US Patent 5,635,497: Claim Scope, Expiration, Orange Book Status, and Patent Landscape

U.S. Patent No. 5,635,497 covers a narrow oil-in-water fatty cream platform defined by a high fatty-phase content, a hydrophilic nonionic surfactant with an HLB of at least 14, approximately 6% fatty alcohols and esters, water, and, in most claims, a topical therapeutic agent other than dithranol or its derivatives. The patent issued on June 3, 1997. Its enforceable U.S. term ended in 2015, subject to any applicable patent-term adjustment or disclaimer recorded in the patent file.[1]

The most commercially relevant claims are claims 1, 9, and 10, which cover the cream platform when used with an anti-inflammatory steroid, particularly hydrocortisone-17α-butyrate. The patent does not currently block generic manufacture or sale because the patent term has expired.

What does US Patent 5,635,497 protect?

The patent protects a composition architecture rather than a single active ingredient. The required formulation characteristics are:

Limitation	Independent claim requirement
Dosage form	Topical oil-in-water fatty cream
Fatty components	60% to 80% by weight
Nonionic hydrophilic surfactant	1.5% to 5% by weight
Surfactant HLB	At least 14
Fatty alcohols and esters	About 6%
Water	Present
Therapeutic agent	Required by claim 1
Excluded active	Dithranol and derivatives
Use	Topical administration to a warm-blooded animal in claim 14

The claims use the transition “comprising.” That term generally makes the claims open-ended. A competing formulation can contain additional excipients, stabilizers, preservatives, buffers, penetration enhancers, or active ingredients and still fall within the claim if it contains every required limitation.

The claim is not limited to hydrocortisone-17α-butyrate unless claim 10 or claim 18 is being evaluated. Claim 1 reaches compositions containing a broad range of topically active therapeutic agents, subject to the stated structural limitations and the dithranol exclusion.

How do the independent claims differ?

Claim 1: Active-containing cream

Claim 1 requires:

A fatty oil-in-water cream.
Fatty components at 60% to 80% by weight.
A nonionic hydrophilic surfactant at 1.5% to 5%.
An HLB of at least 14.
About 6% fatty alcohols and esters.
Water.
A therapeutically effective topical agent.
No dithranol or dithranol derivative.

This is the principal product claim.

Claim 2: Cream base without a required therapeutic agent

Claim 2 covers the same basic formulation but does not require a therapeutically effective active ingredient. It expressly excludes a composition containing a therapeutically effective amount of dithranol or its derivatives.

This claim could historically have covered a vehicle or cream base supplied without an active pharmaceutical ingredient. Its practical scope would depend on whether the accused product was sold as a finished pharmaceutical composition, a vehicle, or an intermediate.

Claim 14: Method of topical administration

Claim 14 requires applying a composition of claim 1 to the skin of a warm-blooded animal. It is narrower than a composition claim because it requires an act of administration in addition to the claimed formulation.

Claims 15 through 18 narrow the method claim by specifying the fatty-phase range, fatty-material mixture, anti-inflammatory steroid, and hydrocortisone-17α-butyrate.

What formulations are protected by the dependent claims?

The dependent claims create several commercially important subranges.

Claim	Added limitation
3	Fatty components at 60% to 70%
4	Cetyl/stearyl alcohol, liquid paraffin, and white soft paraffin
5	Surfactant at 1.5% to 3.5%
6	Cetomacrogol 1000 as the hydrophilic nonionic surfactant
7	Water at 20% to 35%
8	Water at approximately 30%
9	Anti-inflammatory steroid
10	Hydrocortisone-17α-butyrate
11	Buffer maintaining a desired pH
12	Citric acid and sodium citrate buffer
13	Preservative

The narrowest commercially recognizable formulation is therefore a cream containing approximately 60% to 70% fatty materials, approximately 30% water, 1.5% to 3.5% cetomacrogol 1000, about 6% fatty alcohols and esters, a citric acid/sodium citrate buffer, a preservative, and hydrocortisone-17α-butyrate.

How strong is the patent estate for hydrocortisone-17α-butyrate?

The patent estate represented by U.S. Patent 5,635,497 was strongest against a product that reproduced the claimed vehicle and used hydrocortisone-17α-butyrate. Claim 10 is directed to that active and depends on claim 9, while claim 18 reaches the corresponding topical-use method.

The patent was not a broad composition claim covering all hydrocortisone butyrate products. A product could avoid literal infringement by changing one or more critical formulation parameters, such as:

reducing the fatty phase below 60%;
increasing it above 80%;
using a surfactant with an HLB below 14;
using less than the claimed surfactant range;
using a materially different fatty-alcohol or ester concentration;
omitting the claimed combination of fatty materials;
using a non-oil-in-water dosage form;
using a different active ingredient where claim 10 is asserted.

Because the claims are open-ended, adding another excipient alone would not necessarily avoid infringement. A design-around would generally require changing a required limitation rather than merely adding an ingredient.

The exclusion for dithranol and derivatives narrows the claim. It prevents the claims from covering the excluded class but does not remove compositions containing hydrocortisone-17α-butyrate or other corticosteroids.

How should “about 6%” be interpreted?

“About 6%” is a material claim-construction issue. Courts generally assess the term in the context of the specification, prosecution history, technical practice, and whether a skilled person would understand the permitted range. The patent claims do not expressly define the numerical tolerance around 6%.

A formulation containing exactly 6% presents the clearest case. A formulation materially above or below 6% requires analysis of:

the patent specification’s examples;
manufacturing tolerances;
the prosecution history;
whether the percentage is measured before or after processing;
whether the percentage is based on total composition weight;
the role of the fatty alcohols and esters in the claimed cream structure.

The claim also raises an accounting issue because the fatty alcohols and esters may overlap with the broader “fatty components” category. The same ingredient can potentially contribute to both descriptions. The claim does not require the 6% fraction to be additional to the 60% to 80% fatty phase.

What is the patent expiration date?

U.S. Patent 5,635,497 issued June 3, 1997.[1] Its enforceable term ended in 2015 under the applicable U.S. patent-term framework, subject to any recorded patent-term adjustment, terminal disclaimer, or other patent-office calculation.

Event	Date or status
U.S. patent	5,635,497
Issue date	June 3, 1997
Patent type	Pharmaceutical composition and topical-use claims
Term status	Expired
Enforceability today	None based on this patent
Regulatory consequence	No current blocking patent right from this patent

Patent expiration does not invalidate the underlying formulation technology. It removes the patent owner’s right to exclude others from practicing the claimed invention in the United States.

What is the Orange Book status of US Patent 5,635,497?

The Orange Book lists patents submitted by sponsors for approved drug products under the Hatch-Waxman framework. A composition patent can be listed when it claims the approved drug product, while a method-of-use patent can be listed when it covers an approved use.[2]

For a hydrocortisone-17α-butyrate topical product, the relevant Orange Book questions are:

Whether the sponsor submitted the patent for listing.
Whether the patent was listed against the specific NDA.
Whether the listing has been removed or marked expired.
Whether the listed use corresponds to an approved labeling indication.
Whether the patent was still relevant when an ANDA was filed.

Because U.S. Patent 5,635,497 expired in 2015, it cannot create a current Orange Book patent bar. An expired listing would not require a present-day ANDA applicant to provide a Paragraph IV certification directed to an enforceable patent. FDA regulatory exclusivity, if any, is separate from patent term and must be evaluated from the specific NDA record and product history.[2]

When did generic manufacturers face Paragraph IV risk?

Before expiration, an ANDA applicant seeking approval for a product that relied on the reference listed drug could have faced several certification options under 21 U.S.C. § 355(j):

Certification	Effect
Paragraph I	No patent information listed
Paragraph II	Listed patent had expired
Paragraph III	Applicant would wait until patent expiration
Paragraph IV	Patent was invalid, unenforceable, or not infringed

A Paragraph IV certification concerning this patent would have required the applicant to address the formulation limitations, not merely the active ingredient. A generic hydrocortisone-17α-butyrate cream would not automatically infringe simply because it contained the same corticosteroid.

The most credible noninfringement positions would have focused on a formulation outside one or more numerical limitations, a surfactant that did not meet the HLB threshold, a different fatty-phase system, or a different amount of fatty alcohols and esters.

After expiration, the patent no longer creates a Paragraph IV litigation risk. Current applicants can address the patent as expired rather than as an enforceable barrier.

What patent litigation affects US Patent 5,635,497?

The patent number alone does not establish a current litigation threat. Any historical infringement action, ANDA litigation, or settlement involving the patent would no longer preserve exclusivity after expiration.

The principal litigation issues would have been:

whether the accused formulation was an oil-in-water cream;
whether the fatty phase fell within 60% to 80%;
whether the surfactant was nonionic and hydrophilic;
whether the surfactant had an HLB of at least 14;
whether the composition contained about 6% fatty alcohols and esters;
whether the active ingredient was present in a therapeutically effective amount;
whether the accused product fell within the dithranol exclusion;
whether the asserted method claims were practiced by administration to a warm-blooded animal.

A formulation can avoid literal infringement while remaining commercially similar. The doctrine of equivalents could have created residual risk, but numerical ranges and express compositional limitations generally receive close scrutiny. Prosecution history estoppel could further restrict an equivalents theory if the applicant narrowed the claims to secure allowance.

Which companies are challenging the patent?

No current company can be identified as a live challenger to U.S. Patent 5,635,497 because the patent is expired. The relevant competitive group is the generic hydrocortisone-17α-butyrate market, including ANDA applicants and manufacturers of topical corticosteroid creams, ointments, lotions, and solutions.

The commercial competition does not depend on defeating this patent today. It depends on:

FDA approval of the dosage form;
pharmaceutical equivalence;
bioequivalence or other applicable topical-product requirements;
manufacturing capacity;
reference-product availability;
state substitution rules;
reimbursement and formulary access;
residual brand recognition.

A company evaluating an ANDA today should treat this patent as a historical patent-landscape asset, not as a current exclusionary right.

What manufacturing and IP barriers remain?

The patent has expired, but the formulation may still present technical manufacturing barriers. A high-fatty-phase oil-in-water cream can require controlled emulsification, temperature management, mixing intensity, cooling conditions, preservative compatibility, and stability testing.

Potential non-patent barriers include:

emulsion phase inversion during scale-up;
particle or droplet-size variation;
separation during storage;
preservative instability;
pH drift;
corticosteroid crystallization;
content-uniformity problems;
packaging interactions;
microbial-control failures;
differences in skin feel and spreadability that affect product comparability.

These technical constraints are not exclusive rights under the expired patent. They may still affect development cost, approval timing, batch release, and product quality.

How does this patent compare with broader hydrocortisone patents?

U.S. Patent 5,635,497 is a formulation patent. It differs from:

Patent category	Typical subject matter	Relevance today
Active-ingredient patent	Hydrocortisone butyrate or another steroid molecule	Often expired for older corticosteroids
Composition patent	Cream, ointment, lotion, gel, or emulsion architecture	Depends on claim scope and expiration
Method-of-use patent	Treatment of dermatitis or another indication	Must match the approved or marketed use
Manufacturing patent	Emulsification, particle control, or crystallization process	May create separate process risk
Regulatory exclusivity	FDA approval-based exclusivity	Separate from patent term

The patent’s commercial value historically came from combining the active ingredient with a distinctive cream vehicle. That combination is narrower than a patent on hydrocortisone-17α-butyrate itself but more relevant to a branded cream product with a specific formulation.

Are biosimilar issues relevant?

No. Hydrocortisone-17α-butyrate is a chemically synthesized small molecule, not a biologic. The relevant regulatory pathway is generally an ANDA or another small-molecule pathway, not a biosimilar application under the Public Health Service Act.

The patent therefore presents generic-entry issues rather than biosimilar-entry issues.

Key Takeaways

U.S. Patent 5,635,497 claims a high-fat oil-in-water topical cream platform.
The central numerical limitations are 60% to 80% fatty components, 1.5% to 5% hydrophilic nonionic surfactant, HLB of at least 14, and about 6% fatty alcohols and esters.
Claims 9, 10, 17, and 18 are most relevant to anti-inflammatory steroids and hydrocortisone-17α-butyrate.
Claims 11 through 13 add buffer and preservative limitations.
The dithranol exclusion narrows the claims and does not exclude hydrocortisone-17α-butyrate.
The patent issued June 3, 1997 and expired in 2015.
It does not create a current U.S. infringement, Orange Book, or Paragraph IV barrier.
Generic competition is now governed by FDA approval, formulation performance, manufacturing, and commercial access rather than this patent.
The patent is a formulation patent, not a biosimilar patent or a broad active-ingredient patent.

FAQs

Can a generic hydrocortisone-17α-butyrate cream launch after expiration?

Yes. Expiration of U.S. Patent 5,635,497 removes the patent-based exclusionary barrier, although FDA approval and other unexpired intellectual-property rights must still be evaluated.

Does using cetomacrogol 1000 automatically infringe the patent?

No. Cetomacrogol 1000 is only one limitation in dependent claim 6. The formulation must also satisfy the applicable parent-claim limitations, including the fatty-phase range, surfactant amount, HLB requirement, water, and fatty alcohols and esters.

Does a cream with 59% fatty components avoid the patent?

It would not literally satisfy a claim requiring 60% to 80% fatty components. Equivalence would depend on the technical facts, prosecution history, and claim construction. Because the patent is expired, the issue has no current enforcement consequence.

Can the patent cover a cream containing additional excipients?

Yes, potentially. “Comprising” is open-ended. Additional preservatives, buffers, stabilizers, or penetration enhancers do not by themselves avoid the claim if all required elements remain present.

Is hydrocortisone-17α-butyrate subject to biosimilar competition?

No. It is a small-molecule corticosteroid. Competitive products generally proceed through generic-drug pathways rather than the biosimilar pathway.

References

United States Patent and Trademark Office. (1997). U.S. Patent No. 5,635,497.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355(j).
United States Patent and Trademark Office. (2024). Manual of Patent Examining Procedure, patent term and claim construction provisions.

Details for Patent: 5,635,497

Summary for Patent: 5,635,497