Details for Patent: 8,741,885

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Which drugs does patent 8,741,885 protect, and when does it expire?

Patent 8,741,885 protects XARTEMIS XR and is included in one NDA.

Summary for Patent: 8,741,885

Title:	Gastric retentive extended release pharmaceutical compositions
Abstract:	The present disclosure provides extended release pharmaceutical compositions comprising an opioid and an additional active pharmaceutical ingredient, wherein the composition exhibits gastric retentive properties which are achieved by a combination of a physical property of the composition and release of the opioid, wherein upon administration to a subject, the composition has at least one pharmacokinetic parameter that differs by less than about 30% when the subject is in a fasted state as compared to a fed state.
Inventor(s):	Krishna Devarakonda, Michael J Guiliani, Vishal K Gupta, Ralph A Heasley, Susan Shelby
Assignee:	Mallinckrodt LLC
Application Number:	US13/473,571
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,741,885
Patent Claim Types: see list of patent claims	Use; Composition; Formulation; Dosage form;

United States Patent 8,741,885: Oxycodone/Acetaminophen Extended-Release Patent Scope and Landscape

U.S. Patent No. 8,741,885 protects extended-release oxycodone/acetaminophen dosage forms designed to provide immediate analgesia, prolonged gastric retention, and reduced food-effect variability. Its commercially important target is a dosage form containing approximately 7.5 mg oxycodone and 325 mg acetaminophen, administered approximately every 12 hours without regard to food.

The patent is a formulation and method-of-treatment patent, not a patent on oxycodone, acetaminophen, or their combination generally. Its strongest claim limitations are the defined immediate-release/extended-release drug split, gastric-retentive delivery, food-independent pharmacokinetics, and the 7.5 mg/325 mg strength.

What does U.S. Patent 8,741,885 cover?

The patent covers solid oral extended-release compositions containing two active ingredients:

Component	Claimed parameter
Oxycodone, or pharmaceutically acceptable salt	Generally 5-15 mg total
Acetaminophen	Generally 200-650 mg total
Immediate-release oxycodone fraction	About 20%-30% of total oxycodone in claims 13, 22 and 29
Extended-release oxycodone fraction	About 70%-80% of total oxycodone
Immediate-release acetaminophen fraction	About 40%-60% of total acetaminophen
Extended-release acetaminophen fraction	About 40%-60% of total acetaminophen
Commercially important strength	7.5 mg oxycodone/325 mg acetaminophen
Release environment	Upper gastrointestinal tract
Gastric residence	At least about 4 hours; certain claims require at least about 6 hours
Food effect	At least one pharmacokinetic parameter differs by less than about 30% between fed and fasted states

The patent claims a coordinated release system. The immediate-release component supplies early exposure, while the extended-release component continues delivery after the initial dose. The gastric-retention limitations distinguish the claimed dosage forms from conventional matrix tablets that transit rapidly through the gastrointestinal tract.

Which claims are commercially important?

Claims 1-12: composition, polymer, gastric-retention and pharmacokinetic claims

Claim 1 is an independent composition claim. It requires:

1. An immediate-release portion containing approximately 0.5%-2.5% oxycodone and 65%-85% acetaminophen by weight of that portion.
2. An extended-release portion containing approximately 0.3%-1.0% oxycodone and 15%-25% acetaminophen by weight of that portion.
3. Total oxycodone of approximately 5-15 mg.
4. Total acetaminophen of approximately 200-650 mg.
5. Delivery to the upper gastrointestinal tract for approximately 4-12 hours.
6. A fed-versus-fasted pharmacokinetic difference of less than approximately 30% for at least one listed parameter.

Claims 2-4 narrow the pharmacokinetic limitation. Claim 2 reduces the permitted difference to less than approximately 20%. Claim 3 focuses on AUC or Cmax. Claim 4 requires the food-effect limitation for both oxycodone and acetaminophen.

Claims 5 and 9 add functional gastric-retention limitations. Claim 5 requires release sufficient to delay gastric emptying without producing an adverse gastrointestinal effect. Claim 9 requires a water-absorbing, swelling polymer capable of producing a gastric-retentive size.

Claims 6-8 identify extended-release polymers, including polyethylene oxide with a molecular weight of approximately 500,000 to 10,000,000 Daltons. These claims are narrower than claim 1 and create a polymer-specific infringement pathway.

Claim 10 is directed to the 7.5 mg/325 mg strength. Claims 11 and 20 add six-hour and gastric-retentive requirements. Claim 12 covers a multi-part architecture in which oxycodone and acetaminophen may be placed in separate immediate-release and extended-release portions.

Claims 13-18: defined drug allocation and manufacturing process

Claim 13 is a central independent claim. It requires:

• 20%-30% of the total oxycodone in the immediate-release portion;
• 70%-80% in the extended-release portion;
• 40%-60% of the total acetaminophen in the immediate-release portion;
• 40%-60% in the extended-release portion;
• 325 mg total acetaminophen;
• 7.5 mg total oxycodone; and
• bioavailability that is not affected by the absence of food.

The claim does not require a particular tablet shape or manufacturing process. A competing product could therefore infringe claim 13 even if it uses a different tableting process, provided the final dosage form satisfies the allocation and pharmacokinetic limitations.

Claim 14 adds numerical fasted-state AUC ranges:

Active ingredient	Claimed mean fasted-state AUC
Oxycodone	About 9.0-18.5 ng·hr/mL/mg
Acetaminophen	About 35.0-80.0 ng·hr/mL/mg

Claims 15-17 protect a dual-granulation route. The process first forms oxycodone-protected granules, then granulates those particles with acetaminophen and excipients. The protected oxycodone granules may contain binders, fillers, antioxidants and chelating agents.

Claim 18 requires gastric-retentive properties. This limitation can create a product-infringement issue when a generic applicant uses substantially different excipients but produces a dosage form with the same functional gastric-retention characteristics.

Claims 19-21: acute-pain treatment claims

Claims 19 and 21 cover administering the claimed composition to treat acute pain. These claims depend on the composition limitations in claim 13 or claim 1, respectively. They do not independently cover treatment with any oxycodone/acetaminophen product.

Claims 22-30: percentage allocation, bilayer and dosing claims

Claim 22 is another independent composition claim. It uses percentage allocation rather than the absolute composition percentages in claim 1:

• 20%-30% of oxycodone in the immediate-release portion;
• 70%-80% in the extended-release portion;
• 40%-60% of acetaminophen in each release portion;
• 5-15 mg total oxycodone;
• 200-650 mg total acetaminophen;
• at least four hours of upper-gastrointestinal delivery; and
• less than approximately 30% fed/fasted difference for at least one parameter.

Claim 23 narrows claim 22 to a bilayer tablet. Claim 24 specifies 325 mg acetaminophen and 7.5 mg oxycodone. Claim 25 adds an extended-release polymer.

Claims 26-28 cover acute-pain treatment, with claim 28 requiring administration every 12 hours without regard to food. This dosing limitation is commercially significant because a product label that directs twice-daily administration without food restrictions may create a closer correspondence with the claimed method.

Claim 29 covers a solid oral dosage form with 7.5 mg oxycodone and 325 mg acetaminophen, gastric-retentive properties and food-independent bioavailability. Claim 30 covers administering two such dosage forms. At two tablets, the claimed dose would contain 15 mg oxycodone and 650 mg acetaminophen.

What formulations are protected by U.S. Patent 8,741,885?

The patent reaches several formulation architectures:

Formulation architecture	Relevant claims	Commercial significance
Combined immediate-release and extended-release portions	1, 13, 22, 29	Core protection
7.5 mg/325 mg dosage form	10, 13, 24, 29	Closest to the marketed strength
Bilayer tablet	23	Protects a specific physical configuration
Polyethylene oxide matrix	6-8, 25	Polymer-specific protection
Swelling gastric-retentive system	9, 18, 20, 29	Functional retention protection
Dual granulation process	15-17	Manufacturing-process protection
Two-tablet administration	30	Dose-regimen protection
Every-12-hour administration without food	28	Method-of-use protection

The claims do not require every dosage form to be a bilayer tablet. A multilayer tablet, multiparticulate system, capsule containing granules, or other solid oral form could potentially fall within the claims if it satisfies the claimed release allocation and pharmacokinetic requirements.

How strong is the patent estate?

The patent has meaningful claim density but a concentrated technical target. Its strength depends on whether a competing product matches the following four elements:

1. A 20%-30% immediate-release oxycodone allocation.
2. A 70%-80% extended-release oxycodone allocation.
3. A roughly equal split of acetaminophen between immediate-release and extended-release portions.
4. Food-independent pharmacokinetics and gastric retention.

The 7.5 mg/325 mg limitation in several claims narrows the estate but increases product relevance. A generic applicant may attempt to design around the patent by changing the oxycodone allocation, removing gastric retention, using a conventional extended-release technology, or accepting a measurable food effect.

Claim-strength assessment

Claim category	Relative strength	Principal vulnerability
Broad composition claims	Medium	Functional and pharmacokinetic limitations may require extensive proof
7.5 mg/325 mg claims	Strong commercial relevance, narrower scope	Easy to target with alternative strength or release allocation
Gastric-retention claims	Medium to strong if retention is demonstrated	Infringement may depend on complex testing
Polyethylene oxide claims	Narrower but technically clear	Avoidance through another polymer
Dual-granulation claims	Narrow	Process may be changed without changing the product
Method-of-treatment claims	Moderate	Require proof of practicing the claimed regimen
Fed/fasted pharmacokinetic claims	Potentially strong	Variability in clinical testing and claim construction

What is the FDA and Orange Book significance?

XARTEMIS XR, an extended-release oxycodone hydrochloride/acetaminophen product containing 7.5 mg/325 mg per tablet, is the product most closely associated with the claimed formulation profile. FDA approved XARTEMIS XR under NDA 204630 in 2014 for acute pain severe enough to require an opioid analgesic and for which alternative treatments were inadequate.[1]

The relevant regulatory characteristics are:

Regulatory item	Status
Active ingredients	Oxycodone hydrochloride and acetaminophen
Dosage form	Extended-release oral tablet
Key strength	7.5 mg/325 mg
Dosing concept	Every 12 hours
FDA pathway	505(b)(2)/NDA product framework
Orange Book relevance	Patent listing depends on the NDA holder's listing and current FDA records
Biologic status	Not a biologic; Purple Book biosimilar analysis does not apply

A patent listing in the Orange Book does not establish that every patent claim covers every approved product presentation. It identifies patents submitted by the NDA holder as potentially covering the drug, formulation, or approved use. The statutory effect of a Paragraph IV certification depends on the patent listing, the ANDA product, the certification, and any timely infringement action.[2]

When does U.S. Patent 8,741,885 lose exclusivity?

The patent's term is generally measured from the applicable earliest nonprovisional filing date, subject to patent-term adjustment, terminal disclaimers and any patent-term extension. The face of the patent, USPTO Patent Center and current assignment records should control the operative expiration date.[3]

The patent issued on June 3, 2014. Its issuance date does not determine the expiration date. A precise freedom-to-operate conclusion requires the recorded term calculation, including any patent-term adjustment and terminal disclaimer. The patent's enforceable term also differs from FDA regulatory exclusivity.

Relevant exclusivity concepts are separate:

Exclusivity type	Applies to this product?
Patent exclusivity	Yes, if the patent remains enforceable and covers the competing product or use
New chemical entity exclusivity	Generally not applicable to an oxycodone/acetaminophen combination using known active ingredients
Three-year clinical-investigation exclusivity	May apply only if FDA awarded it for the applicable approval or supplement
Orphan exclusivity	Not indicated for this acute-pain product
Pediatric exclusivity	Requires a specific FDA grant
Biosimilar exclusivity	Not applicable

Which companies are challenging the patent?

Public Paragraph IV and ANDA litigation analysis must distinguish between:

• a challenge to U.S. Patent 8,741,885;
• a challenge to other XARTEMIS XR patents;
• a patent certification without litigation;
• litigation against a different oxycodone/acetaminophen extended-release product; and
• a settlement that permits an agreed launch date without invalidating the patent.

No reliable conclusion should treat a generic ANDA filing, a court docket, an Orange Book listing, and an actual commercial launch as interchangeable events. The relevant records are FDA ANDA litigation disclosures, PACER or RECAP complaints, district-court docket entries, Federal Circuit decisions and any settlement reporting.[2,4]

A Paragraph IV challenge would likely focus on:

1. obviousness of combining immediate-release and extended-release oxycodone/acetaminophen;
2. lack of written description or enablement for the broad pharmacokinetic ranges;
3. indefiniteness of terms such as "gastric retentive," "not affected by the absence of food," and "sufficient to delay gastric emptying";
4. noninfringement based on release allocation or lack of gastric retention; and
5. failure to meet the claimed fed/fasted pharmacokinetic limitation.

What generic launch risks exist?

At-risk launch

A generic applicant may launch before patent expiration after a Paragraph IV certification if the NDA holder does not obtain a timely preliminary injunction. Commercial exposure would include patent damages, possible injunctive relief and disruption of controlled-substance distribution.

Authorized or licensed generic

A settlement or license could permit launch before patent expiration. The launch date, product specifications, manufacturing source and royalty terms would determine the commercial effect. A license limited to one formulation would not necessarily clear other claims or continuation patents.

Design-around launch

The most practical design-around options include:

• changing the immediate-release oxycodone fraction outside 20%-30%;
• placing less than 40% or more than 60% of acetaminophen in one release portion;
• using a non-gastric-retentive extended-release matrix;
• changing the polymer system;
• modifying the dose strength;
• accepting a measurable food effect;
• avoiding the dual-granulation process; or
• seeking approval for a different dosing interval or indication.

A design-around must be evaluated against every independent claim. Avoiding claim 15 does not avoid claims 1, 13, 22 or 29.

How does this patent compare with ordinary oxycodone/acetaminophen products?

Product type	Immediate-release component	Extended-release component	Gastric retention	Food-independent claim risk
Conventional Percocet-type tablet	Yes	No	No	Low under this patent
Conventional ER oxycodone tablet	No acetaminophen or different combination	Yes	Usually not the claimed architecture	Depends on product
XARTEMIS XR-type product	Yes	Yes	Yes	High
Alternative oxycodone/APAP matrix tablet	Possible	Possible	May be absent	Depends on allocation and PK
Capsule with multiparticulates	Possible	Possible	Depends on design	Depends on final dosage form

The patent is therefore more relevant to dual-release oxycodone/acetaminophen products than to ordinary immediate-release combination tablets or extended-release oxycodone products lacking acetaminophen.

What manufacturing and intellectual-property barriers remain?

The dual-granulation claims create a process-specific barrier, particularly where oxycodone is first protected in granules before acetaminophen is introduced. This architecture may support abuse-deterrence, content uniformity, release control and manufacturing reproducibility.

The process claims are not coextensive with the product claims. A competitor may use fluid-bed coating, dry granulation, melt processing, direct compression or multiparticulate manufacture and avoid claims 15-17 while still potentially infringing the final-product claims.

Controlled-substance handling adds practical barriers independent of patent rights. Oxycodone manufacturing requires DEA registration, quota compliance, controlled-substance security, supply-chain controls and regulatory reporting. Those requirements increase launch cost but do not extend patent term.

Key Takeaways

• U.S. Patent 8,741,885 targets a gastric-retentive, dual-release oxycodone/acetaminophen dosage form.
• The commercially central formulation is approximately 7.5 mg oxycodone and 325 mg acetaminophen.
• The core allocation is approximately 20%-30% immediate-release oxycodone and 70%-80% extended-release oxycodone.
• Acetaminophen is divided approximately 40%-60% between immediate-release and extended-release portions.
• Food-independent pharmacokinetics is a major claim limitation and a likely litigation issue.
• Polyethylene oxide, swelling gastric-retentive polymers, bilayer tablets and dual granulation are narrower protection layers.
• The patent does not cover conventional immediate-release oxycodone/acetaminophen products merely because they contain the same active ingredients.
• Paragraph IV risk depends on the generic product's release allocation, gastric-retention behavior, pharmacokinetics and manufacturing process.
• Patent expiration must be determined from the USPTO term record, not the 2014 issue date.
• Biosimilar analysis is irrelevant because the product is a small-molecule opioid/acetaminophen combination.

FAQs

Does U.S. Patent 8,741,885 cover Percocet?

No. Conventional immediate-release oxycodone/acetaminophen products generally lack the claimed extended-release portion, gastric-retentive behavior and fed/fasted pharmacokinetic limitations.

Does the patent require a bilayer tablet?

No. Claim 23 requires a bilayer tablet, but the broader independent claims do not uniformly require that physical configuration.

Can a generic avoid the patent by using a different extended-release polymer?

Possibly. A different polymer may avoid the polyethylene oxide-dependent claims, but it would not automatically avoid the broader composition claims if the product satisfies their release, retention and pharmacokinetic limitations.

Is claim 30 directed to one tablet or two tablets?

Claim 30 requires administering two solid dosage forms covered by claim 29. At the stated strength, the administered amount would be 15 mg oxycodone and 650 mg acetaminophen.

Does FDA approval prove infringement?

No. FDA approval and patent infringement are separate determinations. FDA approval establishes regulatory authorization, while infringement depends on claim scope, product characteristics, use, process and applicable patent law.

References

1. U.S. Food and Drug Administration. (2014). XARTEMIS XR approval package and prescribing information. FDA.
2. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. FDA.
3. United States Patent and Trademark Office. (n.d.). Patent Center: U.S. Patent No. 8,741,885. USPTO.
4. U.S. Courts. (n.d.). Public Access to Court Electronic Records. PACER.

Drugs Protected by US Patent 8,741,885

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Mallinckrodt Inc	XARTEMIS XR	acetaminophen; oxycodone hydrochloride	TABLET, EXTENDED RELEASE;ORAL	204031-001	Mar 11, 2014		DISCN	Yes	No			Y			MANAGEMENT OF ACUTE PAIN IN PATIENTS REQUIRING OPIOID ANALGESIA