Patent: 10,172,841

Summary for Patent: 10,172,841

Title:	Inhibition of crystal growth of roflumilast
Abstract:	Roflumilast crystals have been shown to increase in size during storage. The size of the roflumilast crystals can affect the bioavailability and efficacy of a pharmaceutical composition. The growth of roflumilast crystals can be inhibited during storage by including hexylene glycol in the composition. The resulting composition has improved bioavailability and efficacy and can be used to inhibit phosphodiesterase 4 in a patient in need of such treatment.
Inventor(s):	Osborne; David W. (Fort Collins, CO)
Assignee:	ARCUTIS, INC. (Menlo Park, CA)
Application Number:	15/848,462
Patent Claims:	see list of patent claims

Executive summary US Patent 10,172,841 claims a topical combination composition that pairs roflumilast with hexylene glycol and requires that an “additional active agent” is in microparticulate form in a way that the microparticles do not cross the stratum corneum in microparticulate state. The patent is claim-broad on the list of compatible co-actives (spanning small molecules, biologics, corticosteroids, antibiotics, and multiple psoriasis/dermatology agents) but claim-narrow on the formulation logic: hexylene glycol as a penetration-modifying excipient, microparticulate dispersion for the second active, and a non-crossing epidermal boundary condition. The practical patent risk for generics or follow-on formulations is highest for topical roflumilast products that (i) include hexylene glycol, (ii) carry a microparticulate co-active (especially dermatology actives listed), and (iii) are engineered to keep the microparticles within the stratum corneum while allowing the intended pharmacology. The defensibility of the estate turns on whether the prior art already taught the same microparticulate-with-non-crossing skin boundary approach using roflumilast and hexylene glycol, and on claim construction of “microparticulate,” “does not cross,” and “dispersed”/“in a microparticulate state.”

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US Patent 10,172,841 claims chart: roflumilast + hexylene glycol + microparticulate second active

Core independent claim (Claim 1)
A pharmaceutical composition comprising:

• At least two active agents in combination with hexylene glycol
• One active agent is roflumilast
• One active agent is dissolved
• The other active agent is a microparticulate pharmaceutical dispersed in the composition

Key dependent claims that narrow scope

• Claim 2: roflumilast is the dissolved component; the additional active is microparticulate
• Claim 3: the microparticulate additional active does not cross the stratum corneum in microparticulate state
• Claim 4: additional active agent may be selected from a long enumerated list (includes classic dermatology actives and immune biologics such as adalimumab, ustekinumab, infliximab)
• Claims 5-10: topical dosage forms and excipient classes (solvent system for modifying skin permeation; optional surfactants with extensive lists)
• Claims 11-14: numeric ranges for hexylene glycol (0.1–20% w/w; narrower subranges) and roflumilast (0.005–2% w/w)
• Claim 18-19: method limitation tying Claim 3’s “does not cross stratum corneum” logic to co-active being an antibiotic or a corticosteroid, respectively

Claim structure implications for enforcement

1. Bifurcation requirement: Claim 1 requires one active dissolved and the other microparticulate. If a competitor formulation makes both actives molecularly dissolved (no microparticle fraction) or makes both microparticulate, it can fall outside literal scope.
2. Skin boundary as a functional/structural limitation: Claim 3 adds a functional boundary condition (“does not cross the stratum corneum of the epidermis in a microparticulate state”). This can be litigated via particle size distribution, excipient effects on partitioning, and skin deposition tests.
3. Hexylene glycol as a required excipient: Any product without hexylene glycol avoids the claim on literal grounds (unless doctrine of equivalents is asserted).
4. The enumerated co-active list is broad but not unlimited: Claim 4’s list includes many agents, but the claim is still tied to “selected from” that group. If the co-active is not within the enumeration, literal infringement is harder.

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What patents protect roflumilast topical combinations with penetration enhancers and microparticles?

The patent’s claim set is tightly tailored to a formulation pattern rather than a single active. The protection theory implied by the claim language is:

• roflumilast is delivered as a dissolved component
• the co-active is delivered as microparticles that remain in the stratum corneum region
• hexylene glycol and optional permeation-modifying solvent(s) and surfactants tune skin deposition and penetration

Patent landscape logic (how to map US10,172,841 against competitors)

Even without reproducing a complete bibliographic dataset here, the landscape typically divides into:

• Roflumilast topical formulations (solubilization, permeation enhancement, stable topical vehicles)
• Microparticle or localized delivery systems for dermatology actives (topical microparticles designed not to penetrate deeper)
• Combination dermatology therapies (co-delivery of roflumilast with corticosteroids, calcineurin inhibitors, antimetabolites, antibiotics, etc.)
• Penetration enhancer patents centered on hexylene glycol or closely related diols/solvents
• Manufacturing/process patents for preparing microparticulates dispersed in topical vehicles

US10,172,841’s likely overlap points

• It is strong where an accused product uses both hexylene glycol and the microparticulate “non-crossing” behavior for a listed co-active.
• It is weaker where an accused product:
  • uses a different permeation enhancer instead of hexylene glycol
  • delivers the second active dissolved/solubilized rather than microparticulate
  • uses nanoparticles rather than microparticles (arguable definitional distance)
  • uses microparticles but expects cross-stratum-corneum penetration in microparticulate state

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How many claims in US10,172,841 materially narrow the “microparticulate does not cross” limitation?

At least three tiers:

• Claim 1: microparticulate dispersed + dissolved roflumilast concept
• Claim 2: roflumilast dissolved, second active microparticulate
• Claim 3: microparticulate additional active does not cross stratum corneum in microparticulate state
• Claims 18-19: reinforce Claim 3 in specific co-active categories (antibiotics, corticosteroids)

The “does not cross” element is the most likely litigated point because it is both:

• functional (requires performance), and
• dependent on how “microparticulate state” is defined by particle size/spec and in vivo/in vitro deposition evidence.

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When does US Patent 10,172,841 expire, and how much exclusivity time remains?

If you are assessing launch timing, the effective exclusivity story is not only patent expiration but also whether there are:

• earlier-filed priority dates driving term,
• regulatory exclusivity interactions (if any) and
• other blocking patents in the same portfolio.

US10,172,841 is a granted US utility patent, so it carries a presumptive 20-year term from its earliest effective nonprovisional filing date, adjusted for patent term adjustment (PTA) and potential term extension (rare for typical topical products absent qualifying regulatory exclusivity mechanisms).
No expiration date analysis can be completed accurately from the claim text alone because term depends on the patent’s filing and priority data, which are not provided in your prompt.

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What is the Orange Book status of roflumilast topical products under US10,172,841?

Orange Book status requires mapping:

• the specific roflumilast topical NDC(s),
• listed patent numbers, and
• the linkage to US10,172,841 (if listed for the relevant NDA/ANDA).

Your prompt provides claims but no FDA listing data or patent-to-product linkages.
No Orange Book status can be stated accurately from the claim text alone.

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How strong is the patent estate for this formulation concept: hexylene glycol + roflumilast + microparticulate co-active?

Strength drivers

1. Multi-factor “combination-of-characteristics” claim: infringement is conditional on meeting several formulation requirements simultaneously (hexylene glycol + roflumilast + dissolved/microparticulate split + non-crossing microparticles + topical vehicle/solvent/surfactant scope if dependents are asserted).
2. Specific numerical ranges (Claims 11-14): narrow ranges can provide a clean infringement hook for products formulated within those thresholds, but also create design-around opportunity if products are outside the ranges.
3. Functional boundary (Claim 3): if the patentee has strong test evidence during prosecution, this limitation can be a powerful differentiator from prior art microparticle systems that do not explicitly control stratum corneum boundary behavior.

Weakness drivers

1. Breadth on co-active list (Claim 4): the more actives a claim covers, the more prior art and enablement challenges can become relevant depending on specification support and whether the written description and enablement match each listed biologic/small molecule.
2. “Microparticulate pharmaceutical” definitional risk: if the patent does not provide an objective particle-size definition or clear operational thresholds, validity and infringement proofs can become harder and more expensive.
3. “Does not cross” as a moving target: competitors can argue that their microparticles remain but their co-active dissolves from particles and crosses as dissolved molecules, thus not meeting “in microparticulate state” crossing. This becomes an evidence-intensive fight.

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Which design-arounds most plausibly avoid literal infringement of US10,172,841?

Below are the highest-probability carve-outs based strictly on the claim language you supplied:

1. Remove hexylene glycol

   • If the final product excludes hexylene glycol entirely, Claims 1-3 are not met.

2. Make the co-active dissolved (or solubilized) rather than microparticulate

   • If the “additional active agent” is not present as a microparticulate dispersed fraction, Claim 1 is avoided.

3. Allow microparticulate co-active to cross the stratum corneum in microparticulate state

   • If the formulation is intended to carry microparticles deeper (or has data showing stratum corneum crossing), Claim 3 is avoided.

4. Change particle class to nanoparticles with different behavior

   • If a competitor uses sub-micron particles and argues they are not “microparticulate” (depending on how “microparticulate” is construed), they can attack literal infringement.

5. Use a non-enumerated co-active

   • If the additional active is not within Claim 4’s selected list, literal coverage of Claim 4 does not apply, though Claims 1-3 may still be asserted depending on how Claim 1 is interpreted relative to the list.

6. Formulate outside numeric ranges

   • If the product uses hexylene glycol below 0.1% w/w or above 20% w/w, Claims 11-13 are avoided.
   • If roflumilast is outside 0.005–2% w/w, Claim 14 is avoided.

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What formulation and delivery evidence would matter most in an infringement fight? (US10,172,841 Claim 3)

For Claim 3, the central evidentiary questions generally become:

• Particle size distribution of the microparticulate co-active (and whether “microparticulate” has a defined size cut in the patent)
• Stability of microparticles in the topical vehicle and on skin
• Skin permeation/deposition testing showing localization in the stratum corneum region
• Whether the co-active crosses as dissolved species rather than as intact microparticles (implicating the “in a microparticulate state” qualifier)

A strong patentee case typically ties the formulation to controlled deposition outcomes, not merely to existence of microparticles in the vehicle.

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How does US10,172,841 compare with typical topical combination patents for psoriasis/dermatology?

US10,172,841 is distinct in that it:

• requires roflumilast to be the dissolved active, and
• requires the co-active to be microparticulate with stratum corneum boundary control,
• while allowing broad co-active selection across an enumerated therapeutic universe (including immunomodulators).

Most psoriasis/dermatology topical combination patents tend to cover:

• co-formulation stability and permeation,
• generic penetration enhancers,
• or specific drug pair combinations, not a rigid “microparticles remain within the stratum corneum” condition.

That makes Claim 3 a key differentiator, but also the most vulnerable to definitional and evidentiary attack.

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What generic entry risks exist for roflumilast topical if US10,172,841 is listed for an NDA?

If US10,172,841 is listed for an NDA with a relevant topical product, generic entry risk centers on:

• whether the ANDA applicant (or 505(b)(2) filer) includes hexylene glycol,
• whether the co-active system is microparticulate and non-crossing in the required sense,
• and whether any listed dependent limitations (dose ranges, solvent categories, surfactant categories) are also met.

Because the claim language is formulation-specific, the safest generic design space is to change at least one required attribute: hexylene glycol, particle state, or boundary behavior.

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Patent litigation and Paragraph IV risk for US10,172,841

To assess litigation risk, the estate must be mapped to:

• actual district court cases naming the patent and identifying asserted claim numbers,
• ANDA/505(b)(2) filings tied to the same patent,
• settlement dates and consent decrees.

Your prompt includes no litigation history, plaintiff/defendant, court, or asserted claims.
No litigation status can be provided accurately from the claim text alone.

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Key Takeaways

• US Patent 10,172,841 protects a topical combination concept defined by hexylene glycol + roflumilast dissolved + co-active microparticulate dispersed.
• The critical narrowing limitation is that the microparticulate co-active does not cross the stratum corneum in microparticulate state (Claim 3).
• The claim set is broad on co-active selection (Claim 4) but narrow on the formulation physics (Claims 1-3) and on numeric excipient/loading ranges (Claims 11-14).
• Design-around paths are straightforward at the claim-element level: remove hexylene glycol, avoid microparticulate co-active, or change the boundary behavior so microparticles cross (or become effectively non-microparticulate by definition/performance).
• Expiration timing, Orange Book status, and litigation/Paragraph IV posture cannot be determined from the claims alone.

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FAQs

1. Does US10,172,841 require the co-active to be microparticulate, or can it be dissolved?
   Claim 1 requires one active dissolved and the other microparticulate; Claim 2 specifically requires roflumilast dissolved and the additional active microparticulate.

2. What does “does not cross the stratum corneum in a microparticulate state” mean for infringement evidence?
   The key proof question is whether intact microparticles remain at or above the stratum corneum boundary rather than crossing as microparticles.

3. If hexylene glycol is replaced with another penetration enhancer, does US10,172,841 still apply?
   Literal infringement requires hexylene glycol in the claimed amount range if dependent ranges are asserted; omitting hexylene glycol avoids the claim element.

4. Can a formulation that uses nanoparticles avoid US10,172,841?
   Potentially, if “microparticulate” is construed to exclude nanoparticles by size or functional behavior; this is definitional and evidence-dependent.

5. Is the roflumilast loading range (0.005–2% w/w) mandatory to infringe?
   It is required only for dependent coverage under Claim 14; independent coverage under Claim 1-3 may still be asserted depending on how the court treats dependents and asserted claims.

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References

1. US Patent 10,172,841 (claims provided in prompt).

Details for Patent 10,172,841

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Janssen Biotech, Inc.	REMICADE	infliximab	For Injection	103772	August 24, 1998		2037-12-20
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	December 31, 2002		2037-12-20
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	February 21, 2008		2037-12-20
Abbvie Inc.	HUMIRA	adalimumab	Injection	125057	April 24, 2013		2037-12-20