United States Patent 6,765,001: Claim Scope, Fluocinonide Formulation Coverage, and Patent Landscape

U.S. Patent No. 6,765,001 covers high-penetration topical corticosteroid compositions, particularly fluocinonide formulations containing multiple penetration enhancers. Its central limitation is a composition in which penetration enhancers account for at least about 90% of the combined penetration-enhancer, solvent, and emulsifier fraction. The patent is directed primarily to formulation architecture, not to fluocinonide as an active ingredient.

The patent’s 20-year statutory term reached its end in approximately 2020, based on its earliest relevant U.S. filing period. It therefore does not present a current U.S. patent barrier to generic fluocinonide formulations, although historical infringement and product-development questions remain relevant.

What does U.S. Patent 6,765,001 protect?

Claim 1 establishes five core requirements:

The composition must contain one or more corticosteroids.
At least one corticosteroid must be fluocinonide.
The composition must contain at least two listed penetration enhancers.
The formulation must contain solvents, emulsifiers, or both.
Penetration enhancers must constitute at least about 90% of the combined penetration-enhancer, solvent, and emulsifier fraction.

The listed penetration enhancers are:

Diisopropyl adipate
Dimethyl isosorbide
Propylene glycol
1,2,6-hexanetriol or the corresponding trihydroxyhexane nomenclature
Benzyl alcohol

The claim is composition-based. It does not require a particular manufacturing process, package, indication, patient population, or therapeutic result.

What is the key numerical limitation?

The operative ratio is:

[ \frac{\text{penetration enhancers}}{\text{penetration enhancers + solvents + emulsifiers}} \geq 0.90 ]

A formulation may contain large quantities of petrolatum, water, carbomer, fatty alcohols, preservatives, or other excipients, provided those ingredients are not counted as solvents or emulsifiers for purposes of the claimed ratio.

This classification issue is central. A formulation can avoid literal infringement if an ingredient characterized by the patent owner as a solvent or emulsifier causes the ratio to fall below 0.90. Conversely, a generic manufacturer could face a claim if it classifies the same ingredient as a non-solvent or non-emulsifier while the patent owner argues that the ingredient belongs within the denominator.

How do claims 2 through 13 narrow the patent?

Claims 2 through 13 add concentration, ingredient, and composition limitations.

Claim	Additional limitation	Commercial significance
2	Corticosteroid at about 0.10%	Targets low-strength fluocinonide formulations, including the concentration associated with Vanos-type products
3	Corticosteroid at about 0.50%	Covers a higher steroid concentration
4	Corticosteroid at about 0.25%	Covers an intermediate concentration
5	At least two enhancers selected from propylene glycol, diisopropyl adipate, and dimethyl isosorbide	Narrows the enhancer combination
6	One penetration enhancer is propylene glycol	Broadens practical coverage because propylene glycol is common in topical products
7	Ratio of at least about 0.95	Creates a narrower, stronger numerical limitation
8	Specified solvents and emulsifiers	Provides an ingredient-based subgenus
9	One or more non-solvent/emulsifier ingredients	Separates formulation bulk excipients from the ratio calculation
10	Specified non-solvent/emulsifier ingredients	Covers carbomer, petrolatum, glyceryl stearate, water, fatty alcohols, and related excipients
11	Solvents and emulsifiers at about 4% to about 5%	Narrows the formulation profile
12	Non-solvent/emulsifier ingredients at about 11% to about 53%	Broad excipient range
13	Non-solvent/emulsifier ingredients at about 11% to about 27%	Narrower excipient range

Claims 2 through 4 are alternative concentration claims. They do not require all three concentrations. A product containing 0.10% fluocinonide can implicate claim 2 without implicating claims 3 or 4.

Claim 7 is particularly important because it raises the enhancer ratio from approximately 90% to approximately 95%. A product that fails the 0.95 threshold could still fall within claim 1 if it meets the 0.90 threshold.

What formulations are protected by claims 14 through 17?

Claims 14 through 17 are formulation-specific claims. They recite detailed ingredient lists and approximate percentages.

Claim 14

Claim 14 covers a 0.10% fluocinonide formulation containing, among other ingredients:

Approximately 74.9% propylene glycol
Approximately 3.0% diisopropyl adipate
Approximately 2.5% 1,2,6-trihydroxyhexane
Approximately 5.0% isopropyl myristate
Carbopol 980
Diisopropanolamine/propylene glycol
Glyceryl monostearate
PEG stearate
Purified water
Citric acid

The formulation is a high-propylene-glycol emulsion or semisolid system with multiple penetration enhancers.

Claim 15

Claim 15 substitutes a high dimethyl-isosorbide concentration for much of the propylene glycol:

Approximately 0.10% fluocinonide
Approximately 70.0% propylene glycol
Approximately 15.0% dimethyl isosorbide
Carbopol 980
Diisopropanolamine/propylene glycol
Glyceryl monostearate and PEG stearate
Water and citric acid

This claim is significant because dimethyl isosorbide is a recognized dermal penetration enhancer and can materially change solvent capacity, skin partitioning, and product feel.

Claim 16

Claim 16, as reproduced in the supplied text, lists approximately 60% glyceryl monostearate in addition to approximately 66.8% propylene glycol and other ingredients. Those percentages exceed 100% when added together. The internal total is approximately 154%.

That figure is chemically and legally problematic. It is likely a transcription error, with “60% glyceryl monostearate” possibly intended to read “6.0%.” Claim analysis should rely on the issued patent text rather than a secondary transcription.

Claim 17

Claim 17 covers a 0.10% fluocinonide formulation containing:

Approximately 69.9% propylene glycol
Approximately 2.0% diisopropyl adipate
Approximately 5.0% isopropyl myristate
Approximately 5.0% white petrolatum
Approximately 6.0% glyceryl monostearate
Approximately 6.0% PEG-100 stearate
Approximately 5.0% stearyl alcohol
Carbopol 980 and diisopropanolamine/propylene glycol

The listed percentages total approximately 100%. Claim 17 is narrower than claim 1 because it requires the recited ingredient set and approximate concentrations.

How strong is the patent estate for fluocinonide topical products?

The patent estate was technically focused but commercially relevant during its term.

Strengths

The patent had several commercially useful characteristics:

It covered compositions rather than only a particular brand.
It identified multiple enhancer combinations.
It included propylene glycol, a common formulation component.
It claimed both broad ratio ranges and detailed formulation examples.
It included dependent claims directed to 0.10% fluocinonide.
It potentially covered formulations with different non-solvent excipient systems.

Weaknesses

The principal weaknesses were claim-construction and validity risks:

The 90% ratio depends on classifying ingredients as penetration enhancers, solvents, or emulsifiers.
The phrase “about” creates numerical scope but also introduces boundary disputes.
Some listed ingredients may fit more than one functional category.
The claims may face written-description or enablement scrutiny across broad combinations of enhancers and excipients.
The detailed claims are easier to design around by changing enhancer identity, concentration, or excipient classification.
The patent does not broadly cover every fluocinonide topical formulation.

The broadest practical design-around routes would include using only one listed enhancer, substituting an enhancer not named in the claims, reducing the enhancer fraction below the required threshold, or changing the active ingredient concentration and excipient system.

When did U.S. Patent 6,765,001 lose exclusivity?

The patent’s ordinary 20-year term expired approximately 20 years after its earliest effective nonprovisional filing date. Because U.S. Patent No. 6,765,001 issued in 2004, its remaining term was not determined by the issue date. The controlling date was the earliest applicable U.S. nonprovisional or international filing date under 35 U.S.C. §154.

The patent therefore ceased to provide enforceable ordinary U.S. exclusion rights in approximately 2020, subject to any patent-term adjustment reflected in the USPTO patent record. No current generic launch strategy should treat the expired patent as a live blocking right.

What was the Orange Book status of the patent?

The patent’s commercial relevance was associated with topical fluocinonide products, particularly 0.1% fluocinonide cream products. Orange Book relevance depends on whether the patent was submitted for listing against a specific approved new drug application and whether the listing remained active.

A formulation patent does not automatically appear in the Orange Book. The NDA holder must submit the patent for listing, and the FDA must list it against the relevant drug product. Orange Book listing also does not establish validity or infringement. It creates a regulatory pathway for patent certifications by ANDA applicants under the Hatch-Waxman Act. FDA Orange Book records and the relevant NDA patent listing history are the controlling sources for listing status. [FDA, 2024a]

Because U.S. Patent 6,765,001 has reached the end of its ordinary patent term, an Orange Book listing would not create a current enforceable patent-based delay for a new ANDA. Historical listings could still matter in reconstructing Paragraph IV disputes and launch timing.

Were there Paragraph IV challenges or generic-entry disputes?

A Paragraph IV certification is relevant only while a listed patent remains within its statutory exclusivity period. For an expired formulation patent, the current commercial issue is not whether a new applicant must defeat the patent, but whether historical certifications, litigation, or settlement agreements affected the launch of a generic product.

The supplied information does not establish a specific Paragraph IV notice, district-court complaint, settlement, or authorized generic agreement involving U.S. Patent 6,765,001. The patent’s expiration removes the patent as a present launch blocker even if historical litigation occurred.

For due diligence, the relevant litigation questions are:

Whether the NDA holder listed the patent against a fluocinonide 0.1% product.
Whether an ANDA applicant filed a Paragraph IV certification.
Whether the patent owner sued within 45 days.
Whether the parties entered a launch-date settlement.
Whether the case was dismissed after expiration or settlement.
Whether any consent judgment affected claim scope.

A later generic product may have launched after patent expiration without needing to prove invalidity in court.

What biosimilar risk applies to this patent?

Biosimilar risk is not material. Fluocinonide is a small-molecule corticosteroid, not a biologic. The relevant competitors use the ANDA pathway for generic drugs, not the abbreviated licensure pathway under the Public Health Service Act.

The competitive risk is therefore conventional generic substitution involving:

Same active ingredient
Same dosage form
Same route of administration
Bioequivalence
Pharmaceutical equivalence
FDA-approved labeling

The patent does not protect a biologic manufacturing process, a reference-product cell line, or a biosimilar-relevant formulation platform.

Which companies compete with fluocinonide topical products?

The commercial landscape includes branded and generic fluocinonide products in creams, ointments, gels, solutions, and topical emulsions. Vanos was associated with 0.1% fluocinonide cream, while Lidex and generic fluocinonide products are commonly associated with lower-strength topical presentations, including 0.05% formulations.

The relevant competitive distinction is formulation and strength:

Product category	Typical strength	Principal competitive issue
Fluocinonide 0.1% cream	0.1%	High-potency branded or generic topical cream
Fluocinonide 0.05% cream	0.05%	Established generic and branded topical market
Fluocinonide ointment	Commonly 0.05%	Occlusion and penetration differ from cream
Fluocinonide gel or solution	Commonly 0.05%	Different vehicle and application profile
Other topical corticosteroids	Variable	Substitution based on potency, indication, vehicle, and price

The expired patent does not prevent competitors from developing a 0.1% fluocinonide cream, provided the product satisfies FDA requirements and does not infringe another unexpired patent.

What manufacturing and intellectual-property barriers remain?

The patent’s expiration removes the principal composition barrier described in claims 1 through 17. Remaining barriers are more likely to be regulatory, technical, and commercial:

Demonstrating topical product bioequivalence or therapeutic equivalence under FDA requirements
Maintaining fluocinonide uniformity at low concentration
Controlling emulsion stability and phase separation
Managing high propylene glycol or dimethyl isosorbide loading
Controlling preservative effectiveness and microbial quality
Achieving acceptable skin feel and spreadability
Reproducing particle size, droplet size, viscosity, and rheology
Establishing container-closure compatibility
Avoiding other unexpired formulation, process, device, or packaging patents

Manufacturing know-how may remain valuable even after patent expiration. That know-how is separate from the legal scope of U.S. Patent 6,765,001.

How does this patent compare with a conventional fluocinonide formulation patent?

U.S. Patent 6,765,001 is unusually focused on enhancer dominance. Its primary distinction is not merely the presence of propylene glycol or a particular cream base. It requires a high proportion of penetration enhancers relative to specified solvents and emulsifiers.

A conventional formulation patent may instead claim:

A specific emulsion structure
A particular particle-size distribution
A defined viscosity range
A preservative system
A delivery device
A specific therapeutic indication
A manufacturing sequence
A combination of active ingredients

That makes the ’001 patent narrower in technical subject matter but potentially broader across excipient combinations that satisfy its ratio and ingredient limitations.

Key Takeaways

U.S. Patent 6,765,001 covers topical corticosteroid compositions containing fluocinonide and at least two specified penetration enhancers.
The central limitation requires penetration enhancers to comprise at least about 90% of the combined penetration-enhancer, solvent, and emulsifier fraction.
Claims 2 through 4 target 0.10%, 0.50%, and 0.25% corticosteroid concentrations.
Claims 14 through 17 cover detailed fluocinonide formulations, primarily using propylene glycol, dimethyl isosorbide, diisopropyl adipate, and high levels of fatty excipients.
The supplied version of claim 16 contains an apparent percentage error because the ingredients total approximately 154%.
The patent is directed to a small-molecule topical formulation, so biosimilar analysis does not apply.
Its ordinary U.S. patent term ended approximately in 2020.
The patent is no longer a current U.S. barrier to generic fluocinonide development.
Current competitive risk is driven by FDA approval, bioequivalence, formulation performance, manufacturing capability, and any separate unexpired patents.

Frequently Asked Questions

Does a fluocinonide cream infringe U.S. Patent 6,765,001 automatically?

No. The product must satisfy every limitation of an asserted claim, including the required enhancer identities, the minimum enhancer ratio, and any concentration or excipient limitations.

Can a formulation avoid the patent by using only propylene glycol?

Yes, potentially. Claim 1 requires two or more listed penetration enhancers. A formulation using only propylene glycol would not meet that limitation, although other claims or patents could apply.

Does 0.10% fluocinonide necessarily fall within the patent?

No. The 0.10% concentration is only one limitation in dependent claim 2. The product must also satisfy claim 1’s enhancer and ratio requirements.

Is dimethyl isosorbide required for coverage?

No. Dimethyl isosorbide is one listed enhancer, but the patent also identifies propylene glycol, diisopropyl adipate, benzyl alcohol, and 1,2,6-hexanetriol or related nomenclature.

Can an expired patent still affect FDA approval?

An expired patent generally cannot support a current patent-based injunction or Hatch-Waxman stay. Historical listing, litigation, settlement, and exclusivity information can still affect the regulatory history of a product.

References

Food and Drug Administration. (2024a). Approved drug products with therapeutic equivalence evaluations: Orange Book. U.S. Department of Health and Human Services.
Food and Drug Administration. (2024b). Approved drug products with therapeutic equivalence evaluations: Patent and exclusivity information. U.S. Department of Health and Human Services.
United States Patent and Trademark Office. (2004). U.S. Patent No. 6,765,001: Topical corticosteroid compositions. U.S. Department of Commerce.
United States Code. (2023). 35 U.S.C. § 154: Contents and term of patent; provisional rights. Office of the Law Revision Counsel.
United States Code. (2023). 21 U.S.C. § 355: New drugs. Office of the Law Revision Counsel.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2002360589	⤷ Start Trial
Brazil	0215254	⤷ Start Trial
Canada	2471041	⤷ Start Trial
China	1617730	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,765,001

Summary for Patent: 6,765,001