US Patent 5,194,247: Claim Scope, Expiration, Orange Book Status, and Patent Landscape

US Patent 5,194,247 covers topical skin-depigmentation compositions combining 4-hydroxyanisole, also known as mequinol, with specified retinoids. It also covers methods of depigmenting skin using those compositions. The broadest composition claim requires 0.1% to 5% mequinol, 0.001% to 1% of at least one specified retinoid, a pharmaceutically acceptable topical vehicle, and no corticosteroid.

The patent issued on March 16, 1993, and its pre-URAA 17-year term expired on March 16, 2010, subject to any recorded terminal disclaimer or unusual term adjustment. The patent therefore does not create current U.S. blocking rights. Its historical commercial importance is greatest for the Solagé combination of mequinol 4% and tretinoin 0.01%, which falls within claim 1 but outside the narrower concentration limits of claim 3.

What does US Patent 5,194,247 cover?

US 5,194,247 covers a synergistic topical combination of:

Component	Claimed concentration
4-Hydroxyanisole, or mequinol	0.1% to 5% by weight
At least one specified retinoid	0.001% to 1% by weight
Topical vehicle	Pharmaceutically acceptable
Corticosteroid	Expressly excluded

The three recited retinoids are:

All-trans retinoic acid, commonly called tretinoin.
(N-acetyl-4-aminophenyl) retinoate.
11-cis,13-cis-12-hydroxymethyl retinoic acid delta-lactone.

The patent claims both the composition and its topical use for depigmenting skin. The claims do not require a particular diagnosis, skin location, treatment duration, application frequency, vehicle type, pH, packaging system, or manufacturing process (U.S. Patent No. 5,194,247, 1993).

How are the 18 claims organized?

Composition claims 1 through 9

Claims 1 through 9 cover the composition itself.

Claim	Scope
1	Broad combination of mequinol and at least one of the three listed retinoids
2	Claim 1 limited to all-trans retinoic acid
3	Mequinol at 1% to 2%; tretinoin at 0.01% to 0.1%
4	Claim 1 limited to N-acetyl-4-aminophenyl retinoate
5	Broad concentration ranges for mequinol and that retinoate
6	Narrow 1% to 2% mequinol and 0.01% to 0.1% retinoate ranges
7	Claim 1 limited to the delta-lactone retinoid
8	Broad concentration ranges for mequinol and the delta-lactone
9	Narrow 1% to 2% mequinol and 0.01% to 0.1% delta-lactone ranges

Claim 1 is the commercially significant composition claim. It covers a wide concentration window and includes the mequinol-tretinoin combination used in Solagé.

Claims 3, 6, and 9 are narrower species claims. They require both ingredients to fall within a relatively restricted concentration range. A product containing 4% mequinol and 0.01% tretinoin would satisfy claim 1 but would not satisfy claim 3 because the mequinol concentration exceeds 2%.

Method claims 10 through 18

Claims 10 through 18 mirror the composition claims but require topical application to skin for depigmentation.

Claim group	Subject matter
10	Broad method using mequinol and one or more listed retinoids
11-12	Method using tretinoin, including the narrower concentration range
13-15	Method using N-acetyl-4-aminophenyl retinoate
16-18	Method using the delta-lactone retinoid

The method claims do not require a specific pigmentation disorder. On their face, they reach topical use for skin depigmentation generally, subject to ordinary claim-construction limits concerning treatment intent and the meaning of “synergistic composition.”

What is the legal significance of “consists essentially of”?

The phrase “consists essentially of” creates an intermediate claim boundary.

It permits the listed active ingredients, the pharmaceutically acceptable topical vehicle, and excipients that do not materially alter the composition’s basic and novel characteristics. It excludes ingredients that materially change those characteristics. The claims also expressly exclude corticosteroids.

This language is narrower than “comprising” and broader than “consisting of.” A formulation with preservatives, solvents, emollients, antioxidants, penetration enhancers, or other conventional vehicle components would not automatically fall outside the claims. The question would be whether the additional component materially changes the claimed synergistic depigmentation combination.

The corticosteroid exclusion is important. A formulation containing a corticosteroid would face a direct claim-scope issue even if all other ingredients and concentrations were present. The claim language does not exclude other depigmenting agents by name, but additional active ingredients could raise questions under “consists essentially of.”

How does the patent cover mequinol and tretinoin products?

A product with the following composition falls within broad claim 1:

Ingredient	Example concentration
Mequinol	4%
Tretinoin	0.01%
Topical vehicle	Pharmaceutically acceptable
Corticosteroid	None

The commonly marketed Solagé formulation contains mequinol 4% and tretinoin 0.01%. That formulation fits claim 1’s ranges:

Mequinol: 4% is within 0.1% to 5%.
Tretinoin: 0.01% is within 0.001% to 1%.
The formulation is topical.
Tretinoin is one of the listed retinoids.
The formulation does not contain a corticosteroid.

It does not fit claim 3’s narrower mequinol range because 4% exceeds the 1% to 2% limit.

The distinction matters for historical infringement analysis. A product could infringe the independent broad claim even when it avoids a narrower dependent claim.

What formulations are protected by US 5,194,247?

The patent protects formulations that meet all of the following conditions:

They contain mequinol at 0.1% to 5% by weight.
They contain at least one of the three specified retinoids at 0.001% to 1% by weight.
They use a pharmaceutically acceptable topical vehicle.
They do not contain a corticosteroid.
They are characterized as synergistic for skin depigmentation.

The patent does not expressly claim:

Mequinol alone.
Tretinoin alone.
Hydroquinone combinations.
Azelaic acid combinations.
Kojic acid combinations.
Tranexamic acid combinations.
Oral formulations.
Injectable products.
Cosmetic compositions outside the pharmaceutical topical-vehicle limitation.
A manufacturing process.
A particular delivery device.
A specific retinoid derivative not listed in claim 1.

A product using a different retinoid would not fall within the literal scope of claim 1, although doctrine-of-equivalents issues would depend on the facts and the applicable prosecution history.

When did US Patent 5,194,247 lose exclusivity?

The patent expired on March 16, 2010, based on the 17-year term applicable to a patent issued from a pre-June 8, 1995 application. Patent term for that class was generally measured from issue rather than the later 20-year-from-filing standard.

Event	Date
Patent issued	March 16, 1993
Statutory term	17 years from issue
Expected expiration	March 16, 2010
Current status	Expired

The expiration eliminates the patent’s present exclusionary effect in the United States. It does not eliminate the historical relevance of the claims to earlier products, earlier ANDA filings, licensing arrangements, or past litigation.

What is the Orange Book status of the patent?

US 5,194,247 was associated historically with the mequinol/tretinoin topical product Solagé. The relevant reference product was approved by FDA under NDA 020922 for the treatment of solar lentigines, commonly called age spots or liver spots, on the face.

The patent’s practical Orange Book significance ended when the patent expired in 2010. Any listing could no longer support a current patent-based delay of an ANDA under the Hatch-Waxman framework.

FDA regulatory status of mequinol/tretinoin

Solagé is a prescription topical solution containing:

Mequinol 4%.
Tretinoin 0.01%.

The product is regulated as a drug rather than an ordinary cosmetic because it is marketed for treatment of solar lentigines. Its labeling includes warnings associated with tretinoin, including irritation and photosensitivity, and emphasizes sun avoidance and sunscreen use (U.S. Food and Drug Administration, 2000).

The patent did not provide regulatory exclusivity by itself. FDA approval, any applicable new-drug exclusivity, and patent listing operated as separate legal protections.

Were there Paragraph IV challenges?

A Paragraph IV certification would have been relevant during the patent’s term if an ANDA applicant asserted that the patent was invalid, unenforceable, or not infringed. After March 16, 2010, the patent could no longer block approval based on ordinary patent expiration.

The public patent record does not establish a material, continuing Paragraph IV dispute involving US 5,194,247. No current Paragraph IV risk remains because the patent is expired.

The main historical ANDA possibilities were:

Scenario	Historical consequence
Paragraph III certification	ANDA approval deferred until patent expiration
Paragraph IV certification	Potential patent litigation and 30-month stay
Section viii statement	Possible carve-out of patented method of use
No listed patent barrier	Approval subject to other FDA requirements

Because the patent claims both composition and method of use, a section viii carve-out would have been difficult for an ANDA product containing the same active ingredients and concentrations if the proposed labeling retained the patented depigmentation indication.

What patent litigation affects Solagé or this patent?

The patent’s principal litigation relevance would have involved ANDA applicants seeking approval of a mequinol/tretinoin product before expiration. The available patent record does not identify a continuing infringement action that affects present market entry.

Any historical litigation would have focused on:

Whether the accused product contained both claimed actives.
Whether concentrations fell within the claim ranges.
Whether the product contained a pharmaceutically acceptable topical vehicle.
Whether additional ingredients materially altered the basic and novel characteristics.
Whether the composition was synergistic.
Whether the patent was valid and enforceable.
Whether a generic label induced the claimed depigmentation method.

The patent’s expiration makes current infringement litigation under these claims unavailable for post-expiration conduct.

Did the patent protect a method of use or only a formulation?

It protected both.

The composition claims cover the product. The method claims cover topical application for skin depigmentation. This dual structure historically increased the patent’s relevance to ANDA strategy because a generic applicant could face both product-claim and method-claim theories.

The method claims are not independent of the composition requirements. Applying mequinol alone, applying a non-listed retinoid, or using concentrations outside the claim ranges would not literally satisfy the broad method claim.

Claim 12 contains an apparent dependency drafting error. It states that the method is “as defined in claim 1,” although claim 1 is a composition claim. Its substantive language identifies a method using mequinol and tretinoin at the narrow concentration range. The error could have affected enforcement or claim-construction arguments, but it does not revive the expired patent.

How strong was the patent estate?

Strengths

The patent had several commercially useful characteristics:

Claim 1 covered the principal 4% mequinol/0.01% tretinoin formulation.
The claims covered both composition and method of use.
The patent expressly recited synergy, supporting the combination rationale.
The concentration ranges were broad enough to encompass multiple topical formulations.
The claims excluded corticosteroids, distinguishing the combination from steroid-containing depigmentation regimens.
The retinoid Markush structure covered three chemically distinct retinoids.

Weaknesses

The estate also had important limitations:

It contained only one core U.S. patent identified by the patent number.
It did not claim mequinol monotherapy or tretinoin monotherapy.
It did not claim later-generation retinoids outside the listed group.
It did not claim a specific formulation architecture, delivery system, or manufacturing process.
The broad claim depended on the difficult-to-define concept of “synergistic.”
The patent expired in 2010.
The formulation was vulnerable to design-around strategies using concentrations outside the claimed windows or a non-listed retinoid.
The apparent dependency error in claim 12 created a drafting vulnerability.

Overall, the patent was commercially strong during its term for the specific mequinol/tretinoin combination but was not a broad platform patent covering all topical depigmentation products.

How does this patent compare with competing depigmentation patents?

Product or technology	Principal active	Relationship to US 5,194,247
Solagé	Mequinol 4% plus tretinoin 0.01%	Within broad claim 1
Hydroquinone products	Hydroquinone	Outside the literal active-ingredient group
Tretinoin monotherapy	Tretinoin	Outside claim 1 because mequinol is absent
Mequinol monotherapy	Mequinol	Outside claim 1 because a listed retinoid is absent
Triple-combination creams	Hydroquinone, tretinoin, corticosteroid	Not automatically covered; corticosteroid exclusion is material
Azelaic-acid products	Azelaic acid	Outside the listed active-ingredient combination
Cosmetic lightening products	Various	Coverage depends on the listed actives, concentrations, vehicle, and drug-use characterization

The patent did not create a broad monopoly over skin lightening. Its core technology was a particular combination of mequinol and specified retinoids.

What generic entry risks exist today?

There is no current patent-based entry risk from US 5,194,247 because the patent expired in 2010. A present generic or authorized-generic entrant would instead face:

FDA approval requirements.
Reference-product exclusivity issues, if any remain relevant.
Bioequivalence or pharmaceutical-equivalence requirements.
Formulation sameness or permissible difference questions.
Manufacturing and quality-control requirements.
Trade-secret or know-how issues.
Trademark and labeling restrictions.
Other patents unrelated to US 5,194,247.

Biosimilar risk is not applicable. Mequinol and tretinoin are chemically synthesized small molecules, not biologics. The relevant FDA pathway is an ANDA or, depending on the product and regulatory strategy, a 505(b)(2) application. A biosimilar application under the Public Health Service Act is not the appropriate pathway.

Are there licensing deals associated with the patent?

The patent record identifies ownership and assignment information, but a patent document does not establish the full terms of commercial licensing arrangements. Historical commercialization of Solagé involved product-specific corporate rights and FDA sponsorship arrangements, but those commercial agreements should be separated from the patent’s legal scope.

No current licensing premium should be attributed to US 5,194,247. The patent is expired, and any residual value would relate to historical know-how, formulation development, trademarks, regulatory files, manufacturing capabilities, or other unexpired intellectual property.

What is the geographic coverage?

US 5,194,247 provided rights only in the United States. It did not itself protect the formulation in Canada, Europe, Japan, or other markets.

International protection would require separate national or regional applications. Patent expiration analysis must therefore be performed jurisdiction by jurisdiction. A U.S. expiration date cannot be used to determine the status of corresponding foreign patents.

Did the patent create manufacturing or formulation barriers?

During its term, the patent could have created a formulation barrier for a product using:

Mequinol within 0.1% to 5%.
Tretinoin or another listed retinoid within 0.001% to 1%.
A pharmaceutically acceptable topical vehicle.
A depigmentation indication or use.

The patent did not claim a manufacturing method. A competing manufacturer could have pursued a design-around using a different retinoid, a concentration outside the claimed range, or a formulation lacking one of the required elements. After expiration, these formulation barriers no longer apply as patent restrictions.

Key Takeaways

US 5,194,247 covers topical combinations of mequinol and one of three specified retinoids.
Its broadest claim requires 0.1% to 5% mequinol and 0.001% to 1% retinoid.
The Solagé formulation of mequinol 4% and tretinoin 0.01% falls within claim 1.
The same formulation does not fall within narrower claim 3 because its mequinol concentration is above 2%.
Claims 1 through 9 cover compositions; claims 10 through 18 cover topical depigmentation methods.
The “consists essentially of” language permits conventional excipients but may exclude materially altering active ingredients.
The patent issued March 16, 1993, and expired March 16, 2010.
No current Paragraph IV or biosimilar risk arises from this patent.
The patent was a focused combination patent, not a platform patent covering all skin-depigmentation products.
Current commercial barriers would arise from FDA requirements, trademarks, manufacturing know-how, or other unexpired rights rather than US 5,194,247.

FAQs About US Patent 5,194,247

Does US 5,194,247 cover 4% mequinol alone?

No. The claims require mequinol together with at least one of the specified retinoids. Mequinol monotherapy is outside the literal composition claims.

Does a mequinol and tretinoin cream infringe the patent?

It would have fallen within the broad composition claim during the patent term if the concentrations, topical vehicle, retinoid identity, and other claim elements were satisfied. The patent is now expired.

Is Solagé still protected by US 5,194,247?

No. The patent expired in 2010. Any current Solagé protection must be evaluated under other patents, trademarks, regulatory rights, or proprietary know-how.

Could hydroquinone be substituted for mequinol?

A hydroquinone product would not literally satisfy the claim limitation requiring 4-hydroxyanisole. Equivalence would depend on the specific facts and cannot be presumed from the chemical similarity.

Is a generic mequinol/tretinoin product subject to biosimilar approval?

No. Mequinol and tretinoin are small-molecule drugs. A generic product would generally proceed through an ANDA strategy or another applicable small-molecule FDA pathway.

References

U.S. Food and Drug Administration. (2000). Solagé (mequinol and tretinoin) topical solution 4%/0.01% prescribing information. FDA.
U.S. Patent No. 5,194,247. (1993). Synergistic skin depigmentation compositions. U.S. Patent and Trademark Office.
U.S. Patent and Trademark Office. (n.d.). Patent term adjustment and patent term information. USPTO.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. FDA.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	104544	⤷ Start Trial
Brazil	1100177	⤷ Start Trial
Canada	2022917	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,194,247

Summary for Patent: 5,194,247