
Preservation of analgesia at the intended dose.
Aversion at higher doses or in opioid-dependent subjects.
Scalable matrix or coating manufacture.
Bioequivalence to the reference product.
Abuse-deterrent labeling requirements.
Controlled-substance manufacturing and distribution controls.

Later patents often concentrate on those implementation details. They may claim polymer selection, particle size, coating thickness, antagonist sequestration, multiparticulate systems, extraction resistance, or manufacturing processes. Those patents can create a commercial barrier even when the older platform patent has expired.

How does US Patent 6,696,066 compare with later abuse-deterrent patents?

US 6,696,066 is primarily a pharmacologic combination patent. Its central proposition is that an antagonist can be incorporated into a sustained-release opioid dosage form at a ratio that preserves analgesia but produces aversion in abusers.

Later abuse-deterrent patents generally fall into four categories:

Antagonist-sequestration patents, where the antagonist is released disproportionately if the dosage form is manipulated.
Physical-resistance patents, where the tablet resists crushing, grinding, chewing, or extraction.
Tamper-responsive release patents, where manipulation alters gel formation or drug release.
Multiparticulate and coating patents, where opioid release and abuse deterrence are controlled through particle engineering.

The older patent is broader at the concept level. Later patents are often narrower but stronger in implementation because they are tied to specific products, formulations, manufacturing processes, and FDA-approved dosage forms.

Key Takeaways

US Patent 6,696,066 covers sustained-release oral opioid products containing an opioid agonist, an opioid antagonist, and a release-control carrier.
The claims focus on preserving analgesia while producing an aversive response in physically dependent users.
Hydrocodone/naltrexone and oxycodone/naltrexone are expressly claimed.
Morphine, hydromorphone, codeine, levorphanol, meperidine, and methadone are also included.
The patent claims antagonist-to-opioid ratios, 12-to-24-hour release, matrix systems, coatings, and once-daily or twice-daily dosing.
The patent issued on February 24, 2004 and expired in 2019.
It is no longer a current blocking patent or independent Paragraph IV barrier.
Its prior-art value remains relevant to later opioid abuse-deterrent patent validity analyses.
Later commercial products generally rely on newer formulation, sequestration, manufacturing, and abuse-deterrence patents.
Embeda is the closest commercial comparator because it combines an opioid with naltrexone.

FAQs About US Patent 6,696,066

Does US Patent 6,696,066 cover Embeda?

It covers the general concept of a sustained-release opioid combined with an antagonist, including morphine/naltrexone in the broad claim structure. Embeda’s commercial protection depends on later product-specific patents and regulatory listings, not solely on US 6,696,066.

Can a generic manufacturer launch a product covered by the expired patent?

Expiration removes the patent infringement barrier. A generic manufacturer must still address unexpired patents covering the reference product, FDA approval requirements, controlled-substance regulations, and any applicable formulation or manufacturing patents.

Does the patent cover naloxone combinations?

Naloxone is expressly included in the antagonist list in claims 9 and 35. The patent therefore reaches certain naloxone combinations at the claim-category level, although the patent’s expiration prevents current enforcement.

Are the ratio ranges mass ratios?

The claims state ratios of antagonist to agonist. In pharmaceutical claim practice, those ratios ordinarily require analysis of the relevant quantities and the patent specification’s measurement conventions. Product-specific infringement analysis would examine the formulation composition and claim construction.

Does a physical abuse-deterrent oxycodone tablet infringe this patent?

Not automatically. A product using physical resistance without an opioid antagonist may fall outside the combination claims. The answer depends on whether the product contains the claimed agonist-antagonist combination, sustained-release carrier, dosing schedule, and functional limitations.

References

United States Patent No. 6,696,066, "Sustained release opioid antagonist combinations." U.S. Patent and Trademark Office. Issued February 24, 2004.
U.S. Patent and Trademark Office. (2024). Patent Center and Patent Examination Data System records for U.S. Patent No. 6,696,066. Alexandria, VA: USPTO.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book. Silver Spring, MD: FDA.
U.S. Food and Drug Administration. (2015). Abuse-deterrent opioids: Evaluation and labeling guidance for industry. Silver Spring, MD: FDA.
Leahy-Smith America Invents Act, 35 U.S.C. §§ 100 et seq. (2011).
Drug Price Competition and Patent Term Restoration Act, 21 U.S.C. § 355(j). (1984).

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	1685839	⤷ Start Trial	C300619	Netherlands	⤷ Start Trial
European Patent Office	1685839	⤷ Start Trial	92292	Luxembourg	⤷ Start Trial
European Patent Office	1685839	⤷ Start Trial	CA 2013 00052	Denmark	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,696,066

Summary for Patent: 6,696,066