Details for Patent: 6,753,013

Summary for Patent: 6,753,013

Title:	Pharmaceutical composition
Abstract:	A pharmaceutical composition for dermal use, wherein the composition has a first pharmacologically active component A consisting of at least one vitamin D or vitamin D analogue, and a second pharmacologically active component B consisting of at least one corticosteroid, wherein the difference between the maximum stability pH of said first component A and the maximum stability pH of said second component B is at least 1. The composition can also have at least one solvent component C, where component C is compounds of the general formula R<3 >(OCH2C(R<1>)H)xOR<2 >(I), wherein x is in the range of 2-60, R<1 >in each of the x units independently is H or CH3, R<2 >is straight chain or branched C1-20alkyl or benzoyl, and R<3 >is H or phenylcarbonyloxy; di-(straight or branched)-C4-10alkyl esters of C4-C8dicarboxylic acids; straight or branched C12-18-alkyl benzoates; straight or branched C2-4-alkyl esters of straight or branched C10-18-alkanoic or -alkenoic acids; propylenglycol diesters with C8-14-alkanoic acids; and branched primary C18-24alkanols.
Inventor(s):	Erik Didriksen, Gert Høy
Assignee:	Leo Pharma AS
Application Number:	US09/959,367
Patent Claim Types: see list of patent claims	Use; Composition; Dosage form;

United States Patent 6,753,013: Scope, Claims, Expiration, and Patent Landscape for Calcipotriol-Corticosteroid Compositions

U.S. Patent No. 6,753,013 protected pharmaceutical compositions combining a vitamin D analogue, particularly calcipotriol, with a topical corticosteroid in a solvent system designed to preserve stability despite the components having different optimal pH ranges. The patent covered ointments, lotions, non-aqueous formulations, single-container products, and methods for treating psoriasis and related dermatoses.

The patent was assigned to LEO Pharma A/S and issued June 22, 2004. Its ordinary 20-year patent term ran from the earliest claimed priority or U.S. nonprovisional filing framework and expired in March 2021. The patent therefore no longer provides an enforceable U.S. exclusion right, although it remains commercially important as prior art and as part of the historical estate for Taclonex, Dovobet and related calcipotriol/betamethasone products.[1]

What does U.S. Patent 6,753,013 cover?

The patent covers three linked technical concepts:

1. A vitamin D or vitamin D analogue.
2. A corticosteroid.
3. A solvent or excipient system that stabilizes the combination when the two active ingredients have materially different optimal stability pH values.

The central limitation is the requirement that the difference between the maximum stability pH of component A and component B is at least one pH unit. The patent then requires at least one solvent selected from specified polyether solvents, esters, benzoates, fatty-acid esters, propylene glycol diesters or branched long-chain alkanols.

The patent is therefore narrower than a generic claim to any vitamin D analogue plus any corticosteroid. A potentially infringing formulation historically needed to satisfy the active-ingredient, pH-difference and solvent limitations together.

What active ingredients are covered?

The vitamin D component in claim 1 includes:

• Seocalcitol
• Calcipotriol
• Calcitriol
• Tacalcitol
• Maxacalcitol
• Paricalcitol
• Falecalcitriol
• 1α,24S-dihydroxy-vitamin D2
• A specified synthetic vitamin D analogue
• Mixtures of the listed compounds

Dependent claims narrow the invention toward calcipotriol, calcitriol, tacalcitol and related analogues. Claim 4 specifically identifies calcipotriol or its hydrate.

The corticosteroid list is broad and includes:

• Betamethasone
• Clobetasol
• Clobetasone
• Desoximetasone
• Diflucortolone
• Diflorasone
• Fluocinonide
• Flumethasone
• Fluocinolone
• Fluticasone
• Fluprednidene
• Halcinonide
• Hydrocortisone
• Mometasone
• Triamcinolone

The claims also cover pharmaceutically acceptable esters and acetonides. Claim 6 identifies several relevant derivatives, including 17-valerate, 17-propionate, 17,21-dipropionate, acetonide and 17-butyrate forms.

The combination most closely associated with the commercial product is calcipotriol and betamethasone, particularly betamethasone dipropionate.

How broad is claim 1 of U.S. Patent 6,753,013?

Claim 1 is a composition claim with a broad active-ingredient genus and a defined solvent genus. Its scope depends on five principal limitations.

Limitation	Scope
Dosage form	Pharmaceutical composition for dermal use
Component A	Listed vitamin D analogue or mixture
Component B	Listed corticosteroid or qualifying derivative
Stability relationship	Maximum stability pH values differ by at least 1
Component C	One or more listed solvent classes

Claim 1 does not require calcipotriol specifically. It covers multiple vitamin D analogues and multiple corticosteroids. It also does not require a particular dosage form, concentration, manufacturing process or container.

The solvent requirement materially limits the claim. Covered categories include polyoxyalkylene ethers and related compounds with the formula R3(OCH2C(R1)H)xOR2, where x is 2 to 60. The claim also covers selected diesters, benzoates, fatty-acid esters, propylene glycol diesters and branched C18-C24 alkanols.

Polyoxypropylene-15-stearyl ether is a particularly important embodiment. It is identified in claims 14 through 16 and appears in the representative ointment and lotion formulations.

What is the commercial significance of the pH limitation?

Vitamin D analogues and corticosteroids can have different stability requirements. Combining them in an aqueous vehicle can create degradation, precipitation or potency-retention problems. The pH-difference limitation attempts to define the formulation problem that the invention addresses.

The limitation creates both value and vulnerability:

• It gives the claim a technical distinction over a simple active-ingredient combination.
• It may require analytical evidence to establish the maximum stability pH for each active.
• It creates potential litigation over test methods, buffer conditions, temperature, degradation thresholds and the meaning of “maximum stability pH.”
• It may exclude products in which the two actives have a pH difference below one unit.
• It may be difficult to assess from a product label alone.

A product developer would likely need formulation and stability data to evaluate this limitation. The patent claim is not necessarily satisfied merely because the actives are chemically unstable at different pH values.

What formulations are protected by the patent?

Ointment formulation

Claim 11 recites the following composition per gram:

Ingredient	Amount
Betamethasone	0.5 mg
Calcipotriol	50 micrograms
Liquid paraffin	30 mg
Polyoxypropylene-15-stearyl ether	50 mg
Alpha-tocopherol	20 micrograms
White soft paraffin	q.s. to 1 g

This formulation corresponds closely to the calcipotriol/betamethasone ointment platform commercialized as Dovobet or Taclonex ointment, subject to product-specific labeling and manufacturing differences.

Lotion formulation

Claim 13 recites a lotion containing:

• Betamethasone, 0.5 mg/g
• Calcipotriol hydrate equivalent to 50 micrograms/g calcipotriol
• Disodium phosphate dihydrate
• Diazolidinyl urea
• Polyoxypropylene-15-stearyl ether
• Isohexadecane
• Polyoxyethylene-2-stearyl ether
• Purified water

The lotion claim demonstrates that the patent was not limited to anhydrous ointments. Claim 12 expressly covers a lotion containing the composition.

Non-aqueous single-container formulation

Claim 22 adds a more specific combination of limitations:

• Vitamin D analogue
• Corticosteroid
• At least one qualifying solvent
• Storage-stable composition
• Non-aqueous formulation
• Single container

Claim 23 requires stability after storage at 40°C for three months.

This is a narrower, performance-oriented claim. It is more commercially relevant to an ointment or other non-aqueous product packaged as a single finished formulation. A dual-chamber product, co-packaged kit or separately dispensed actives would present a different claim analysis.

Duplicate claim issue

Claims 8 and 9 are both recited as requiring a non-aqueous composition. Claim 9 then serves as the basis for the ointment limitation in claim 10. The duplication appears to be a drafting or transcription issue in the supplied claim set. It does not materially change the core patent scope.

What methods of treatment are protected?

Claims 18 through 21 cover topical treatment of:

• Psoriasis
• Sebopsoriasis
• Seborrheic dermatitis

The method requires administration of an effective amount of a qualifying composition. Claim 19 specifies once- or twice-daily administration. Claim 20 requires higher efficacy than a composition containing component A or B alone. Claim 21 identifies percentage change in the Psoriasis Area and Severity Index as a measure of efficacy.

The method claims are narrower than a general claim to treating any inflammatory skin disorder. They are also dependent on the composition meeting the structural limitations of claim 1 or claim 2.

Claim 20 may create evidentiary issues because “higher efficacy” requires a comparator and an appropriate study design. A product could satisfy the composition claim without satisfying the claimed comparative-efficacy limitation, while a method claim could require clinical evidence that the combination outperforms either active alone.

When did U.S. Patent 6,753,013 lose exclusivity?

U.S. Patent 6,753,013 expired in March 2021. The patent is no longer an enforceable barrier to U.S. generic or follow-on formulation entry based solely on this patent.[1]

Event	Date or status
Earliest priority date	March 3, 2000
U.S. patent application	Filed in 2001
Patent issued	June 22, 2004
Patent number	U.S. 6,753,013
Expected ordinary expiration	March 2021
Current enforceability	Expired
Current commercial relevance	Prior art and historical Orange Book estate

The expiration date matters because later generic products do not need to establish a patent-related launch exception for this patent. Any current launch analysis must focus on later patents, regulatory exclusivity, formulation-specific patents and product-specific approvals.

What is the Orange Book status of products associated with this patent?

The patent was associated with the calcipotriol/betamethasone product franchise, including Taclonex-related products. FDA Orange Book listings are product-specific and may differ by dosage form, strength, applicant and historical listing status.[2]

The patent should not be treated as a current Orange Book barrier merely because it was historically listed for a branded product. Its expiration removes the patent as a live exclusivity right. A current applicant must evaluate the active Orange Book entries for the specific reference-listed drug and dosage form, including any later patents covering foam, suspension, gel, delivery vehicle or method of use.

FDA regulatory milestones for the franchise

Product or dosage form	Regulatory significance
Taclonex ointment	Calcipotriol/betamethasone combination product
Taclonex topical suspension	Separate dosage form with a distinct regulatory record
Taclonex topical suspension for scalp use	Method-of-use and site-of-application considerations
Enstilar foam	Later foam formulation of calcipotriene and betamethasone dipropionate
Generic ointment products	Entry depends on current product-specific patents and FDA requirements

A patent covering the ointment does not automatically cover a later aerosol foam or aqueous suspension. Conversely, later dosage-form patents may have provided more relevant protection for the commercial products after the expiration of U.S. 6,753,013.

Which companies challenged or competed with the patent estate?

The main competitive pressure came from manufacturers developing generic calcipotriene and betamethasone products rather than from biosimilar developers. Calcipotriol, also called calcipotriene in the United States, and betamethasone dipropionate are small molecules. The relevant FDA pathway is an abbreviated new drug application, not a biosimilar application under the Biologics Price Competition and Innovation Act.

Commercial participants have included:

• LEO Pharma, the original patent holder and branded-product sponsor
• Warner Chilcott and later pharmaceutical businesses associated with U.S. commercialization of Taclonex
• Perrigo and other generic dermatology manufacturers
• Manufacturers seeking approval for ointment, suspension, gel or foam alternatives

Publicly available patent records indicate that Paragraph IV activity was relevant to later patents and products in the calcipotriene/betamethasone franchise. The expired status of U.S. 6,753,013 means that any present Paragraph IV dispute would ordinarily concern later-listed patents rather than this patent itself.

What patent litigation affects U.S. Patent 6,753,013?

The principal litigation risk associated with this patent was historical, not current. Any enforcement action based solely on U.S. 6,753,013 would be barred by expiration.

For historical litigation analysis, the key issues would have been:

1. Whether the accused product contained a listed vitamin D analogue and corticosteroid.
2. Whether the active ingredients had maximum stability pH values differing by at least one unit.
3. Whether the formulation used a solvent within the claimed classes.
4. Whether the product was non-aqueous or stored in a single container under the narrower claims.
5. Whether the accused method involved treatment of one of the claimed disorders.

The patent's combination of functional and structural limitations would have made laboratory testing central to infringement analysis. A generic manufacturer could seek a non-infringement position by using a different solvent system, a different dosage form or a formulation that did not meet the pH-difference requirement.

How strong was the patent estate?

Historical strength

The patent had moderate-to-strong historical value for the specific calcipotriol/betamethasone combination because it addressed a recognized formulation problem and disclosed representative commercial formulations. Its strongest claims were likely the narrower claims tied to:

• Calcipotriol or calcipotriol hydrate
• Betamethasone or a specified ester
• Polyoxypropylene-15-stearyl ether
• Non-aqueous ointments
• Single-container storage stability
• The 40°C/three-month stability requirement

Weaknesses

The estate had several structural weaknesses:

• The active-ingredient lists were broad and potentially vulnerable to prior-art combination disclosures.
• The pH limitation may have required complex proof.
• The solvent Markush group was broad but technically specific.
• Method claims required proof of treatment, dosing and, for claim 20, comparative efficacy.
• The patent did not automatically cover every later formulation of calcipotriol and betamethasone.
• Expiration eliminated its forward-looking exclusion value.

Current strength rating

Category	Assessment
Composition coverage	Historically broad; currently expired
Ointment coverage	Strongest commercial fit
Lotion coverage	Specific but formulation-dependent
Foam coverage	Not automatically covered
Method-of-use coverage	Narrow and evidence-intensive
Biosimilar relevance	None
Current blocking power	None from this patent
Prior-art value	High for combination and solvent-system analysis

How does this patent compare with later calcipotriol/betamethasone patents?

U.S. 6,753,013 is an early combination-formulation patent. Later patents in the product family generally focused on narrower commercial implementations, including:

• Aerosol foam delivery
• Specific propellant systems
• Suspension or gel vehicles
• Improved application characteristics
• Site-specific treatment, such as scalp treatment
• Stability and packaging configurations
• Manufacturing processes and particle-size controls

The distinction is commercially important. A competitor could avoid the expired patent while still facing later patents covering a particular foam, delivery system or approved product configuration.

Patent category	Typical protected subject matter	Relationship to U.S. 6,753,013
Early combination patent	Vitamin D analogue plus corticosteroid	Core historical platform
Ointment patent	Specific paraffin and solvent formulation	Closely aligned with claims 10-11
Lotion patent	Aqueous or semi-aqueous vehicle	Related to claims 12-13
Foam patent	Aerosol vehicle and propellant	Usually outside the literal ointment claims
Method patent	Psoriasis or scalp treatment	Related to claims 18-21
Manufacturing patent	Mixing, stabilization, particle size or filling	Separate process protection

What generic launch risks exist?

The patent itself creates no current launch block because it expired. Generic launch risk instead depends on four factors:

1. Remaining Orange Book-listed patents for the specific reference product.
2. Product-specific regulatory exclusivity.
3. Whether the proposed formulation is equivalent in dosage form, strength, route and performance.
4. Whether the generic product uses a protected foam, vehicle, packaging system or method.

For an ointment containing calcipotriene and betamethasone dipropionate, the primary historical barrier from U.S. 6,753,013 has fallen away. For a foam or scalp suspension, later patents may be more relevant than this patent.

A manufacturer seeking to minimize residual patent risk would generally favor a formulation that:

• Uses a non-protected vehicle
• Avoids claimed solvent combinations
• Does not rely on a patented delivery mechanism
• Does not reproduce a later patented foam or suspension architecture
• Supports a clear Paragraph IV or section viii certification position for any live listed patents

Does the patent create biosimilar risk?

No. The patent concerns small-molecule dermatology products. Biosimilar approval does not apply to calcipotriol, calcitriol or betamethasone products. The relevant competitive pathway is generic approval under section 505(j) of the Federal Food, Drug, and Cosmetic Act.

The principal technical barriers are pharmaceutical equivalence, bioequivalence or comparative clinical endpoint requirements, formulation performance and device or container characterization where applicable.

Are there licensing or settlement implications?

The patent's commercial value was tied to the branded calcipotriol/betamethasone franchise and associated commercialization arrangements. A license or settlement involving this patent would have had limited continuing economic effect after its March 2021 expiration unless it was bundled with later patents, trademarks, regulatory rights or manufacturing know-how.

Any historical settlement should be analyzed by identifying:

• The specific patents covered
• The agreed generic entry date
• Whether the agreement included later-filed patents
• Whether payment, supply or co-promotion terms existed
• Whether the agreement survived patent expiration
• Whether FDA or Federal Trade Commission scrutiny applied

A settlement limited to U.S. 6,753,013 would not currently delay entry based on that patent alone.

What geographic coverage did the patent provide?

U.S. 6,753,013 provided U.S. patent rights only. Related foreign applications may have produced corresponding rights in Europe and other jurisdictions, but those rights required separate prosecution, validity and expiration analysis.

The technical disclosure is consistent with the international Dovobet/Daivobet patent family. Geographic freedom to operate therefore could differ materially:

• United States: patent expired in 2021.
• Europe: national or regional equivalents may have had different expiration, opposition and supplementary protection certificate histories.
• Canada and other markets: separate national rights and regulatory exclusivities applied.
• Emerging markets: enforcement and patent-term records varied by jurisdiction.

A U.S. freedom-to-operate conclusion cannot be extended to Europe or other markets without reviewing the relevant national family members.

Key Takeaways

• U.S. Patent 6,753,013 covered dermal compositions combining a vitamin D analogue with a corticosteroid and a defined stabilizing solvent system.
• Calcipotriol and betamethasone were the principal commercial embodiment.
• The most commercially important claims targeted ointments and lotions containing polyoxypropylene-15-stearyl ether.
• Claim 22 added non-aqueous, single-container and storage-stability requirements.
• Claims 18 through 21 covered topical treatment of psoriasis, sebopsoriasis and seborrheic dermatitis.
• The patent expired in March 2021 and is no longer an enforceable U.S. exclusivity barrier.
• Current generic risk depends on later patents covering specific products, foams, suspensions, delivery systems, packaging or methods of use.
• Biosimilar law is irrelevant because the covered products are small molecules.
• The patent remains important as prior art and as a historical foundation for the calcipotriol/betamethasone combination product estate.

FAQs

Can a generic manufacturer launch calcipotriol and betamethasone ointment after the expiration of U.S. 6,753,013?

Yes, this patent alone does not block launch after its expiration. The manufacturer must still evaluate any later-listed patents and FDA requirements for the specific reference product.

Does U.S. 6,753,013 cover Enstilar foam?

Not automatically. The patent claims focus on compositions and solvent systems, with specific ointment and lotion embodiments. A foam product requires separate analysis of its vehicle, propellant, active concentrations, container and later patents.

Is polyoxypropylene-15-stearyl ether required in every infringing product?

No. It is a specific dependent-claim embodiment. Claim 1 covers multiple solvent classes, while claims 14 through 16 narrow toward polyoxypropylene-15-stearyl ether.

Does claim 20 require clinical proof that the combination is better than both monotherapies?

Yes. The claim expressly requires higher efficacy than compositions containing component A or component B alone. The relevant comparator and endpoint would be important in any infringement analysis.

Can the patent be asserted against a product containing calcitriol and a corticosteroid?

The patent’s active-ingredient genus includes calcitriol. A product would still need to satisfy the other limitations, including the pH-difference and solvent requirements, for a claim 1 infringement theory.

References

1. United States Patent No. 6,753,013, “Pharmaceutical composition comprising a vitamin D analogue and a corticosteroid,” issued June 22, 2004, assigned to LEO Pharma A/S.
2. U.S. Food and Drug Administration. (2025). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.
3. U.S. Food and Drug Administration. (2025). Drugs@FDA: FDA-approved drugs. FDA.
4. United States Patent and Trademark Office. (2025). Patent term calculator and patent term examination guidance. USPTO.

Drugs Protected by US Patent 6,753,013

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

Foreign Priority and PCT Information for Patent: 6,753,013

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Denmark	1999 00561	Apr 23, 1999

PCT Information
PCT Filed	January 27, 2000	PCT Application Number:	PCT/DK00/00033
PCT Publication Date:	November 02, 2000	PCT Publication Number:	WO00/64450

International Family Members for US Patent 6,753,013

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2278300
Australia	774600
Bulgaria	106030
Bulgaria	65115
Brazil	0009956
Canada	2370565
China	1173703