United States Patent 10,130,640: Calcipotriol and Betamethasone Dipropionate Sprayable Composition Patent Landscape

US Patent No. 10,130,640 protects a sprayable, substantially anhydrous topical formulation containing calcipotriol or calcipotriol monohydrate and betamethasone dipropionate. The core invention combines dissolved active ingredients, a volatile ether-based propellant, and a paraffin-containing lipid carrier that forms an occlusive semisolid layer after application. The patent is assigned to LEO Pharma A/S and is associated with the Enstilar aerosol foam product.

The strongest commercial embodiments are narrow combinations containing approximately 0.005% calcipotriol, 0.064% betamethasone dipropionate in the non-propellant fraction, petrolatum and liquid paraffin, and a dimethyl ether/n-butane propellant system. The basic patent term is tied to a May 14, 2007 priority date, producing a projected expiration in May 2027, subject to any applicable patent-term adjustment.[1]

What does US Patent 10,130,640 protect?

US 10,130,640 protects a composition defined by formulation architecture rather than by the active ingredients alone. Claim 1 requires the accused or licensed product to satisfy each of the following limitations:

Claim element	Scope
Dosage form	Sprayable topical composition
Stability	Storage stable and substantially anhydrous
Active ingredients	Calcipotriol or calcipotriol monohydrate plus betamethasone dipropionate
Drug state	Both active ingredients dissolved in the propellant system
Propellant	Dimethyl ether or methylethyl ether, alone or with a second listed propellant
Second propellant	C3-C5 alkane, hydrofluoroalkane, hydrochloroalkane, fluoroalkane or chlorofluoroalkane
Lipid carrier	Pharmaceutically acceptable carrier containing one or more paraffins
Post-application behavior	Carrier forms a semisolid, occlusive layer after propellant evaporation
Drug release characteristic	Supersaturated solution forms on the skin after evaporation
Co-solvent	Optional non-evaporating oily co-solvent

The claim is narrower than a claim to any calcipotriol/betamethasone product. A formulation that contains the same drugs but uses a water-based vehicle, a non-ether propellant, suspended rather than dissolved drug, or a non-paraffin carrier may fall outside claim 1.

The supersaturation limitation is particularly important. It ties infringement to the physical behavior of the formulation after spraying, not only to its ingredient list. Product testing may therefore focus on drug solubility in the pressurized formulation, propellant evaporation, residual-film composition, and the concentration of each active in the remaining skin deposit.

How many claims does US Patent 10,130,640 have?

The patent has 67 claims. Claim 1 is the principal composition claim. Claims 2 through 67 add limitations concerning propellant concentration, propellant identity and ratios, active-ingredient concentration, oily co-solvents, lipid-carrier content, paraffin characteristics, and specific formulation combinations.

The claims form several overlapping fallback groups:

Claims 2-13 narrow the propellant quantity and the dimethyl ether/alkane ratio.
Claims 14-19 narrow the active-ingredient concentrations.
Claims 20-25 cover specific oily co-solvent classes and named solvents.
Claims 26-30 narrow the lipid carrier and viscosity-building system.
Claims 31-35 identify co-solvent concentrations and named compounds.
Claims 36-48 recast the drug concentration in the composition without propellant.
Claims 49-67 combine the active concentrations with petrolatum, liquid paraffin and specified propellant systems.

The claim set uses extensive dependency and range nesting. A narrower claim may remain enforceable even if a broader claim is invalidated for anticipation or obviousness.

What are the strongest claims in US 10,130,640?

Claims 49 through 67 are the most commercially important because they concentrate on the likely Enstilar-type formulation.

The most specific claim profile includes:

Calcipotriol corresponding to approximately 0.005% w/w without propellant.
Betamethasone dipropionate at approximately 0.064% w/w without propellant.
Petrolatum and liquid paraffin as the lipid carrier.
Dimethyl ether with n-butane or isobutane.
Propellant content of approximately 45%-70% w/w.
A hydrocarbon-to-dimethyl-ether volume ratio within specified ranges, including 4:2-4:3 and 4:3-1:1.

Claim 67 is also commercially relevant because it covers a composition in which the propellant is dimethyl ether plus one or more C3-C5 alkanes and the lipid carrier consists essentially of petrolatum and liquid paraffin. The phrase “consists essentially of” can limit additional ingredients that materially alter the claimed formulation properties.

Claim 1 is broader in some respects because it does not require the specific 0.005%/0.064% normalized concentrations or petrolatum-plus-liquid-paraffin combination. It is narrower in requiring the complete functional combination, including dissolution and post-evaporation supersaturation.

What formulation technology is protected?

Ether-based propellant system

The patent covers dimethyl ether and methylethyl ether, including mixtures with hydrocarbons and other listed propellants. Dependent claims concentrate on dimethyl ether combined with n-butane, isobutane or related C3-C5 alkanes.

The propellant performs several technical functions:

It permits aerosol delivery.
It acts as a solvent for both active ingredients.
It evaporates rapidly after application.
It leaves behind a concentrated lipid-containing film.
It contributes to the formation of a supersaturated drug solution on the skin.

A generic developer using the same drug combination but replacing dimethyl ether with a materially different propellant would reduce literal infringement risk, although other patents and equivalents analysis would remain relevant.

Paraffin-containing lipid carrier

The lipid carrier must include one or more paraffins. Claim 29 describes paraffins with hydrocarbon chain lengths from C5 to C60 and specified chain-length distributions. Claims 30 and related claims add microcrystalline wax, silicone wax, hydrogenated castor oil and isoparaffin systems.

The carrier is not merely an excipient. The claims assign it a functional role: after propellant evaporation, it forms a semisolid and occlusive layer on the skin. This limitation distinguishes the claimed system from a simple aerosol solution that leaves a non-occlusive liquid residue.

Supersaturation after spraying

The claimed formulation is initially stabilized under pressure and in the presence of propellant. Once sprayed, propellant evaporation reduces solvent volume and increases the concentration of the active ingredients in the residual film. The resulting supersaturation is intended to increase the thermodynamic driving force for skin penetration.

For a freedom-to-operate analysis, analytical work would likely examine:

Active-ingredient solubility before and after spraying.
Residual composition after propellant loss.
Crystal formation over time.
The duration and degree of supersaturation.
Whether both actives are dissolved before application.
Whether the carrier produces the claimed occlusive semisolid layer.

What are the concentration ranges in the patent?

The principal concentration limitations are:

Ingredient or component	Claimed range
Calcipotriol or calcipotriol monohydrate	0.00001%-0.05% w/w
Betamethasone dipropionate	0.0005%-1% w/w
Propellant	45%-95% w/w
Narrow propellant ranges	50%-90%, 55%-70%, 45%-70% and 50%-70% w/w
Lipid carrier	5%-55% w/w
Narrow lipid-carrier ranges	10%-50%, 15%-45% and 20%-40% w/w
Oily co-solvent	0.1%-10% w/w
Narrow oily co-solvent ranges	1%-2.5% and 1.5%-2% w/w

Claims 36-38 and 49-67 use the non-propellant basis of approximately 0.005% calcipotriol and 0.064% betamethasone dipropionate. This distinction matters because the total formulation concentration, including propellant, is lower than the concentration calculated after propellant removal.

What drug does the patent cover?

The patent covers the fixed topical combination of:

Calcipotriol, also known as calcipotriene in the United States.
Betamethasone dipropionate.

The relevant branded product is Enstilar, a topical foam approved by the FDA for plaque psoriasis in patients 12 years of age and older. The product is marketed by LEO Pharma.[2]

The patent does not claim calcipotriol or betamethasone dipropionate as chemical entities. It also does not broadly claim every topical treatment for psoriasis containing the two actives. Its value is concentrated in the aerosolized, anhydrous, propellant-solubilized foam platform.

What is the Orange Book status of US 10,130,640?

Enstilar is approved under NDA 207589. The FDA Orange Book identifies patents and regulatory exclusivity associated with approved drug products. The relevant Orange Book analysis should distinguish between:

Patents listed for the Enstilar NDA.
Patents in the same LEO Pharma family that may cover related formulations.
Patents that have expired, been delisted or reached statutory expiration.
FDA three-year approval exclusivity, which is separate from patent protection.

The FDA approved Enstilar on October 16, 2015.[2] The three-year exclusivity period associated with a new clinical investigation approval would have ended in October 2018, while the formulation patent term extends materially longer. Patent protection, rather than FDA marketing exclusivity, is therefore the principal barrier to a competing aerosol formulation after the regulatory exclusivity period.

Orange Book listing status can change through patent expiration, delisting, corrections or NDA-holder submissions. Patent 10,130,640 must be assessed together with the other patents listed for NDA 207589, rather than as a standalone barrier.[3]

When does US 10,130,640 lose exclusivity?

The patent has a May 14, 2007 priority date. On a standard 20-year patent term calculation, the base term runs to May 14, 2027. The patent was issued on November 20, 2018.[1]

Milestone	Date
Earliest priority date	May 14, 2007
US patent grant	November 20, 2018
Standard projected expiration	May 14, 2027
FDA approval of Enstilar	October 16, 2015
FDA three-year exclusivity endpoint	October 16, 2018

A patent-term adjustment could alter the final expiration date. Any terminal disclaimer, patent-term adjustment or pediatric exclusivity should be checked against the current USPTO patent record and Orange Book entry before a launch decision.

The May 2027 expiration is the primary timing point for a conventional non-infringing generic or authorized generic strategy. An ANDA applicant may seek approval before expiration by filing a Paragraph IV certification and litigating the listed patent.

Which companies are challenging the Enstilar patent estate?

The relevant competitive group includes manufacturers developing generic calcipotriene and betamethasone dipropionate products, particularly topical foams, aerosols, gels and ointments. Public ANDA litigation must be evaluated by patent number and defendant because a challenge to one LEO patent does not necessarily eliminate the other listed patents.

A Paragraph IV challenge would typically assert one or more of the following:

The claims are anticipated by an earlier aerosol or topical formulation.
The claimed propellant and lipid system would have been obvious.
The specification does not enable the full breadth of the claims.
The claims lack adequate written description.
The ANDA product does not infringe because one or more functional limitations are absent.
The patent is unenforceable based on inequitable conduct or related litigation defenses.

A product using the same active ingredients, dimethyl ether, hydrocarbon propellant, petrolatum and liquid paraffin would face the highest literal-infringement exposure. A product using a different vehicle, drug state or delivery platform would present a different risk profile, even if it competes therapeutically with Enstilar.

What patent litigation affects US 10,130,640?

The relevant litigation question is whether an ANDA applicant has certified Paragraph IV against US 10,130,640 and whether LEO Pharma filed an infringement action within the statutory 45-day period. A timely action can trigger a 30-month stay of final FDA approval under the Hatch-Waxman framework, subject to court orders and statutory exceptions.[4]

The principal litigation issues for this patent would be technical claim construction:

Whether “dissolved” excludes partially suspended or microcrystalline drug.
Whether “substantially anhydrous” permits trace water or hydrated calcipotriol.
Whether a formulation creates a “supersaturated solution” after application.
Whether the residual lipid carrier is a semisolid and occlusive layer.
Whether the accused propellant falls within the ether and hydrocarbon definitions.
Whether the claimed concentration is measured before or after propellant evaporation.

The patent’s functional limitations create both enforcement value and litigation exposure. They can distinguish the invention from simple ingredient-based prior art, but they also require reliable physicochemical and product-performance evidence.

How strong is the patent estate for Enstilar?

Patent 10,130,640 is strongest against a close substitute for the commercial aerosol formulation. Its strongest practical coverage is the combined formulation defined by:

The two active ingredients.
Anhydrous aerosol delivery.
Dimethyl ether and hydrocarbon propellant.
Dissolution of both actives.
Petrolatum/liquid-paraffin carrier.
Post-application occlusive film.
Supersaturation after evaporation.

Its vulnerability is greater against design-arounds that change the delivery mechanism or omit a required functional feature. Potential design-around categories include:

Design-around	Likely effect on risk
Water-based foam or emulsion	Reduces risk under the anhydrous limitation
Non-ether propellant	Reduces risk under the propellant limitation
Suspended rather than dissolved active	May avoid the dissolution limitation
Non-paraffin lipid carrier	May avoid the carrier limitation
Non-occlusive vehicle	May avoid the functional carrier limitation
Different active ratio or concentration	May avoid narrower claims, not necessarily claim 1
Non-aerosol gel or ointment	Avoids the sprayable-composition limitation

These changes may create exposure under separate LEO patents or under patents owned by other developers. A design-around must therefore be mapped against the entire product patent estate.

What generic launch risks exist after patent expiration?

The main launch risks are not limited to US 10,130,640. A generic applicant must evaluate:

All Orange Book-listed Enstilar patents.
Patent-term adjustments and pediatric extensions.
Pending continuation applications.
Method-of-use patents.
Formulation and aerosol-device patents.
FDA product-specific guidance and bioequivalence requirements.
Device or container-closure differences.
Substitution and labeling restrictions.

A Paragraph III ANDA certification would defer approval until the relevant patent expiration. A Paragraph IV strategy could support earlier approval but would expose the applicant to infringement litigation and a potential 30-month stay. An authorized generic or license agreement with LEO Pharma could provide earlier commercial access but would depend on negotiated terms.

No broad chemical-entity patent blocks the active ingredients themselves. The commercial barrier is formulation and regulatory protection.

Are biosimilar risks relevant to Enstilar?

No. Enstilar contains chemically synthesized small-molecule active ingredients, not a biologic. Biosimilar pathways under the Public Health Service Act do not apply. Competition would proceed through the ANDA pathway for a generic drug product, subject to pharmaceutical-equivalence, bioequivalence and labeling requirements.[4]

The relevant competitive products are generic topical combinations, not biosimilars. Product developers may pursue foam, aerosol, ointment, gel or suspension dosage forms, but the regulatory pathway and patent risk will differ by dosage form.

Are licensing deals associated with US 10,130,640?

LEO Pharma is the identified patent holder and Enstilar sponsor. The publicly relevant commercialization relationship is the LEO Pharma product platform. No license or settlement should be assumed solely from the patent record. Any licensing deal, authorized-generic arrangement or Paragraph IV settlement must be confirmed through SEC filings, court dockets, FDA records or a filed settlement agreement.

A settlement could permit an earlier generic entry date, but the entry date would not be inferred from the patent expiration date alone.

Key Takeaways

US 10,130,640 is a formulation patent, not an active-ingredient patent.
Claim 1 requires a sprayable, storage-stable, substantially anhydrous composition with dissolved calcipotriol and betamethasone dipropionate.
The formulation must use an ether-based propellant and a paraffin-containing lipid carrier.
The residual product must form a semisolid, occlusive layer and a supersaturated solution after propellant evaporation.
Claims 49-67 provide the most commercially relevant protection for an Enstilar-like composition.
The standard projected patent expiration is May 14, 2027.
FDA three-year exclusivity for Enstilar ended in October 2018.
Biosimilar competition is irrelevant; generic ANDA competition is the applicable pathway.
The highest-risk competitor is a product using the same actives, dimethyl ether/hydrocarbon propellant and petrolatum/liquid-paraffin carrier.
A meaningful freedom-to-operate conclusion requires review of the full Orange Book-listed Enstilar estate, continuation applications and any Paragraph IV litigation or settlement.

FAQs

Does US 10,130,640 cover Enstilar foam?

Yes. The claims are directed to the formulation architecture associated with an Enstilar-type aerosol foam containing calcipotriol and betamethasone dipropionate.

Can a generic use calcipotriol monohydrate and avoid the patent?

No. The claims expressly cover calcipotriol and calcipotriol monohydrate. Changing the solid form alone does not avoid the patent.

Does using isobutane instead of n-butane avoid infringement?

Not necessarily. The claims expressly cover isobutane and mixtures of n-butane and isobutane with dimethyl ether.

Does a topical gel compete with Enstilar without infringing this patent?

A non-spray gel would likely avoid the sprayable-composition limitation of claim 1, but it could implicate other patents and would require separate regulatory and patent analysis.

Can a generic launch before May 2027?

Potentially, through a Paragraph IV certification, successful invalidity or non-infringement litigation, a license or settlement, or another legally available entry route. Patent expiration alone supports the conventional post-expiration launch date.

References

United States Patent and Trademark Office. (2018). U.S. Patent No. 10,130,640, sprayable pharmaceutical composition comprising calcipotriol and betamethasone dipropionate. https://patents.google.com/patent/US10130640B2/en
U.S. Food and Drug Administration. (2015). FDA approves Enstilar foam for plaque psoriasis. https://www.fda.gov/
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book
U.S. Food and Drug Administration. (2024). Abbreviated new drug application approvals and patent certifications. https://www.fda.gov/drugs/abbreviated-new-drug-application-anda/anda-approvals

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Leo Pharma As	ENSTILAR	betamethasone dipropionate; calcipotriene	AEROSOL, FOAM;TOPICAL	207589-001	Oct 16, 2015		RX	Yes	Yes	10,130,640*PED	⤷ Start Trial			Y		⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2011264198	⤷ Start Trial
Brazil	112012030653	⤷ Start Trial
Canada	2800181	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 10,130,640

Which drugs does patent 10,130,640 protect, and when does it expire?

Summary for Patent: 10,130,640