Executive summary: U.S. Patent No. 5,456,851 covers a ketoconazole anti-dandruff shampoo defined by a specific combination of active concentration, pH, viscosity, antioxidant, surfactant system, excipients and manufacturing sequence. Its broadest independent composition claim requires all core elements in claim 1. Claims 2-13 narrow the formulation by pH, ketoconazole concentration, antioxidant, surfactant, foaming agent, conditioner, pearlizer and quantitative composition. Claim 14 covers a staged manufacturing process.

The patent was issued in 1995 and, as a pre-1995 U.S. patent, had a 17-year term measured from grant. Its ordinary expiration date was October 10, 2012. The patent is therefore expired and no longer creates an enforceable U.S. exclusionary right. Current commercial risk from ketoconazole shampoo products arises from regulatory, formulation, trade-secret, trademark and product-quality issues rather than infringement of this patent.

U.S. Patent 5,456,851 Ketoconazole Shampoo: Claims, Scope, Expiration and Patent Landscape

What does U.S. Patent 5,456,851 cover?

U.S. Patent No. 5,456,851 covers aqueous shampoo formulations containing ketoconazole for combating scaling associated with dandruff. The patent is not limited to a particular brand, bottle, fragrance or commercial package. Its claims focus on formulation architecture and, in claim 14, the order in which the formulation is manufactured.

The central technical combination in claim 1 is:

Required element	Claim 1 limitation
Dosage form	Aqueous shampoo
Active ingredient	Ketoconazole
Ketoconazole concentration	About 0.3% to about 3% by weight
Intended use	Combating scaling due to dandruff
Surfactant	Required, but not limited in claim 1 to a specific surfactant
Foaming agent	Required
Viscosity	About 4,000 to about 9,000 cps at room temperature
Antioxidant	0.01% to 1% by weight
Antioxidant identity	Butylated hydroxytoluene, or BHT, or butylated hydroxyanisole, or BHA
pH control	Acid, base or buffer
pH	About 4 to about 10
Preservative	Sufficient to retard degradation of the final composition

The claim uses the term “comprising,” which generally makes the claim open-ended. A product can contain ingredients not expressly listed in claim 1 and still fall within the claim if every required limitation is present.

The patent’s commercial concept was a stable ketoconazole shampoo. The antioxidant requirement is particularly important because ketoconazole degradation is addressed through BHT or BHA. The viscosity range and pH limitations distinguish the claimed formulation from a generic aqueous ketoconazole mixture.

When did U.S. Patent 5,456,851 expire?

U.S. Patent 5,456,851 issued on October 10, 1995. Because it was issued from an application subject to the pre-Uruguay Round patent-term regime, its ordinary term was 17 years from grant rather than 20 years from the earliest effective U.S. filing date. The ordinary expiration date was October 10, 2012.

Event	Date or status
Patent	U.S. 5,456,851
Technology	Ketoconazole shampoo
Issue date	October 10, 1995
Ordinary patent term	17 years from grant
Ordinary expiration	October 10, 2012
Current status	Expired
Current infringement exposure	None for the expired patent

The expiration analysis should be separated from regulatory exclusivity. Patent expiration does not itself authorize sale. A later manufacturer still must satisfy FDA approval, labeling, manufacturing and quality requirements. It does mean that the patent owner cannot use this patent to block a competing ketoconazole shampoo.

The governing pre-1995 term rule appears in 35 U.S.C. § 154, while the USPTO provides patent-term and expiration guidance for issued U.S. patents (U.S. Patent and Trademark Office, n.d.-a; 35 U.S.C. § 154).

How many patents cover the core ketoconazole shampoo formulation?

U.S. Patent 5,456,851 is the principal patent identified by the supplied claims for this specific shampoo formulation and process. The claim set contains 14 claims:

Claim group	Scope
Claim 1	Broad aqueous ketoconazole shampoo composition
Claims 2-6	Narrower pH, antioxidant and ketoconazole-concentration limitations
Claims 7-11	Specified surfactants, foaming agents, conditioner, pearlizer, fragrances and colorants
Claims 12-13	Quantitative formulation ranges
Claim 14	Manufacturing process and ingredient-addition sequence

The patent should not be treated as covering every ketoconazole shampoo. A product outside the specified pH, viscosity, antioxidant or ketoconazole range may avoid literal infringement of claim 1, even if it uses ketoconazole for dandruff.

The reverse is also important. A formulation does not escape the claim merely because it uses a different brand name or adds additional ingredients. If it contains the required elements within the claimed ranges, the open-ended claim language may still be relevant. That issue is academic for this patent because the rights expired in 2012.

What is the scope of claim 1?

Claim 1 is a combination claim. Each listed element is required for literal infringement.

A product would generally need to satisfy all of the following:

It must be an aqueous shampoo.
It must contain ketoconazole at approximately 0.3% to 3%.
It must be directed to combating dandruff-associated scaling.
It must contain a surfactant.
It must contain a foaming agent.
It must have a viscosity of approximately 4,000 to 9,000 cps at room temperature.
It must contain BHT or BHA at 0.01% to 1%.
It must have a pH of approximately 4 to 10.
It must contain a preservative sufficient to retard degradation.

The claim does not require a 2% ketoconazole concentration. A 2% product is within the claimed 0.3% to 3% range. The claim also does not require any specific surfactant, foaming agent, preservative or thickener, provided the formulation satisfies the functional and quantitative limitations.

The terms “about,” “sufficient,” and “at room temperature” introduce claim-construction questions. Their interpretation would depend on the patent specification, prosecution history, technical evidence and the relevant measurement method. Those questions have no current enforcement consequence because the claim is expired.

What do claims 2 through 6 add?

Claims 2-6 narrow claim 1 in a logical hierarchy.

Claim	Additional limitation
2	pH approximately 6.5 to 8
3	pH approximately 6.9 to 7.4
4	BHT at 0.1% plus or minus 0.025%
5	Ketoconazole approximately 0.8% to 2.0%
6	Ketoconazole approximately 0.9% to 1.1%

Claim 3 is a narrow pH claim nested within claims 1 and 2. Claim 6 is a narrow active-concentration claim nested within claim 5 and claim 1. A formulation at 1.0% ketoconazole and pH 7.1 would fall within the numerical limitations of claims 3 and 6 if it also satisfied every limitation inherited from claim 1.

Claim 4 is directed to BHT rather than BHA. The stated range of 0.075% to 0.125% reflects the “0.1 ± 0.025%” limitation.

Which surfactants are protected by claim 7?

Claim 7 narrows the shampoo to one or more listed surfactants:

Sodium C14-16 olefin sulfonates
Sodium lauryl sulfate
Sodium laureth sulfate
Cocamidopropylamine oxide
Lauramido diethanolamine
Cocamidopropyl betaine
Sodium cocoyl sarcosinate
Disodium oleamido monoisopropanolamine sulfosuccinate
Disodium cocamido monoisopropanolamine sulfosuccinate
Disodium laureth sulfosuccinate
Cocoamphocarboxy-glycinate
Disodium oleamido monoethanolamine sulfosuccinate

Because claim 7 depends on claim 1, the listed surfactant alone is not enough. The formulation also must contain ketoconazole, the claimed antioxidant, the viscosity range, pH range, foaming agent and preservative.

A product using a surfactant not listed in claim 7 could still implicate claim 1 if it meets claim 1’s broader surfactant requirement. It would not, however, satisfy claim 7 literally based on an unlisted surfactant.

What formulations are protected by claims 8 through 13?

Foaming agents under claim 8

Claim 8 identifies fatty acid mono- and di-alkanolamides:

Cocamide monoethanolamine
Cocamide diethanolamine
Oleamide monoethanolamine
Oleamide diethanolamine

Conditioning systems under claim 9

Claim 9 adds polyquaternium-7 as a conditioner. The claim does not require a particular concentration of polyquaternium-7 beyond the inherited limitations of claim 1.

Pearlizing agents under claim 10

Claim 10 covers:

Ethylene glycol distearate
Ethylene glycol monostearate

Fragrance and color under claim 11

Claim 11 permits one or more fragrances and colorants. These features are not essential to claim 1. They narrow the dependent claim but do not define the core invention.

Quantitative formulation in claim 12

Claim 12 specifies approximate weight ranges:

Component	Claimed range
Surfactants	36% to 45%
Foaming agent	2% to 6%
Ketoconazole	0.3% to 3%
Thickener	0.2% to 1.3%
BHT	0.1% to 1%
Preservatives	Sufficient amount
pH	6.9 to 7.4
Water	Quantity sufficient to 100%

Claim 12 is narrower than claim 1 because it requires a particular quantitative profile. A commercial product with lower surfactant content, a different thickener level or pH outside 6.9 to 7.4 would not literally satisfy those limitations, subject to interpretation of “approximately.”

Quantitative formulation in claim 13

Claim 13 adds:

Component	Claimed range
Conditioner	0.4% to 8%
Pearlizing agent	1% to 1.5%
Preservatives	0.5% to 1%
BHT	0.075% to 0.125%
Fragrance and colorant	Required
Other inherited ranges	Same general structure as claim 12

Claim 13 contains an apparent drafting inconsistency. Claim 12 identifies a thickener range of 0.2% to 1.3%, while claim 13 lists conditioner at 0.4% to 8% and separately retains the thickener limitation. The claim should therefore be read as requiring both a conditioner and a thickener within their respective stated ranges.

What process is protected by claim 14?

Claim 14 is a process claim. It requires a specified sequence:

Heat a solution of thickener and deionized water.
Add surfactants, foaming agent and, optionally, pearlizer.
Add BHT or BHA.
Add ketoconazole.
Cool somewhat, then add preservative, sodium chloride and optional conditioner, fragrance and colorant.
Adjust pH to 4 to 10.
Add deionized water to reach 100%.

The process claim is narrower than a claim covering any method of making a ketoconazole shampoo. A process using the same ingredients but adding ketoconazole before the antioxidant, or adjusting pH before the preservative, could avoid literal infringement depending on the exact sequence and claim construction.

Claim 14 also contains typographical errors, including “ketocanazole” and “detoconazole.” Courts generally interpret obvious typographical errors in light of the claim, specification and prosecution history. The intended reference is plainly ketoconazole.

The process claim could have mattered for contract manufacturing or internal production operations, but it expired with the patent.

What was the FDA and Orange Book status of ketoconazole shampoo?

Ketoconazole shampoo is an FDA-regulated prescription drug product when marketed under an approved drug application. The regulatory product is generally a topical antifungal shampoo containing ketoconazole, commonly at a 2% concentration.

FDA approval and patent protection are separate systems:

Issue	Effect
FDA approval	Authorizes marketing of an approved product for approved uses
Orange Book listing	Identifies patents submitted for approved drug products
Patent expiration	Removes patent-based exclusion after the expiration date
Regulatory exclusivity	Can delay approval or marketing independently of patent term
ANDA approval	Allows an eligible generic to rely on the reference product’s safety and efficacy findings

The Orange Book is the relevant FDA source for approved drug applications, therapeutic equivalence and listed patents (U.S. Food and Drug Administration, n.d.-a). An expired patent such as U.S. 5,456,851 does not create a current Paragraph IV barrier.

The patent is also not a biologic patent. Ketoconazole is a conventional small-molecule active pharmaceutical ingredient. Biosimilar rules under the Biologics Price Competition and Innovation Act do not apply. Competition proceeds through generic-drug or abbreviated-approval pathways, not biosimilar substitution.

Were Paragraph IV challenges or settlements relevant?

A Paragraph IV certification is relevant when an ANDA applicant asserts that a listed patent is invalid, unenforceable or not infringed. The applicant may also use a Paragraph III certification if it accepts that the patent remains valid and waits for expiration.

For U.S. Patent 5,456,851, the relevant commercial period ended in 2012. Any historical ANDA challenge would have had to address the patent before that date. The expiration of the patent eliminates the continuing need for a Paragraph IV challenge against this patent.

No current litigation or settlement can preserve the patent’s exclusionary force after expiration. A settlement agreement could still contain commercial terms, but it cannot extend the patent term beyond the statutory expiration date. The patent should therefore be treated as having no current Paragraph IV launch-blocking value.

Which companies are challenging the ketoconazole shampoo market?

The market has historically included the branded Nizoral ketoconazole shampoo product and generic ketoconazole shampoo products from multiple FDA-approved manufacturers and labelers. The relevant competitive set is determined by:

Ketoconazole concentration, especially 2%
Prescription versus nonprescription status
Approved indication
Bottle size and channel
Therapeutic-equivalence rating
Manufacturing source
Retail, dermatology and institutional distribution

The expired patent does not identify a current proprietary formulation barrier. A manufacturer’s competitive advantage may instead depend on FDA approval, supply reliability, contract manufacturing capacity, dermatology distribution, private-label relationships and brand recognition.

How strong is the patent estate for ketoconazole shampoo?

The patent was technically meaningful when active because it combined several formulation parameters rather than claiming ketoconazole shampoo at a high level. Its strength can be assessed as follows:

Factor	Assessment
Breadth of composition claim	Moderate; claim 1 requires multiple formulation limitations
Dependence on measured properties	Significant; viscosity, pH and concentration matter
Ingredient flexibility	Relatively broad for surfactants, thickeners and preservatives in claim 1
Antioxidant limitation	Restrictive; BHT or BHA is required
Process claim	Narrower because sequence is expressly required
Design-around potential during term	Meaningful through antioxidant, pH, viscosity or process changes
Current legal strength	None; patent expired
Biosimilar relevance	None
Generic-entry barrier today	None from this patent

The claim set was stronger against close copies of the disclosed formulation than against all ketoconazole shampoos. A competitor could have explored different antioxidants, a different pH, a viscosity outside the claimed range or a different manufacturing sequence. Such a strategy would have required technical and regulatory validation, not merely a change in marketing language.

What generic launch risks exist today?

The patent creates no current generic-launch risk because it expired in 2012. The remaining risks are primarily regulatory and commercial.

Regulatory risks

A new product may require an ANDA or another FDA approval route depending on its formulation and reference-product relationship. Differences in inactive ingredients, labeling, concentration, dosage form or manufacturing site can affect approval requirements.

Manufacturing and IP risks

Although the patent’s process claim has expired, manufacturers still must control:

Ketoconazole assay and impurity profile
Antioxidant stability
Microbial preservation
Viscosity and rheology
pH throughout shelf life
Suspension or dispersion uniformity
Packaging compatibility
Batch-to-batch appearance and fragrance

Manufacturing know-how may remain confidential even though the patent is expired. Trade secrets, supplier agreements and quality systems can create practical barriers without creating patent exclusivity.

Commercial risks

Revenue exposure is linked to the size of the ketoconazole shampoo market, prescription volume, reimbursement, dermatology prescribing and retail substitution. The absence of a live patent usually increases price competition and limits sustainable premium pricing.

How does U.S. Patent 5,456,851 compare with competing ketoconazole products?

Product or category	Active ingredient	Patent position	Regulatory position
Original branded ketoconazole shampoo	Ketoconazole, commonly 2%	U.S. 5,456,851 expired	Approved reference-product framework
Generic ketoconazole shampoo	Ketoconazole, commonly 2%	No current barrier from U.S. 5,456,851	ANDA or applicable FDA pathway
Non-ketoconazole dandruff shampoos	Other antifungal or keratolytic actives	Outside this patent’s active limitation	Separate FDA regulatory framework
Compounded ketoconazole shampoo	Ketoconazole	Patent expired, but compounding rules remain relevant	Subject to applicable compounding and drug-law requirements

The main differentiation between products is no longer patent position. It is formulation performance, approval status, tolerability, supply, price and distribution.

What is the geographic coverage of the patent?

U.S. Patent 5,456,851 covered the United States only. It did not directly control sales, manufacture or use in Canada, Europe, Japan or other jurisdictions.

International protection would have required separate national or regional patents. The U.S. expiration date does not establish the expiration date of any corresponding foreign patent. For a current cross-border launch, the relevant analysis must be conducted jurisdiction by jurisdiction, including national-phase status, terminal disclaimers, patent-term extensions and supplementary protection certificates where applicable.

Key takeaways

U.S. Patent 5,456,851 claims a ketoconazole aqueous shampoo with defined active concentration, pH, viscosity, antioxidant and preservative requirements.
Claim 1 is the central composition claim and uses open-ended “comprising” language.
Claims 2-13 narrow the formulation through pH, BHT concentration, ketoconazole concentration, surfactants, foaming agents, conditioners, pearlizers and quantitative ranges.
Claim 14 covers a specific manufacturing sequence.
The patent issued October 10, 1995 and ordinarily expired October 10, 2012.
The patent is not a current barrier to generic ketoconazole shampoo launch.
Ketoconazole is a small molecule, so biosimilar analysis is not applicable.
Current market barriers are FDA approval, manufacturing quality, supply, commercial distribution and branding.
Any related foreign patent rights must be assessed separately by country.
The patent’s formulation and process claims have historical significance for close-copy products but have no present enforceable exclusionary value in the United States.

FAQs about U.S. Patent 5,456,851 and ketoconazole shampoo

Can a company sell a 2% ketoconazole shampoo without licensing U.S. Patent 5,456,851?

Yes. The patent expired in 2012, so a license is not required based on this patent. FDA authorization and other applicable legal requirements still govern marketing.

Does using BHT in ketoconazole shampoo create patent infringement risk?

No current risk arises from U.S. Patent 5,456,851 because the patent is expired. During the patent term, BHT at approximately 0.075% to 0.125% could have implicated dependent claim 4 if the other inherited limitations were met.

Does a ketoconazole cream fall within U.S. Patent 5,456,851?

No. The claims are directed to an aqueous shampoo. A cream, gel or other dosage form does not satisfy the shampoo limitation.

Is claim 14 broad enough to cover every ketoconazole shampoo manufacturing process?

No. Claim 14 requires the listed ingredients and a defined order of addition, including antioxidant before ketoconazole and pH adjustment before final water addition. Other manufacturing sequences would not necessarily meet the claim.

Does the patent cover ketoconazole shampoo outside the United States?

No. A U.S. patent has territorial effect in the United States. Foreign commercialization requires separate analysis of any corresponding foreign patents and local regulatory requirements.

References

United States Patent No. 5,456,851. (1995). Ketoconazole shampoo. U.S. Patent and Trademark Office.
United States Code, Title 35, § 154. (2024). Contents and term of patent; provisional rights.
U.S. Food and Drug Administration. (n.d.-a). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book
U.S. Patent and Trademark Office. (n.d.-a). Patent term adjustment and patent term extension. https://www.uspto.gov/patents/laws/patent-term-adjustment-patent-term-extension-prioritizing-examination-rules/term-adjustment/patent-term-calculator

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
African Regional IP Organization (ARIPO)	641	⤷ Start Trial
African Regional IP Organization (ARIPO)	9600865	⤷ Start Trial
Austria	187325	⤷ Start Trial
Australia	2159795	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,456,851

Summary for Patent: 5,456,851