Details for Patent: 8,465,765

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Which drugs does patent 8,465,765 protect, and when does it expire?

Patent 8,465,765 protects QUILLIVANT XR and is included in one NDA.

This patent has nine patent family members in eight countries.

Summary for Patent: 8,465,765

Title:	Orally effective methylphenidate extended release powder and aqueous suspension product
Abstract:	An oral methylphenidate powder which is reconstitutable into a final oral aqueous sustained release formulation containing at least about 50%, or at least about 80% by weight water based on the total weight of the suspension, is provided. The powder is a blend containing a combination of an uncoated methylphenidate-ion exchange resin complex, a barrier coated methylphenidate-ion exchange resin complex-matrix, and a water soluble buffering agent such that upon formed into an aqueous liquid formulation, the formulation has a pH in the range of about 3.5 to about 5, or about 4 to about 4.5. Following administration of a single dose of the oral aqueous methylphenidate suspension, a therapeutically effective amount of methylphenidate is reached in less than one hour and the composition provides a twelve-hour extended release profile.
Inventor(s):	Ketan Mehta, Yu-Hsing Tu, Ashok Perumal
Assignee:	Tris Pharma Inc
Application Number:	US13/611,183
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,465,765
Patent Claim Types: see list of patent claims	Use; Composition; Formulation; Dosage form;

United States Patent 8,465,765: Claim Scope, Quillivant XR Coverage, Expiration and Generic-Risk Analysis

U.S. Patent No. 8,465,765 protects a multipart methylphenidate extended-release platform centered on an aqueous suspension containing immediate-release and sustained-release methylphenidate-ion exchange resin complexes. The patent is closely associated with Quillivant XR, an extended-release methylphenidate hydrochloride oral suspension marketed by Tris Pharma.

The strongest coverage is concentrated in claim 1 and its formulation-dependent claims. The patent also covers a dry powder product that is reconstituted with water, tablets or capsules containing that powder blend, specified pharmacokinetic profiles, buffering systems, and minimum stability performance. The patent’s nominal expiration is in November 2029, subject to the controlling USPTO and FDA records for patent-term adjustment and Orange Book listing status.

What product and technology does U.S. Patent 8,465,765 protect?

The patent protects an extended-release methylphenidate delivery system that combines:

1. An immediate-release methylphenidate fraction.
2. A sustained-release methylphenidate fraction based on a methylphenidate-ion exchange resin complex.
3. A water-insoluble, water-permeable, pH-independent barrier coating.
4. An aqueous vehicle with an acidic pH, generally 3.5 to 5.
5. A pharmacokinetic profile producing one principal plasma concentration peak over approximately 12 hours.

The technology is designed to avoid the multiple plasma peaks commonly associated with separate immediate-release and extended-release doses. The ion-exchange resin controls release of methylphenidate, while the diffusion barrier moderates water penetration and drug release from the resin complex.

Claim 1 is the principal composition claim. A competing product must generally satisfy each required limitation to fall within its literal scope. The claim is not limited to one named commercial polymer, resin, excipient, or methylphenidate stereochemical form.

What are the required elements of independent claim 1?

Claim element	Scope
Dosage form	Methylphenidate aqueous extended-release oral suspension
Immediate-release component	Immediate-release methylphenidate
Sustained-release component	Barrier-coated methylphenidate-ion exchange resin complex
Barrier properties	Water-insoluble, water-permeable, pH-independent
Vehicle	Water
pH	About 3.5 to about 5
Pharmacokinetics	Single mean average methylphenidate plasma peak
Duration	Therapeutically effective profile for about 12 hours

The claim requires both formulation architecture and performance. A formulation using an ion-exchange resin without the claimed barrier coating may avoid literal infringement. A formulation using a conventional polymer matrix rather than an ion-exchange resin complex presents a similar design-around path.

How broad is the claim language in Patent 8,465,765?

The patent has meaningful breadth because claim 1 defines the technology at a functional and structural level rather than limiting it to a single commercial composition.

The phrase “water-insoluble, water-permeable, pH-independent, barrier coated” captures multiple coating technologies. Claim 3 expressly identifies three alternatives:

• A cured polyvinyl acetate coating with a plasticizer.
• A solvent-based ethylcellulose coating.
• An acrylate-based coating based on methyl methacrylate polymers or copolymers.

Claim 4 narrows the acrylate alternative to a polymer system corresponding to a commercial ammonio methacrylate copolymer technology, including poly(ethyl acrylate-co-methyl methacrylate-co-trimethylammonioethyl methacrylate chloride).

The claim language also permits substantial compositional variation. Claim 14 covers racemic methylphenidate and dexmethylphenidate. Claims 11 and 12 cover either hydrophilic polyvinylpyrrolidone or hydrophobic polyvinyl acetate as matrix-forming polymers. Claim 17 permits multiple pharmaceutically acceptable acidic buffers.

The result is a genus claim that reaches beyond one commercial suspension, provided that the accused product retains the required resin-complex, barrier-coating, pH, and pharmacokinetic characteristics.

Which claims are most commercially important?

Claims 1 through 5: core formulation architecture

These claims define the principal commercial risk. Claim 1 covers the combination of immediate-release and sustained-release methylphenidate in an aqueous suspension. Claims 2 through 5 add pH, coating, and immediate-release component limitations.

A generic suspension that uses the same ion-exchange resin technology and a comparable pH range would face the greatest infringement exposure.

Claims 6 through 9: pharmacokinetic profile claims

Claims 6 through 9 require specified AUC, Cmax, Tmax, and half-life ranges following administration of defined methylphenidate doses.

These claims can strengthen enforcement against products that replicate the same release profile, but they may create validity and infringement issues:

• Pharmacokinetic ranges can be vulnerable to enablement and written-description challenges if the specification does not support the full claimed ranges.
• Infringement may depend on clinical testing, statistical treatment, subject population, dose normalization, and assay methodology.
• A product may have similar therapeutic duration but fall outside one or more numerical PK ranges.
• A generic applicant may attempt to avoid these claims through a different release curve while maintaining comparable clinical efficacy.

Claim 7 is particularly narrow because it recites specific d-methylphenidate values: AUC of approximately 143.65 ng-hr/mL, Cmax of approximately 13.61 ng/mL, Tmax of about five hours, and half-life of approximately 5.65 hours.

Claims 10 through 18: formulation subcombinations

These claims cover:

• A 5% to 20% polymer matrix fraction.
• Polyvinylpyrrolidone or polyvinyl acetate.
• At least 80% water.
• A 10:90 to 30:70 immediate-release-to-sustained-release methylphenidate ratio.
• Acidic buffering systems.
• Sodium citrate and anhydrous citric acid.

These limitations may be important for assessing product-by-process similarity, but they are narrower than claim 1. A product could avoid some dependent claims by using a different polymer concentration, buffer, or immediate-release ratio while remaining exposed under claim 1.

Claims 19 and 20: treatment-method claims

Claims 19 and 20 cover treating a patient with the claimed suspension, including delivery of a therapeutically effective amount within 45 minutes and a single average plasma peak.

These claims are potentially relevant in Hatch-Waxman litigation, but enforcement against generic applicants is constrained by the content of the ANDA, proposed labeling, and the scope of the certification. A generic applicant may use a section viii statement to carve out a patented method of use when the labeling permits a non-infringing use. A formulation claim remains more significant because it can be implicated by the product itself.

Claims 21 through 27: dry powder and solid dosage forms

Claim 21 covers a methylphenidate extended-release powder blend containing:

• Immediate-release methylphenidate.
• Sustained-release barrier-coated resin-complex particles.
• A water-soluble buffer that creates a pH of 3.5 to 5 after reconstitution.
• Optional excipients.

Claim 27 extends coverage to tablets and capsules containing the powder blend. This is commercially important because it prevents the patent from being limited solely to a ready-to-drink suspension.

Claims 23 through 26 add water-soluble diluent granules, surfactants, sweeteners, preservatives, poloxamers, and acidic buffer systems. These claims create additional combination claims but are easier to design around than claim 21.

Claims 28 through 30: stability claims

These claims require:

• At least four months of ambient-temperature stability.
• Less than 5% potency loss.
• Less than 3% potency loss.

Stability claims may be difficult to enforce without access to manufacturing records and controlled stability data. They also raise claim-construction questions concerning storage conditions, assay method, initial potency, batch-to-batch variation, and the meaning of “room temperature.”

What patents protect Quillivant XR and related methylphenidate suspensions?

Quillivant XR is an extended-release methylphenidate hydrochloride oral suspension approved under NDA 022805. The FDA-approved labeling describes a 12-hour extended-release formulation and identifies methylphenidate hydrochloride as the active ingredient (FDA, 2024a).

The Orange Book has been the principal public source for patents listed against approved drug products. Patent 8,465,765 is associated with the Quillivant XR patent estate. Related continuation or follow-on patents may cover additional formulation, release, or manufacturing limitations. The controlling status should be confirmed against the current FDA Orange Book entry and the USPTO patent record because Orange Book listings, patent-term calculations, and litigation outcomes can change over time (FDA, 2024b).

Patent category	Relevance to Quillivant XR
U.S. 8,465,765	Core aqueous suspension, powder blend, PK and stability claims
Related formulation patents	May cover narrower release systems, particle coatings, or dosage-form variants
Orange Book listings	Determine patents relevant to ANDA certification and Hatch-Waxman timing
FDA exclusivity	Separate from patent protection and controlled by the NDA exclusivity record

Patent 8,465,765 should not be treated as the entire commercial estate without reviewing continuation patents, issued patents with overlapping disclosure, and any patent-use codes listed for the NDA.

When does Patent 8,465,765 lose exclusivity?

The patent’s earliest priority date is associated with a November 2008 filing. Its nominal 20-year patent term therefore runs into November 2029, subject to patent-term adjustment and any other statutory term calculation reflected in the USPTO record.

The practical exclusivity date depends on four separate questions:

1. The patent’s adjusted expiration date.
2. Whether the patent remains listed in the Orange Book.
3. Whether a valid patent-term extension applies.
4. Whether litigation or settlement agreements delay commercial generic entry beyond patent expiration.

Patent-term extension under 35 U.S.C. § 156 is generally limited to one patent per approved product and requires satisfaction of statutory conditions. Patent-term adjustment under 35 U.S.C. § 154 can alter the expiration date for USPTO delay. The patent face, USPTO Patent Center, and FDA Orange Book control these calculations (USPTO, 2024; FDA, 2024b).

Exclusivity timeline

Event	Timing or status
Earliest relevant priority	November 2008
Patent issuance	2013
Quillivant XR FDA approval	2012
Nominal patent expiration	November 2029, subject to official term calculation
FDA drug exclusivity	Separate from patent term and generally shorter than the patent term
Generic entry	Potentially before expiration only through a successful Paragraph IV challenge, settlement, or authorized launch

What Paragraph IV challenges could target this patent?

A Paragraph IV certification asserts that an Orange Book-listed patent is invalid, unenforceable, or will not be infringed by the proposed ANDA product. The principal attack vectors against Patent 8,465,765 would be:

Obviousness

A challenger could combine known methylphenidate ion-exchange resin complexes with known sustained-release coatings, immediate-release components, acidic suspensions, and buffer systems. The central question would be whether the claimed combination, including the single-peak 12-hour profile, would have been predictable to a skilled formulator.

The patentee would likely rely on unexpected pharmacokinetic behavior, improved tolerability, reduced peak-to-trough variation, and the ability to provide a stable aqueous product.

Written description and enablement

The claims cover several coating classes, two methylphenidate forms, broad pH ranges, multiple polymers, different buffer systems, powder products, tablets, capsules, and broad PK windows. A challenger could argue that the specification does not adequately support or enable the full scope of those alternatives.

Indefiniteness

Potential disputes could concern:

• “About” the specified pH, PK values, and percentages.
• “Single mean average plasma concentration peak.”
• “Therapeutically effective plasma profile.”
• “Water-permeable.”
• “pH-independent.”
• “Stable shelf-life.”
• “Room temperature.”

The specification and prosecution history would be central to interpreting those terms.

Infringement avoidance

A generic applicant could attempt to design around the patent by using:

• A non-ion-exchange-resin extended-release matrix.
• A pH-dependent coating.
• A different release-controlling polymer.
• A suspension outside the claimed pH range.
• A release profile with multiple peaks or a materially different Tmax.
• A formulation that uses only sustained-release methylphenidate.
• A different reconstitution buffer.

The feasibility of each design-around depends on whether related patents cover the alternative technology.

Which companies are challenging or competing with Quillivant XR?

The relevant competitive field includes branded methylphenidate products, authorized generics, ANDA products, and alternative dosage forms.

Product or company	Dosage form	Competitive relevance
Quillivant XR, Tris Pharma	Aqueous extended-release suspension	Reference product associated with Patent 8,465,765
QuilliChew ER, Tris Pharma	Extended-release chewable tablet	Competes for pediatric and swallowing-challenged patients
Concerta, Janssen	Extended-release tablet	Established once-daily methylphenidate alternative
Ritalin LA, Novartis and authorized generic channels	Extended-release capsule	Biphasic release profile
Cotempla XR-ODT, Neos Therapeutics	Extended-release orally disintegrating tablet	Competes on administration convenience
Generic methylphenidate ER products	Tablets, capsules or suspensions	Price-driven competition, subject to product-specific patents

A biosimilar pathway is not relevant. Methylphenidate hydrochloride is a chemically synthesized small molecule, and generic competition proceeds through the ANDA pathway rather than the 351(k) biosimilar pathway.

What FDA regulatory issues affect generic entry?

A generic Quillivant XR applicant must establish pharmaceutical equivalence and bioequivalence to the reference listed drug. Oral suspensions create additional regulatory issues involving:

• Particle-size distribution.
• Resin loading.
• Coating weight and permeability.
• Redispersibility.
• Dose uniformity after shaking.
• Reconstitution or storage requirements.
• Microbial limits and preservative performance.
• Assay and degradation products.
• Food-effect and alcohol-interaction studies.
• Comparative PK performance.

The FDA label instructs patients to shake Quillivant XR before use and use a calibrated oral dosing device. Those instructions reflect product-specific suspension attributes and may create regulatory differences between a generic suspension and a tablet or capsule alternative (FDA, 2024a).

A Paragraph IV ANDA filing can trigger a 30-month stay if the NDA holder or patent owner files a timely infringement action. The commercial launch date may therefore depend on litigation, settlement terms, court judgment, and pediatric exclusivity rather than patent expiration alone.

How strong is the patent estate?

Patent 8,465,765 has moderate-to-strong commercial relevance because claim 1 combines the product’s key dosage-form characteristics. Its strength is highest against a generic suspension that substantially copies the ion-exchange resin and barrier-coating architecture.

The estate is weaker in the following situations:

• The challenger uses a different release technology.
• The product does not use a pH-independent barrier coating.
• The product’s PK profile falls outside the numerical ranges.
• The accused formulation does not include both immediate- and sustained-release methylphenidate.
• The accused product is a different dosage form not covered by the powder-blend claims.
• The patent’s broad functional limitations face written-description or obviousness attacks.

The commercial risk remains significant because formulation patents can block an ANDA product even when the active ingredient itself is long off-patent.

What generic launch scenarios exist?

Early launch after a successful Paragraph IV case

A generic applicant could launch before November 2029 if a court holds the patent invalid or not infringed and no enforceable related patent blocks launch.

Settlement-based launch

A settlement could establish an agreed launch date before patent expiration. The commercial terms would depend on the settlement’s entry restrictions, authorized-generic provisions, and any FTC or court review issues.

At-risk launch

A company could launch while litigation remains unresolved. This exposes it to damages, possible injunctive relief, and potential loss of market share if the patent is upheld.

Post-expiration launch

A conventional launch after patent expiration remains the lowest litigation-risk scenario, but related patents, pediatric exclusivity, regulatory exclusivity, or manufacturing patents could still affect timing.

What manufacturing and intellectual-property barriers remain?

The principal technical barriers are not limited to the active ingredient. A competitor must reproduce or replace:

• Ion-exchange resin loading.
• Particle coating uniformity.
• Controlled diffusion through a pH-independent membrane.
• Immediate-release fraction.
• Acidic buffered suspension chemistry.
• Physical stability and redispersibility.
• Palatability and preservative performance.
• Twelve-hour exposure with one principal peak.

The manufacturing process may also create trade-secret barriers even if the patent claims are designed around. Coating thickness, curing conditions, resin particle size, and suspension handling parameters can affect release performance without appearing directly in the finished-product label.

Key Takeaways

• U.S. Patent 8,465,765 covers a multipart methylphenidate extended-release platform associated with Quillivant XR.
• Claim 1 is the principal claim and requires an aqueous suspension, immediate-release methylphenidate, sustained-release barrier-coated ion-exchange resin methylphenidate, pH of about 3.5 to 5, and a single approximately 12-hour plasma peak.
• Claims 21 through 27 extend protection to reconstitutable powder blends, tablets, and capsules.
• Claims 6 through 9 add pharmacokinetic protection but may be more difficult to enforce because of testing and claim-construction issues.
• Claims 28 through 30 add ambient stability and potency-retention requirements.
• The nominal expiration is in November 2029, subject to the official USPTO term calculation and any applicable statutory adjustment.
• Generic competition is governed by the ANDA and Paragraph IV framework, not the biosimilar pathway.
• The strongest design-around strategy is to replace the ion-exchange resin and pH-independent barrier-coating architecture with a materially different release technology.
• A complete freedom-to-operate analysis must include related Quillivant XR continuation patents, current Orange Book entries, FDA exclusivity, and any Paragraph IV litigation or settlement agreements.

Frequently Asked Questions

Is Patent 8,465,765 a patent on methylphenidate itself?

No. It is a formulation and method patent. It covers particular extended-release suspension, powder-blend, dosage-form, pharmacokinetic, treatment, and stability combinations.

Does a generic methylphenidate tablet infringe Patent 8,465,765?

Not necessarily. A conventional tablet that does not contain the claimed ion-exchange resin, barrier coating, aqueous suspension, or powder-blend architecture may avoid literal infringement. Related patents must still be reviewed.

Does the patent cover dexmethylphenidate?

Yes. Claim 14 expressly permits methylphenidate in the immediate-release or sustained-release component to be racemic methylphenidate or dexmethylphenidate.

Can a competitor avoid the patent by changing the suspension pH?

Potentially, but pH modification alone may not be sufficient. The product would also need to avoid the other limitations of the asserted claim, and related patents may cover alternative pH ranges or release systems.

Is Quillivant XR protected by FDA exclusivity after the patent expires?

FDA regulatory exclusivity and patent protection are separate. Any remaining exclusivity must be confirmed in the FDA’s current exclusivity and Orange Book records for NDA 022805.

References

1. Food and Drug Administration. (2024a). Quillivant XR prescribing information. U.S. Department of Health and Human Services. https://www.accessdata.fda.gov

2. Food and Drug Administration. (2024b). Approved drug products with therapeutic equivalence evaluations, Orange Book. U.S. Department of Health and Human Services. https://www.accessdata.fda.gov/scripts/cder/ob/

3. United States Patent and Trademark Office. (2024). U.S. Patent No. 8,465,765, Patent Center and patent-term information. https://patentcenter.uspto.gov

4. United States Patent and Trademark Office. (2024). Manual of Patent Examining Procedure, Chapter 2700: Patent term. https://www.uspto.gov/web/offices/pac/mpep/mpep-2700.html

5. U.S. Code. (2024). 21 U.S.C. § 355: New drugs; approval; patent certifications and exclusivity. https://uscode.house.gov

6. U.S. Code. (2024). 35 U.S.C. §§ 154 and 156: Patent term adjustment and patent term extension. https://uscode.house.gov

Drugs Protected by US Patent 8,465,765

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Nextwave	QUILLIVANT XR	methylphenidate hydrochloride	FOR SUSPENSION, EXTENDED RELEASE;ORAL	202100-001	Sep 27, 2012	AB	RX	Yes	Yes			Y			TREATING A PATIENT HAVING A CONDITION SUSCEPTIBLE TO TREATMENT WITH METHYLPHENIDATE, SUCH AS ADHD, BY ADMINISTERING THE FORMULATION RECITED IN CLAIMS 1 OR 2

International Family Members for US Patent 8,465,765

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2011359405
Australia	2017202955
Brazil	112013020537