Details for Patent: 12,440,474

Which drugs does patent 12,440,474 protect, and when does it expire?

Patent 12,440,474 protects JAVADIN and is included in one NDA.

Summary for Patent: 12,440,474

Title:	Stable pharmaceutical compositions of clonidine
Abstract:	The present invention relates to liquid pharmaceutical compositions of clonidine or its pharmaceutically acceptable salts thereof. Preferably, the liquid pharmaceutical compositions are suitable for oral administration, and are stable for extended periods of time. More specifically, stable liquid pharmaceutical compositions of clonidine at concentrations of 1 μg/mL or more are provided. The present invention further relates to stable oral liquid compositions of clonidine, methods for their administration, processes for their production, and use of these compositions for treatment of diseases treatable by clonidine.
Inventor(s):	Shailendra Mandge, Harish GUNDA, Naga Venkata Durga Prasad Ketha, Venkateshwar Reddy Keesara, BALASUBRAMANIAN Satheesh, Sumitra Ashokkumar PILLAI
Assignee:	Azurity Pharmaceuticals Inc
Application Number:	US19/021,882
Patent Claim Types: see list of patent claims	Composition; Formulation;

United States Patent 12,440,474 (Clonidine HCl oral solution) claims scope, claim-construction map, and US patent estate landscape

US Patent 12,440,474 claims a tightly specified clonidine hydrochloride oral liquid defined by (i) a low dose concentration (about 20 µg/mL), (ii) stabilizer and preservative concentration windows, (iii) explicit exclusion of buffer, (iv) oral solution with specific excipients (sweetener, flavor, water, optional pH adjuster), (v) a degradation/impurity performance criterion after 3 months at 25°C/40% RH or 25°C/60% RH (not more than 2% w/w total impurities formed), and (vi) multi-dose container configurations (including PET/HDPE/glass/BFS vials) as dependent claim subjects.

Based on the claim set provided, the effective US scope is most likely to be read narrowly around: use of clonidine HCl at ~20 µg/mL in a non-buffered oral solution with (a) selected stabilizers, (b) selected preservatives at specific mg/mL and/or wt% ranges, and (c) impurity-control performance, plus separate infringement hooks in container-specific multi-dose packaging claims.

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What patents protect clonidine hydrochloride oral solution at ~20 µg/mL without buffer?

Featured-snippet answer: Patent 12,440,474 protects a specific non-buffered formulation of clonidine HCl in water at ~20 µg/mL, using defined stabilizer and preservative systems, with defined performance for impurities over 3 months at 25°C under controlled humidity, and with protected multi-dose container formats. The closest “core” features are “about 20 µg/mL” + “free of buffer” + impurity limit criterion + stabilizer/preservative windows.

Core independent claim 1: scope anchors

Claim 1 builds infringement around a conjunctive set of structural and functional limitations:

1. Active concentration

   • Clonidine hydrochloride at about 20 µg/mL.
   • “About” introduces some numerical tolerance in claim construction, but the claim still fixes the invention at an ultra-low oral solution concentration rather than a general clonidine liquid category.

2. Liquid pharmaceutical composition

   • “Liquid” + “oral solution” limits the dosage form to a solution (not suspensions or emulsions).

3. Buffer exclusion

   • “Free of buffer” is a hard boundary.
   • This matters because many clonidine oral formulations may use buffer systems to manage pH/chemical stability. A product that uses a buffer salt/couple to maintain pH likely avoids the “free of buffer” limitation depending on how “buffer” is construed.

4. Stabilizer concentration window

   • “Stabilizer” at about 0.001% to 20% w/w.
   • This is broad in absolute % terms but narrowed by dependent claim species (histidine, arginine, meglumine, tromethamine, sodium chloride, or mixtures).

5. Preservative concentration window

   • Preservative at about 0.01% to 5.0% w/w.

6. Mandatory excipients

   • Sweetener + flavoring agent + water.
   • Optional pH adjusting agent.

7. pH ranges (open in claim 1)

   • Claim 1 only says pH adjusting agent is optional, with no explicit pH limit in claim 1 itself.
   • Dependent claims 5 and 6 later lock pH windows.

8. Stability/performance limitation

   • “Not more than 2% w/w of total impurities are formed” after storage for at least 3 months at:
     • 25°C/40% RH, or
     • 25°C/60% RH.

   This is a functional claim element tied to stability testing. It often becomes central in infringement analysis because accused products must meet (or not meet) the impurity criterion under the claimed storage conditions.

9. Multi-dose packaging (dependent claims)

   • Claims 15-19 add infringement hooks for “multi-dose container” formats.

Dependent claims that narrow the “in practice” protected formulations

• Claim 2 (stabilizer species): stabilizer selected from histidine, arginine, meglumine, tromethamine, sodium chloride.
• Claim 3 (preservative species + concentration): potassium sorbate and/or sodium propionate at 2.5 mg/mL.
• Claims 5 and 6 (pH windows):
  • claim 5: pH 3 to 9
  • claim 6: pH 4 to 6
• Claims 7-8 (stabilizer concentration narrower):
  • claim 7: 0.01% to 15% w/w
  • claim 8: 0.1% to 10% w/w
• Claims 9-10 (clonidine-to-stabilizer ratio):
  • claim 9: 1:50 to 1:150
  • claim 10: about 1:125
• Claims 11-13 (clonidine-to-preservative ratio and preservative wt% range):
  • claim 11: preservative 0.05% to 1.0% w/w
  • claim 12: clonidine-to-preservative 1:20 to 1:70
  • claim 13: about 1:50
• Claim 14 (in-use shelf life):
  • at least one month at room temperature.
• Claims 15-19 (container types):
  • multi-dose container generally (15)
  • PET bottle (16)
  • HDPE bottle (17)
  • glass bottle (18)
  • blow-fill sealed vials (19)

Claim-construction impact: where design-arounds most likely sit

Because claim 1 uses multiple conjunctive limits, product avoidance tends to be strongest when you change at least one “anchor” limitation:

1. Avoid “free of buffer”

   • Switch to a formulation that uses a buffer system (or uses components that could be characterized as a buffer) and hold pH by buffer action.
   • Conversely, if your product is non-buffered, this design-around fails.

2. Move away from ~20 µg/mL

   • If you launch at a different concentration, you avoid literal coverage.
   • “About” could still capture close values, so the safest path is a meaningful shift outside claim construction tolerance.

3. Fail the impurity criterion

   • If the formulation cannot maintain total impurities ≤ 2% w/w after the claimed storage conditions, it may avoid infringement depending on how “total impurities” is defined in the spec and whether that limit is treated as a strict product property.

4. Change preservative/stabilizer systems

   • Dependent claims narrow species and specific concentrations/ratios, but claim 1 already broadens stabilizer/preservative classes to “a stabilizer” and “a preservative.”
   • Design-around typically targets species and exact concentration windows that map to claims 2-3, 7-8, 11-13, or ratio claims.

5. Packaging route

   • Independent claim 1 does not require a particular container.
   • Dependent claims 15-19 do. Packaging design-around is mainly relevant to claim 15+ rather than claim 1.

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How broad are the stabilizer and preservative concentration ranges, and what does that mean for generic design?

Featured-snippet answer: Claim 1 is broad on stabilizer (0.001% to 20% w/w) and preservative (0.01% to 5.0% w/w), but the claim is narrowed by dependent claim species and specific preservative concentrations (notably 2.5 mg/mL potassium sorbate and/or sodium propionate) and ratio limits (e.g., clonidine-to-stabilizer about 1:125). The tightest practical coverage is likely driven by impurity performance plus the “free of buffer” limitation.

Stabilizer: broad range in claim 1, narrower in claims 2, 7, 8, and ratio claims 9-10

• Claim 1: stabilizer 0.001% to 20% w/w.
• Claim 2: stabilizer restricted to specific amino/base or salt species.
• Claims 7-8: narrower stabilizer wt% bands.
• Claims 9-10: clonidine-to-stabilizer weight ratio windows, including a target around 1:125.

Design implication: Even if you fit claim 1’s broad range, dependent claims can still be infringed if you use the listed stabilizers at wt% or ratios that align.

Preservative: broad in claim 1, narrowed in claims 3 and 11-13

• Claim 1: preservative 0.01% to 5.0% w/w.
• Claim 3: potassium sorbate and/or sodium propionate at 2.5 mg/mL.
• Claim 11: preservative 0.05% to 1.0% w/w.
• Claims 12-13: clonidine-to-preservative ratio windows.

Design implication: If a competitor avoids these species or concentration/ratio targets, it may weaken dependent-claim exposure. But claim 1 can still read on other preservatives within the broad window.

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Does “free of buffer” make this patent easier to design around?

Featured-snippet answer: Yes. “Free of buffer” is an explicit exclusion that can be targeted by formulation strategy. If an accused product uses a buffer system to control pH, it may fall outside the claim depending on how “buffer” is interpreted and whether pH is maintained by buffer action rather than by non-buffer components.

Buffer exclusion: what it likely covers in infringement practice

• Many oral solutions are adjusted with non-buffering acid/base systems (no buffer pair) to reach a pH target.
• Others include buffer couples (e.g., acetate, phosphate, citrate, borate) that provide buffering capacity.

If “buffer” is construed as requiring measurable buffering capacity, a non-buffer acid/base adjuster may still avoid “buffer,” but adding a buffer salt/couple increases design-around probability.

Related boundary: optional pH adjusting agent

Claim 1 permits “optionally, a pH adjusting agent” while still requiring “free of buffer.” That means the patent contemplates pH adjustment without buffer capacity. Competitors can use pH adjusters, but if they add buffer couples they likely step outside the literal claim language.

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What performance tests and stability endpoints matter for infringement of the impurity limit?

Featured-snippet answer: Claim 1 requires that “not more than 2% w/w of total impurities are formed” after storage for at least 3 months at 25°C/40% RH or 25°C/60% RH. Stability test design and analytical method definitions for “total impurities” become central.

Impurity clause: why it is often the decisive claim element

• The claim defines a quantitative limit tied to time and storage conditions.
• In litigation, this can drive:
  • expert reliance on accelerated/real-time data,
  • whether the impurity profile matches “total impurities” measured by the patent’s method,
  • whether packaging/container influences impurities (relevant to dependent packaging claims).

Container dependence: interplay with impurity formation

Claims 15-19 add multi-dose containers, including PET/HDPE/glass/BFS vials. In practice, container materials can affect leachables, adsorption, and degradation pathways, which may influence “total impurities” outcomes.

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Which multi-dose containers are covered, and can packaging design avoid infringement?

Featured-snippet answer: Dependent claims 15-19 require a multi-dose container and specify container types: PET, HDPE, glass, and blow-fill sealed vials. Changing container type is the most direct design-around for those dependent claims, but it does not avoid claim 1 if the formulation still meets its limitations.

Dependent packaging hooks

• Claim 15: multi-dose container.
• Claim 16: PET bottle.
• Claim 17: HDPE bottle.
• Claim 18: glass bottle.
• Claim 19: blow-fill sealed vials.

Practical packaging avoidance logic

• If a product uses the same formulation but a different packaging format not captured by these dependent claims, claim 1 exposure remains.
• If a product uses a covered container but changes formulation to avoid claim 1, packaging does not create infringement by itself.

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How strong is the patent estate likely to be around this clonidine oral solution platform?

Featured-snippet answer: On the claim language alone, strength is likely moderate-to-high for very specific competitors because the invention is constrained by a narrow active concentration, a “free of buffer” exclusion, a defined stabilizer/preservative system, and a quantitative impurity-stability endpoint. Weakness risk exists if a competing product can either (i) use a buffer system, (ii) use a different concentration, or (iii) demonstrate impurity formation above the claimed threshold under the claimed conditions.

Claim-set structure suggests “barricade” coverage

• Independent claim 1 sets the scaffold (non-buffered clonidine solution at ~20 µg/mL with stabilizer + preservative + excipients + impurity limit).
• Dependent claims then:
  • lock stabilizer and preservative species,
  • lock specific concentration and ratio windows,
  • lock pH ranges,
  • lock in-use shelf-life,
  • lock container types.

This pattern is consistent with a patent drafted to catch both “formula copycats” and “near-miss” variants that retain the same excipient logic and performance.

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How would a Paragraph IV or biosimilar-style strategy map to this formulation patent?

Featured-snippet answer: For a small molecule like clonidine, “biosimilar” is not applicable. For generic strategy, the litigation posture would turn on whether an ANDA product meets claim 1’s conjunctive limitations. The strongest non-infringement arguments are typically buffer exclusion (“free of buffer”), active concentration mismatch (not about 20 µg/mL), or failure of the impurity limit under the claimed storage conditions.

Typical generic attack surfaces for this claim set

1. Non-infringement

   • Show buffer present (if accused formulation uses buffer).
   • Show concentration is not “about 20 µg/mL.”
   • Show impurity formation >2% w/w after required storage conditions (or that “total impurities” does not match the claim’s operational definition).

2. Invalidity

   • Requires a prior-art and claim-to-reference mapping exercise not derivable from claim language alone. Without the patent’s specification text, prosecution history, and identified prior art, a definitive invalidity forecast cannot be produced here.

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What is the Orange Book status of US 12,440,474, and which FDA product is it associated with?

Featured-snippet answer: No Orange Book or FDA label linkage information is provided in the prompt. Without the corresponding Orange Book listing, application number, NDA/ANDA reference drug name, strength, dosage form, and approval dates, the status mapping cannot be completed from the claim text alone.

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Key claim-by-claim scope map (infringement “yes/no” checklist)

Claim 1 (independent): formulate-to-avoid checklist

A product likely falls within claim 1 if it is:

• An oral liquid solution containing:
  • clonidine HCl at ~20 µg/mL
  • stabilizer at ~0.001% to 20% w/w
  • preservative at ~0.01% to 5% w/w
  • sweetener + flavoring agent + water
  • optionally pH adjuster
• Free of buffer
• Meets impurity performance:
  • ≤2% w/w total impurities formed after ≥3 months at 25°C/40% RH or 25°C/60% RH

Claims 2-14: narrower sub-scopes

• Claim 2: stabilizer is from a defined species list.
• Claim 3: preservative is potassium sorbate and/or sodium propionate at 2.5 mg/mL.
• Claims 5-6: pH 3-9 or 4-6.
• Claims 7-8: stabilizer % narrowed.
• Claims 9-10: clonidine-to-stabilizer ratio windows.
• Claims 11-13: preservative % and ratios.
• Claim 14: in-use shelf life ≥1 month at room temperature.

Claims 15-19: container-dependent sub-scopes

• Claim 15: multi-dose container.
• Claims 16-18: PET, HDPE, glass bottle types.
• Claim 19: blow-fill sealed vials.

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Patent landscape summary: what this claim set is likely designed to dominate

Featured-snippet answer: The patent is designed to dominate a specific segment of clonidine oral liquid competition: non-buffered formulations at ~20 µg/mL with amino/salt stabilizers, typical preservative systems (sorbate/propionate at defined levels), controlled pH, and stability that limits impurity formation under humid storage. Packaging-dependent coverage adds friction for alternative multi-dose container choices.

Competitive risk drivers

• Products that keep the same excipient logic and pH control method but vary slightly in stabilizer/preservative levels can still fall within dependent claims.
• Products that keep the same formulation but change container may avoid dependent packaging claims, but still risk claim 1 infringement if formulation limitations are met.
• The “free of buffer” clause is the largest categorical design-around lever.

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Key Takeaways

• US 12,440,474 claim 1 targets a highly specific formulation profile: clonidine HCl ~20 µg/mL oral solution, explicitly non-buffered, with defined stabilizer/preservative concentration windows, and an impurity-performance requirement after 3 months at 25°C with 40% or 60% RH.
• Dependent claims narrow to specific stabilizer species, potassium sorbate/sodium propionate at 2.5 mg/mL, pH windows, ratio targets, in-use shelf life, and specific multi-dose containers (PET/HDPE/glass/BFS vials).
• The highest-value design-around paths, based purely on claim language, are: (i) introduce a buffer system to avoid “free of buffer,” (ii) move off the ~20 µg/mL concentration, and/or (iii) fail the ≤2% total impurities criterion under required storage conditions.
• Packaging changes can avoid dependent claims 15-19 but do not avoid claim 1 if the formulation meets all claim 1 limitations.

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FAQs

1) If a competitor uses clonidine HCl at 20 µg/mL but with a citrate/phosphate buffer, does that likely avoid claim 1?

Claim 1 requires the composition to be “free of buffer.” A buffer system is a direct confrontation with that limitation, and likely avoids literal coverage depending on claim construction of “buffer.”

2) What excipient changes are most likely to avoid dependent claim 3?

Dependent claim 3 is tied to potassium sorbate and/or sodium propionate at 2.5 mg/mL. Using different preservatives or different concentrations can avoid claim 3 while still risking claim 1 if the preservative is within claim 1’s broad window.

3) Can a product infringe claim 15 (multi-dose container) but avoid claim 1?

Yes. Claim 15 is dependent on claim 1. If claim 1 is not met, claim 15 cannot be infringed even if the container is PET/HDPE/glass/BFS.

4) How does the impurity limit affect infringement strategy for a stability-testing dispute?

It forces product-property proof under specific time and humidity conditions. The impurity measurement protocol and comparator definition of “total impurities” become central.

5) Are biosimilar issues relevant to this patent?

No. This is a small-molecule formulation patent covering clonidine hydrochloride oral solution composition, not a biologic.

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References (APA)

No external sources were provided or cited in the request.

Drugs Protected by US Patent 12,440,474

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Azurity	JAVADIN	clonidine hydrochloride	SOLUTION;ORAL	220256-001	Oct 23, 2025		RX	Yes	Yes			Y