U.S. Patent 5,763,426: Calcipotriol Monohydrate Claims, Expiration, Orange Book Status, and Patent Landscape

U.S. Patent No. 5,763,426 covers calcipotriol monohydrate, pharmaceutical compositions containing that hydrate, and processes for preparing and wet-milling it into creams and gels. The patent was assigned to Leo Pharmaceutical Products Ltd. and issued on June 9, 1998. Its enforceable term has expired. The patent therefore has no current blocking effect against generic calcipotriol products, although its disclosure remains relevant to formulation, solid-state, and freedom-to-operate analyses.

The patent is important because it claims a particular physical form of calcipotriol rather than merely claiming the active ingredient as a chemical structure. Its commercial value was tied to Dovonex and related calcipotriol topical products.

What does U.S. Patent 5,763,426 cover?

U.S. Patent 5,763,426 covers four related subject areas:

Calcipotriol monohydrate as a defined solid form.
Pharmaceutical compositions containing the hydrate.
Cream and gel formulations containing the hydrate.
A precipitation process and wet-ball-milling process using the hydrate.

The patent does not claim all calcipotriol products. Its central limitation is the use of calcipotriol monohydrate having the stated stability, wettability, and wet-milling characteristics.

Patent identification

Item	Information
U.S. patent	5,763,426
Title	Calcipotriol monohydrate
Applicant/assignee	Leo Pharmaceutical Products Ltd.
Inventor	Leo Pharmaceuticals researchers, as identified in the issued patent
Filing date	November 20, 1995
Priority date	November 21, 1994
Issue date	June 9, 1998
Technology	Calcipotriol solid form and topical formulations
Principal products implicated	Dovonex and calcipotriol topical products
Patent term	Expired in November 2015, subject to any recorded term adjustment or regulatory exclusivity
Current blocking status	No current patent exclusivity based on this patent

The priority filing was Danish. The U.S. application entered from the international patent filing associated with the 1994 priority application. The issued claims and specification should control any historical infringement analysis. (U.S. Patent No. 5,763,426, 1998.)

What are the claims of U.S. Patent 5,763,426?

The seven claims form a product, composition, process, and formulation-improvement claim set.

Claim-by-claim scope

Claim	Claim category	Principal limitation	Commercial relevance
1	Product	Calcipotriol monohydrate characterized by 40°C storage stability after 12 months, ready wettability, and wet-ball-milling properties	Core solid-form claim
2	Composition	Pharmaceutical composition containing the compound of claim 1	Captures formulations using the hydrate
3	Composition	Composition of claim 2 that is a cream	Cream formulations
4	Composition	Composition of claim 2 that is a gel	Gel formulations
5	Composition	Gel under claim 4 containing 1-100 μg/g active component	Concentration-limited gel claim
6	Process	Dissolving calcipotriol in an organic solvent, adding water, and precipitating the hydrate	Manufacturing route
7	Process/use improvement	Wet-ball-milling calcipotriol hydrate before adding it to a gel base	Gel manufacturing process

Claim 1: calcipotriol monohydrate

Claim 1 is the broadest and most commercially significant claim. It is directed to calcipotriol monohydrate, but the claim defines the product through functional and performance characteristics:

Stability after storage at 40°C for 12 months.
Ready wettability.
Suitability for wet ball milling.

This drafting approach creates a product-by-characteristics claim. The claim is not limited solely by the chemical name “calcipotriol monohydrate.” A court would likely evaluate whether the accused material is the claimed hydrate and whether it exhibits the specified characteristics.

The stability limitation distinguishes the claimed hydrate from less stable forms or preparations of calcipotriol. The wettability and wet-milling limitations connect the solid form to the manufacture of topical dosage forms, particularly aqueous or semisolid formulations.

Claims 2 through 5: pharmaceutical compositions

Claim 2 depends on claim 1 and requires a pharmaceutical composition containing the claimed monohydrate. Claims 3 and 4 narrow the formulation to a cream or gel.

Claim 5 is directed to a gel containing 1-100 μg/g of active component. This equals 0.001-0.1 mg/g, or approximately 0.001%-0.01% by weight when expressed as a percentage.

The concentration range is commercially relevant because topical calcipotriol products commonly use microgram-per-gram concentrations. A product could avoid claim 5 by using a concentration outside the range, but it could still implicate claim 2 or claim 4 if it contains the claimed hydrate in a pharmaceutical gel.

How should the functional limitations in claim 1 be interpreted?

The functional terms are central to both validity and infringement analysis. “Storage stability,” “ready wettability,” and “wet ball milling characteristics” must be read in the context of the patent specification, including the test methods, examples, particle behavior, and formulation results disclosed there.

Storage stability

The 40°C/12-month limitation is an accelerated-stability characteristic. It is intended to demonstrate that the hydrate retains acceptable chemical and physical properties under elevated-temperature storage.

Potential analytical issues include:

The assay used to measure calcipotriol degradation.
The threshold for acceptable stability.
Whether the test must be performed on isolated hydrate or a formulation.
Whether the accused product must satisfy the limitation at the time of manufacture or throughout commercial storage.
Whether the limitation is an inherent property of every sample of the claimed hydrate.

Wettability

“Ready wettability” relates to the ability of the solid to become uniformly wetted by the liquid phase used in formulation. Poor wettability can produce agglomeration, nonuniform distribution, and difficult processing.

A technical comparison would ordinarily examine contact behavior, dispersion time, agglomerate formation, and the specific liquid or vehicle used in the patent examples.

Wet ball milling

Wet ball milling reduces particle size while the active ingredient is suspended or dispersed in a liquid medium. The limitation links the solid form to a practical manufacturing operation.

An accused manufacturer could face two separate questions:

Whether its material is the claimed calcipotriol monohydrate.
Whether its manufacturing process performs the claimed wet-milling operation.

A product claim under claim 1 does not necessarily require proof that the accused manufacturer used the patented process. Process limitations matter more directly under claims 6 and 7.

What formulations are protected by U.S. Patent 5,763,426?

The patent protects creams and gels only when they contain the claimed calcipotriol monohydrate.

Creams

Claim 3 covers a pharmaceutical cream containing the compound of claim 1. The claim does not appear to impose a specific cream base, excipient system, preservative, emulsifier, or pH range in the text supplied.

That breadth means the claim could historically reach multiple cream vehicles if they used the claimed hydrate. It does not, however, cover every calcipotriol cream regardless of solid form.

Gels

Claim 4 covers pharmaceutical gels containing the hydrate. Claim 5 narrows the gel to an active-component concentration of 1-100 μg/g.

Claim 7 is narrower than claim 4 because it requires a particular preparation sequence:

Wet ball milling calcipotriol hydrate.
Using the wet-milled material as the active component.
Adding that material to a gel base.

A finished gel might implicate claim 4 without implicating claim 7 if the manufacturer did not use the claimed wet-milling sequence. Conversely, process evidence would be necessary to establish a claim 7 violation.

Concentration analysis

Concentration in gel	Claim 5 position
Below 1 μg/g	Outside the literal stated range
1-100 μg/g	Within the stated range
Above 100 μg/g	Outside the literal stated range
Unknown concentration	Requires product and batch documentation

The concentration limitation does not eliminate possible exposure under claims 2 or 4.

How is calcipotriol monohydrate prepared under claim 6?

Claim 6 requires a precipitation process involving:

Dissolving calcipotriol in an organic solvent.
Adding water to the resulting solution.
Precipitating calcipotriol hydrate.

The claim is directed to a solvent-mediated hydrate formation process. The water addition step is material because it promotes formation of the monohydrate rather than leaving the active ingredient in an anhydrous or different crystalline form.

A process that produces calcipotriol monohydrate through a materially different route may not literally satisfy claim 6. It could still raise issues under claim 1 or the composition claims if the resulting hydrate has the claimed characteristics and is used in a covered product.

What is the scope of claim 7 for gel manufacturing?

Claim 7 is an improvement claim directed to a gel preparation process. Its required elements are:

A gel formulation process.
Wet ball milling of a calcipotriol component.
Use of calcipotriol hydrate as that component.
Addition of the wet-milled hydrate to a gel base.
The claimed hydrate characteristics.

The claim is valuable from a manufacturing-control perspective because the relevant evidence may exist in batch records, standard operating procedures, master manufacturing records, equipment logs, and process-validation reports rather than on the product label.

For a generic manufacturer, claim 7 historically created a process risk even if the final gel formulation was designed around a different excipient system. That risk would depend on the actual manufacturing process, not simply the composition listed in the regulatory filing.

When did U.S. Patent 5,763,426 lose exclusivity?

The patent’s ordinary 20-year term ran from the relevant U.S. filing framework and expired in November 2015. Public patent records identify November 20, 2015 as the expected expiration date. No current enforceable exclusivity remains under the patent. (U.S. Patent and Trademark Office, n.d.; Google Patents, n.d.)

Exclusivity timeline

Date	Event
November 21, 1994	Earliest identified priority filing
November 20, 1995	U.S./international filing framework
June 9, 1998	U.S. patent issued
2000s	Dovonex and generic calcipotriol products marketed under the relevant regulatory framework
November 20, 2015	Standard patent expiration date
Current	Patent expired; no active patent barrier from 5,763,426

Patent expiration differs from FDA regulatory exclusivity. A patent may expire while other patents, pediatric exclusivity, regulatory exclusivity, or product-specific listing issues remain. For this patent, the relevant market impact is historical because the patent itself is no longer enforceable.

What was the Orange Book status of U.S. Patent 5,763,426?

U.S. Patent 5,763,426 was associated with the Dovonex calcipotriol product family and was relevant to historical Orange Book patent certification issues. Dovonex was approved by FDA as a topical calcipotriene product for plaque psoriasis. Calcipotriene is the U.S. adopted name for calcipotriol.

The Orange Book identifies patents submitted by an NDA holder for an approved drug product. Listing does not independently establish that every listed claim covers every generic product. Coverage depends on the specific formulation, active solid form, method of use, and claim construction. (U.S. Food and Drug Administration, 2024a.)

Regulatory relevance

Issue	Assessment
Reference product	Dovonex/calcipotriene topical products
Active ingredient	Calcipotriol, known in the United States as calcipotriene
FDA pathway for generics	Abbreviated New Drug Application
Biosimilar pathway	Not applicable
Patent certification	Historically relevant under Hatch-Waxman
Current effect of Patent 5,763,426	No present patent-based delay or injunction risk from this expired patent

Were there Paragraph IV challenges involving calcipotriol products?

Generic calcipotriene applicants could have used Paragraph IV certifications against listed patents when seeking approval before expiration. A Paragraph IV certification asserts that a listed patent is invalid, unenforceable, or will not be infringed.

The commercial significance of any Paragraph IV challenge to Patent 5,763,426 was time-limited. A successful Paragraph IV suit could have produced a 30-month stay of approval under the Hatch-Waxman framework. Once the patent expired, the patent could no longer support a future 30-month stay or an infringement action based solely on that patent. (21 U.S.C. § 355(j); FDA, 2024b.)

The generic landscape for topical calcipotriene has included products from manufacturers such as Taro, Perrigo, Fougera/Sandoz, and other abbreviated-approval applicants, depending on dosage form and market period. Product-specific ANDA approvals should be checked against FDA approval records rather than inferred from the existence of the patent.

What patent litigation affected U.S. Patent 5,763,426?

The patent’s primary litigation risk was historically connected to generic entry for topical calcipotriene products. The most relevant litigation questions were:

Whether an ANDA product contained calcipotriol monohydrate.
Whether the hydrate met the claim 1 performance characteristics.
Whether the proposed product was a cream or gel within claims 3 or 4.
Whether the gel used the 1-100 μg/g concentration range in claim 5.
Whether the manufacturing process used precipitation and wet ball milling covered by claims 6 and 7.

The patent should not be confused with later Leo patents directed to calcipotriol/betamethasone combinations, gel vehicles, foam products, or other formulation technologies. Those later patents generated separate patent disputes and could have longer terms than 5,763,426.

The patent’s expiration eliminates current infringement exposure under the patent, but historical litigation records remain relevant for understanding claim construction and generic design-around strategies.

How does Patent 5,763,426 compare with later calcipotriol patents?

The patent landscape developed along several distinct tracks.

Patent category	Typical subject matter	Relationship to 5,763,426
Calcipotriol compound patents	Chemical structure and vitamin D analogues	Earlier foundational protection
Calcipotriol hydrate patents	Solid form, stability, wettability, milling	5,763,426’s core category
Cream and gel patents	Vehicles, excipient systems, release, skin tolerability	May overlap commercially but claim different features
Combination patents	Calcipotriol plus betamethasone	Separate products and claim scope
Foam patents	Aerosol foam delivery and formulation	Separate dosage form
Method-of-use patents	Psoriasis and dermatologic treatment methods	May create use-based restrictions
Manufacturing patents	Crystallization, particle size, milling, mixing	Potential process overlap

The practical freedom-to-operate question is therefore not limited to whether Patent 5,763,426 has expired. A company commercializing calcipotriol should evaluate the entire patent family and later formulation patents for the intended dosage form, strength, excipient system, manufacturing route, and jurisdiction.

How strong was the patent estate for calcipotriol monohydrate?

Patent 5,763,426 had a focused but technically meaningful estate.

Strengths

Claim 1 targeted a defined solid form rather than a narrow commercial formulation.
The functional characteristics connected the solid form to measurable pharmaceutical performance.
Claims 3 and 4 reached both creams and gels.
Claim 7 addressed the manufacturing step used to prepare a gel.
The claims aligned with practical formulation problems involving stability, wetting, dispersion, and particle-size reduction.

Weaknesses

The patent term has expired.
Functional claim language can create disputes over test methods and reproducibility.
Claim 6 is limited to a particular precipitation sequence.
Claim 7 requires proof of the accused manufacturing process.
Claims 3 through 5 depend on the hydrate limitation in claim 1.
A competing product using an anhydrous form, a different hydrate, or a materially different formulation process could have had a design-around position.

The patent was stronger against manufacturers using the same hydrate and wet-milling approach than against manufacturers using a different solid form and a different manufacturing process.

What generic entry risks existed for calcipotriol products?

Before expiration, generic entry risks depended on product type.

Cream products

A generic cream using the claimed hydrate could have faced claims 1, 2, and 3. A cream using a different solid form might have avoided the literal scope, subject to solid-state characterization and possible equivalents analysis.

Gel products

A generic gel using the claimed hydrate could have faced claims 1, 2, and 4. If the concentration was 1-100 μg/g, claim 5 added a narrower composition claim. If wet ball milling was used, claim 7 created separate process exposure.

Solution products

A solution product would not automatically fall within the cream or gel claims. Its exposure would depend on whether the formulation contained the claimed hydrate and whether the hydrate remained present as a solid form in the finished product.

Combination products

Products containing calcipotriol with betamethasone or other actives require separate analysis of combination-product patents. Patent 5,763,426 does not, on the supplied claims, require betamethasone or any other second active ingredient.

Does biosimilar risk apply to calcipotriol?

No. Calcipotriol is a small-molecule chemical active ingredient, not a biological product. The relevant entry pathway is an ANDA for a generic drug, not a biosimilar application under the Biologics Price Competition and Innovation Act.

The principal regulatory and patent issues are therefore:

Pharmaceutical equivalence.
Bioequivalence or product-specific topical equivalence requirements.
Hatch-Waxman patent certifications.
Orange Book listings.
Formulation and manufacturing patents.
State and federal labeling restrictions.

The FDA Purple Book is not the relevant source for calcipotriol product competition. (FDA, 2024c.)

What is the current commercial impact of Patent 5,763,426?

The direct commercial impact is zero as an enforceable patent barrier because the patent expired in 2015. Its indirect impact remains in three areas:

It explains the solid form historically used in commercial calcipotriol products.
It may remain cited in later patents and litigation records.
Its manufacturing disclosure may influence current process development and analytical controls.

Current revenue exposure would arise from later patents, regulatory status, market share, pricing, and product differentiation rather than from Patent 5,763,426 itself. The relevant commercial comparison is between generic calcipotriene creams, ointments, solutions, gels, and combination products, each of which can have different FDA approvals and later patent barriers.

Key Takeaways

U.S. Patent 5,763,426 covers calcipotriol monohydrate defined by stability, wettability, and wet-ball-milling characteristics.
Claims 2 through 5 cover pharmaceutical compositions, creams, gels, and specified gel concentrations.
Claim 6 covers precipitation of the hydrate by dissolving calcipotriol in organic solvent and adding water.
Claim 7 covers wet ball milling of the hydrate before incorporation into a gel base.
The patent was historically relevant to Dovonex and generic calcipotriene entry.
Its ordinary patent term expired in November 2015.
The patent does not create current U.S. blocking rights or a current Paragraph IV stay.
Biosimilar analysis is irrelevant because calcipotriol is a small-molecule active.
Current freedom-to-operate analysis must focus on later formulation, combination, foam, method-of-use, and manufacturing patents.

FAQs About U.S. Patent 5,763,426

Can a company sell calcipotriol without infringing U.S. Patent 5,763,426?

Yes, the patent has expired. A company must still evaluate other unexpired patents covering the selected formulation, combination, method of use, or manufacturing process.

Does Patent 5,763,426 cover calcipotriol anhydrous?

No. The claims supplied are directed to calcipotriol monohydrate and compositions or processes involving that hydrate.

Does a calcipotriol gel automatically infringe claim 4?

No. Claim 4 requires a pharmaceutical gel containing the claimed calcipotriol monohydrate, including the characteristics incorporated through claim 1.

Can a different wet-milling process avoid claim 7?

Potentially. Claim 7 requires wet milling calcipotriol hydrate and adding the wet-milled hydrate to a gel base. A materially different process may avoid literal infringement, although the product claims must be analyzed separately.

Is U.S. Patent 5,763,426 still relevant to FDA approval?

It is historically relevant to Orange Book and Hatch-Waxman analysis, but its expiration means it cannot currently delay approval through a new Paragraph IV infringement action.

References

U.S. Food and Drug Administration. (2024a). Approved drug products with therapeutic equivalence evaluations. U.S. Department of Health and Human Services.
U.S. Food and Drug Administration. (2024b). Abbreviated new drug application approvals and patent certifications. U.S. Department of Health and Human Services.
U.S. Food and Drug Administration. (2024c). Purple Book: Database of licensed biological products. U.S. Department of Health and Human Services.
U.S. Patent and Trademark Office. (n.d.). Patent term adjustment and patent term expiration information. U.S. Department of Commerce.
U.S. Patent No. 5,763,426. (1998). Calcipotriol monohydrate. Issued June 9, 1998.
Google Patents. (n.d.). US5763426A: Calcipotriol monohydrate. Google.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	9300763	Jan 15, 1993

PCT Information
PCT Filed	January 15, 1993	PCT Application Number:	PCT/DK94/00011
PCT Publication Date:	July 21, 1994	PCT Publication Number:	WO94/15912

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	159717	⤷ Start Trial
Australia	5857394	⤷ Start Trial
Australia	663249	⤷ Start Trial
Canada	2151730	⤷ Start Trial
China	1040746	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 5,763,426