US Patent 10,660,908: Claim Scope, Exclusivity, Orange Book Position and Competitive Patent Landscape

US Patent 10,660,908 protects substantially anhydrous aerosol compositions combining calcipotriol or calcipotriol monohydrate with betamethasone dipropionate. The core technology uses a volatile propellant, principally dimethyl ether, to dissolve both active ingredients and a lipid carrier, such as white soft paraffin and liquid paraffin, to create an occlusive semisolid layer after application.

The patent is directed to the formulation architecture associated with calcipotriol/betamethasone dipropionate aerosol foam products, including Enstilar. Its strongest commercial relevance is against formulations that use the same active ingredients, propellant system, paraffin carrier, concentration ranges and propylene-glycol-free design.

Based on the stated priority framework, the patent has a nominal expiration date in March 2035, subject to any patent-term adjustment or extension reflected in USPTO records. The patent does not protect calcipotriol or betamethasone dipropionate as active pharmaceutical ingredients generally. It protects specific topical compositions and one treatment method using those compositions.

What does US Patent 10,660,908 protect?

The patent protects three connected concepts:

A substantially anhydrous topical aerosol composition.
A two-active formulation in which calcipotriol and betamethasone dipropionate are dissolved in a propellant.
A lipid carrier that remains on the skin and forms a semisolid, occlusive layer after propellant evaporation.

The independent claims are claims 1, 14 and 66.

Independent claim	Subject matter	Main limitation
Claim 1	One-propellant composition	Propellant, lipid carrier, two actives, no propylene glycol
Claim 14	Two-propellant composition	First and second propellants, lipid carrier, no propylene glycol
Claim 66	Treatment method	Topical administration of claim 1 composition for psoriasis

The patent is composition-focused. A product can potentially avoid claim 1 by omitting a required element, using a materially different solvent system, including propylene glycol, failing to dissolve the actives in the propellant or using a non-lipid vehicle that does not form the claimed post-evaporation layer.

What are the essential elements of independent claim 1?

Claim 1 requires all of the following:

Calcipotriol or calcipotriol monohydrate.
Betamethasone dipropionate.
A pharmaceutically acceptable propellant.
A pharmaceutically acceptable lipid carrier.
Both active ingredients dissolved in the propellant.
A substantially anhydrous composition.
Formation of a semisolid and occlusive layer after propellant evaporation.
No propylene glycol.

The claim does not require a particular dosage form label such as “foam.” A product marketed as an aerosol, spray, mousse or foam could fall within the claim if its physical and compositional characteristics satisfy the limitations.

The phrase “substantially anhydrous” is narrowed by dependent claim 3, which specifies free water of no more than about 1% by weight. Claims 1 and 14 do not themselves state a numerical water threshold, but claim 3 provides a clear preferred embodiment.

How broad are the propellant limitations?

The propellant limitations are commercially important because the patent requires the active ingredients to be dissolved in the propellant.

Dimethyl ether

Claims 9, 10 and 15 specifically identify dimethyl ether. Dimethyl ether is the principal propellant with the greatest infringement relevance because it can dissolve the lipophilic active ingredients and support an aerosol formulation.

Claim 15 requires dimethyl ether as the first propellant and requires the actives to be dissolved in that dimethyl ether.

Mixed propellant systems

Claims 14 through 20 cover compositions using a first and second propellant. The second propellant can be:

A C3-C5 alkane.
A hydrofluoroalkane.
A hydrochloralkane.
A fluoroalkane.
A chlorofluoroalkane.

Claims 18 through 20 narrow the second propellant to propane, isopropane, n-butane or isobutane, with claim 20 specifically reciting n-butane.

Claims 43 through 48 further define volume ratios between the C3-C5 alkane and dimethyl ether. The most commercially focused ranges are:

Claim	C3-C5 alkane:dimethyl ether ratio
43	About 6:1 to 0:1
44	About 5:1 to 1:2
45	About 4:1 to 1:1
46	About 4:2 to 1:1
47	About 4:2 to 4:3
48	About 4:3 to 1:1

A competing product that uses dimethyl ether and n-butane must be assessed against both the composition limitations and the applicable ratio claims.

What lipid carriers are covered?

The lipid carrier limitation is broad but technically meaningful. The carrier must function as the material that forms a semisolid and occlusive layer after evaporation of the propellant.

The claims expressly cover:

Hydrocarbons.
Paraffins.
Waxes.
White soft paraffin.
Liquid paraffin.
Isoparaffins.
Microcrystalline wax.
Silicone wax.

Claim 58 adds a hydrocarbon chain-length profile. It covers hydrocarbons containing at least five and no more than 60 carbon atoms, with gas-chromatographic peaks at specified ranges, including C14-C16, C18-C22, C20-C26, C28-C40 and C40-C44.

Claims 22 and 23 are particularly relevant to Enstilar-type formulations because they recite white soft paraffin and liquid paraffin. A product using the same carrier combination creates a materially higher literal infringement risk than a product using a non-paraffin emollient system.

What formulations are protected by the concentration claims?

Claims 4, 5 and 49 through 57 define concentration ranges.

Component	Broad claimed range
Calcipotriol or calcipotriol monohydrate	About 0.00001% to 0.05% w/w
Betamethasone dipropionate	About 0.0005% to 1% w/w
Lipid carrier	About 5% to 55% w/w
Propellant	About 45% to 95% w/w
Oily co-solvent	About 0.1% to 10% w/w

The narrower commercial ranges include:

Calcipotriol: about 0.002% w/w.
Betamethasone dipropionate: about 0.02% to 0.03% w/w.
Lipid carrier: about 20% to 40% w/w.
Propellant: about 55% to 70% w/w.
Oily co-solvent: about 1.5% to 2% w/w.

Claim 51 recites betamethasone dipropionate at about 0.026% w/w. Claims 61 through 65 address concentration changes after propellant evaporation, reciting post-application concentrations of approximately 0.005% calcipotriol and 0.064% betamethasone dipropionate.

These claims are designed to capture a formulation that is dilute while contained in the pressurized package but becomes more concentrated after the volatile propellant evaporates.

Does the patent cover oily co-solvents?

Yes. Claims 24 through 38 cover oily co-solvents used with the lipid carrier.

The Markush definition in claim 25 includes:

Polyoxypropylene ethers.
Isopropyl esters, including isopropyl myristate and isopropyl palmitate.
Propylene glycol diesters.
C8-C24 alcohols and alkenols.
Highly purified vegetable oils.
N-alkylpyrrolidones and N-alkylpiperidones.
Medium-chain triglycerides.

Claims 26 and 33 specifically identify polyoxypropylene-11-stearyl ether and related compounds. Claims 30 and 37 identify myristyl alcohol and oleyl alcohol. Claim 32 covers medium-chain triglycerides.

The exclusion of propylene glycol in claims 1 and 14 does not exclude every propylene-glycol-derived compound. The claims separately recite propylene glycol diesters as possible oily co-solvents. The legal analysis therefore turns on the precise chemical identity of the excipient, not simply whether the word “propylene” appears in the ingredient list.

What performance and stability requirements are claimed?

Claims 6 through 8 add functional performance limitations.

Stability

Claims 6 and 7 require that no more than about 10% of either active degrade after storage at 40°C for at least two or three months.

Claim 8 requires that the active ingredients do not precipitate from the propellant during storage for at least 12 months at 25°C.

These limitations can create evidentiary issues in litigation. Infringement may require testing the accused product under specified storage conditions, analyzing degradation products and determining whether precipitation occurs. The claims are not limited to a specific test method in the supplied text, which may generate disputes concerning analytical protocols and statistical variation.

Skin penetration

Claim 39 requires an approximately two-fold or greater increase in penetration of one or both active ingredients into the dermis, epidermis or both after at least six hours, compared with an identical composition without propellant.

This is a narrow functional limitation. A product may satisfy the structural limitations of claim 1 but avoid claim 39 if the required comparative penetration result is not established. Conversely, claim 39 creates a potential infringement theory based on comparative skin-permeation data.

How do claims 1 and 14 differ?

Claim 1 covers a composition with a pharmaceutically acceptable propellant. Claim 14 expressly requires a first and second propellant.

Issue	Claim 1	Claim 14
Propellant structure	One propellant broadly recited	First and second propellants
Dimethyl ether	Covered by dependent claims	Covered as first propellant
n-Butane combination	Covered through dependent claims	Expressly supported
Active dissolution	In the propellant	In one or both propellants
Lipid carrier	Required	Required
Propylene glycol	Excluded	Excluded

The two- propellant claims provide separate coverage for formulations containing dimethyl ether plus an alkane such as n-butane. This gives the patent a second infringement path even if a challenger disputes the scope of the single-propellant claims.

What is the scope of the psoriasis method claim?

Claim 66 covers a method of treating psoriasis by topically administering a composition of claim 1.

The method claim is narrower than a general psoriasis treatment claim because it incorporates every limitation of claim 1. It does not cover:

Oral administration.
A composition lacking the claimed propellant.
A formulation containing propylene glycol.
A composition in which the actives are suspended rather than dissolved in the propellant.
A product using a non-lipid carrier that does not form the claimed occlusive layer.

The method claim is relevant to induced infringement theories involving manufacturers, distributors and prescribers. Product labeling that directs use of a formulation for psoriasis could be relevant to intent and induced-infringement analysis.

What is the relationship to Enstilar?

Enstilar is a topical aerosol foam containing calcipotriene and betamethasone dipropionate. FDA labeling identifies the product as containing calcipotriene 0.005% and betamethasone dipropionate 0.064% in the applied foam, with paraffin-based excipients and hydrocarbon/ether propellant components.[2]

The claimed pre-evaporation concentrations in US 10,660,908 are lower than the labeled active concentrations after evaporation. Claims 61 through 65 expressly address this concentration shift.

Enstilar-related characteristic	Patent relevance
Calcipotriene plus betamethasone dipropionate	Central claim element
Aerosol foam delivery	Consistent with claimed propellant system
Dimethyl ether	Expressly claimed
n-Butane or related hydrocarbon propellant	Expressly claimed
White soft paraffin	Expressly claimed
Liquid paraffin	Expressly claimed
Propylene-glycol-free formulation	Expressly claimed
Post-evaporation concentration increase	Addressed by claims 61-65

A commercial product does not infringe solely because it is an aerosol foam containing the same active ingredients. The relevant question is whether it satisfies the complete combination of structural, compositional and functional limitations.

What is the patent expiration date?

The patent issued in 2020. Its nominal term is calculated from the applicable earliest nonprovisional or international filing date, not from the issue date. Based on the stated priority framework, the nominal expiration falls in March 2035.

Event	Date or period
Earliest stated priority	March 2014
Patent issue	2020
Nominal 20-year term endpoint	March 2035
Possible adjustment	USPTO patent-term adjustment may alter the endpoint

Patent-term adjustment, terminal disclaimers and any patent-term extension must be checked in the USPTO Patent Center record before relying on a final expiration date. FDA regulatory exclusivity, if any, is separate from patent term.[1][3]

What is the Orange Book status?

The relevant reference product is Enstilar, approved under NDA 207589. The Orange Book is the controlling source for patents submitted to FDA for that NDA and for any pediatric-exclusivity or regulatory-exclusivity entries.[1]

US 10,660,908 should not be treated as Orange Book-listed solely because it is technically relevant to Enstilar. Orange Book listing is a regulatory submission made by the NDA holder and is product-specific. A patent may be highly relevant to commercial freedom to operate without appearing in the Orange Book, particularly where the patent claims a formulation or method that the NDA holder did not submit for listing or where FDA determines that the statutory listing criteria are not met.

For an ANDA applicant, the practical review should include:

Current Orange Book patent listings for NDA 207589.
Any delisting or expiration updates.
The applicant’s Paragraph IV certification.
FDA approval timing under 21 U.S.C. § 355(j).
District-court litigation and any automatic 30-month stay.

Are Paragraph IV challenges or generic launches known?

A Paragraph IV challenge must be evaluated patent by patent. The existence of a generic calcipotriene/betamethasone product, an ANDA filing or a patent litigation docket does not establish that US 10,660,908 has been invalidated or carved out.

The principal generic design-around routes are:

Use a non-aerosol cream, ointment, gel or lotion.
Use a nonvolatile solvent system.
Include propylene glycol, where clinically and technically acceptable.
Suspend rather than dissolve one or both actives.
Replace the paraffin-based lipid carrier.
Avoid the claimed propellant ratio.
Develop a product outside the claimed concentration ranges.
Challenge enablement, written description, anticipation, obviousness or indefiniteness.

The most difficult design-around is likely a therapeutically equivalent aerosol foam that retains dimethyl ether, n-butane, paraffin carriers and the same active concentrations. Such a product could encounter overlapping claim limitations across claims 1, 14, 22, 23, 34, 49 and 61 through 65.

How strong is the patent estate?

US 10,660,908 has strong formulation relevance but its enforceability depends on claim construction and proof of the functional limitations.

Strength factor	Assessment
Core formulation architecture	Strong if accused product uses the same aerosol-paraffin system
Active ingredients	Narrow to the specific combination
Propellant coverage	Broad, with specific dimethyl ether and alkane claims
Carrier coverage	Broad across paraffins, hydrocarbons and waxes
Concentration coverage	Broad, with commercially targeted narrow claims
Functional stability claims	Potentially valuable but testing-intensive
Skin-penetration claim	Narrow and evidence-dependent
Method claim	Dependent on all claim 1 limitations
Design-around potential	Moderate for creams, nonvolatile systems and non-lipid carriers
Biosimilar relevance	None, because the product is a small-molecule topical drug

The patent is stronger against copycat aerosol foams than against conventional generic creams or ointments.

What licensing and commercial issues matter?

The commercial rights should be analyzed through the ownership and license chain for the patent family, the Enstilar NDA and the marketed product. Patent ownership, regulatory sponsorship and commercialization rights can reside with different entities.

The principal commercial exposure is branded topical-foam revenue during the remaining patent term. The most relevant competitive products include:

Enstilar aerosol foam.
Generic calcipotriene/betamethasone creams or ointments.
Calcipotriene-only products.
Betamethasone dipropionate-only products.
Other topical psoriasis therapies, including corticosteroid combinations and nonsteroidal agents.

A generic cream does not automatically compete on the same formulation claims because the patent is directed to a propellant-based composition. The greatest revenue risk would come from an approved generic aerosol foam that demonstrates pharmaceutical equivalence or therapeutic equivalence while successfully addressing the Orange Book patents through Paragraph IV litigation or settlement.

Key Takeaways

US 10,660,908 covers substantially anhydrous aerosol compositions containing calcipotriol or calcipotriol monohydrate and betamethasone dipropionate.
The claims require dissolution of the active ingredients in a propellant and formation of an occlusive semisolid lipid layer after application.
Dimethyl ether, n-butane, white soft paraffin and liquid paraffin are specifically important claim elements.
Claims 61 through 65 address concentration changes after evaporation and align with the applied concentrations associated with Enstilar.
The patent excludes propylene glycol, but does not necessarily exclude every propylene-glycol-derived ester or excipient.
The nominal patent term extends to approximately March 2035, subject to USPTO term adjustments.
The patent is most powerful against aerosol-foam copies using the same dimethyl ether/paraffin architecture.
Conventional creams, ointments and nonvolatile formulations have more substantial design-around opportunities.
Biosimilar analysis is not applicable because calcipotriol and betamethasone dipropionate are small-molecule active ingredients.
Orange Book listing must be confirmed separately from technical relevance and cannot be inferred from the patent claims alone.

FAQs

Does US Patent 10,660,908 cover all calcipotriol and betamethasone products?

No. It covers specified topical compositions and a psoriasis treatment method using those compositions. It does not cover every cream, ointment, gel or foam containing the two active ingredients.

Can a formulation avoid the patent by replacing dimethyl ether?

Potentially. Replacing dimethyl ether may avoid several dependent claims, but claim 1 broadly covers a pharmaceutically acceptable propellant. The replacement must also avoid the other limitations, including dissolution of both actives and formation of the claimed occlusive lipid layer.

Does adding propylene glycol avoid infringement?

It may avoid claims 1 and 14 because those claims expressly exclude propylene glycol. The complete formulation and the doctrine of equivalents would still require separate analysis.

Are claims 61 through 65 product-by-process claims?

They are composition claims that define active-ingredient amounts before and after propellant evaporation. Their enforceability will depend on how the concentration and post-application limitations are construed and measured.

Is US 10,660,908 relevant to biosimilar competition?

No. Biosimilar pathways apply to biological products. Calcipotriol and betamethasone dipropionate are small-molecule drug substances, so competition proceeds through generic-drug pathways, including ANDA filings and Paragraph IV certifications.

References

U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.accessdata.fda.gov/scripts/cder/ob/
U.S. Food and Drug Administration. (2024). Enstilar prescribing information. LEO Pharma A/S.
United States Patent and Trademark Office. (2024). Patent Center. https://patentcenter.uspto.gov/
United States Patent No. 10,660,908. (2020). Topical pharmaceutical composition comprising calcipotriol and betamethasone dipropionate. United States Patent and Trademark Office.

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	⤷ Start Trial	⤷ Start Trial	Y			TOPICAL TREATMENT OF PLAQUE PSORIASIS IN PATIENTS 12 YEARS AND OLDER	⤷ 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
China	102939078	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 10,660,908

Which drugs does patent 10,660,908 protect, and when does it expire?

Summary for Patent: 10,660,908