Details for Patent: 10,682,364

Which drugs does patent 10,682,364 protect, and when does it expire?

Patent 10,682,364 protects ENSTILAR and is included in one NDA.

This patent has thirty-six patent family members in twenty-five countries.

Summary for Patent: 10,682,364

Title:	Pharmaceutical spray composition comprising a vitamind D analogue and a corticosteroid
Abstract:	The present invention relates to a topical spray composition comprising a biologically active vitamin D derivative or analogue and a corticosteroid, and its use in the treatment of dermal diseases and conditions.
Inventor(s):	Marianne Lind, Gritt Rasmussen, Mette Rydahl Sonne, Jens Hansen, Karsten Petersson
Assignee:	Leo Pharma AS
Application Number:	US16/554,603
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,682,364
Patent Claim Types: see list of patent claims	Composition; Compound;

US Patent 10,682,364: Claim Scope, Enforcement Risk, and Calcipotriol-Betamethasone Patent Landscape

US Patent 10,682,364 protects a narrow but commercially important class of substantially anhydrous aerosol compositions containing calcipotriol or calcipotriol monohydrate and betamethasone dipropionate. The claims focus on four technical features: hydrocarbon or dimethyl ether propellant systems, lipid carriers, exclusion of propylene glycol, and demonstrated calcipotriol stability at elevated temperature. The strongest commercial overlap is with aerosol formulations corresponding to calcipotriol/betamethasone products such as Enstilar.

The patent does not broadly cover every topical calcipotriol-betamethasone product. It is directed to sprayable compositions meeting the specified excipient, concentration, propellant, and stability limitations.

What does US Patent 10,682,364 protect?

Claim 1 is the controlling independent claim. It requires a composition that:

1. Is sprayable.
2. Is substantially anhydrous.
3. Contains calcipotriol or calcipotriol monohydrate.
4. Contains betamethasone dipropionate.
5. Contains a pharmaceutically acceptable propellant at 45% to 95% w/w.
6. Contains a pharmaceutically acceptable lipid carrier at 5% to 55% w/w.
7. Contains a pharmaceutically acceptable antioxidant.
8. Does not contain propylene glycol.
9. Has no more than 10% degradation of calcipotriol or calcipotriol monohydrate after three months at approximately 40°C.

The claim uses the transitional term "comprising." That language generally permits additional ingredients unless the added ingredient contradicts an express limitation. The propylene glycol exclusion is therefore significant: an otherwise qualifying formulation containing propylene glycol would fall outside claim 1.

Core claim limitations

Limitation	Commercial and legal significance
Sprayable	Targets aerosol delivery rather than conventional cream, ointment, gel, or lotion dosage forms
Substantially anhydrous	Excludes ordinary water-rich emulsions and aqueous creams; the exact boundary may require claim construction
Calcipotriol or calcipotriol monohydrate	Covers either active form
Betamethasone dipropionate	Requires the specific corticosteroid, not another betamethasone ester
Propellant at 45%-95% w/w	Captures high-propellant aerosol systems
Lipid carrier at 5%-55% w/w	Requires a substantial nonaqueous lipid phase
Antioxidant	A mandatory element of claim 1
No propylene glycol	Creates a direct design-around route
Stability at 40°C	Adds an objective product-performance limitation

Claims 2 through 27 narrow the composition by adding stability, strength, propellant, carrier, cosolvent, and excipient limitations. They do not create independent protection for the active ingredients by themselves.

How do claims 2 through 27 narrow the patent scope?

Stability claims

Claim 2 reduces the allowed degradation threshold from 10% to 6% after three months at approximately 40°C. This is a narrower and potentially stronger formulation claim if the accused product satisfies the test.

The stability limitation creates evidentiary issues. An infringement analysis would need to establish:

• The test temperature and duration.
• The analytical method used to quantify degradation.
• Whether degradation is measured against the initial active concentration.
• Whether the result applies to calcipotriol, calcipotriol monohydrate, or both.
• Whether the tested commercial batch represents the accused composition.

A product may meet the formulation limitations but fail claim 1 or claim 2 because its measured degradation exceeds the specified threshold.

Active-strength claims

Claim 3 requires, for each gram excluding propellant:

• 52.2 micrograms of calcipotriol monohydrate; and
• 0.643 milligrams of betamethasone dipropionate.

Claims 20 and 21 provide corresponding nominal concentrations:

• Calcipotriol: 0.005% w/w, excluding propellant.
• Calcipotriol monohydrate: 0.00522% w/w, excluding propellant.
• Betamethasone dipropionate: 0.064% w/w, excluding propellant.

The exclusion of propellant from the denominator is important. A formulation can have a lower concentration when calculated over the total filled package but still satisfy these claims if the nonpropellant portion has the specified concentration.

Propellant claims

Claims 5 through 8 divide the propellant coverage into two principal groups:

Claims	Propellant scope
5-7	C3-C5 alkanes, including propane, isopropane, n-butane, and isobutane
8	Dimethyl ether
23-24	Dimethyl ether combined with liquid paraffin and petrolatum, with optional oily cosolvent

Claim 7 is particularly narrow because it requires n-butane. Claim 8 is separately directed to dimethyl ether and does not require a hydrocarbon alkane.

A product using an alternative propellant, such as a non-listed fluorinated propellant, may avoid literal infringement of claims 5-8. That product would still require analysis under claim 1 if the alternative propellant satisfies the broader "pharmaceutically acceptable propellant" language and all other limitations.

Lipid-carrier claims

Claims 9, 11, and 25-27 concentrate on petrolatum, including white soft paraffin. Claim 23 covers a mixture of liquid paraffin and petrolatum.

These claims create a high-overlap zone for aerosol products using:

• White soft paraffin.
• Liquid paraffin.
• Petrolatum/mineral-oil combinations.
• Hydrocarbon propellants.
• Dimethyl ether.
• Oily penetration or spreading agents.

A formulation using a non-petrolatum lipid carrier could avoid claims 9, 11, and 25-27 but could remain within claim 1 if its lipid carrier otherwise satisfies the broader carrier limitation.

Oily cosolvent claims

Claims 10 through 19 and 22 cover multiple classes of oily cosolvents:

• Polyoxypropylene-polyoxyethylene-type ethers and related compounds under formula I.
• Isopropyl esters, including isopropyl myristate and isopropyl palmitate.
• C8-C24 alkanols and alkenols.
• Myristyl alcohol specifically in claim 18 and claim 22.

These claims are composition-specific. They are valuable against a competitor that copies the excipient architecture while changing only the propellant or package.

What formulations are protected by US 10,682,364?

The commercially most important protected formulation profile is a substantially anhydrous aerosol containing:

• Calcipotriol or calcipotriol monohydrate at approximately 0.005% or 0.00522%, respectively, excluding propellant.
• Betamethasone dipropionate at approximately 0.064%, excluding propellant.
• White soft paraffin or petrolatum.
• Liquid paraffin or another lipid carrier.
• An oily cosolvent such as myristyl alcohol or a polyoxypropylene ether.
• n-Butane, dimethyl ether, or another qualifying propellant.
• An antioxidant.
• No propylene glycol.
• Stability within the claimed degradation limit.

The patent is therefore directed to the product architecture associated with an aerosolized fixed-dose combination rather than to a general topical psoriasis composition.

How strong is the patent estate for calcipotriol-betamethasone aerosol products?

US 10,682,364 is strongest when the accused product reproduces the complete formulation profile. The patent has several features that improve practical enforcement value:

1. It claims the combination of active ingredients and excipient system.
2. It includes both broad and narrow propellant alternatives.
3. It claims commercially recognizable active strengths.
4. It covers petrolatum and white soft paraffin.
5. It includes multiple dependent cosolvent classes.
6. It includes stability limitations that can be tested on the finished product.

Its principal weakness is claim breadth. Claim 1 requires simultaneous satisfaction of numerous limitations. A competitor may avoid infringement by changing one material element, including:

• Using propylene glycol.
• Using an aqueous formulation.
• Using a non-lipid carrier.
• Reducing propellant below 45% w/w.
• Increasing propellant above the claimed range.
• Selecting a different corticosteroid.
• Using a different active concentration.
• Using a non-sprayable dosage form.
• Failing the claimed stability threshold.
• Using a different propellant and avoiding the narrower propellant claims.

The stability limitation is both a strength and a litigation burden. It may prevent an easy noninfringement determination based solely on the ingredient list.

What is the FDA and Orange Book relevance?

The FDA approved Enstilar foam, a topical fixed combination of calcipotriene and betamethasone dipropionate, for plaque psoriasis. The product contains the same active-ingredient strengths reflected in claims 3, 20, and 21, although the patent claims must be compared against the FDA-approved formulation and its manufacturing specifications rather than against the active strengths alone.[2]

The Orange Book is relevant if US Patent 10,682,364 is listed against an approved drug product. An Orange Book listing can require an ANDA applicant to address the patent through:

• Paragraph I certification, if the patent information is not applicable.
• Paragraph II certification, if the patent has expired.
• Paragraph III certification, if the applicant will wait for expiration.
• Paragraph IV certification, if the applicant asserts that the patent is invalid, unenforceable, or not infringed.

The Orange Book listing date, listed expiration date, and associated product number must be checked against the FDA’s current patent-and-exclusivity data. Patent grant date is not the expiration date, and a continuation patent can have a different enforceability profile from an earlier family member.[1]

When does US Patent 10,682,364 lose exclusivity?

US Patent 10,682,364 has a 20-year patent term measured principally from the earliest effective nonprovisional filing date of the relevant application chain, subject to patent-term adjustment, terminal disclaimer, and any applicable patent-term extension.[3]

The patent’s June 16, 2020 issue date does not determine expiration. A reliable expiration analysis requires the USPTO’s continuity data and patent-term calculation, including:

• The earliest effective US nonprovisional filing date.
• Any priority claims that do not count toward the 20-year term.
• Patent-term adjustment.
• Terminal disclaimers.
• Whether the patent is listed in the Orange Book and with what expiration date.

For commercial planning, the relevant date is the enforceable patent expiration shown in USPTO term records and, where applicable, the FDA Orange Book, not an estimate based on the grant date.

Are Paragraph IV challenges likely for this patent?

A Paragraph IV challenge would be legally available for an ANDA applicant seeking approval of a generic aerosol or foam containing the same active ingredients. The applicant would need to address the patent claims that are listed for the reference product.

The most viable challenge theories would involve:

Noninfringement

A generic applicant could design around one or more claim limitations by:

• Including propylene glycol.
• Using an aqueous or materially hydrated formulation.
• Selecting a propellant outside the claimed classes.
• Using less than 45% or more than 95% propellant.
• Replacing petrolatum or the claimed lipid carrier.
• Altering the active concentration.
• Using a different dosage form that is not sprayable.

Invalidity

Potential validity issues would focus on:

• Anticipation by earlier aerosol formulations containing the same active ingredients.
• Obviousness based on known calcipotriol-betamethasone combinations and conventional aerosol excipients.
• Written-description and enablement support for the broad propellant, carrier, cosolvent, and stability genus.
• Definiteness of "substantially anhydrous," "sprayable," and "about 40°C."
• Whether the stability limitation supplies patentable distinction or merely describes an expected property of a known formulation.

The patent’s dependent claims may be more difficult to invalidate as a group because they identify specific commercial excipients and concentration combinations. Their narrower scope, however, gives a generic manufacturer more opportunities to design around them.

What patent litigation affects US 10,682,364?

The patent number alone does not establish an active infringement case, settlement, or Paragraph IV proceeding. Litigation status must be determined from the USPTO Patent Center, PACER, FDA Orange Book records, and the relevant district-court docket.[1,4]

For diligence, the critical litigation questions are:

Issue	Required review
ANDA notice	Whether an applicant served a Paragraph IV notice
Filing date	Whether a suit was filed within 45 days
Automatic stay	Whether approval was stayed under Hatch-Waxman
Claim construction	Treatment of "sprayable," "substantially anhydrous," and degradation
Product testing	Whether the accused product meets the 40°C stability limitation
Settlement	Any license date, launch date, or authorized-generic provision
Final outcome	Dismissal, consent judgment, invalidity, noninfringement, or settlement

A settlement can materially change generic-entry timing even when the patent remains formally valid. The settlement terms, rather than the patent expiration date alone, would control the commercial launch risk.

Does biosimilar risk apply?

No. Calcipotriol and betamethasone dipropionate are small-molecule active ingredients. A competing product would generally proceed through the generic-drug pathway, including an ANDA, rather than the biosimilar pathway under the Biologics Price Competition and Innovation Act.

The relevant competitive risk is therefore generic aerosol or foam entry, not biosimilar substitution. FDA approval would depend on pharmaceutical equivalence, bioequivalence or applicable comparative requirements, device and container performance, product quality, and labeling.[2]

How does US 10,682,364 compare with competing dosage forms?

Product or technology	Main dosage form	Relationship to US 10,682,364
Aerosol calcipotriol-betamethasone product	Foam or sprayable aerosol	Highest potential overlap
Calcipotriol-betamethasone cream	Cream or emulsion	Generally outside the sprayable, substantially anhydrous aerosol claims
Calcipotriol-betamethasone ointment	Ointment	Generally outside the propellant limitations
Calcipotriol-only products	Cream, foam, solution, or ointment	Lack required betamethasone dipropionate
Betamethasone-only products	Cream, ointment, lotion, or foam	Lack required calcipotriol
Aqueous fixed combinations	Cream, suspension, or emulsion	Potentially outside the substantially anhydrous requirement

Wynzora, an aqueous cream formulation, is a different technical platform from the aerosol formulation claimed here. Taclonex suspension and ointment products also use different dosage-form architectures. Product-by-product patent clearance still requires comparison of the full formulation, device, manufacturing process, and approved labeling.

What manufacturing and IP barriers exist?

The patent claims the final composition, not merely the manufacturing process. A competitor may therefore avoid process-based infringement but still infringe if it sells the claimed composition.

Manufacturing barriers include:

• Maintaining active stability during propellant filling.
• Achieving uniform distribution of low-dose actives.
• Controlling aerosol discharge and particle or foam characteristics.
• Preventing oxidation of calcipotriol.
• Selecting a compatible valve, canister, and actuator.
• Controlling white soft paraffin and liquid-paraffin rheology.
• Demonstrating stability after filling rather than only in bulk.
• Meeting flammability and packaging requirements for hydrocarbon propellants.

The patent’s stability claims increase the value of formulation know-how. A competitor that avoids the literal claims may still face practical development barriers in reproducing dose uniformity, spray performance, physical stability, and shelf life.

What generic launch scenarios exist?

Scenario 1: No Paragraph IV challenge

The generic applicant files with a Paragraph III certification or waits for patent expiration. Entry is deferred to the applicable patent term.

Scenario 2: Formulation design-around

The applicant changes the propellant, carrier, water content, active concentration, or excipient system. This can reduce patent risk but may require new product-development work and may prevent a close pharmaceutical-equivalence position.

Scenario 3: Paragraph IV litigation

The applicant certifies that the patent is invalid, unenforceable, or not infringed. A timely patent suit can trigger the statutory 30-month stay, subject to court action and settlement.

Scenario 4: Narrow-label entry

If method-of-use patents remain relevant, a generic may seek approval with a carved-out indication or labeling strategy. US 10,682,364 is a composition patent, so a label carve-out would not by itself resolve infringement of the composition claims.

Key Takeaways

• US 10,682,364 is a formulation patent for substantially anhydrous, sprayable calcipotriol-betamethasone aerosol compositions.
• Claim 1 requires propellant, lipid carrier, antioxidant, the active combination, exclusion of propylene glycol, and a defined calcipotriol stability result.
• Claims 3, 20, and 21 align with the commercial active strengths of aerosol calcipotriol-betamethasone products.
• Claims 9, 23, and 25-27 create substantial exposure for products using petrolatum, white soft paraffin, and liquid paraffin.
• Claims 5-8 cover hydrocarbon propellants and dimethyl ether through separate dependent-claim pathways.
• The patent does not broadly cover aqueous creams, ointments, calcipotriol-only products, or betamethasone-only products.
• Generic risk is primarily an ANDA and Paragraph IV issue, not a biosimilar issue.
• Patent expiration must be determined from the USPTO term record and any Orange Book listing, not from the 2020 grant date.
• The most credible design-around routes involve propylene glycol, aqueous formulation, alternative lipid systems, alternative propellants, or concentrations outside the claimed ranges.
• Commercial exposure is highest for a close copy of the Enstilar-type aerosol formulation.

FAQs

Can a product containing propylene glycol infringe US 10,682,364?

A product containing propylene glycol would not literally satisfy claim 1 because claim 1 expressly excludes propylene glycol. The same product could still require review against other patents in the relevant formulation family.

Does the patent cover Enstilar by brand name?

No. Patent claims cover compositions, not brand names. Enstilar must be compared against each claim limitation, including propellant percentage, lipid carrier, antioxidant, active concentration, propylene glycol exclusion, and stability.

Can a competitor avoid the patent by using a different aerosol actuator?

Changing the actuator alone may not avoid infringement if the composition satisfies the claims. The actuator becomes more important where separate device or container patents cover the delivery system.

Is white soft paraffin independently important in the patent?

Yes. Claims 25 through 27 expressly identify white soft paraffin as a narrower petrolatum embodiment. A product using white soft paraffin with the claimed active strengths and propellant system faces a higher overlap risk than a product using a materially different lipid carrier.

Does claim 2 provide separate protection from claim 1?

Claim 2 is a dependent claim and includes every limitation of claim 1 while reducing calcipotriol degradation to no more than 6% after three months at approximately 40°C. It provides narrower protection, not an independent claim category.

References

1. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.accessdata.fda.gov/scripts/cder/ob/
2. U.S. Food and Drug Administration. (2016). Enstilar (calcipotriene and betamethasone dipropionate) aerosol, foam: Prescribing information. FDA.
3. United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term calculation. https://www.uspto.gov/patents/laws/patent-term-calculator
4. United States Patent and Trademark Office. (n.d.). Patent Center. https://patentcenter.uspto.gov/
5. United States Patent No. 10,682,364. (2020). Calcipotriol and betamethasone dipropionate sprayable pharmaceutical composition. U.S. Patent and Trademark Office.

Drugs Protected by US Patent 10,682,364

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	10,682,364		Y

International Family Members for US Patent 10,682,364

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2011264198
Brazil	112012030653
Canada	2800181
China	102939078
Cyprus	1115991
Denmark	2579852
European Patent Office	2579852