United States Patent 5,932,622: Scope, Claim Analysis, Expiration, and Alitretinoin Patent Landscape

U.S. Patent No. 5,932,622 covers methods of using 9-cis-retinoic acid, also known as alitretinoin, to modulate specified non-malignant skin disorders and the development of benign skin tumors. The claims are method-of-treatment claims, not composition, formulation, manufacturing, or product-by-process claims. The patent’s U.S. term has expired, so it does not create a current blocking patent right for alitretinoin use in the United States.

What does U.S. Patent 5,932,622 cover?

The patent covers administering an effective amount of 9-cis-retinoic acid, either as the active compound or in a pharmaceutically acceptable carrier, to achieve modulation of specified skin conditions.

The two independent claims have different subject matter:

Claim	Covered subject	Required active	Required result
1	Non-malignant skin disorders	9-cis-retinoic acid	In vivo modulation of aging, wrinkling, acne, keratinization, differentiation, or proliferation disorders
2	Benign skin tumors	9-cis-retinoic acid	In vivo modulation of benign tumor development

The patent does not require a particular dosage, route of administration, formulation, concentration, treatment duration, patient age, disease severity, or clinical endpoint. Those omissions broaden the literal scope of the claims, subject to the requirements that the accused conduct satisfy every claim element.

How should claim 1 be construed?

Claim 1 requires the following elements:

A method.
In vivo treatment of a subject.
A non-malignant skin disorder.
The disorder must fall within the listed categories:
- aging;
- wrinkling;
- acne;
- keratinization disorders;
- differentiation disorders; or
- proliferation disorders.
Administration of an effective amount of 9-cis-retinoic acid.
The compound may be administered in a pharmaceutically acceptable carrier.

What does “in vivo modulation” require?

“In vivo” limits the claim to treatment of a living subject. In vitro assays, ex vivo skin cultures, isolated-cell experiments, and purely cosmetic formulations without administration to a subject would not satisfy that element.

“Modulation” is broader than complete treatment or cure. It can include increasing, decreasing, regulating, altering, or otherwise affecting a biological or clinical process. For an infringement case, the patent owner would still need to establish that the accused use produces the claimed modulation and that the administered amount is “effective.”

Are aging and wrinkling separate claim categories?

Yes. “Aging” and “wrinkling” are separately listed disorders. A product used to reduce facial wrinkles could potentially fall within the wrinkling category without also requiring a diagnosis of a broader aging disorder.

The specification and prosecution history would be relevant to determine whether “wrinkling” is limited to pathological skin wrinkling or includes cosmetic treatment. The claim language itself does not expressly restrict the use to a prescription dermatologic disease or to medically diagnosed skin aging.

Does claim 1 cover acne treatment?

Yes. Acne is expressly identified. The claim is not limited to a particular type of acne, lesion, age group, treatment regimen, or combination therapy. A method using alitretinoin to treat acne could have fallen within the claim during the patent term if the other limitations were met.

The claim would not necessarily cover every retinoid acne treatment. 9-cis-retinoic acid is a specific retinoid and is chemically distinct from tretinoin, isotretinoin, adapalene, tazarotene, and trifarotene.

What are keratinization, differentiation, and proliferation disorders?

These categories create broader functional and pathological coverage than the expressly named conditions. They may encompass disorders involving abnormal epidermal keratin production, altered cellular differentiation, or abnormal skin-cell proliferation.

Potentially relevant conditions could include disorders characterized by hyperkeratosis, abnormal epidermal maturation, or excessive proliferation. The scope would depend on the specification, prosecution history, and the ordinary meaning of the terms at the relevant filing date.

The claim does not expressly require that the disorder be named in a regulatory label. A therapeutic use can fall within a method patent even if the use is off-label, provided the claim elements are satisfied.

How should claim 2 be construed?

Claim 2 covers administering 9-cis-retinoic acid to modulate the development of benign tumors in the skin.

Its core limitations are:

a living subject;
benign tumors located in the skin;
administration of an effective amount of 9-cis-retinoic acid; and
modulation of tumor development.

The claim does not require tumor regression. “Modulation of development” could include inhibiting growth, delaying progression, reducing formation, altering differentiation, or affecting tumor biology. The absence of a specific tumor type expands the apparent claim scope, although courts would construe the term “benign tumors” in light of the patent disclosure and prosecution record.

The claim is narrower than claim 1 in one respect because it is directed specifically to benign skin tumors. It is broader in another respect because it does not list particular tumor types or require a specific mechanism of action.

Does the patent cover alitretinoin formulations?

The patent covers administration of 9-cis-retinoic acid “or pharmaceutically acceptable carriers containing same.” That language permits the active ingredient to be administered in a carrier, but it does not independently claim the carrier or a specific formulation.

What formulations could have been implicated?

During the patent term, the claims could potentially have reached:

topical gels;
creams;
ointments;
lotions;
emulsions;
oral dosage forms;
injectable or other systemic preparations; and
compounded dermatologic preparations.

The claims do not specify a topical route. A topical product would be relevant because the conditions are cutaneous, but oral or systemic administration is not excluded by the claim language.

What does the patent not claim?

U.S. Patent 5,932,622 does not, based on the supplied claims, independently claim:

a composition containing a defined concentration of alitretinoin;
a gel with specified excipients;
a particular particle size or crystal form;
a dosing schedule;
a delivery device;
a manufacturing process;
a stability profile;
a combination with another active ingredient; or
a specific commercial product.

Those subjects would require separate claims in the patent or in related patents.

What is the relationship between 9-cis-retinoic acid and Panretin?

9-cis-retinoic acid is alitretinoin. The U.S. Food and Drug Administration approved Panretin, a topical alitretinoin gel, for the topical treatment of cutaneous lesions associated with AIDS-related Kaposi’s sarcoma. The approved product is a prescription topical gel, not an FDA-approved acne or cosmetic anti-wrinkle product.[2]

Attribute	U.S. Patent 5,932,622	Panretin
Active ingredient	9-cis-retinoic acid	Alitretinoin, 9-cis-retinoic acid
Patent subject	Broad treatment methods for specified skin disorders and benign tumors	Commercial topical product
FDA status	Patent document, not an approval	FDA-approved topical gel
Approved U.S. indication	None by patent itself	Cutaneous lesions of AIDS-related Kaposi’s sarcoma
Dosage form required by patent claims	None	Topical gel
Current patent barrier from ’622	None; expired	Product-specific regulatory and commercial considerations may remain

The approved indication for Panretin does not automatically establish infringement of every claim in the ’622 patent. A marketed product would need to be evaluated against each claim element, including the claimed disorder and the required modulation.

When did U.S. Patent 5,932,622 lose exclusivity?

The patent’s original 20-year U.S. patent term expired in the early 2010s, calculated from the earliest effective nonprovisional filing date in the relevant family. U.S. Patent 5,932,622 is therefore expired and cannot presently be asserted to block generic, compounded, or other alitretinoin use in the United States.

The patent’s 1999 issue date does not control expiration. Under the Uruguay Round Agreements Act, utility patents filed after June 8, 1995 generally receive a term measured from the earliest effective nonprovisional filing date, rather than 17 years from issuance. Earlier priority filings and continuation relationships can materially affect the calculation.[3]

The expired status has several consequences:

no current injunction can be based solely on the ’622 patent;
no current Paragraph IV certification is needed against an expired patent;
the patent cannot support a new Hatch-Waxman stay;
historical infringement claims remain subject to applicable limitation periods; and
later patents must be analyzed separately for formulation, manufacturing, or product-specific protection.

What is the Orange Book status of alitretinoin?

Panretin was approved by FDA as a prescription drug. Orange Book analysis must distinguish the approved product from the expired method patent.

An Orange Book-listed patent must meet the statutory and regulatory requirements for listing against the approved drug. A broad method patent that is expired is not a current barrier to ANDA approval. Even if a related alitretinoin patent was historically listed, its expiration eliminates its ability to delay approval based on the Hatch-Waxman patent-certification framework.[4]

The ’622 patent should not be treated as a live Orange Book exclusivity asset. It does not provide current market exclusivity for Panretin or for a new alitretinoin product.

Were Paragraph IV challenges relevant?

Paragraph IV certifications are relevant only when an ANDA applicant seeks approval before expiration of a listed patent and alleges that the patent is invalid, unenforceable, or not infringed.

For U.S. Patent 5,932,622:

a Paragraph IV challenge could have been relevant while the patent was unexpired and listed against an approved reference product;
a Paragraph IV certification is no longer commercially meaningful against the expired patent;
the patent cannot generate a 30-month stay for a present-day ANDA; and
any current ANDA dispute would more likely concern other listed patents, regulatory exclusivity, product sameness, labeling, or manufacturing issues.

No current Paragraph IV risk should be assigned to the ’622 patent itself.

What patent landscape surrounds alitretinoin?

The relevant landscape divides into five categories.

1. Core active-ingredient and therapeutic-use patents

These patents cover alitretinoin, retinoid receptor activity, treatment of dermatologic disorders, and particular therapeutic applications. U.S. Patent 5,932,622 belongs to the therapeutic-use category.

Because the patent is expired, it has historical rather than current blocking value.

2. Formulation patents

Formulation patents can cover:

topical gel composition;
solubilization of alitretinoin;
excipient systems;
stability improvement;
skin penetration;
preservation systems;
viscosity and rheology;
packaging; and
methods of reducing irritation.

A formulation patent can remain relevant after an older method patent expires if it has a later priority date and has not expired. A competitor may avoid such claims by using different excipients, concentrations, packaging, or manufacturing conditions.

3. Method-of-use patents

Later patents may target:

specific dermatologic diseases;
defined patient populations;
combination treatment;
dosing frequency;
lesion-specific therapy;
treatment of precancerous or neoplastic conditions; or
cosmetic applications.

A later method patent cannot restore the expired term of the ’622 patent. It can, however, create a separate infringement risk if a later use falls within its claims.

4. Manufacturing and process patents

Manufacturing protection may concern:

stereoisomer control;
synthesis of 9-cis-retinoic acid;
purification;
isomerization control;
crystallization;
polymorph selection;
impurity limits; and
prevention of light- or oxidation-driven degradation.

These rights can create practical market-entry barriers even when the principal treatment patent has expired. They do not prevent all lawful manufacture if a noninfringing process is available.

5. Regulatory exclusivity

Alitretinoin is a small molecule, so biosimilar rules do not apply. A competing product would use an ANDA, 505(b)(2) application, or potentially a full NDA, depending on the reference product, formulation, route, and proposed labeling.

Relevant regulatory considerations include:

pharmaceutical equivalence;
bioequivalence or comparative clinical data;
topical product performance;
inactive-ingredient differences;
labeling scope;
safety data; and
any remaining listed patents.

Is there biosimilar risk for alitretinoin?

No. Alitretinoin is a chemically synthesized small molecule, not a biologic subject to the Public Health Service Act biosimilar pathway. The appropriate competitive framework is generic or follow-on small-molecule approval, not biosimilar substitution.

A topical alitretinoin product may present more complex development issues than a conventional oral tablet. FDA may focus on formulation sameness, local delivery, pharmacokinetic comparability, irritation, and product performance. Those regulatory requirements do not extend the expired patent term.

How strong is the patent estate for the claimed uses?

The ’622 patent had relatively broad claim architecture during its term because it:

covered multiple disorder categories;
did not specify a dosage;
did not require a particular formulation;
did not limit administration to topical treatment; and
used functional language such as “modulation.”

Its weaknesses included:

lack of composition or formulation claims in the supplied claims;
dependence on proof that 9-cis-retinoic acid was administered;
dependence on proof of an “effective amount”;
potential written-description and enablement issues for broad disorder categories;
possible obviousness arguments based on prior retinoid pharmacology; and
the need to establish that the accused condition falls within the claimed disorder category.

Today, its legal strength is zero as a blocking patent because it has expired. Historical breadth does not create present exclusivity.

Which companies are challenging the patent or competing with alitretinoin?

No current competitive challenge against the ’622 patent is required because the patent has expired. The commercial competitive set includes:

Product or class	Active ingredient	Principal competitive area
Panretin	Alitretinoin	Cutaneous AIDS-related Kaposi’s sarcoma
Tretinoin products	Tretinoin	Acne, photoaging
Isotretinoin products	Isotretinoin	Severe acne
Adapalene products	Adapalene	Acne
Tazarotene products	Tazarotene	Acne, plaque psoriasis, photoaging
Trifarotene products	Trifarotene	Acne
Bexarotene products	Bexarotene	Cutaneous T-cell lymphoma

These products are not automatically substitutes for Panretin. They differ in receptor selectivity, approved indications, safety profiles, formulation, and regulatory labeling.

What generic-entry scenarios exist?

Three scenarios are commercially plausible:

Scenario 1: Generic topical alitretinoin

A sponsor could pursue a topical product referencing Panretin, subject to FDA requirements and any remaining product-specific patent listings. The expired ’622 patent would not prevent entry.

Scenario 2: 505(b)(2) alitretinoin product

A reformulated product, new strength, new route, or new indication could use the 505(b)(2) pathway. A sponsor may need additional clinical or pharmacology data, particularly if the proposed product differs materially from the approved topical gel.

Scenario 3: New indication or cosmetic product

An acne, photoaging, or benign-tumor product could require a new regulatory strategy. Cosmetic positioning does not eliminate patent analysis if the product is marketed with disease-treatment claims. The expired ’622 patent itself would not block the use.

What patent litigation affects U.S. Patent 5,932,622?

The supplied patent claims do not establish a current litigation dispute. The patent’s expired status means that present litigation cannot seek prospective exclusion based solely on the ’622 patent.

Historical litigation analysis should distinguish:

infringement claims filed during the patent term;
validity challenges;
ownership or inventorship disputes;
ANDA litigation concerning Panretin or related patents; and
disputes involving later formulation or manufacturing patents.

The existence of a patent number, FDA approval, or commercial product does not establish that the ’622 patent was listed, litigated, or asserted against a specific company.

What is the geographic coverage of the patent?

U.S. Patent 5,932,622 covered conduct within the territorial scope of U.S. patent law. It did not directly protect alitretinoin use in Europe, Japan, Canada, or other jurisdictions.

International protection would require separate national or regional patents. A U.S. expiration date has no automatic legal effect on foreign patent rights, although related foreign family members may also have expired based on similar filing dates.

Key Takeaways

U.S. Patent 5,932,622 covers in vivo use of 9-cis-retinoic acid, or alitretinoin, for specified non-malignant skin disorders and benign skin tumors.
Claim 1 expressly includes aging, wrinkling, acne, keratinization, differentiation, and proliferation disorders.
Claim 2 covers modulation of benign skin-tumor development.
The supplied claims are method claims, not formulation, composition, manufacturing, or product claims.
The patent does not require a specific dose, route, formulation, concentration, or treatment duration.
The patent’s U.S. term expired in the early 2010s.
The ’622 patent is not a current blocking right and cannot support a present Paragraph IV stay.
Alitretinoin is a small molecule, so biosimilar rules do not apply.
Panretin remains the principal U.S. alitretinoin reference product, with FDA approval for cutaneous AIDS-related Kaposi’s sarcoma.
Current freedom-to-operate analysis should focus on later formulation, manufacturing, packaging, regulatory, and product-specific patents rather than the expired ’622 patent.

Frequently Asked Questions

Can a company market alitretinoin for acne now without infringing U.S. Patent 5,932,622?

Yes. The patent has expired, so it no longer blocks alitretinoin use for acne. FDA approval, labeling, safety, and any later unexpired patents remain separate issues.

Does U.S. Patent 5,932,622 cover tretinoin or isotretinoin?

No. The claims identify 9-cis-retinoic acid. Tretinoin is all-trans-retinoic acid, and isotretinoin is 13-cis-retinoic acid. Chemical identity matters to literal infringement.

Does the patent cover cosmetic anti-wrinkle products?

Historically, claim 1 expressly included wrinkling and did not state that treatment had to be for a prescription disease. The expired patent cannot presently block such a product.

Can a generic alitretinoin product use a different topical gel formulation?

Yes, subject to any unexpired formulation or manufacturing patents and FDA requirements. The ’622 claims do not require a particular carrier or gel composition.

Is Panretin protected by exclusivity today?

The ’622 patent does not provide current exclusivity. Any present protection would have to arise from other patents, regulatory protections, manufacturing rights, trademarks, or commercial barriers.

References

United States Patent and Trademark Office. (1999). U.S. Patent No. 5,932,622: Methods for treating skin disorders using 9-cis-retinoic acid.
U.S. Food and Drug Administration. (1999). Panretin (alitretinoin) gel 0.1% prescribing information.
United States Code, 35 U.S.C. §§ 154, 156, 271, and 282.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0617614	⤷ Start Trial	CA 2001 00012	Denmark	⤷ Start Trial
European Patent Office	0617614	⤷ Start Trial	SPC/GB01/014	United Kingdom	⤷ Start Trial
European Patent Office	0617614	⤷ Start Trial	C300043	Netherlands	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 5,932,622