US Patent 8,361,499: Hydrocodone Extended-Release Dosage-Form Scope and Patent Landscape

US Patent 8,361,499 covers solid oral controlled-release hydrocodone dosage forms defined by both formulation architecture and pharmacokinetic performance. Its broadest independent claim reaches matrix, coated multiparticulate, spheroid, and osmotic systems if they deliver hydrocodone over 8 to at least 24 hours, meet specified in-vitro dissolution ranges, and produce a relatively flat plasma profile with a C24/Cmax ratio of about 0.55 to 1.0.

The patent is commercially relevant to extended-release hydrocodone products, particularly Zohydro ER-type formulations. The principal enforcement risk is not the use of hydrocodone alone. It is the combination of hydrocodone, a controlled-release mechanism, dissolution performance, and human pharmacokinetic results.

What does US Patent 8,361,499 claim?

The patent claims a solid oral dosage form containing:

An analgesically effective amount of hydrocodone or a pharmaceutically acceptable salt;
A controlled-release material;
An 8-hour to at least 24-hour release period;
Defined in-vitro dissolution behavior; and
A relatively flat hydrocodone plasma profile after peak concentration.

Claim 1 is the central claim. Claims 2 through 30 narrow it by adding pharmacokinetic, formulation, manufacturing, and dosage-form limitations.

Claim 1: broad composition and performance claim

Claim 1 is an open-ended "comprising" claim. That drafting expands its reach because additional excipients, layers, coatings, or release-control mechanisms do not avoid the claim if all required elements remain present.

The controlled-release material may be selected from:

Hydrophobic polymers;
Hydrophilic polymers;
Gums;
Protein-derived materials;
Waxes;
Shellac;
Oils; and
Mixtures of those materials.

The claim does not require a particular polymer, hydrocodone salt, tablet geometry, manufacturing process, or commercial brand. It instead uses a performance-defined boundary.

Required in-vitro dissolution profile

The claimed formulation must meet the following hydrocodone release ranges when tested using the USP Basket Method at 100 rpm in 900 mL of aqueous buffer at pH 1.6 to 7.2 and 37°C:

Time point	Claimed hydrocodone release
1 hour	0% to about 35%
4 hours	about 10% to about 70%
8 hours	about 20% to about 75%
12 hours	about 30% to about 80%
18 hours	about 40% to about 90%
24 hours	greater than about 60%

The ranges are broad and overlap many conventional extended-release designs. The pH range also matters. A formulation that complies at one pH but falls outside the claimed profile at another relevant test condition may create a non-infringement position, depending on how the claim and test protocol are construed.

Required pharmacokinetic profile

The formulation must provide a C24/Cmax ratio of approximately 0.55 to 1.0 after maximum plasma concentration is reached. Claim 4 narrows this range to 0.55 to 0.75.

This limitation creates a substantial technical barrier to infringement analysis. A generic manufacturer generally cannot determine the final risk from the ingredient list alone. Human pharmacokinetic studies, dose normalization, sampling intervals, and the comparator product may determine whether the claimed ratio is met.

How do the dependent claims narrow the patent scope?

The dependent claims divide into four principal clusters: pharmacokinetics, matrix systems, multiparticulates, and osmotic systems.

Pharmacokinetic limitations

Claims 2 through 4 add clinical and pharmacokinetic requirements:

Claim	Added limitation
2	Administration is the first administration
3	Therapeutic hydrocodone concentration for about 12 hours or longer and W50 of 4 to 22 hours
4	C24/Cmax ratio of 0.55 to 0.75

Claim 2 is unusual because "first administration" may implicate the intended pharmacokinetic study design rather than a structural product characteristic. Its enforceability may depend on claim construction and how the product is administered in the accused use.

W50 generally refers to the duration during which plasma concentration remains within 50% of the peak concentration. Claim 3 therefore adds a sustained exposure requirement beyond the dissolution profile.

Matrix formulations

Claims 5 through 15 cover matrix-based systems and coated granules.

Key limitations include:

Controlled-release material incorporated into a matrix;
A sustained-release coating over a hydrocodone substrate;
Alkylcellulose or hydroxyalkylcellulose;
A hydrophobic material with a melting point of about 30°C to 200°C;
Fatty acids, fatty alcohols, glyceryl fatty-acid esters, waxes, or polyalkylene glycols;
A coating containing an alkylcellulose, acrylic polymer, or both;
Granules containing water-soluble hydroxyalkyl cellulose and hydrocodone;
Wax as a water-insoluble coating material.

Claim 7 is particularly relevant to conventional hydrophilic matrix tablets because it identifies alkylcellulose and hydroxyalkylcellulose, including materials such as hydroxypropyl methylcellulose or hydroxypropyl cellulose. Claims 8 through 10 add lipid or wax components.

The presence of a polymer such as hypromellose does not by itself establish infringement. The accused dosage form must also satisfy the claim 1 dissolution and pharmacokinetic limitations unless the relevant dependent claim is being asserted together with all incorporated limitations.

Multiparticulate and spheroid formulations

Claims 16 and 17 cover multiparticulate formulations and spheroids. Claim 20 specifies spheroid diameters from 0.1 mm to 2.5 mm.

Claims 21 through 30 address combination-release products containing:

Controlled-release spheroids;
Immediate-release spheroids;
Acrylic-resin coatings;
Release-modifying agents;
Erosion-promoting agents;
Starch;
Talc;
Surfactants; and
Povidone.

Claim 30 covers a capsule containing both immediate-release and controlled-release spheroids. This architecture is relevant to products designed to provide an initial hydrocodone exposure followed by sustained delivery.

Osmotic systems

Claims 18 and 19 cover osmotic dosage forms containing:

A single-layer or bilayer core;
Hydrocodone;
An expandable polymer;
A semipermeable membrane; and
A passageway through the membrane.

These claims reach osmotic pump designs rather than conventional hydrophilic matrix tablets. The required passageway and expandable polymer provide identifiable structural limitations for freedom-to-operate analysis.

What formulations are protected by US 8,361,499?

The patent potentially covers the following formulation categories:

Formulation type	Relevant claims	Principal risk driver
Hydrophilic matrix tablet	1, 5-10	Polymer matrix plus claimed dissolution and PK profile
Hydrophobic matrix tablet	1, 5-10	Hydrophobic release-control material and performance
Coated granules	12-15	Hydroxyalkylcellulose core and polymer or wax coating
Multiparticulate capsule	16, 21-30	Mixed immediate-release and controlled-release spheroids
Acrylic-coated spheroids	17, 22-28	Acrylic resin coating and release modifiers
Osmotic pump	18-19	Membrane, expandable polymer, and passageway
Combination-release product	21, 30	Immediate-release and extended-release populations

The claim set is technically broad but commercially differentiated by the pharmacokinetic requirement. A formulation can resemble the claimed architecture and still avoid infringement if its plasma profile or dissolution curve falls outside the specified ranges. Conversely, a different excipient system may remain exposed if it produces the claimed performance.

When does US Patent 8,361,499 lose exclusivity?

Public patent records associate US 8,361,499 with the controlled-release hydrocodone patent family used in the Zohydro ER commercial context. The reported nominal expiration date for the relevant patent family is in November 2027, commonly identified as November 14, 2027 for this family. The operative date must be confirmed against the USPTO patent-term calculation, including any patent-term adjustment, terminal disclaimer, or patent-term extension.

Patent expiration is only one part of the exclusivity analysis. FDA regulatory exclusivity, listed patents, pediatric exclusivity, and any later patents covering abuse-deterrent formulations or manufacturing processes may create separate barriers.

FDA and Orange Book status

Zohydro ER received FDA approval under NDA 202880 in 2013. The product was developed initially by Zogenix and later became associated with successor commercial entities. The FDA Orange Book has historically listed patents for extended-release hydrocodone products, including patents in the 8,337,886 and 8,361,499 family.

An Orange Book listing creates a statutory framework for ANDA certification. It does not independently establish that every generic product infringes every listed claim. The legal issue remains whether the proposed product, its labeling, or its manufacturing process meets the asserted claims.

What Paragraph IV challenges and generic entry risks exist?

A generic applicant seeking approval before patent expiry may submit a Paragraph IV certification asserting that the listed patent is invalid, unenforceable, or not infringed. For US 8,361,499, the principal attack routes would include:

Non-infringement based on dissolution. The proposed product may fall outside one or more release ranges at the specified time points.
Non-infringement based on pharmacokinetics. The product may not produce a C24/Cmax ratio of 0.55 to 1.0 or a W50 of 4 to 22 hours.
Claim construction. The applicant may challenge the meaning of "relatively flat serum plasma profile," "first administration," or the test conditions.
Indefiniteness. The applicant may argue that functional or pharmacokinetic boundaries do not provide objective notice, although the numerical limitations strengthen the patentee's position.
Written description and enablement. The breadth of the polymer, wax, gum, oil, and formulation categories may be challenged against the examples and disclosure.
Obviousness. Prior art involving controlled-release hydrocodone, opioid matrix tablets, multiparticulates, and osmotic delivery could be combined to challenge the claimed result.
Anticipation. A single prior-art formulation would need to disclose the hydrocodone dosage form, release profile, and plasma profile or their inherent equivalents.

The strongest generic strategy would normally combine a Paragraph IV invalidity position with a formulation designed to avoid the numerical limitations. That approach may require clinical data because the PK limitation cannot reliably be assessed from dissolution testing alone.

Which companies are challenging the patent estate?

The provided claim text does not establish a complete litigation or Paragraph IV history. Patent litigation should be checked in the Federal Court docket, FDA Orange Book, and USPTO assignment and maintenance records before relying on a company-specific challenger, settlement date, or launch commitment.

The relevant commercial participants have included:

Purdue Pharma and affiliated patent entities, associated with the broader controlled-release opioid patent platform;
Zogenix, the original sponsor of Zohydro ER;
Pernix Therapeutics, which acquired Zogenix;
Subsequent holders or licensees of Zohydro-related commercial rights;
Generic opioid manufacturers evaluating ANDA entry.

No conclusion about a particular Paragraph IV settlement, authorized generic arrangement, or license should be drawn solely from the claim language.

How strong is the patent estate?

Strengths

Claim 1 covers multiple release technologies.
The use of "comprising" broadens compositional coverage.
Hydrocodone salt selection is not narrowly limited.
The claims combine formulation structure with measurable dissolution and PK outcomes.
Dependent claims provide fallback positions for matrix, spheroid, capsule, and osmotic systems.
The C24/Cmax range targets the clinical behavior expected from a long-acting opioid product.

Vulnerabilities

The broad list of controlled-release materials may create written-description and enablement pressure.
The claims depend on variable dissolution conditions, including pH and apparatus parameters.
Pharmacokinetic results can vary with dose, food, patient population, sampling schedule, and study design.
The claimed ranges may overlap prior-art extended-release opioid technologies.
Some dependent claims may be difficult to assert if the accused product lacks the specified structure.
A generic applicant may design around the release profile while preserving therapeutic equivalence.

The estate is stronger against products that intentionally reproduce the same hydrocodone release and plasma profile. It is weaker against products using a different release mechanism and engineered to fall outside the numerical boundaries.

How does US 8,361,499 compare with competing patent categories?

Patent category	What it protects	Design-around potential
US 8,361,499-type formulation patent	Hydrocodone dosage form plus dissolution and PK profile	Moderate
Salt or polymorph patent	Specific hydrocodone solid form	Often high if alternative salt or form is available
Abuse-deterrent formulation patent	Physical or chemical resistance to manipulation	Product-specific
Method-of-use patent	Treatment of pain with extended-release hydrocodone	Depends on labeling and induced-use theories
Manufacturing patent	Granulation, coating, compression, or release-control process	Usually high if process can be changed
Device or delivery patent	Osmotic membrane, passageway, or delivery platform	Moderate to high

US 8,361,499 is primarily a formulation and performance patent. It is distinct from a narrow hydrocodone salt patent and from later abuse-deterrence patents directed to crushing, extraction, or tampering resistance.

What generic launch scenarios are most likely?

Launch after patent expiry

This is the lowest litigation-risk scenario if no later listed patents remain enforceable. The applicant can pursue approval without relying on a successful Paragraph IV challenge, subject to FDA requirements and regulatory exclusivity.

At-risk launch after Paragraph IV litigation

A generic company may launch before final resolution if it receives approval and accepts potential damages or an injunction risk. This strategy depends on the patent's remaining term, litigation posture, market size, and the strength of non-infringement or invalidity defenses.

Design-around launch

A generic may use a different release mechanism, alter the dissolution curve, or target a plasma profile outside the claimed C24/Cmax range. The product must still satisfy FDA bioequivalence requirements, which limits the practical distance from the reference product.

Settlement or licensed entry

A settlement may establish a delayed entry date, authorized generic terms, or a license. The commercial value of such an agreement depends on remaining patent life, expected generic price erosion, and whether other patents block entry.

Key Takeaways

US 8,361,499 is a broad hydrocodone controlled-release formulation patent.
Claim 1 requires both formulation structure and performance.
The most important numerical limitations are the dissolution profile and C24/Cmax ratio of about 0.55 to 1.0.
Claims 5 through 15 cover matrix tablets and coated granules.
Claims 16 through 17 and 20 through 30 cover multiparticulates, spheroids, and mixed immediate-release/controlled-release capsules.
Claims 18 and 19 cover osmotic pump designs.
The patent is associated with the Zohydro ER controlled-release hydrocodone product family.
The reported nominal expiration is in November 2027, subject to USPTO term calculations.
A Paragraph IV applicant has credible non-infringement arguments based on dissolution and pharmacokinetic performance.
The strongest enforcement position exists against products intentionally matching both the claimed release curve and the claimed plasma profile.
Orange Book listing, current ownership, litigation, settlements, and remaining enforceable term must be confirmed from current FDA, USPTO, and court records.

FAQs

Does US 8,361,499 cover all extended-release hydrocodone tablets?

No. It covers products meeting the claim limitations, including the specified dissolution and pharmacokinetic requirements. An extended-release hydrocodone tablet outside those boundaries may avoid infringement.

Does using hydrocodone bitartrate avoid US 8,361,499?

No. Claim 1 expressly covers hydrocodone and pharmaceutically acceptable salts. Hydrocodone bitartrate is therefore within the potential scope if the remaining limitations are met.

Can a generic avoid the patent by changing the polymer?

Not necessarily. The claim lists broad categories of hydrophobic and hydrophilic polymers, gums, waxes, oils, and mixtures. A polymer change avoids the patent only if the complete claim is no longer satisfied.

Are osmotic hydrocodone products automatically covered?

No. Claims 18 and 19 require specific osmotic architecture, including an expandable polymer, semipermeable membrane, and passageway, along with the claim 1 limitations.

Does bioequivalence prove non-infringement?

No. FDA bioequivalence and patent infringement use related but distinct analyses. A generic product can be bioequivalent to the reference product while still requiring analysis under the patent's dissolution, formulation, and pharmacokinetic limitations.

References

U.S. Patent No. 8,361,499. (2013). Controlled release hydrocodone formulations. United States Patent and Trademark Office.
U.S. Food and Drug Administration. (2013). Zohydro ER approval history and prescribing information. FDA.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.
United States Patent and Trademark Office. (2024). Patent term adjustment and patent term extension records. USPTO.
U.S. Food and Drug Administration. (2017). Abbreviated new drug application approvals and patent certification procedures. FDA.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2002227383	⤷ Start Trial
Australia	2738302	⤷ Start Trial
Brazil	0115382	⤷ Start Trial
Canada	2427815	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 8,361,499

Summary for Patent: 8,361,499