US Patent 10,688,108: Claim Scope, Enstilar Patent Landscape, and Generic Entry Risk

US Patent 10,688,108 protects method-of-treatment use of a propellant-driven, substantially anhydrous psoriasis composition containing calcipotriol or calcipotriol monohydrate and betamethasone dipropionate. The patent does not claim every calcipotriol/betamethasone product. Its principal limitations are the aerosol format, propellant and lipid-carrier ranges, exclusion of propylene glycol, and one of three performance requirements: chemical stability, absence of visible crystals, or increased skin permeation.

The claims closely track the formulation profile of Enstilar aerosol foam, marketed by LEO Pharma for plaque psoriasis. The strongest infringement risk applies to a product using dimethyl ether, petrolatum or white soft paraffin, liquid paraffin, myristyl alcohol, and the claimed active concentrations.

What does US Patent 10,688,108 protect?

The patent protects methods of treating psoriasis by administering a specific topical aerosol composition. The independent claims are claims 1, 8, and 13.

Independent claim	Core protected feature	Principal performance limitation
Claim 1	Substantially anhydrous aerosol composition with calcipotriol, betamethasone dipropionate, propellant, lipid carrier, antioxidant, and no propylene glycol	No more than 10% calcipotriol degradation after three months at approximately 40°C
Claim 8	Same core composition	No visible active-ingredient crystals after 12 months at approximately 25°C by polarized light microscopy
Claim 13	Same core composition	Increased calcipotriol skin permeation versus a specified non-aerosol ointment comparator

All three independent claims require:

Calcipotriol or calcipotriol monohydrate
Betamethasone dipropionate
A substantially anhydrous topical composition
A pharmaceutically acceptable propellant at 45% to 95% w/w
A pharmaceutically acceptable lipid carrier at 5% to 55% w/w
A pharmaceutically acceptable antioxidant
No propylene glycol
Administration for treatment of psoriasis

The claims are method claims rather than composition claims. A commercial formulation may fall within the technical formulation definition but still require analysis of whether the product is promoted, labeled, or administered for the claimed psoriasis treatment.

How are claims 1 through 28 structured?

Claims 2 through 7 depend from claim 1. Claims 9 through 12 depend from claim 8. Claims 14 through 28 depend from claim 13 or its dependent claims.

The recurring narrower formulation includes:

Component	Claimed amount or identity
Calcipotriol monohydrate	0.00522% w/w excluding propellant, or 52.2 mcg/g excluding propellant
Betamethasone dipropionate	0.064% w/w excluding propellant, or 0.643 mg/g excluding propellant
Lipid carrier	Petrolatum, including white soft paraffin
Oily co-solvent	0.1% to 10% w/w
Specific oily co-solvent	Myristyl alcohol
Propellant	Dimethyl ether
Additional lipid system	Mixture of liquid paraffin and petrolatum

The claims use two concentration conventions. Claims 2, 9, and 14 express active concentration as a percentage of the composition excluding propellant. Claims 3, 10, and 15 use the same formulation on a per-gram basis, also excluding propellant. This exclusion is material because the finished aerosol can contain a much larger propellant fraction while retaining the claimed drug concentration in the non-propellant concentrate.

What formulations are protected by US 10,688,108?

The most commercially relevant embodiment is an aerosol suspension or foam containing calcipotriol monohydrate and betamethasone dipropionate in a hydrocarbon or oily base, propelled by dimethyl ether.

A formulation is most exposed when it contains the following combination:

Calcipotriol monohydrate at approximately 52.2 mcg/g of non-propellant formulation.
Betamethasone dipropionate at approximately 0.643 mg/g of non-propellant formulation.
Petrolatum or white soft paraffin.
Liquid paraffin.
Myristyl alcohol or another claimed oily co-solvent.
Dimethyl ether at a level within the 45% to 95% w/w propellant range.
An antioxidant.
No propylene glycol.
Stability and crystal-control characteristics matching claims 1 or 8, or increased permeation matching claim 13.

The claims do not require every listed dependent feature. A product can potentially infringe claim 1 without using myristyl alcohol, liquid paraffin, or white soft paraffin if it satisfies the broader independent-claim limitations.

What are the key technical limitations?

Substantially anhydrous composition

The claims require a substantially anhydrous composition. This limitation distinguishes the claimed aerosol from aqueous sprays, gels, emulsions, and other water-containing topical systems. The patent language provided does not establish a numerical water threshold. Product specifications, manufacturing records, and stability data would therefore be important in any infringement analysis.

Propellant range

The propellant must comprise 45% to 95% w/w of the total composition. This is a broad range, but it excludes low-propellant sprays and non-aerosol ointments.

Dimethyl ether is expressly included in dependent claims 6, 7, and 12. A hydrocarbon propellant or another pharmaceutically acceptable propellant could satisfy the independent claims if it meets the general limitations.

Lipid-carrier range

The lipid carrier must comprise 5% to 55% w/w of the total composition. Petrolatum, liquid paraffin, white soft paraffin, and mixtures of these materials are the principal claimed examples.

A formulation using a non-lipid vehicle, such as a predominantly aqueous vehicle or a polymeric hydrogel without a qualifying lipid carrier, presents a stronger design-around position.

Propylene glycol exclusion

The independent claims expressly exclude propylene glycol. This exclusion can create a relatively direct formulation design-around if a competing product otherwise uses the claimed actives and aerosol format but contains propylene glycol.

The exclusion also narrows the claims against prior-art formulations that rely on propylene glycol as a solvent, humectant, or penetration enhancer.

Antioxidant requirement

An antioxidant is required, but the independent claims do not identify a single antioxidant. Dependent claims do not narrow this feature to alpha-tocopherol in the text supplied. A product would likely be evaluated based on the formulation's actual excipient function and composition.

How do the stability and crystal limitations affect infringement?

Claims 1 through 7 require a degradation result. The relevant threshold is no more than 10% degradation of calcipotriol or calcipotriol monohydrate after three months at approximately 40°C. Claim 5 narrows the threshold to no more than 6% degradation.

Claims 8 through 12 require no visible crystals of calcipotriol, calcipotriol monohydrate, or betamethasone dipropionate after 12 months at approximately 25°C, as determined by polarized light microscopy.

These are performance limitations, not merely ingredient limitations. Two formulations with identical nominal ingredients may have different infringement exposure if one fails the specified stability or microscopy test. Testing methodology, sample preparation, batch variability, storage conditions, and the meaning of "visible crystals" may become central in litigation.

What does claim 13 add regarding skin permeation?

Claim 13 protects a composition that produces increased calcipotriol skin permeation compared with a specified ointment comparator. The comparison uses:

Full-thickness pig ear skin
A Franz diffusion cell
Twenty-one hours of exposure
The percentage of applied calcipotriol reaching receptor fluid

Claim 17 requires at least about a two-fold increase in calcipotriol permeation. Claims 18 and 19 address increased betamethasone dipropionate penetration into the dermis and epidermis, with claim 19 requiring at least about a two-fold increase.

These claims create an evidentiary issue. The relevant comparison is not simply whether the aerosol has higher permeation than a generic ointment. The claim identifies a specific comparator composition containing calcipotriol monohydrate, betamethasone dipropionate, alpha-tocopherol, polyoxypropylene-11-stearyl ether, liquid paraffin, and white soft paraffin.

How strong is the patent estate based on the asserted claims?

The patent has moderate-to-strong formulation specificity but narrower legal breadth than a composition claim.

Strength factor	Assessment
Aerosol format	Strong limitation against non-aerosol topical products
Active ingredients	Narrowed to a known combination used in psoriasis products
Propellant range	Broad enough to cover most high-propellant aerosols
Lipid carrier	Broad, with petrolatum and paraffin embodiments
No propylene glycol	Clear limitation and potential design-around
Stability limitation	Potentially difficult to prove without testing
Crystal limitation	Dependent on microscopy protocol and batch evidence
Permeation limitation	Requires comparative testing and may be vulnerable to factual disputes
Method-of-treatment format	Requires analysis of use, labeling, and induced infringement
Dependent claims	Stronger product-specific positions but narrower scope

The claims are strongest against a product deliberately designed to reproduce the Enstilar-type formulation and performance profile. They are weaker against a formulation that changes the propellant system, removes the lipid carrier, includes propylene glycol, uses materially different active concentrations, or does not demonstrate the required performance.

What is the relationship to Enstilar?

Enstilar is an FDA-approved aerosol foam containing calcipotriene, the USAN name for calcipotriol, and betamethasone dipropionate. FDA approved Enstilar under NDA 207589 for topical treatment of plaque psoriasis in patients 12 years and older.[2]

The claimed concentrations correspond closely to the active-ingredient strengths associated with the product's formulation after accounting for the claim's exclusion of propellant. Enstilar's product labeling identifies calcipotriene and betamethasone dipropionate as the active ingredients and describes an aerosol foam dosage form.[2]

That commercial correspondence increases the practical relevance of the patent, but claim coverage cannot be established solely from product similarity. The precise formulation, propellant percentage, excipient identity, storage data, and comparator-performance results must align with the claim limitations.

What is the Orange Book status of US 10,688,108?

The claims supplied do not establish the patent's Orange Book listing status, current patent-use codes, or whether the patent is listed against NDA 207589. Orange Book analysis must distinguish between:

Patent listing against the approved NDA
Listed expiration date
Use codes
Any terminal disclaimer
Patent-term adjustment
Patent-term extension
Delisting or correction history

The FDA Orange Book is the controlling public source for current listed-patent information for approved drug products.[1] US Patent 10,688,108 is an issued US patent dated June 23, 2020, but the issue date does not establish its expiration date. Patent term generally runs 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, terminal disclaimers, priority issues, and other statutory modifications.[3]

When does US Patent 10,688,108 lose exclusivity?

An exact expiration date cannot be derived from the issued patent number or the claims alone. The controlling calculation requires the patent's effective filing chain and any patent-term adjustment or terminal disclaimer.

For commercial planning, the relevant dates are:

Event	Date or status
Patent issued	June 23, 2020
Patent type	US utility patent
Claim category	Method of treating psoriasis
FDA product association	Potentially relevant to Enstilar, subject to current Orange Book confirmation
Statutory expiration	Requires prosecution and term records
FDA regulatory exclusivity	Determined from NDA approval and exclusivity records, not from the patent claims

FDA approval of Enstilar occurred in 2015. The approval date does not by itself determine the patent expiration date or the end of all market protection. Regulatory exclusivity and patent exclusivity are separate rights.[1][2]

What Paragraph IV challenges and litigation risks exist?

A generic applicant seeking approval of a product that relies on Enstilar or an equivalent aerosol product could submit a Paragraph IV certification against listed patents. The principal challenge theories would likely include:

Non-infringement based on propellant content below 45% or above 95%.
Use of a composition containing propylene glycol.
Absence of a qualifying lipid carrier.
Different active concentrations.
Failure to satisfy the stability, crystal, or permeation limitations.
Invalidity based on anticipation or obviousness.
Lack of enablement or written description for broad functional limitations.
Inapplicability of the method claims to the proposed labeling or use.

The most vulnerable limitations may be the comparative permeation results and the stability or microscopy results if the patent specification does not provide adequate support across the full breadth of the claimed composition ranges. The strongest invalidity analysis would require review of the complete specification, cited prior art, prosecution history, and any claim amendments.

The supplied materials do not establish a current Paragraph IV notice, ANDA litigation docket, settlement agreement, or final judgment involving US 10,688,108. Those matters cannot be inferred from the claim language.

What generic launch scenarios are most credible?

Generic design	Relative patent risk
Same active ingredients, dimethyl ether, petrolatum, liquid paraffin, and matching concentrations	High
Same actives and aerosol format, but propylene glycol added	Lower under the supplied claims
Same actives in a non-aerosol ointment	Low under these claims, subject to other patents
Aerosol with less than 45% propellant	Lower, if the formulation remains outside every claim
Aerosol with no qualifying lipid carrier	Lower
Changed calcipotriol or betamethasone concentration	Moderate to lower, depending on all other limitations
Alternative propellant with claimed ranges and matching performance	Moderate to high
Product with no demonstrated increased permeation	Does not avoid claims 1 or 8 if those limitations are met

A generic developer cannot rely on a single formulation difference unless that difference avoids all independent claims and any separately asserted patent family members.

How does this patent compare with earlier topical psoriasis patents?

US 10,688,108 is narrower than patents directed generally to calcipotriol/betamethasone combinations. Its differentiation is the delivery system and associated performance characteristics.

Patent category	Typical scope	Relationship to US 10,688,108
Active-combination patents	Calcipotriol plus betamethasone	Potentially broader chemically, but may not cover aerosol delivery
Ointment patents	Non-aerosol lipid formulations	Prior-art relevance and possible separate barriers
Foam or aerosol patents	Propellant-based topical delivery	Closest competitive estate
Stability patents	Reduced degradation or crystal control	Overlapping functional subject matter
Method-of-use patents	Psoriasis treatment regimens	Could create additional labeling risk

A freedom-to-operate review should therefore cover the entire LEO Pharma calcipotriol/betamethasone patent family, continuation patents, formulation patents, and Orange Book-listed patents, not only US 10,688,108.

Key Takeaways

US 10,688,108 is directed to psoriasis treatment using a substantially anhydrous aerosol composition, not to every calcipotriol/betamethasone product.
The core formulation requires a 45% to 95% propellant fraction, a 5% to 55% lipid-carrier fraction, an antioxidant, and no propylene glycol.
The commercially important dependent claims cover calcipotriol monohydrate, betamethasone dipropionate, petrolatum or white soft paraffin, liquid paraffin, myristyl alcohol, and dimethyl ether.
Claims 1, 8, and 13 use separate performance paths based on chemical stability, crystal absence, and increased skin permeation.
The patent presents meaningful risk to an Enstilar-like aerosol but leaves potential design-around routes through vehicle selection, propellant level, propylene glycol inclusion, active concentration, and delivery format.
The patent's exact expiration date, Orange Book status, current use codes, Paragraph IV activity, and litigation history cannot be established from the claims supplied.

FAQs

Is US Patent 10,688,108 a composition patent?

No. The supplied claims are method-of-treatment claims. They require administering the composition to a patient for psoriasis treatment.

Does using calcipotriene instead of calcipotriol avoid the patent?

No. Calcipotriene is the US name commonly used for calcipotriol. The chemical identity is the same active ingredient.

Does a product containing propylene glycol avoid all patent risk?

It may avoid the no-propylene-glycol limitation in these claims, but it does not necessarily avoid other patents covering calcipotriol/betamethasone formulations or aerosol delivery.

Are the Franz-cell permeation claims automatically satisfied by an aerosol foam?

No. The claims require comparative testing against the specified ointment comparator under the stated pig-skin and exposure conditions.

Can a generic launch before patent expiration occur?

A launch may occur through a Paragraph IV challenge, a settlement arrangement, a successful invalidity or non-infringement judgment, licensing, or authorized-generic strategy. The claims alone do not identify which path is available.

References

U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book.
U.S. Food and Drug Administration. (2015). Enstilar aerosol foam prescribing information, NDA 207589.
United States Patent and Trademark Office. (2024). Patent term adjustment and patent term calculation guidance.
United States Patent and Trademark Office. (2020). US Patent No. 10,688,108, topical pharmaceutical composition and method of treating psoriasis.

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				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
Cyprus	1115991	⤷ Start Trial
Denmark	2579852	⤷ Start Trial
European Patent Office	2579852	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 10,688,108

Which drugs does patent 10,688,108 protect, and when does it expire?

Summary for Patent: 10,688,108