Details for Patent: 9,072,680

Which drugs does patent 9,072,680 protect, and when does it expire?

Patent 9,072,680 protects COTEMPLA XR-ODT and is included in one NDA.

This patent has two patent family members in two countries.

Summary for Patent: 9,072,680

Title:	Compositions comprising methylphenidate complexed with ion-exchange resin particles
Abstract:	Pharmaceutical compositions of methylphenidate complexed with ion-exchange resin particles to form drug-resin particles are provided. The compositions have a first plurality of drug-resin particles that are uncoated and a second plurality of drug-resin particles that are coated with a delayed release coating. Preferably, the second plurality of drug-resin particles are coated with a triggered-release coating triggered by a pH change and a diffusion barrier coating.
Inventor(s):	Mark Tengler, Russell McMahen
Assignee:	Neos Therapeutics LP
Application Number:	US13/844,584
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 9,072,680
Patent Claim Types: see list of patent claims	Composition; Formulation; Compound; Dosage form;

Scope, Claims, and Patent Landscape Analysis for US Drug Patent 9,072,680

US 9,072,680 claims a specific methylphenidate ion-exchange resin particle system that combines (i) immediate-release drug-resin particles and (ii) pH-triggered, diffusion-barrier-controlled triggered-release drug-resin particles, plus explicit human pharmacokinetic (PK) and dissolution parameter targets. The claims are structured to capture both formulation architecture and in vivo performance (bioequivalence/similarity to defined reference profiles), which narrows the set of “design-around” options.

What is claimed in the core independent claim? (Claim 1)

1) Core composition architecture

Claim 1 requires a pharmaceutical composition comprising:

• An ADHD effective agent that is methylphenidate
• Complexed with ion-exchange resin particles to form drug-resin particles
• Two distinct particle populations:
  • First plurality of drug-resin particles: immediate release
  • Second plurality of drug-resin particles: triggered-release
  • Triggered by a pH change
  • Includes both:
    • a triggered-release coating
    • a diffusion barrier coating

This claim is “biphasic” by design: it requires both immediate-release particles and triggered-release particles in the same oral composition.

2) Functional in vivo PK requirement (central limiting element)

Claim 1 adds a performance constraint: administration in humans produces a mean plasma concentration profile for d-methylphenidate with one or more parameters (chosen from a broad list) that is “substantially similar” to at least one in vivo serum profile shown in FIG. 20A.

The allowed PK parameters listed are:

• AUC0-3
• AUC0-5
• AUC0-Tmax
• AUC5-12
• AUC5-24
• AUC T max -24
• AUC T max -12
• AUC5-t
• AUC T max -t
• AUC0-24
• AUC0-∞

“Substantially similar” is anchored to FIG. 20A serum profiles, making FIG. 20A the key technical target for infringement analysis.

3) Claim 1 is broad on drug salt identity, but narrow on the resin-based delivery system

Claim 1 mandates methylphenidate as the ADHD effective agent, but the salt form is not explicitly limited in Claim 1 text you provided. Dependent claims and the PK/dose equivalence language reference methylphenidate hydrochloride equivalence, which typically constrains salt usage in practice.

What are the material dependent claim limits? (Claims 2 to 10, 12, 13)

Triggered-release coating chemistries (Claim 2)

Claim 2 limits the triggered-release coating to at least one of:

• Cellulose acetate phthalate
• Cellulose acetate trimellitate
• Hydroxypropyl methylcellulose phthalate
• Polyvinyl acetate phthalate
• Carboxymethylethylcellulose
• Copolymerized methacrylic acid / methacrylic acid methyl esters
• Copolymerized methacrylic acid / acrylic acid ethyl esters
• Mixtures thereof

This is a tight list. Many enteric or pH-responsive polymers are outside it (unless they fall within the listed chemistries or mixtures).

Additional resin additives (Claim 3)

Claim 3 adds the composition may additionally contain:

• Polistirex
• Polacrilex
• Cholestyramine
• Polacrilin
• Mixtures thereof

This dependent claim expands coverage to formulations that include additional ion-exchange resins besides the main drug-resin particles (or uses them in composition design).

Diffusion barrier coating polymer types (Claim 4)

Claim 4 limits the diffusion barrier coating to at least one of:

• Polyvinylpyrrolidone
• Polyvinylacetate
• Polyvinylalcohol
• Mixtures thereof

Diffusion barrier coating as a membrane + ethylcellulose (Claims 5-6)

• Claim 5: the diffusion barrier coating is a water insoluble, water permeable membrane
• Claim 6: that membrane is ethylcellulose

This is a second, narrower formulation constraint: even if the barrier polymer is outside the Claim 4 list, Claim 6 fixes ethylcellulose if Claim 6 is asserted.

Layering relationship (Claims 7-8)

• Claim 7: the triggered-release coating covers the diffusion barrier coating
• Claim 8: diffusion barrier coating is ethylcellulose

The coating stack order is part of the claim logic.

Resin selection for drug complexation (Claim 9)

Claim 9 specifies “strong acidic cation exchange resins”:

• Polistirex
• Polacrilex
• Cholestyramine
• Polacrilin
• Mixtures thereof

Particle number ratio split (Claims 10-11)

Claim 10 requires:

• First plurality: 20% to 30% by number
• Second plurality: 70% to 80% by number

Claim 11 narrows to approximate:

• First: about 25%
• Second: about 75%

This is a key quantitative design constraint. Altering the fraction of immediate-release vs triggered-release particles is a principal design-around lever, but the claims make those ratios limiting.

Dosage form scope (Claim 12)

Claim 12 covers:

• Liquid suspension
• Chewable composition
• Orally disintegrating tablet (ODT)

Dose range (Claim 13)

Claim 13 limits methylphenidate amount to:

• 10 mg to 60 mg

What dissolution and in vivo performance targets are built into the claims? (Claims 14, 15, 18-27)

Dissolution profile anchor (Claim 14)

Claim 14 requires an in vitro dissolution profile with:

• Medium: 0.1 N HCl for initial phase, then after 2 hours adjust to pH ~6.8
• Apparatus: USP Apparatus 2
• Release targets (by weight):
  • 30% to 33% released within first 30 minutes
  • 34% to 42% released within 2 hours
  • 40% to 80% released within 4 hours
  • 80% to 100% released within 24 hours

This claim makes the formulation’s release kinetics and pH transition behavior a direct infringement element.

Statistical similarity to specified in vivo profiles (Claim 15)

Claim 15: in vivo serum profile is “statistically similar” to at least one profile selected from:

• FIGS. 27A, 27B, 28A, 28B

This provides multiple candidate reference curves, likely increasing the chance of meeting “substantially similar” thresholds depending on which curves are used in equivalency testing.

Ethanol sensitivity claim (Claim 16)

Claim 16: in presence of ethanol, a mammal receiving the composition experiences a reduced amount of methylphenidate compared to an extended release composition without resin particles comprising methylphenidate HCl.

This is a conditional PK effect, likely tied to resin-based complexation and triggered-release behavior.

Dose equivalence language (Claims 17, 18-22)

• Claim 17: methylphenidate in composition is equivalent to 10, 20, 30, 40, 50, or 60 mg methylphenidate hydrochloride dose levels.

Claims 18-21 and 22 provide numeric PK targets for an ODT and a “60 mg total dose equivalence” framework (or proportionally scaled doses).

Numeric mean PK targets for ODT in adults (Claims 18-21)

These are explicit windows:

• AUC and Cmax values have -20% / +25% bounds around stated means.

Claim 18: AUC0-3 and Cmax For d-methylphenidate:

• AUC0-3: 20.53 ng·hr/mL (± -20%/+25%)
• Cmax: 20.17 ng/mL (± -20%/+25%)

For l-methylphenidate:

• AUC0-3: 0.62 ng·hr/mL (± -20%/+25%)
• Cmax: 0.44 ng/mL (± -20%/+25%)

For total methylphenidate:

• AUC0-3: 21.29 ng·hr/mL (± -20%/+25%)
• Cmax: 20.60 ng/mL (± -20%/+25%)

Claim 19: AUC0-5

• d-methylphenidate:
  • AUC0-5: 50.16 ng·hr/mL (± -20%/+25%)
  • Cmax: 20.17 ng/mL (± -20%/+25%)
• l-methylphenidate:
  • AUC0-5: 1.07 ng·hr/mL (± -20%/+25%)
  • Cmax: 0.44 ng/mL (± -20%/+25%)
• total methylphenidate:
  • AUC0-5: 51.43 ng·hr/mL (± -20%/+25%)
  • Cmax: 20.60 ng/mL (± -20%/+25%)

Claim 20: AUC5-24

• d-methylphenidate:
  • AUC5-24: 103.84 ng·hr/mL (± -20%/+25%)
  • Cmax: 20.17 ng/mL (± -20%/+25%)
• l-methylphenidate:
  • AUC5-24: 0.96 ng·hr/mL (± -20%/+25%)
  • Cmax: 0.44 ng/mL (± -20%/+25%)
• total methylphenidate:
  • AUC5-24: 105.07 ng·hr/mL (± -20%/+25%)
  • Cmax: 20.60 ng/mL (± -20%/+25%)

Claim 21: AUC0-24

• d-methylphenidate:
  • AUC0-24: 156.72 ng·hr/mL (± -20%/+25%)
  • Cmax: 20.17 ng/mL (± -20%/+25%)
• l-methylphenidate:
  • AUC0-24: 2.19 ng·hr/mL (± -20%/+25%)
  • Cmax: 0.44 ng/mL (± -20%/+25%)
• total methylphenidate:
  • AUC0-24: 159.25 ng·hr/mL (± -20%/+25%)
  • Cmax: 20.60 ng/mL (± -20%/+25%)

Overall exposure band (Claim 22)

For total methylphenidate:

• AUC0-∞: about 160 to 180 ng·hr/mL when dose is “equivalent to about a 60 mg total dose of methylphenidate hydrochloride.”

Bioequivalence-style CI constraint (Claim 23)

Claim 23 requires a 90% confidence interval for PK parameters, with upper/lower bounds within:

• 90% to 115% of the reference composition’s parameter values

This is a standard numeric scaffold for bioequivalence and increases enforceability against competing formulations that aim to be “similar enough.”

Tmax and peak shape constraints (Claims 24-26)

• Claim 24: Tmax approximately 6 hours
• Claim 25: bimodal profile with two peaks:
  • first peak at approximately 3 hours
• Claim 26: first and second peaks exist; second peak is the Cmax

These peak-shape claims are practical barriers to formulation design-around. Many modified-release systems do not naturally produce the same bimodal pattern.

Cmax minimum for 60 mg equivalent dose (Claim 27)

• With dose equivalent to about 60 mg total methylphenidate HCl:
  • Cmax > 16.55 ng/mL

What other claim constraints matter for infringement mapping? (Claim 28 + Claim 17)

• Claim 28: the first plurality of drug-resin particles is uncoated.

This matters for immediate-release particle engineering. If a competitor coats the “immediate-release” particles with even a thin barrier/enteric layer, it may exit Claim 28 while still potentially entering Claim 1 depending on claim interpretation, but Claim 28 is a direct dependent narrowing element.

How the claim set defines the “protected product” space

A. Two-population system is mandatory

You cannot satisfy Claim 1 without both: 1) Immediate-release drug-resin particles
2) Triggered-release, pH-responsive, diffusion-barrier-controlled drug-resin particles

A formulation that uses only one kind of resin particle population does not meet the claim architecture.

B. Polymer chemistry and layer order become limiting as you drill into dependents

At the dependent-claim level, the legal space collapses into specific polymers:

• Triggered-release coatings: limited to listed phthalate/trimellitate/cellulose acetate phthalate and methacrylate copolymers, plus listed cellulose derivatives.
• Diffusion barrier: limited to specific polymers and specifically membrane language, with ethylcellulose as a further narrowing path.
• Coating stack order: triggered-release coating covers diffusion barrier.

C. Quantitative performance gates

The claim set then gates infringement by:

• dissolution release percent windows under specific pH transition and USP apparatus
• human PK similarity to defined figures
• numeric PK windows for AUC and Cmax for d-, l-, and total methylphenidate
• Tmax and bimodality plus Cmax minimum
• 90% confidence interval overlap with a reference composition

This means a design-around is not purely mechanistic (resin + coating). It must hit a performance profile.

Patent landscape: likely coverage and overlap vectors

A robust landscape requires the full claims and citations of all related family members, continuations, and reference patents. With only the Claim 1 to 28 text provided, the landscape can still be mapped by identifying what the patent is “doing” technologically and legally, which predicts where competitive claims will overlap.

1) Likely overlap with other methylphenidate controlled-release/resin systems

This patent targets:

• methylphenidate resin complexation with ion-exchange resins such as polistirex/polacrilex/cholestyramine/polacrilin (Claim 9)
• enteric/pH-triggered polymers (Claim 2)
• ethylcellulose diffusion barrier membranes (Claims 5-6, 8)
• biphasic particle populations (Claim 1, plus ratios Claims 10-11)

Competitors designing around usually choose one of:

• different trigger modality (enzyme, time-dependent, osmotic, matrix diffusion)
• different pH-responsive polymer chemistry not in Claim 2 list
• different barrier mechanism (matrix diffusion instead of a distinct diffusion barrier membrane)
• single-population release system (no immediate vs triggered split)
• alternative PK targets that avoid the numeric windows

The tighter the claim is (dependents with explicit polymers and PK), the more difficult these routes become.

2) Likely overlap with “equivalence” and regulatory-driven follow-on strategies

Claims 23 and 18-22 embed bioequivalence-style CI overlap and explicit numeric PK bands. This is characteristic of a patent that may align with a specific NDA/ANDA development program where performance needs to map to a reference.

A competitor attempting to match PK would likely fall into the same parameter space, increasing the risk of overlap.

3) Landscape implications for ODT and adult ADHD PK profiles

The numeric PK claims are tied to orally disintegrating tablets (Claim 18-21). If a competitor targets an ODT with similar dosing equivalence and PK match goals, it will likely collide with those dependent claims.

A competitor using a different dosage form (e.g., capsule, tablet with different disintegration kinetics) could still infringe Claim 1 and Claim 12 if the system architecture and release kinetics are met, but the numeric dependent claims for ODT would be easier to avoid.

Practical infringement map: “what to test” on an accused product

For enforcement or FTO screening, the claim set implies a test stack.

Formulation tests

• Determine if drug is complexed with ion-exchange resins and exists as drug-resin particles
• Confirm presence of two particle populations:
  • one uncoated immediate-release (Claim 28 if applicable)
  • one triggered-release with pH-triggered coating plus diffusion barrier
• Verify polymer identities:
  • triggered-release coating in Claim 2 list (or mixtures)
  • diffusion barrier polymer and membrane attributes, especially ethylcellulose (Claims 5-6, 8)
• Verify coating layering: triggered-release coating covers diffusion barrier (Claim 7)
• Quantify particle number fraction: immediate vs triggered at Claim 10-11 ratios (20-30% vs 70-80%)

In vitro dissolution tests

• Run dissolution in 0.1 N HCl then shift to pH 6.8 after 2 hours
• USP Apparatus 2
• Check weight percent release within:
  • 30 minutes: 30% to 33%
  • 2 hours: 34% to 42%
  • 4 hours: 40% to 80%
  • 24 hours: 80% to 100%

In vivo PK tests

• d-methylphenidate mean plasma profile similarity to FIG. 20A parameters (Claim 1)
• For ODT designs: check numeric AUC/Cmax windows (Claims 18-21) and AUC0-∞ band (Claim 22)
• Check peak shape and Tmax:
  • Tmax ~6 hours (Claim 24)
  • bimodal with first peak ~3 hours (Claim 25)
  • second peak is Cmax (Claim 26)
• Check Cmax minimum at 60 mg equivalent dose (Claim 27)
• Check CI overlap 90% to 115% for key parameters vs reference (Claim 23)

Key Takeaways

• US 9,072,680 is anchored by a two-population methylphenidate ion-exchange resin system with immediate-release and pH-triggered triggered-release particles that also require a diffusion barrier.
• The claim set progressively narrows to specific polymer chemistries:
  • triggered-release: enumerated cellulose phthalates/trimellitate and specific methacrylate or cellulose derivatives (Claim 2)
  • diffusion barrier: limited to listed polymers and in membrane form, with ethylcellulose as a key narrowing species (Claims 4-6, 8)
• Infringement is not only structural; it is gated by specific dissolution kinetics and human PK similarity/numeric targets, including Tmax ~6 hours and bimodal peak behavior.
• Design-around is constrained by quantitative gates: particle number ratios, dissolution release percentages under defined pH transitions, and numeric AUC/Cmax bands for adult ADHD ODT dosing equivalents.

FAQs

1) Can a single-population modified-release methylphenidate resin product infringe Claim 1?

No. Claim 1 requires both a first plurality of immediate-release drug-resin particles and a second plurality of triggered-release drug-resin particles within the same composition.

2) Does Claim 1 require ethylcellulose specifically?

No. Ethylcellulose is required only if you reach dependent claims that specify it (Claims 6 and 8). Claim 1 requires a diffusion barrier coating, but Claim 1 does not lock the barrier polymer identity.

3) What are the explicit in vitro dissolution conditions used to define Claim 14?

Initial medium is 0.1 N HCl, then after 2 hours it is adjusted to pH ~6.8, with testing using USP Apparatus 2, and specific weight-percent release targets at defined time points.

4) Are the PK requirements limited to AUC and Cmax only?

No. Claim 1 lists multiple AUC-based and Tmax-linked parameters (AUC0-3, AUC0-5, AUC0-Tmax, AUC5-12, AUC5-24, AUC T max -24, AUC T max -12, AUC0-24, AUC0-∞, among others). Dependent claims then set numeric targets for several of these.

5) Which claim elements are most likely to drive “hard” design-around constraints?

The combination of (i) two-population architecture with defined particle number ratios, (ii) specific coating and barrier polymer chemistries at the dependent level, and (iii) numeric dissolution and human PK windows for ODT dosing equivalents.

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References

1. United States Patent No. 9,072,680. Claims 1-28 (as provided in the prompt).

Drugs Protected by US Patent 9,072,680

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Neos Theraps Inc	COTEMPLA XR-ODT	methylphenidate	TABLET, ORALLY DISINTEGRATING, EXTENDED RELEASE;ORAL	205489-001	Jun 19, 2017		RX	Yes	No	9,072,680		Y
Neos Theraps Inc	COTEMPLA XR-ODT	methylphenidate	TABLET, ORALLY DISINTEGRATING, EXTENDED RELEASE;ORAL	205489-002	Jun 19, 2017		RX	Yes	No	9,072,680		Y
Neos Theraps Inc	COTEMPLA XR-ODT	methylphenidate	TABLET, ORALLY DISINTEGRATING, EXTENDED RELEASE;ORAL	205489-003	Jun 19, 2017		RX	Yes	Yes	9,072,680		Y

International Family Members for US Patent 9,072,680

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2726066
World Intellectual Property Organization (WIPO)	2013003622