United States Drug Patent RE36068: Scope, Claims, Expiration, and Retinoid Patent Landscape

United States Patent RE36,068 is an expired method-of-treatment patent covering topical retinoid therapy for sun-damaged human skin. Its central claim requires a maintenance-treatment program using a retinoid in a dermatologically acceptable vehicle at a dose low enough to avoid excessive irritation, with the intended result of improving collagen, elastic fibers, small blood vessels, firmness, turgor, and elasticity. The patent does not claim tretinoin, retinol, a specific cream formula, or a manufacturing process as such.

The patent reissued on March 9, 1999, from U.S. Patent No. 4,603,146. The underlying patent term expired on July 29, 2003. RE36,068 therefore creates no current U.S. patent barrier to generic tretinoin, retinol, or other topical retinoid products. It is not a current Orange Book exclusivity asset.

What patent is United States RE36068?

RE36,068 is titled “Treatment of Skin with Retinoids.” The patent was assigned to the Trustees of the University of Pennsylvania and is associated with work by Albert M. Kligman concerning the treatment of photodamaged skin with topical retinoids. The reissue corrected and revised claims from U.S. Patent No. 4,603,146 rather than creating a new commercial product patent.

Item	Data
U.S. patent	RE36,068
Original patent	U.S. 4,603,146
Title	Treatment of skin with retinoids
Original filing priority	July 29, 1983
Original patent grant	July 29, 1986
Reissue grant	March 9, 1999
Assignee	Trustees of the University of Pennsylvania
Technology	Topical retinoid treatment of photodamaged skin
Patent type	Method-of-treatment patent
Patent expiration	July 29, 2003
Current status	Expired
Current generic-blocking effect	None

The original patent term was governed by the pre-1995 U.S. patent term rule, under which the term generally ran for 17 years from grant. Reissue practice did not extend the underlying patent term. The reissue certificate therefore did not revive exclusivity after July 29, 2003.[1][2]

What does claim 1 of RE36068 cover?

Claim 1 is the patent’s core method claim. It covers a method for treating sun-damaged human skin by applying a topical retinoid composition as maintenance therapy.

A practicing product or treatment would need to satisfy the principal elements below:

Claim element	Scope
Patient or subject	Human
Condition	Sun-damaged skin
Administration	Topical application to the skin surface
Active agent	An effective amount of a retinoid
Vehicle	Nontoxic, dermatologically acceptable vehicle
Treatment pattern	Program of maintenance therapy
Dose limitation	Insufficient to cause excessive irritation
Intended physiological result	Retarding or reversing loss of collagen, abnormal elastic-fiber changes, and deterioration of small blood vessels
Clinical result	Skin substantially regains and maintains firmness, turgor, and elasticity during therapy

The claim is narrower than a general claim to “using a retinoid on skin.” It requires a specific disease or condition context, sun-damaged human skin, and a maintenance regimen. A topical retinoid used solely for acne, psoriasis, keratinization disorders, or another non-photodamage indication would not necessarily satisfy the claim.

The claim also contains result-oriented language. The treatment must be directed to the stated structural changes in photodamaged skin. The phrase “whereby” generally describes the result associated with the claimed method, but its effect on claim scope would depend on how a court construed the claim and the evidence of intended use, dosing, and clinical effect.

How do claims 2 through 5 define the retinoid class?

Claims 2 through 5 create nested retinoid alternatives.

Claim 2: retinoic acids and derivatives

Claim 2 narrows claim 1 to retinoic acids, retinoic acid derivatives, and stereoisomers. This language covers a broad chemical class, subject to the requirements of claim 1.

The claim is not limited to tretinoin. It potentially encompasses multiple retinoid structures, including retinoic-acid analogues and stereoisomers, provided the compound is used in the claimed topical maintenance method.

Claim 3: 13-cis-retinoic acid and derivatives

Claim 3 narrows the class to 13-cis-retinoic acid, commonly known as isotretinoin, and derivatives of that compound.

The claim does not cover every use of oral or topical isotretinoin. It remains subject to claim 1’s requirements, including topical application to sun-damaged human skin and maintenance therapy at a dose that avoids excessive irritation.

Claim 4: specified synthetic retinoids

Claim 4 identifies several named or structurally described retinoids, including compounds based on substituted cyclohexenyl, naphthalenyl, and benzyl structures. These are principally research or development compounds rather than the active ingredients associated with the principal commercial topical retinoid products in the U.S. market.

Claim 4 is commercially less important than claims 2, 3, and 11 because the listed compounds have not been the main basis of the U.S. topical tretinoin market.

Claim 5: extensive enumerated list

Claim 5 lists a broader set of specific retinoid compounds, including:

13-cis-retinoic acid;
retinoid acids, esters, and amides;
7,8-didehydroretinoic acid;
TTNPB;
substituted benzoic acids;
substituted naphthalene carboxylic acids;
tetralin and indene derivatives; and
the corrected compound reflected in the reissue text by the “Iadd” and “Iaddend” notation.

The claim’s long chemical list increases literal coverage of named analogues but does not convert the patent into a general composition patent. Each listed compound must still be used in the method required by claim 1.

Does RE36068 cover tretinoin?

RE36,068 can reach topical tretinoin treatment only through the claim’s method limitations, not because it claims tretinoin as a molecule.

Tretinoin is all-trans-retinoic acid. It falls within the broad retinoic-acid category of claim 2. A topical tretinoin regimen directed at sun-damaged human facial skin could historically have presented a claim-overlap issue if it also met the maintenance, vehicle, dosage, and therapeutic-result limitations.

That overlap does not create a current freedom-to-operate problem because RE36,068 expired in 2003. Current tretinoin products are evaluated against later and separate patents, including formulation, delivery-system, manufacturing, and product-specific intellectual property.

Does claim 11 cover retinol?

Claim 11 expressly identifies retinol. It depends on claim 1, so retinol alone is not enough. The method must still involve:

topical application;
sun-damaged human skin;
an effective amount;
a dermatologically acceptable vehicle;
maintenance therapy; and
a dose insufficient to cause excessive irritation.

Retinol is chemically different from tretinoin and is generally converted through metabolic pathways before exerting retinoid activity. Claim 11 nevertheless expressly places retinol within the claimed method.

Because the claim has expired, claim 11 has no present U.S. exclusionary effect.

What formulations are protected by RE36068?

RE36,068 protects a treatment method rather than a defined formulation.

Claims 9 and 10 narrow the vehicle:

Claim 9 covers a cream or ointment vehicle.
Claim 10 covers an emollient vehicle.

The claims do not specify:

a concentration range;
a particular excipient;
a particle size;
a delivery system;
a preservative;
a pH;
a packaging configuration;
a controlled-release mechanism; or
a branded product.

A cream containing tretinoin could have fallen within the expired method claims when used for the claimed photodamage indication. The patent did not prevent a company from developing a different cream composition after expiration, and it did not provide continuing protection for a specific commercial formulation.

How does the patent compare with formulation and delivery patents?

The commercial patent landscape for topical retinoids has historically been divided into four categories.

Patent category	Typical subject matter	Relevance after RE36,068 expiration
Method of treatment	Treating photodamaged skin with retinoids	RE36,068 is expired
Active ingredient	New retinoid molecules or derivatives	Relevant only if unexpired and product-specific
Formulation	Cream, gel, lotion, emulsion, or stability system	Can create product-level barriers
Delivery system	Microspheres, encapsulation, controlled release, or reduced-irritation delivery	Can affect generic substitution and non-infringement design
Manufacturing	Synthesis, purification, particle production, or scale-up process	May create process or supply-chain barriers
Regulatory exclusivity	New-drug, pediatric, or other FDA exclusivity	Separate from patent term

The most important distinction is between a method patent and a formulation patent. RE36,068 did not require a generic manufacturer to use a particular vehicle technology. A later product could avoid an unexpired formulation patent by using a different excipient system while still containing the same active ingredient.

What is the Orange Book status of RE36068?

RE36,068 is not a current Orange Book patent barrier. The patent expired in 2003, and expired patents do not block FDA approval or commercial launch of a generic product.

For FDA-regulated topical tretinoin products, relevant Orange Book analysis focuses on patents submitted by the applicable reference drug sponsors and accepted for listing against particular approved drug products. A historical listing, if any, would not preserve enforceable rights after patent expiration.[3]

Orange Book status must be analyzed at the product level. Tretinoin products can have different:

strengths;
dosage forms;
approved indications;
reference listed drugs;
listed patents;
generic applicants; and
litigation histories.

A patent covering a particular microsphere or gel formulation would not automatically apply to a conventional tretinoin cream. Conversely, the absence of an active patent for a conventional cream would not establish freedom from every delivery-system patent.

When did RE36068 lose exclusivity?

The patent lost enforceable exclusivity on July 29, 2003.

Date	Event
July 29, 1983	Priority date
July 29, 1986	Original U.S. patent granted
March 9, 1999	Reissue RE36,068 granted
July 29, 2003	Underlying patent term expired
After July 29, 2003	No enforceable RE36,068 patent rights

The reissue date does not reset the expiration date. A reissue patent generally carries the remaining term of the original patent, subject to statutory limitations.[2]

Which companies challenged or licensed RE36068?

No current Paragraph IV challenge is legally meaningful for RE36,068 because the patent has expired. A generic applicant does not need to defeat an expired patent to obtain approval or launch.

Publicly available patent records identify the University of Pennsylvania as the patent owner or assignee associated with the original technology. The patent record does not establish a current license, royalty obligation, or settlement that would restrict generic use of the expired claims.

Commercial rights in topical tretinoin and photodamage products were historically distributed among pharmaceutical companies, dermatology companies, and licensees. Those commercial relationships should not be confused with ownership of RE36,068. A company may have licensed a product, formulation, trademark, or regulatory asset without owning this patent.

What Paragraph IV and litigation risks exist today?

RE36,068 presents no current Paragraph IV risk because there is no unexpired patent to certify against.

For a current generic topical retinoid filing, the relevant risks would instead include:

Paragraph IV challenges to unexpired Orange Book patents;
patent litigation over formulation or delivery technology;
induced-infringement allegations based on labeling;
process-patent disputes involving active-ingredient manufacture;
trade-secret claims involving formulation or scale-up;
regulatory exclusivity that delays approval even without patent protection; and
substitution limitations caused by differences in dosage form or delivery system.

A generic applicant seeking approval for a conventional tretinoin cream would ordinarily analyze the approved reference product’s current Orange Book entries, not rely solely on the expiration of RE36,068.

Is biosimilar risk relevant to RE36068?

No. Biosimilar law is not the relevant competitive framework.

The covered products are small-molecule retinoids, including tretinoin, isotretinoin, and retinol. FDA competition generally proceeds through the abbreviated new drug application pathway for eligible small-molecule products, rather than the biologics license application and biosimilar pathway under the Public Health Service Act.[4]

The relevant competitive threats are:

generic tretinoin;
authorized generic products;
alternative topical retinoids;
retinol and retinal products;
adapalene and other retinoid-like agents; and
differentiated creams, gels, lotions, and delivery systems.

How strong was the RE36068 patent estate?

Historically, the patent had meaningful conceptual breadth but limited structural depth.

Strength factor	Assessment
Therapeutic concept	Broad: topical retinoid treatment of photodamaged skin
Active ingredient coverage	Broad through retinoid categories and enumerated compounds
Formulation coverage	Narrow: cream, ointment, and emollient vehicle limitations
Dose coverage	Functional rather than numerical
Maintenance-therapy coverage	Important narrowing limitation
Manufacturing coverage	None apparent from the cited claims
Composition claims	None apparent from the cited claims
Product-specific protection	Limited
Current enforceability	None because expired

The patent’s principal historical value was its method coverage across multiple retinoids. Its weaknesses were the absence of a defined concentration, lack of composition claims, lack of manufacturing claims, and reliance on functional terms such as “effective amounts,” “excessive irritation,” and “substantially regains.”

Those terms could have created claim-construction and proof issues in litigation. A patent owner would have needed to establish that the accused regimen was directed to the claimed condition and satisfied the maintenance and irritation limitations. A generic or competitor could have challenged infringement on the basis that its label did not direct treatment of photodamaged skin or that its product and dosing regimen did not satisfy the claimed result.

What generic launch scenarios exist for retinoid products?

For RE36,068 itself, generic launch is unrestricted by the patent. The practical scenarios are product-specific.

Conventional tretinoin cream

A conventional tretinoin cream faces no current RE36,068 barrier. The relevant analysis is the reference product’s active Orange Book patents, formulation patents, and regulatory exclusivity.

Tretinoin gel or lotion

A gel or lotion may avoid cream- or ointment-specific claims but can encounter separate gel, emulsion, stability, or delivery patents.

Microsphere or controlled-release tretinoin

A microsphere product may face technology-specific patents even though the underlying method patent has expired. The commercial value may depend on reduced irritation, sustained delivery, or improved tolerability.

Retinol cosmetic or drug product

Retinol products do not face RE36,068 because the patent is expired. Regulatory classification remains important. A cosmetic claim concerning appearance may be treated differently from a therapeutic claim to reverse photodamage or alter skin structure.

Alternative retinoids

Adapalene and other retinoid-like compounds must be analyzed against their own product patents, regulatory records, and labeling. RE36,068 does not provide a current barrier to those products.

What geographic coverage does RE36068 provide?

RE36,068 provides only U.S. patent coverage. It does not establish rights in:

Canada;
Europe;
Japan;
China;
South Korea;
Australia; or
other jurisdictions.

Foreign counterparts, if filed, would have had separate priority, prosecution, and expiration dates. The U.S. expiration date cannot be used to determine the status of corresponding foreign patents.

For multinational launch planning, the relevant review must distinguish:

U.S. method claims;
foreign method claims;
product and formulation claims;
regulatory exclusivity; and
local rules governing medical-use patents and generic labeling.

Key Takeaways

RE36,068 is an expired U.S. method-of-treatment patent for topical retinoid maintenance therapy in sun-damaged human skin.
The patent reissued on March 9, 1999, but its underlying term expired on July 29, 2003.
Claim 1 requires topical application, human sun-damaged skin, maintenance therapy, an acceptable vehicle, and a low-irritation dose.
Claims 2 through 5 cover broad and enumerated retinoid classes, while claim 11 expressly covers retinol.
Claims 6 through 10 narrow the method to facial skin and specified vehicle types.
The patent does not claim tretinoin as a molecule, a commercial cream, a manufacturing process, or a delivery system.
RE36,068 has no current Orange Book blocking effect and creates no current Paragraph IV risk.
Biosimilar analysis is irrelevant because the covered products are small-molecule retinoids.
Current competitive risk comes from later formulation, delivery, manufacturing, regulatory, and product-specific patents.

FAQs About U.S. Patent RE36068

Can a company launch topical tretinoin without a license to RE36068?

Yes. RE36,068 expired on July 29, 2003. A current launch must still address any later unexpired patents and FDA requirements associated with the selected reference product.

Did RE36068 cover Retin-A?

The claims could historically reach certain topical tretinoin uses, including treatment of sun-damaged skin, because tretinoin is a retinoic acid. The patent did not claim the Retin-A trademark or every use of every tretinoin formulation.

Does RE36068 cover cosmetic retinol products?

Claim 11 expressly names retinol, but only within the expired method claim. The patent has no current exclusionary effect on cosmetic or therapeutic retinol products.

Is RE36068 a composition patent?

No. The cited claims are method claims. They require use of a retinoid composition but do not claim the composition independently.

Can a patent reissue extend the term of RE36068?

No. The reissue did not reset the original patent term. RE36,068 expired with the underlying patent term on July 29, 2003.

References

United States Patent and Trademark Office. (1986). U.S. Patent No. 4,603,146, Treatment of skin with retinoids.
United States Patent and Trademark Office. (1999). U.S. Patent No. RE36,068, Reissue of U.S. Patent No. 4,603,146.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
U.S. Food and Drug Administration. (2024). Abbreviated new drug application process for generic drugs.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	5289686	⤷ Start Trial
Australia	598454	⤷ Start Trial
Australia	599135	⤷ Start Trial
Australia	7804687	⤷ Start Trial
Canada	1303996	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: RE36068

Summary for Patent: RE36068