Details for Patent: 12,576,032

Which drugs does patent 12,576,032 protect, and when does it expire?

Patent 12,576,032 protects ONYDA XR and is included in one NDA.

Summary for Patent: 12,576,032

Title:	Liquid clonidine extended release composition
Abstract:	An oral clonidine dosage unit providing a twenty-four hour extended release profile following a single dose administration is provided. The dosage unit comprises a pharmaceutically effective amount of a coated complex comprising clonidine bound to a cationic exchange resin, which is characterized by a twenty-four hour release profile. Dosage units may also provide an immediate release component.
Inventor(s):	Grishma Patel
Assignee:	Tris Pharma Inc
Application Number:	US18/419,883
Patent Claim Types: see list of patent claims	Use;

United States Patent 12,576,032: Scope, Claims, and U.S. Patent Landscape for Once-Daily Extended-Release Oral Clonidine Suspension for ADHD

What is covered by US 12,576,032?

US 12,576,032 is a US-method patent that claims treatment of attention deficit hyperactivity disorder (ADHD) using a single-daily dose of an extended-release oral clonidine aqueous suspension. The core claim scope is defined by a specific drug architecture:

• Modified-release component (majority of dose): clonidine bound to a cation exchange resin in a matrix formed with a hydrophilic polymer (or copolymer), and then overcoated with a pH-independent, water-insoluble barrier coating that includes a plasticizer.
• Immediate-release component (minority of dose): clonidine in immediate release form, which is either:
  • an immediate release clonidine-cation exchange resin complex, or
  • a combination of immediate release clonidine-cation exchange resin complex plus clonidine uncomplexed to an ion exchange resin and/or a clonidine salt that is also uncomplexed to an ion exchange resin.
• Dose construction: the claims fix dose form and percentage splits, and constrain composition ranges in w/w terms and in clonidine HCl-equivalent terms.

The independent claims are directed to ADHD treatment with once-daily administration and, in several dependent claims, to once-daily dosing under specific pharmacokinetic behavior (single plasma peak in fasting conditions) and patient populations (including pediatrics).

What are the independent claims and their gating limitations?

Claim 1 (method; extended-release clonidine aqueous suspension; ADHD; single dosage)

Claim 1 sets the blueprint for the composition and dosing scheme.

A. Modified-release barrier coated particles (major portion) Particles each comprise:

1. Clonidine bound to a cationic exchange resin
2. A matrix comprising a hydrophilic polymer or copolymer
3. A modified release barrier coating that is:
   • pH-independent
   • water-insoluble
   • includes a plasticizer
   • formed as a layer over the clonidine-resin-matrix particles

Key quantitative gates:

• Barrier coating thickness composition by particle weight pre-coating:
  • 50% w/w to about 80% w/w of (clonidine-cation exchange resin complex-matrix particles) basis (as recited in claim 1 text).
• Hydrophilic polymer content in matrix (as % w/w based on particle weight pre-barrier coating):
  • about 5% w/w to about 20% w/w
• Fraction of clonidine delivered by modified-release particles:
  • at least about 70% w/w to about 95% w/w of total clonidine in suspension
  • measured based on clonidine HCl-equivalent

B. Immediate-release clonidine components (minor portion) Immediate-release component(s) comprising:

• (1) an immediate release clonidine-cation exchange resin complex, or
• (2) a combination of:
  • immediate release clonidine-cation exchange resin complex and
  • clonidine uncomplexed to an ion exchange resin and/or
  • a pharmaceutically acceptable salt of clonidine uncomplexed to an ion exchange resin

Immediate release portion is dispensed in an aqueous suspension base.

Claim 25 (method; ADHD; “once a day”; constrained split)

Claim 25 is the tightest independent framing for the once-daily regimen.

Same architecture as claim 1, but with a distinctive fixed “core” split and narrower composition ranges:

A. Modified-release particles

• Barrier coating proportion (same structural concept):
  • 50% w/w to about 80% w/w
• Hydrophilic polymer in matrix:
  • about 3% w/w to about 20% w/w (lower floor than claim 1)
• Modified-release clonidine fraction:
  • 70% w/w to about 95% w/w of clonidine (clonidine HCl-equivalent basis)

B. Immediate-release fraction

• about 5% w/w to about 30% w/w clonidine in immediate release form
• Immediate-release is specified as:
  • immediate release clonidine-cation exchange resin complex, plus
  • clonidine uncomplexed and/or clonidine salt uncomplexed to an ion exchange resin
• Delivered in suspension base.

Claim 30 (method; ADHD; “once a day”; near-fixed 90/10 split)

Claim 30 sets a near-fixed ratio:

• Modified-release portion: about 90% w/w of clonidine in suspension (explicit)
• Immediate-release portion: about 10% w/w of clonidine in suspension
• Matrix polymer in range about 3% w/w to about 20% w/w
• Barrier coating:
  • 50% w/w to about 80% w/w
  • pH-independent, water-insoluble polymer + plasticizer

What dependent claims narrow the dosing and pharmacokinetics?

Dose concentration gates (clonidine per mL; clonidine HCl-equivalent)

• Claim 2: dose includes 0.1 mg/mL or 0.2 mg/mL
• Claim 19: dose includes 0.1 mg/mL or 0.2 mg/mL
• Claim 20: dose includes up to 0.4 mg/mL (equivalent basis)
• Claim 23: pediatric patient aged 6 to 17 (population gate)

Immediate-release fraction gates

• Claim 3: suspension comprises 5% w/w to about 30% w/w clonidine in immediate release form
• Claim 14: duplicates same range (5% to 30%) as a dependent narrowing
• Claim 21: specifies about 90% w/w modified release and about 10% w/w immediate release
• Claim 27: specifies about 5% w/w immediate release clonidine-cation exchange resin complex plus about 5% w/w clonidine uncomplexed to an ion exchange resin (total based on clonidine equivalent HCl)

Plasma concentration behavior (fasting)

• Claim 4: provides a single plasma concentration peak post-dosing under fasting conditions
• Claim 15: same limitation in the claim family

Dosing schedule

• Claim 17: administering the suspension prior to bed time
• Claim 16 and Claim 25/30: treatment effective for a twenty-four hour period and once a day method framing

Pediatric and age framing

• Claim 22: subject is a pediatric patient
• Claim 23: aged 6 to 17

What composition limitations define the particle chemistry?

Antioxidant and excipient-related constraints

• Claim 5: includes about 0.1% w/v to about 0.5% w/v antioxidant

• Claim 6: antioxidant comprises:

  • EDTA or a pharmaceutically acceptable water soluble salt, and/or
  • ethyl maltol, or mixtures

• Claim 24: further comprises a buffering component

• Claim 28 and Claim 32: suspension can further include one or more of:

  • buffering agent
  • anti-oxidant
  • preservative
  • suspending agent
  • flavoring agent
  • solvents
  • combinations

Barrier coating polymer families (explicit list)

• Claim 10: modified release barrier coating is selected from:

  • pH-independent barrier coating polymer including:
    • ethylcellulose + plasticizer
    • cured polyvinyl acetate + plasticizer
    • pH-independent acrylate-based coating + optional plasticizer
    • mixtures of the above

• Claim 11: barrier coating comprises:

  • about 70% w/w to about 90% w/w polyvinyl acetate
  • about 2.5% w/w to about 20% w/w plasticizer

Hydrophilic matrix polymer

• Claim 12: hydrophilic polymer is polyvinylpyrrolidone (PVP)
• Claim 29: duplicates the matrix-forming polymer as PVP

Cation exchange resin specifications

• Claim 13: cation exchange resin comprises:
  • sulfonated copolymer of styrene and divinylbenzene
  • average particle size: 10% to 25% in the range 0.075 mm, and no more than 1% greater than 0.150 mm
  • heavy metals content < 10 ppm

These details are material because they narrow product-by-process and product-by-structure variations and can support invalidity arguments tied to prior art resin specifications if the prior art uses substantially the same resin characteristics.

What is the practical “scope map” of coverage?

Core “must-have” elements (literal claim coverage)

A method falls within the independent claim scaffold if it includes:

1. ADHD treatment
2. single oral dose (and in claims 25/30, explicitly once daily)
3. extended-release oral clonidine aqueous suspension
4. a two-component clonidine exposure system:
   • majority clonidine delivered by modified-release barrier-coated clonidine-resin-matrix particles
   • minority clonidine delivered by immediate-release clonidine resin complex and/or uncomplexed clonidine and/or clonidine salt uncomplexed
5. particle architecture constraints:
   • pH-independent, water-insoluble barrier coating + plasticizer
   • clonidine bound to cationic exchange resin
   • hydrophilic polymer matrix at the specified % range
6. clonidine distribution % gates:
   • modified release: at least about 70% w/w to about 95% w/w (claim 1)
   • and in claim 30: explicit ~90/10 split

“Optional” dependent coverage knobs

Dependent claims narrow but do not necessarily define the independent claim. They include:

• exact concentration (0.1, 0.2 mg/mL; up to 0.4 mg/mL)
• fasting single-peak PK
• antioxidant identity and concentration range
• barrier coating polymer identity (ethylcellulose, cured PVA, acrylate)
• barrier composition (e.g., PVA: plasticizer range)
• cation exchange resin specs (particle size distribution; heavy metals)
• pediatric population including age 6 to 17
• bedtime administration and food/no-food flexibility (claim 18)

Where are the highest risk claim interpretation pivots?

1. Percentage terms and measurement basis

   • Several percent compositions are expressly based on clonidine HCl-equivalent.
   • This can shift infringement analysis from “active in particle weight” to “active equivalent in finished suspension.”

2. Immediate-release “uncomplexed” clonidine and salts

   • Claims expressly cover clonidine uncomplexed to an ion exchange resin and pharmaceutically acceptable salts that are also uncomplexed.
   • Products that use immediately released clonidine salt in a resin-complexed form may sit outside certain immediate-release subranges, depending on whether “uncomplexed” is required by the claim embodiment.

3. Barrier coating pH independence

   • Coverage hinges on barrier coating being pH-independent. Many enteric or pH-responsive coatings can be designed to be pH-sensitive; this claim requires pH-independent behavior.

4. Hydrophilic matrix polymer content

   • Claim 1 fixes a hydrophilic polymer content of about 5% to about 20% in matrix.
   • Claim 25/30 expand to about 3% to about 20%.
   • A formulation with lower than 3% matrix polymer could avoid those dependent-limited claim versions, but would still need to escape independent claim 1 wording if pursued.

5. PK “single peak under fasting” limitations

   • Claims 4 and 15 impose a functional PK attribute. In litigation, these can be interpreted as requiring the claimed PK profile in the claimed conditions.

What does the patent landscape likely look like in the U.S. (strategic view)?

Because only the asserted claims were provided (no bibliographic data, filing dates, assignee, related family members, specification data, or citation list), a complete, defensible U.S. landscape cannot be reconstructed. The only actionable landscape description that can be stated from the claim text itself is the technology cluster this patent sits in:

Technology cluster anchored by claim elements

The claimed system blends three known chemistry categories into one oral suspension:

• Ion-exchange complexation of clonidine with cation exchange resin (sulfonated styrene-divinylbenzene)
• Matrix-forming hydrophilic polymer (notably PVP) to embed particles
• Modified-release barrier coating that is pH-independent and water-insoluble and uses plasticizer, with specific polymer options (ethylcellulose, cured polyvinyl acetate, acrylate-based)

Within U.S. patent practice, that combination is typically surrounded by families that separately claim:

• resin selection and complexation ratios
• coated particle preparation processes
• oral suspension excipient systems for clonidine or other centrally acting agents
• PK-optimized two-stage (immediate + modified) release profiles
• pediatric ADHD dosing regimens and formulation forms (once-daily)

Where competitors usually differentiate

Given the claim’s granular percentage and material constraints, competitors seeking non-infringing designs usually move one or more of:

• the polymer identity in the barrier coat (outside listed options) or remove/replace plasticizer functionality
• the hydrophilic polymer identity or content below claimed floors
• resin type (outside sulfonated styrene-divinylbenzene) or resin particle size distribution / heavy metals profile
• the clonidine split ratio (move outside 70-95 modified-release fraction, or outside 90/10 for claim 30)
• the uncomplexed immediate-release element (avoid uncomplexed clonidine salts if not required, or reverse the immediate-release form to all resin-complexed)

Potential enforceability and freedom-to-operate pressure points

Within this claim set, enforceability strength typically concentrates on:

• composition-defined elements (polymer classes, coating characteristics, resin specs)
• dose ratio and PK profile limitations (especially for “single plasma peak” claims)
• explicit pediatric claims (age gate can strengthen targeted enforcement where label labeling aligns)

Freedom-to-operate risk is highest when a candidate product:

• uses a clonidine-resin complex in a hydrophilic matrix
• applies a pH-independent water-insoluble barrier with plasticizer
• delivers 70-95% of dose via modified-release particles
• pairs it with an immediate-release resin complex and/or uncomplexed clonidine/salt

Key Takeaways

• US 12,576,032 claims once-daily extended-release oral clonidine aqueous suspensions for ADHD built from two clonidine forms: modified-release barrier-coated clonidine-cation exchange resin-matrix particles (majority) plus immediate-release clonidine (minority).
• The independent claim scope is defined by tight composition architecture: pH-independent, water-insoluble barrier coating + plasticizer, hydrophilic matrix polymer at ~3-20% (depending on claim) and a defined modified-release clonidine fraction (generally 70-95%, with ~90/10 in claim 30).
• The most decision-driving limitations for infringement are the measured clonidine HCl-equivalent basis, the uncomplexed immediate-release clonidine/salt requirement in certain embodiments, the pH-independence of the barrier coat, and the single plasma peak under fasting limitation.
• The claim text points to a dense technical prior-art zone around ion-exchange complexation, coated controlled-release particles, and clonidine formulation for pediatric ADHD dosing, where competitor design-arounds typically target matrix polymer content, barrier polymer/plasticizer selection, resin characteristics, and dose split.

FAQs

1) Is the invention limited to clonidine HCl-equivalent dosing?

Yes. Multiple limitations specify percent composition “as determined based on the amount of clonidine equivalent to clonidine HCl,” tying the claims to an equivalent-based accounting method.

2) Does the claim require both immediate release and modified release components?

Yes. Claim 1 requires (A) modified-release barrier coated resin-matrix particles and (B) an immediate-release clonidine component(s), with dose split ranges.

3) Are pH-dependent or enteric coatings within scope?

No. The barrier coating is explicitly pH-independent and water-insoluble.

4) What barriers matter most for designing around this patent?

The highest leverage levers are the hydrophilic matrix polymer content range, barrier coat polymer family and plasticizer role, cation exchange resin specifications, and the modified vs immediate clonidine dose split.

5) Do any claims cover pediatric patients specifically?

Yes. Claim 22 covers pediatric patients, and claim 23 narrows to ages 6 to 17.

References

[1] United States Patent 12,576,032. (Claim text provided in prompt).

Drugs Protected by US Patent 12,576,032

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Tris Pharma Inc	ONYDA XR	clonidine hydrochloride	SUSPENSION, EXTENDED RELEASE;ORAL	217645-001	May 24, 2024		RX	Yes	Yes	12,576,032					METHOD OF TREATING ATTENTION DEFICIT HYPERACTIVITY DISORDER (ADHD)