Details for Patent: 12,491,163

Which drugs does patent 12,491,163 protect, and when does it expire?

Patent 12,491,163 protects TWYNEO and is included in one NDA.

This patent has six patent family members in six countries.

Summary for Patent: 12,491,163

Title:	Stabilized microcapsules, method of their preparation and uses thereof
Abstract:	The present application is directed to stabilized core-shell microcapsules comprising a core of benzoyl peroxide (BPO) or all trans retinoic acid (ATRA) and a metal-oxide shell; and to pharmaceutical compositions and methods of use thereof.
Inventor(s):	Ofer Toledano, Karine Neimann, Danil FINKEL-MOISEEV, Maya Erlich, Dorit Marco
Assignee:	Mayne Pharma LLC
Application Number:	US17/327,732
Patent Claim Types: see list of patent claims	Use; Composition; Formulation; Dosage form;

US Patent 12,491,163 Scope and Claim Landscape for Topical Acne Microcapsules (Tretinoin + Benzoyl Peroxide) in the United States

Executive summary: United States Patent US 12,491,163 claims a topical acne treatment method that uses two distinct microcapsule populations in a single pharmaceutical composition: (i) microcapsules containing tretinoin as the only active agent in those microcapsules, and (ii) microcapsules containing benzoyl peroxide as the only active agent in those microcapsules, with tightly defined core dispersion properties, phase-changing excipient selection, microcapsule physical parameters, shell materials, and measurable release/dissolution and stability performance thresholds. The independent claim is framed to be hard to design around because it requires the combination of (a) specific microencapsulation architecture for tretinoin, (b) defined non-liquid phase-changing materials of limited chemical classes, and (c) quantitative dissolution, encapsulation efficiency, and storage degradation controls, paired with (d) benzoyl peroxide in a separate microcapsule class rather than as unencapsulated or co-encapsulated actives.

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How broad are the claims in US 12,491,163 (what exactly must a product do)?

Core claim structure (Claim 1, method claim): A method for treating acne by topical administration of a composition that includes:

1. Two microcapsule types in the same pharmaceutical composition

• Tretinoin microcapsules: tretinoin (or a pharmaceutically acceptable salt) is the only active agent in the tretinoin microcapsules.
• Benzoyl peroxide microcapsules: benzoyl peroxide is the only active agent in the benzoyl peroxide microcapsules.

2. Tretinoin microcapsule internal architecture

• Each tretinoin microcapsule includes:
  • a core encapsulated by a shell,
  • the core comprises a dispersion,
  • the dispersion includes:
    • an oil phase with tretinoin in solid form at 17% to 25% w/w in the oil phase,
    • optionally at least one phase changing material (PCM).

3. PCM must be non-liquid at room temperature and selected from a narrow list

• PCM is not liquid at room temperature and is selected from:
  • natural or synthetic paraffin (CnH2n+2),
  • C10–C100 alkanes, alkenes, alkynes,
  • waxes,
  • aliphatic alcohols of formula CH3(CH2)nOH,
  • fatty acids of formula CH3(CH2)nCOOH,
  • or combinations thereof, where n = 10–100.

4. Quantitative actives in the final composition

• Tretinoin is 0.1% by weight of the overall composition.
• Benzoyl peroxide is 3% by weight of the overall composition.

5. Relief clauses via dependent claims

• Claim 1 is further restricted by multiple performance and structural dependent limitations (Claims 2–15), including:
  • shell material (silicon dioxide or metal oxides),
  • metal oxide shell thickness (50 nm to 5000 nm “according to energy selective backscattered-detector”),
  • microcapsule diameter (5 to 50 µm),
  • dissolution rate windows for tretinoin and benzoyl peroxide under defined media/temperatures,
  • stability (degradation of a specified retinoid impurity),
  • encapsulation efficiency floors,
  • and tighter encapsulation efficiency variations.

Implication for claim breadth: The independent claim is not a generic “tretinoin + BPO microcapsules for acne.” It is a highly specific microencapsulation-and-performance recipe with explicit chemical classes for PCM and explicit release/stability metrics in dependent claims. Any “design around” must typically avoid at least one required element: the two-population microcapsule structure, tretinoin solid-in-oil at 17–25% w/w oil phase, PCM chemical class/non-liquid requirement, the 0.1% / 3% overall dosing ratio, or the measurable dissolution and encapsulation performance.

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Which parts of US 12,491,163 are likely most litigated: dissolution, stability, or shell/size?

What dissolution metrics are claimed (tretinoin and benzoyl peroxide)?

Dependent claims specify dissolution rate windows using defined media and temperatures.

• Claim 6 (tretinoin dissolution): tretinoin microcapsules provide dissolution of 5% to 35% weight/h measured in 30%:70% v/v water:isopropyl alcohol at 32° C.
• Claim 11 (tretinoin + benzoyl peroxide dissolution):
  • tretinoin: 5% to 35% weight/h in 30%:70% v/v water:isopropyl alcohol at 32° C.
  • benzoyl peroxide: 10% to 60% weight/h in 55%:45% water:acetonitrile at ambient temperature.

Litigation exposure: Dissolution tests are commonly outcome-determinative in infringement disputes. Here the claims lock in (i) test media composition, (ii) temperature, and (iii) rate bounds. A challenger can attempt to argue non-infringement by showing measured dissolution falls outside the stated bands under the claimed test method.

What stability/degradation requirement is claimed?

• Claims 10 and 13 (same concept): after two weeks at 40° C. and 75% RH, concentration of all-trans 5,6-epoxy retinoic acid is < 1% by weight of the initial tretinoin amount.

Litigation exposure: Stability claims often reduce the chance of “passive” equivalence. To design around, a competitor may need to demonstrate either different degradation pathways or different results under the precise storage stress.

What microcapsule physical parameters are claimed?

• Claim 5: tretinoin microcapsule average diameter 5 to 50 µm (per “energy selective backscattered-detector”).

Litigation exposure: Size and measurement method language can create technical dispute. Also, if a competitor uses different measurement instrumentation or yields a different size distribution, that may support non-infringement.

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What is protected in the microcapsule structure: silica shells, metal oxide shells, and thickness?

Silicon dioxide vs metal oxide shell

• Claim 2: shell is silicon dioxide.
• Claim 3: shell is a metal oxide.
• Claim 4 (metal oxide thickness): shell thickness 50 nm to 5000 nm (per energy selective backscattered-detector).

Core composition: tretinoin solid form in oil phase

The independent claim requires:

• tretinoin in solid form in an oil phase at 17% to 25% w/w in that oil phase.

This is not typical “solubilized tretinoin” language. It is directed to a solid-state dispersion architecture in the oil phase plus optional PCM.

Design-around levers at the structure level:

• Avoiding “tretinoin in solid form” in the oil phase,
• changing the oil-phase concentration outside 17–25% w/w,
• replacing the permitted PCM classes,
• using a different microcapsule architecture that fails the “core comprising dispersion” requirement as written.

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What does the claim require about phase-changing materials (PCMs)?

PCM chemical class constraint and physical state

The claim specifies PCMs that:

• are not liquid at room temperature, and
• fall within selected families, including paraffins (C chains), broad C10–C100 hydrocarbons, waxes, aliphatic alcohols, and fatty acids with specified formulas and n = 10–100.

“Optionally at least one phase changing material” meaning

Claim 1 states PCM is optional. So infringement does not necessarily require a PCM if the other limitations are met. However, other dependent claims may still narrow the product. Based on the provided claims alone, Claim 1 itself contains the PCM limitation only where the dispersion “optionally” includes PCM, meaning a product could potentially avoid PCM and still fall within Claim 1 if the rest is satisfied. Practically, the strongest design-around may be to eliminate one of the non-optional elements: solid-form tretinoin at 17–25% w/w in oil phase, the dual-microcapsule requirement, or the specified final composition percentages.

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How many active-agent microcapsule “types” must be present? (dual-population requirement)

Claim 1 requires:

• tretinoin is the only active agent in tretinoin microcapsules,
• benzoyl peroxide is the only active agent in benzoyl peroxide microcapsules,
• and both microcapsule types are in the single composition administered topically.

Key consequence

A product that co-encapsulates both actives in the same microcapsule population would likely fail the “only active agent in said microcapsules” requirement for each active type as written. A product that uses a mixture of:

• tretinoin microcapsules plus
• benzoyl peroxide unencapsulated in the carrier, could fail because Claim 1 says the composition further comprises microcapsules comprising benzoyl peroxide.

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What encapsulation efficiency thresholds are claimed?

Dependent claims add minimum encapsulation efficiency performance:

• Claim 9: tretinoin microencapsulation efficiency ≥ 90% by weight, with up to 10% not encapsulated.
• Claims 12, 14, 15: benzoyl peroxide encapsulation efficiency and corresponding unencapsulated allowances, paired with tretinoin efficiency:
  • Claim 12: benzoyl peroxide ≥ 75% (up to 25% not encapsulated) and tretinoin ≥ 90% (up to 10% not encapsulated).
  • Claim 14: benzoyl peroxide ≥ 85% (up to 15% not encapsulated) and tretinoin ≥ 90% (up to 10% not encapsulated).
  • Claim 15: benzoyl peroxide ≥ 90% (up to 10% not encapsulated) and tretinoin ≥ 90% (up to 10% not encapsulated).

Implication: These dependent claims support narrower infringements where the accused product hits a specific encapsulation performance profile. A competitor with lower encapsulation efficiency could attempt to avoid these dependent claims, but they could still face exposure under Claim 1 if Claim 1 does not itself incorporate an encapsulation-efficiency limitation. Based on the text provided, Claim 1 does not expressly include encapsulation efficiency. The performance limitations are in dependent claims.

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What is the dosing and composition scope: is this limited to 0.1% tretinoin + 3% benzoyl peroxide?

Claim 1 is explicit:

• tretinoin amount in composition: 0.1% by weight,
• benzoyl peroxide amount in composition: 3% by weight.

Dependent Claim 8 broadens the carrier type:

• carrier can be ointment, cream, lotion, oil, solution, emulsion, gel, paste, milk, aerosol, powder, or foam.

Implication: Carrier form is flexible. The actives are not. If a generic uses different strengths (e.g., 0.05% tretinoin or 2.5% BPO), it likely falls outside the exact claim terms for Claim 1 as written.

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What shell materials and microcapsule sizes are covered (Claim 2–5)?

• Silicon dioxide shell: Claim 2
• Metal oxide shell: Claim 3
• Metal oxide thickness: Claim 4, 50 nm to 5000 nm
• Tretinoin microcapsule average diameter: Claim 5, 5 to 50 µm

What’s not specified: The provided claims do not list specific metal oxides (e.g., TiO2, ZnO, SiO2 is covered by Claim 2). The claim reads broadly as “metal oxide,” though practical infringement will depend on whether the accused shell qualifies as a metal oxide and whether thickness matches the measurement scope for Claim 4.

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What would a generic or branded competitor have to avoid to reduce infringement risk?

High-probability design-around categories

1. Break the dual-microcapsule structure

• Avoid benzoyl peroxide microcapsules, or do not use a separate benzoyl peroxide microcapsule population.

2. Change the tretinoin microcapsule internal oil phase

• Avoid solid-state tretinoin in oil phase,
• avoid 17–25% w/w in the oil phase.

3. Change PCM class or use a PCM that is liquid at room temperature

• The claim narrows PCM chemical families and non-liquid physical state.

4. Avoid the exact strength ratio

• Change from 0.1% by weight tretinoin and 3% by weight benzoyl peroxide.

5. Miss the performance windows in dependent claims

• Ensure dissolution rate targets fall outside specified windows under claimed test media.
• Ensure stability does not meet the specified degradation limit under the claimed stress conditions.
• Adjust particle size distribution and measurement outcomes.

Where the risk concentrates

• Any product that already uses microencapsulated tretinoin and microencapsulated benzoyl peroxide with controlled release and stability performance, plus specific strength ratios, will be aligned with the claim’s likely core inventive concept.
• Even if encapsulation efficiency is lower (protecting against certain dependent claims), Claim 1 could still capture the structure and composition requirements if the independent limitations are met.

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Key takeaways

• US 12,491,163 is a composition+method IP right focused on topical acne treatment using a two-microcapsule-system: tretinoin-only microcapsules and benzoyl-peroxide-only microcapsules.
• The independent claim requires solid-form tretinoin dispersed in an oil phase at 17–25% w/w, with optional non-liquid PCM from defined paraffin/hydrocarbon/wax/alcohol/fatty-acid families (n=10–100).
• The claimed final composition is locked to 0.1% by weight tretinoin and 3% by weight benzoyl peroxide, while carrier vehicle can vary broadly.
• Dependent claims introduce high-friction, measurable constraints: dissolution rate windows, all-trans 5,6-epoxy retinoic acid degradation limits after stress, encapsulation efficiencies, and microcapsule size/shell material and thickness.

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FAQs

1) Does US 12,491,163 require a PCM in the tretinoin core?
Claim 1 makes PCM “optional” in the dispersion, so PCM inclusion is not inherently mandatory where the rest of the independent claim is met.

2) Can a product avoid infringement by co-encapsulating tretinoin and benzoyl peroxide in the same microcapsules?
Co-encapsulation could undermine the “only active agent” requirement for each microcapsule population as written, but infringement will still turn on the claim construction of “microcapsules comprising” each active and the accused product’s formulation architecture.

3) Are the dissolution test conditions part of the claim scope?
Yes. Dependent claims specify dissolution media compositions, temperatures, and rate ranges, which can be outcome-determinative in infringement analysis.

4) Are shell materials limited to silicon dioxide and metal oxides?
The provided dependent claims explicitly cover silicon dioxide shells (Claim 2) and metal oxide shells (Claims 3–4). Claim 1 does not limit the shell material in the text provided, so shell identity becomes a differentiator mostly through the dependent claims.

5) Is the carrier type limited to creams or gels?
No. The carrier can be many common topical forms, including creams, gels, emulsions, foams, powders, and aerosols (Claim 8).

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References (APA)

1. United States Patent 12,491,163. (n.d.). Claims excerpt provided in prompt.

Drugs Protected by US Patent 12,491,163

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Mayne Pharma	TWYNEO	benzoyl peroxide; tretinoin	CREAM;TOPICAL	214902-001	Jul 26, 2021		RX	Yes	Yes	12,491,163		Y			TOPICAL TREATMENT OF ACNE

International Family Members for US Patent 12,491,163

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2021274996
Brazil	112022023798
Chile	2022003284
Colombia	2022018620
South Korea	20230027073
World Intellectual Property Organization (WIPO)	2021234716