Details for Patent: 5,635,497

Summary for Patent: 5,635,497

Title:	Topical application compositions
Abstract:	A stable topical application composition in the form of a fatty cream comprising 50 to 80% by weight of fatty components, 1.5 to 5% by weight of at least one hydrophilic non-ionic surfactant, a therapeutically effective amount of at least one topically active therapeutic agent and water and a novel method of administering a topically active therapeutic agent.
Inventor(s):	Adrianus P. Molenaar
Assignee:	Astellas Pharma Europe BV
Application Number:	US08/414,040
Patent Claim Types: see list of patent claims	Use; Composition; Formulation; Dosage form;

US Patent 5,635,497: Scope, Claim Structure, and U.S. Patent Landscape

United States Patent 5,635,497 covers a specific oil-in-water, fatty topical cream with defined quantitative ranges for fatty components and a constrained surfactant system, plus (in dependent claims) defined excipient packages, pH control, and specific therapeutic use. The patent is organized around (i) a composition claim set that is broadly framed by functional limitation on the therapeutic agent (with a dithranol carve-out), and (ii) a method-of-use claim set that ties administration to the claimed cream.

This creates a patent surface that is narrow in excipient ratios but broad in the choice of topical active, so long as it is not dithranol or its derivatives.

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What exactly does claim 1 cover? (Core composition scope)

Independent claim 1 (composition)

Claim 1 requires the following elements in one oil-in-water, fatty cream for topical administration:

• Oil-in-water, fatty cream (topical vehicle characterization)
• Fatty components: 60 to 80 wt%
• Non-ionic, hydrophilic surfactant: 1.5 to 5 wt%
  • Surfactant must have HLB at least 14
• Fatty alcohols and esters: about 6%
• Therapeutically effective amount of at least one topically active therapeutic agent
• Water
• Exclusion: the topically active therapeutic agent is not dithranol or its derivatives

Interpretive consequence: claim 1 is not limited to any single active ingredient; it is limited by (a) the vehicle composition ranges and (b) the active exclusion. That is a classic “vehicle + actives (except X)” structure.

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How does claim 2 change the scope? (Dithranol-specific carve-out alternative)

Independent claim 2 (composition)

Claim 2 restates the same vehicle limitations as claim 1, but it replaces the active limitation with an explicit negative limitation:

• Same:
  • 60 to 80 wt% fatty components
  • 1.5 to 5 wt% non-ionic hydrophilic surfactant, HLB ≥ 14
  • about 6% fatty alcohols and esters
  • water
• Exclusion: composition does not contain a therapeutically effective amount of dithranol or its derivatives

Interpretive consequence: claim 2 broadens drafting clarity for enforcement by eliminating the ambiguity that can arise from “provided the therapeutic agent is not dithranol.” It is still vehicle-constrained and still carves out dithranol at a “therapeutically effective amount” threshold.

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What dependent claims narrow the vehicle? (Ratios, fatty package, surfactant, water)

Fatty component range and proportional narrowing

• Claim 3: fatty components 60 to 70 wt% (narrows claim 1’s 60 to 80 band)
• Claim 15: method limitation echoing claim 3 (see method section)

Specific fatty material mixture

• Claim 4: fatty materials are a mixture of cetyl/stearyl alcohol, liquid paraffin and white soft paraffin
• Claim 16: method counterpart echoing claim 4

This is a significant narrowing because it anchors “fatty components” to a defined class mix.

Surfactant range

• Claim 5: surfactant is 1.5 to 3.5 wt% (narrows 1.5 to 5)

Specific surfactant species

• Claim 6: hydrophilic nonionic surfactant is cetomacrogol 1000
  • Claim 6 is the clearest single-specification constraint in the vehicle portion.

Water content

• Claim 7: water 20 to 35 wt%
• Claim 8: water about 30 wt%
  • Note the claim set does not separately specify water vs other constraints as independent ranges in claim 1; these dependent claims operationalize the practical formulation window.

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What dependent claims narrow the active(s)? (Anti-inflammatory steroid, specific steroid)

Anti-inflammatory steroid limitation

• Claim 9: therapeutic agent is an anti-inflammatory steroid
• Claim 10: steroid is hydrocortisone-17α-butyrate

Method claims mirror the same active constraints

• Claim 17: therapeutic agent is an anti-flammatory steroid
• Claim 18: steroid is hydrocortisone-17α-butyrate

Interpretive consequence: the patent supports enforcement not only at the generic “topically active except dithranol” layer, but also at the narrower “anti-inflammatory steroid” and even narrower “hydrocortisone-17α-butyrate” layer.

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What excipient system features are claimed? (buffering and preservative)

pH buffering

• Claim 11: composition contains a buffering agent to maintain desired pH
• Claim 12: buffering agent is a combination of citric acid and sodium citrate

Preservative

• Claim 13: composition contains a preservative

Interpretive consequence: these dependent claims build additional patentability islands. If an accused cream uses the vehicle system but omits buffer/preservative, claim 11-13 are avoidable. If it includes them, these claims can create tighter enforcement hooks.

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What method-of-use scope exists? (administration of the claimed composition)

Independent method claim 14

• Method: topically administering a therapeutic agent to a warm-blooded animal
• Act: applying to skin a composition of claim 1

Interpretive consequence: claim 14 is a direct-use claim anchored to claim 1’s composition. It does not independently constrain excipients beyond claim 1, but it expands jurisdictional coverage to method infringement theories where formulation is applied in the claimed way.

Dependent method claims

• Claim 15: fatty component 60 to 70 wt%
• Claim 16: fatty mixture is cetyl alcohol, stearyl alcohol, liquid paraffin, white soft paraffin
• Claim 17: therapeutic agent is an anti-inflammatory steroid
• Claim 18: steroid is hydrocortisone-17α-butyrate

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How broad is the claim set in practice? (Scope grid)

Vehicle boundaries (high constraint)

The patent is constrained by:

• Fatty components at 60-80 wt%
• One specific type of surfactant:
  • non-ionic, hydrophilic, HLB ≥ 14
• Surfactant at 1.5-5 wt%
• Additional fatty alcohol/ester component around 6%
• Must be an oil-in-water, fatty cream

Active boundaries (moderate flexibility)

• Any topical active therapeutic agent is allowed except dithranol and derivatives (claims 1-2)
• Dependent layers then narrow to anti-inflammatory steroids and to hydrocortisone-17α-butyrate.

Most “enforceable” narrowing points (where design-arounds get difficult)

The narrowest hardpoints are:

• Cetomacrogol 1000 (claim 6)
• Specific fatty mixture (claim 4 and claim 16)
• Hydrocortisone-17α-butyrate (claim 10 and claim 18)
• Citric acid + sodium citrate (claim 12)
• Water around 30% (claim 8)

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Patent landscape analysis in the U.S.: where infringement and validity risks concentrate

A reliable landscape requires access to the full prosecution file, publication family members, and any cited references, which are not included in the provided input. With only the claim text, the landscape can still be characterized along structural lines that dictate where other patents and products typically overlap: (i) hydrocortisone-17α-butyrate topical formulations, (ii) fatty creams with oil-in-water emulsions and high-HLB non-ionic surfactants, and (iii) vehicle excipient systems using fatty alcohols/esters, paraffins, and poly(ethylene glycol)-type surfactants (the functional role “HLB ≥ 14 non-ionic hydrophilic surfactant” is strongly suggestive of that class).

1) Likely overlap zones with other U.S. topical formulation patents

The claim architecture maps onto common patent categories:

• Topical steroid creams/ointments with specific steroid actives, especially hydrocortisone-17α-butyrate.
• Oil-in-water fatty cream vehicles where the emulsion stability and skin feel depend on:
  • fatty phase ratio (60-80 wt%)
  • non-ionic surfactant selection and level (HLB ≥ 14; 1.5-5 wt%)
  • fatty alcohol/ester content (~6%)
• Emulsion excipient packages using:
  • cetyl/stearyl alcohol
  • liquid paraffin
  • white soft paraffin
  • often combined with buffering systems for pH stability.

2) Key design-around levers that change claim scope

The claims are easy to map to infringement defenses:

• Surfactant HLB/species avoidance
  • If a competitor uses a non-ionic hydrophilic surfactant but with HLB < 14, it can fall outside claim 1/2.
  • If it uses a different surfactant class (ionic or non-ion but not hydrophilic as claimed, depending on interpretation) it can try to avoid the “HLB ≥ 14” limitation.
• Fatty component ratio avoidance
  • Moving outside 60-80 wt% fatty components avoids claim 1.
  • Narrower dependent claims avoid if target is outside 60-70 wt%.
• Fatty alcohol/ester content
  • Claim 1 requires “about 6% of fatty alcohols and esters.” A formulation that has a materially different level can escape.
• Dithranol active avoidance
  • Claims 1-2 exclude dithranol/dithranol derivatives at therapeutically effective levels.
  • If a formulation targets dithranol, it falls outside these claims by design (but may be covered by other patents).
• Buffer and preservative
  • Buffering and preservative appear only in dependent claims.
  • A competitor can use the vehicle but omit citric acid/sodium citrate and preservative to avoid claims 11-13.

3) Where method claims add risk

Claim 14 is a straightforward dependent tie to the composition of claim 1. If a product formulation falls within claim 1, marketing and administration of the product to warm-blooded animals creates pathway for method theories.

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Practical claim-to-product matching framework

Use this checklist for any U.S. formulation evaluation against 5,635,497:

1. Does the product have an oil-in-water fatty cream structure?
2. Fatty components 60-80 wt%?
3. Non-ionic hydrophilic surfactant at 1.5-5 wt% and HLB ≥ 14?
4. Fatty alcohols/esters at about 6%?
5. Active is topical and not dithranol or derivatives?
6. If yes, check dependent constraints:
   • 60-70 wt% fatty components (claim 3)
   • cetyl/stearyl alcohol + liquid paraffin + white soft paraffin (claim 4)
   • surfactant level 1.5-3.5 wt% (claim 5)
   • cetomacrogol 1000 (claim 6)
   • water 20-35 wt% or about 30 wt% (claims 7-8)
   • anti-inflammatory steroid (claim 9) and hydrocortisone-17α-butyrate (claim 10)
   • citric acid + sodium citrate (claim 12)
   • preservative (claim 13)

If a candidate misses any of the independent claim 1 requirements (2-4 in practice), it is out of claim 1 and claim 14. If it matches claim 1 but not dependent points, dependent claims drop away.

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Key takeaways

• Core protection is the vehicle: a defined oil-in-water fatty cream with 60-80 wt% fatty components, 1.5-5 wt% non-ionic hydrophilic surfactant with HLB ≥ 14, and about 6% fatty alcohols and esters, containing water.
• Active coverage is broad but bounded: any topically active therapeutic agent is allowed except dithranol/dithranol derivatives.
• Narrow enforcement islands exist for:
  • hydrocortisone-17α-butyrate (claims 10 and 18)
  • cetomacrogol 1000 (claim 6)
  • specific fatty package (claim 4 and claim 16)
  • citric acid + sodium citrate buffer (claim 12)
  • and water about 30% (claim 8).
• Design-around levers are directly tied to claim numerics: fatty fraction, surfactant HLB, surfactant level, fatty alcohol/ester level, and buffer/preservative presence.

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FAQs

1) Is the patent limited to hydrocortisone-17α-butyrate?

No. Hydrocortisone-17α-butyrate appears in dependent claim 10, while claim 1 allows “at least one topically active therapeutic agent” except dithranol/dithranol derivatives.

2) What is the most critical formulation parameter in claim 1?

The combination of fatty components (60-80 wt%), non-ionic hydrophilic surfactant (1.5-5 wt%, HLB ≥ 14), and about 6% fatty alcohols and esters.

3) Can a formulation with a different surfactant avoid claim 1?

Yes, if it fails the “HLB at least 14” and/or the “non-ionic, hydrophilic surfactant” requirement, or if the level is outside 1.5-5 wt%.

4) Do claims 11-13 matter if a product omits buffer and preservative?

Claims 11-13 add limitations in dependent form, so omission of buffering and/or preservative can avoid those dependent claims while still potentially matching claim 1.

5) What does claim 14 add beyond the composition claims?

Claim 14 is a method claim tied to applying the claimed cream to the skin of a warm-blooded animal; it tracks composition scope through claim 1.

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References

No sources were provided in the input beyond the claim text; therefore, no inline citations or reference list entries can be constructed.

Drugs Protected by US Patent 5,635,497

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