Details for Patent: 5,721,275

Summary for Patent: 5,721,275

Title:	Slow release vehicles for minimizing skin irritancy of topical compositions
Abstract:	PCT No. PCT/US90/03219 Sec. 371 Date Jan. 21, 1992 Sec. 102(e) Date Jan. 21, 1992 PCT Filed Jun. 7, 1990 PCT Pub. No. WO90/14833 PCT Pub. Date Dec. 13, 1990Staple, aqueous gel vehicles are provided for the topical application to the skin of irritating active ingredients such as retinoids, particularly tretinoin, with slow release of the active ingredient and minimal irritancy to the skin. The vehicles include a gelling agent effective to form a gel and hold the active ingredient in the aqueous medium for slow release on the skin, and an effective amount of an antioxidant to retard decomposition of the active ingredient. The vehicles and formulations are preferably aqueous emulsions which contain a solubilizing agent for the generally non-water soluble active ingredients, as well as usually an emulsifying agent and/or surfactant. Chelating agents, emollients, preservatives and other adjuvants and additives may also be included in the vehicles and formulations.
Inventor(s):	Gail S. Bazzano
Assignee:	Alyzan Inc
Application Number:	US07/856,157
Patent Claim Types: see list of patent claims	Use; Composition; Compound;

US Patent 5,721,275: Scope, Claims, Expiration, and Retinoid Patent Landscape

US Patent 5,721,275 covers stable, aqueous topical retinoid compositions that use a neutralized high-molecular-weight polyacrylic acid gel to slow retinoid release and an antioxidant to limit degradation. The independent claim is a formulation combination claim, not a claim to tretinoin itself, a method of treating acne, or a manufacturing process. The patent has expired, eliminating current patent-enforcement risk from this patent in the United States.

What does US Patent 5,721,275 protect?

The patent protects a topical aqueous retinoid composition containing four required elements:

Required element	Claim 1 requirement	Technical function
Aqueous medium	At least about 40 wt% water	Provides a water-rich topical vehicle
Retinoid	Therapeutically effective amount	Treats a skin condition
Polyacrylic acid gelling agent	High molecular weight; neutralized to pH about 3-7	Forms a gel and holds retinoid for slow release
Antioxidant	Effective amount	Retards retinoid decomposition

The central inventive concept is the combination of a water-rich vehicle, a neutralized polyacrylic acid gel, and an antioxidant. The claim does not cover every aqueous tretinoin product. A competing product must satisfy the limitations of the claim, either literally or under a possible doctrine-of-equivalents theory.

Claim 1 uses the transitional term “comprising.” That language generally permits additional ingredients unless those ingredients defeat another express limitation. A product may therefore contain preservatives, solvents, surfactants, oils, emulsifiers, chelating agents, fragrance, or other excipients and still fall within the literal scope of claim 1.

How should claim 1 be construed?

Claim 1 is the key scope-bearing claim. Its limitations should be analyzed as a complete combination.

“Stable, aqueous retinoid composition”

The preamble identifies the composition as stable, aqueous, intended for topical application, and designed for slow retinoid release with reduced irritation. The operative formulation limitations appear in paragraphs (a) through (d). The terms “stable,” “slow release,” and “minimal irritancy” may be relevant to claim construction and infringement analysis, particularly if the specification defines testing methods or performance thresholds.

The claim does not state a specific shelf-life period, degradation limit, release rate, particle size, viscosity, or irritation score. Unless the specification supplies a limiting definition, those functional terms may be argued to describe the intended performance of the claimed formulation rather than impose a precise numerical requirement.

“At least about 40 weight percent water”

This limitation excludes anhydrous products and many conventional oil-in-water creams with lower water content. It also creates a meaningful distinction from ointments and low-water emulsion systems.

The word “about” creates numerical flexibility. The relevant calculation is the composition’s total weight, including active ingredient and excipients. Claim 2 narrows the water content to at least about 50 weight percent.

“High molecular weight polyacrylic acid gelling agent”

This is the principal structural limitation. The claim requires a polyacrylic acid-based gelling agent with sufficiently high molecular weight to produce a gel after neutralization. Commercial carbomer-type polymers would be natural candidates for analysis, although infringement depends on the product’s actual polymer identity, molecular-weight characteristics, neutralization state, and formulation behavior.

The claim does not name a specific carbomer grade. It also does not specify the polymer concentration in claim 1. Claim 2 supplies a narrower range of about 0.1 to 10 wt%.

“Neutralized to a pH of about 3 to 7”

The gelling agent must be neutralized within the stated pH range. This limitation links the polymer’s gel-forming function to the acidity of the finished composition or to the relevant formulation stage, depending on how the specification describes the process.

A product with a finished pH above 7 may fall outside the literal wording of this limitation, although the analysis would depend on whether the patent treats pH as a property of the composition, the polymer phase, or the formulation during preparation.

“Hold said retinoid for slow release”

This is a functional limitation. The formulation must retain the retinoid in the gel sufficiently to provide slow release. The patent’s examples, release-testing methods, viscosity data, and comparative irritation results would be important in determining whether a product satisfies the limitation.

A formulation that simply dissolves tretinoin in a water-miscible solvent without a qualifying polyacrylic acid gel would present a weaker literal infringement case.

“Antioxidant effective to retard decomposition”

The antioxidant requirement is separate from the gelling-agent requirement. The composition must contain an antioxidant in an amount that performs the stated stabilizing function. Claim 4 identifies five specific antioxidant groups:

• dl-alpha-tocopherol;
• butylated hydroxyanisole;
• butylated hydroxytoluene;
• ascorbyl palmitate; and
• propyl gallate.

Claim 1 is not limited to those five materials. Claim 4 is narrower because it requires one of the listed antioxidant types.

What are the dependent claims and formulation branches?

Claims 2 through 15 create separate narrowing positions. They should not be read as requiring every listed excipient at the same time.

Claim	Additional limitation	Commercial significance
2	0.01-0.1 wt% retinoid; 0.1-10 wt% gelling agent; 0.01-4 wt% antioxidant; at least about 50 wt% water	Captures a more defined topical gel formulation
3	Retinoid is tretinoin or an acceptable salt, isomer, or derivative	Focuses the claim set on tretinoin-related products
4	Antioxidant selected from five named materials	Narrows antioxidant identity
5	0.1-20 wt% solubilizing agent	Covers solvent-assisted retinoid incorporation
6	Solubilizing agent is ethanol	Narrow ethanol formulation branch
7	0.1-20 wt% nonionic emulsifier	Covers stable retinoid emulsions
8	Emulsifier includes a normally liquid glycol	Narrows the emulsion branch
9	Specific surfactant classes	Covers listed surfactant systems
10	Up to about 10 wt% lipophilic agent	Adds an oil-phase or lipophilic component
11	Specific fatty alcohols, esters, petrolatum, plant oils, or mineral oils	Narrows the lipophilic-agent branch
12	0.05-2 wt% preservative	Adds a preservative range
13	Methyl paraben, ethyl paraben, or sorbitol	Narrows preservative identity
14	Up to about 0.5 wt% chelating agent	Adds a chelator limitation
15	Sodium or calcium EDTA salts	Narrows chelator identity

Claim 3 is commercially important because it expressly reaches tretinoin formulations. Claims 5 through 15 broaden the formulation architecture around the core gel but do not independently claim a product lacking the requirements of claim 1.

What formulations are protected by US 5,721,275?

The strongest literal coverage is directed to a water-rich tretinoin gel that contains a neutralized polyacrylic acid polymer and an antioxidant.

A formulation is more likely to fall within the claim set if it has the following profile:

Formulation characteristic	Relevance
Tretinoin concentration of 0.01-0.1 wt%	Matches claim 2
Water content of at least 50 wt%	Matches claim 2
Carbomer or comparable polyacrylic acid polymer	Potentially matches the gelling-agent limitation
Finished pH between approximately 3 and 7	Matches claim 1
Tocopherol, BHA, BHT, ascorbyl palmitate, or propyl gallate	Matches claim 4
Ethanol at 0.1-20 wt%	Matches claims 5 and 6
Glycol-based emulsifier	Matches claims 7 and 8
Oil, petrolatum, fatty alcohol, or fatty ester	Matches claims 10 and 11
Paraben or sorbitol preservative	Matches claims 12 and 13
EDTA salt	Matches claims 14 and 15

The patent does not require a specific dosage regimen, indication, package, applicator, particle-size distribution, or manufacturing sequence. Its commercial reach is therefore formulation-specific.

Does the patent cover Retin-A, Retin-A Micro, Altreno, or generic tretinoin?

The patent number alone does not establish infringement by a branded or generic product. Product-level analysis requires comparison of the finished formulation against the claim limitations.

Conventional tretinoin creams and gels

A conventional tretinoin cream may contain a high percentage of water and an antioxidant, but it would not necessarily infringe unless it also uses the claimed high-molecular-weight polyacrylic acid gelling system neutralized to the claimed pH range.

Microsphere formulations

Microsphere products use a distinct delivery technology. A microsphere formulation may avoid claim 1 if it does not use the required neutralized high-molecular-weight polyacrylic acid gel to hold the retinoid for slow release. Separate patents have historically covered microsphere delivery systems and should be analyzed independently.

Lotion formulations

A lotion may contain water, tretinoin, emulsifiers, glycols, oils, and antioxidants. It could present a claim issue if it also contains a qualifying polyacrylic acid gel. The presence of an emulsion does not itself avoid claim 1 because claims 7 and 8 expressly contemplate emulsion systems.

Generic products

Generic tretinoin approval does not itself establish patent infringement or freedom to operate. FDA approval and patent scope are separate questions. A generic applicant may have relied on a Paragraph IV certification against listed patents, a Paragraph III certification, or an approved product pathway after the relevant patents expired.

When did US Patent 5,721,275 lose exclusivity?

US Patent 5,721,275 is expired. Its ordinary US patent term ended in approximately 2015, based on the post-1995 20-year patent-term framework applicable to the underlying application. The patent cannot currently block a US formulation launch.

Event	Date or status
US patent	5,721,275
Title	Stable aqueous retinoid compositions
Issue date	February 24, 1998
Patent term framework	20 years from the applicable earliest nonprovisional filing date
Approximate expiration	2015
Current enforceability	Expired
Current blocking value	None as an enforceable US patent

The exact expiration date should be taken from the USPTO Patent Center record and any recorded term adjustment or disclaimer data. Expiration does not erase historical litigation exposure, past damages issues, or the relevance of the patent as prior art.

What is the Orange Book status of US Patent 5,721,275?

The patent does not create a current Orange Book barrier. FDA Orange Book listings are tied to approved drug applications and their listed patents, not to every patent that might have covered a pharmaceutical formulation.

For a tretinoin product, the relevant questions are:

1. whether the NDA holder listed the patent against a specific approved product;
2. whether the FDA accepted the listing;
3. whether the patent was later removed or expired;
4. whether a generic applicant certified against the listing; and
5. whether any later formulation patent remains active.

Because US 5,721,275 is expired, it cannot support a current 30-month stay based on a new Paragraph IV certification. The Orange Book should be checked by product, NDA, active ingredient, dosage form, and patent status rather than by patent number alone. The FDA describes Orange Book patent listings and certification procedures in its approved-drug and patent-listing materials. [1]

Were Paragraph IV challenges or litigation associated with this patent?

A Paragraph IV challenge would have been relevant only while the patent was listed against an approved drug application and unexpired. The patent’s current status means that any historical Paragraph IV dispute would now be closed as a prospective market-entry barrier.

Public patent litigation analysis should distinguish among:

• a complaint alleging infringement of US 5,721,275;
• an ANDA litigation case involving a listed tretinoin formulation patent;
• a declaratory-judgment action;
• a settlement agreement with a licensed launch date;
• a case dismissed after patent expiration; and
• litigation involving a different patent covering microspheres, delivery systems, or a branded product.

A patent-number search in PACER, CourtListener, USPTO records, and FDA Orange Book materials is necessary to attribute litigation to this specific patent rather than to the broader tretinoin portfolio. The patent’s expiration removes current injunction risk even if the patent was previously asserted.

How strong is the patent estate for the claimed formulation?

The patent was commercially meaningful during its term but is weak as a current exclusivity asset because it has expired.

Historical strengths

The claim set had several commercially useful characteristics:

• Claim 1 covered a broad combination rather than a single named product.
• Claim 3 expressly reached tretinoin.
• “Comprising” permitted additional formulation ingredients.
• Claims 5 through 15 covered common solvent, emulsion, surfactant, oil, preservative, and chelator systems.
• The water-content threshold could reach many topical gels and lotions.

Historical weaknesses

The claim set also had vulnerabilities:

• “High molecular weight” may require interpretation from the specification.
• “Slow release” and “minimal irritancy” are functional terms without numerical limits in the claims.
• “About” introduces boundary questions for percentages and pH.
• Polyacrylic acid gels were a known pharmaceutical formulation platform.
• Antioxidants, surfactants, glycols, preservatives, and chelators were conventional excipients.
• Obviousness arguments could combine known retinoid stabilization, aqueous gels, and controlled-release formulation teachings.
• A product using a non-polyacrylic controlled-release system could avoid the central structural limitation.

The likely litigation value would have depended on formulation testing, source-code or batch records, polymer identity, pH, antioxidant concentration, and release data.

How does US 5,721,275 compare with other tretinoin patent categories?

Patent category	Primary technology	Relationship to US 5,721,275
Aqueous polyacrylic acid gel	Water-rich gel with antioxidant stabilization	Directly within the patent’s core
Conventional cream	Tretinoin in a cream vehicle	May avoid the patent if no qualifying polyacrylic acid gel is present
Microsphere delivery	Encapsulated or particulate controlled release	Usually analyzed under separate patents
Lotion or emulsion	Water, oils, glycols, and emulsifiers	Could implicate claims 7-11 if the required gel is present
Manufacturing process	Mixing, neutralization, homogenization, filling	Not claimed by US 5,721,275
Method of treatment	Applying tretinoin to acne or photoaged skin	Not claimed by US 5,721,275
Device or packaging	Pump, tube, applicator, or metered dispenser	Not claimed by US 5,721,275

The patent is therefore one component of a broader tretinoin landscape. A freedom-to-operate review must separately evaluate active formulation, process, use, packaging, and jurisdictional patents.

Are biosimilars relevant to this patent?

No. Tretinoin is a chemically defined small molecule, not a biologic. Biosimilar pathways do not apply. The competitive risk comes from generic or authorized-generic topical tretinoin products, reformulated brands, and alternative retinoid delivery systems.

Relevant FDA pathways include ANDAs for therapeutically equivalent topical products and, depending on the product and formulation, NDA-based products with distinct clinical or formulation characteristics. The patent does not create biologic exclusivity, reference-product exclusivity, or biosimilar interchangeability issues.

What generic launch risks remain?

US 5,721,275 does not create a current generic launch risk because it is expired. Remaining barriers may come from:

• later-expiring formulation patents;
• active patents covering microspheres or encapsulation;
• product-specific lotion or emulsion patents;
• method-of-use patents;
• manufacturing patents;
• device or packaging patents;
• regulatory exclusivity;
• pediatric exclusivity attached to another listed patent; and
• state or federal regulatory requirements unrelated to patent term.

A generic launch strategy should therefore treat US 5,721,275 as historical prior art and a possible formulation-design reference, not as an active exclusion right.

What geographic coverage does the patent have?

The patent is a United States right. It has no direct legal effect in Canada, Europe, Japan, China, or other jurisdictions. Foreign counterparts must be assessed separately for:

• filing and publication status;
• grant status;
• national-phase or priority relationships;
• maintenance-fee payment;
• patent-term adjustment or supplementary protection;
• opposition or revocation history; and
• expiration.

Because topical tretinoin products are marketed globally, the US expiration does not establish freedom to operate elsewhere.

What manufacturing and formulation barriers remain after expiration?

The patent’s expiration removes the patent barrier but does not eliminate technical development barriers. A commercial developer still must address:

• tretinoin oxidation and photodegradation;
• uniform dispersion or solubilization;
• polymer hydration and neutralization;
• viscosity control;
• preservative effectiveness;
• microbial limits;
• pH drift;
• container compatibility;
• dose uniformity;
• release-rate consistency;
• skin tolerability; and
• stability through shelf life.

These are technical and regulatory barriers rather than enforceable rights under US 5,721,275. A developer may use the disclosed formulation concept without needing a license from the expired patent owner, subject to other active rights.

Key Takeaways

• US 5,721,275 claims a stable aqueous topical retinoid composition, especially a tretinoin formulation.
• Claim 1 requires water, a retinoid, a neutralized high-molecular-weight polyacrylic acid gel, and an antioxidant.
• Claim 2 narrows the formulation to defined retinoid, polymer, antioxidant, and water ranges.
• Claims 5 through 15 cover optional solvent, emulsifier, surfactant, lipophilic, preservative, and chelator branches.
• The patent does not claim tretinoin itself, a treatment method, manufacturing process, device, or packaging system.
• The patent expired in approximately 2015 and has no current US blocking effect.
• Paragraph IV and Orange Book relevance is historical unless tied to another active product-specific patent.
• Biosimilar analysis is inapplicable because tretinoin is a small molecule.
• Current freedom-to-operate risk is more likely to arise from later formulation, microsphere, manufacturing, method-of-use, device, or foreign patents.

FAQs

Does US 5,721,275 cover any tretinoin gel?

No. The product must also contain the required neutralized high-molecular-weight polyacrylic acid gelling agent, antioxidant, and water content specified by the applicable claim.

Can a company commercialize a product based on the disclosed formulation after patent expiration?

Yes, the expiration of the US patent removes this patent as an enforceable barrier. Other active patents and regulatory requirements must still be evaluated.

Does the patent cover carbomer-based tretinoin products?

Potentially. A carbomer-based product may fall within the claims if the carbomer qualifies as the claimed high-molecular-weight polyacrylic acid gelling agent, is neutralized within the claimed pH range, and performs the required slow-release function.

Does claim 1 require ethanol?

No. Ethanol appears only in dependent claim 6 through the solubilizing-agent branch. Claim 1 does not require ethanol.

Is US 5,721,275 relevant to a tretinoin microsphere product?

It may be relevant as prior art or as a historical formulation reference, but a microsphere product must be tested against the specific polyacrylic-acid-gel limitations. Separate microsphere patents may be more relevant to that product.

References

1. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. FDA, Center for Drug Evaluation and Research. https://www.accessdata.fda.gov/scripts/cder/ob/
2. United States Patent and Trademark Office. (1998). U.S. Patent No. 5,721,275, Stable aqueous retinoid compositions. Patent Center and Patent Public Search. https://patents.google.com/patent/US5721275
3. United States Code. (2024). 35 U.S.C. § 154: Contents and term of patent; provisional rights. https://www.law.cornell.edu/uscode/text/35/154
4. United States Food and Drug Administration. (n.d.). Citizen petitions, petitions for stay of action, and petitions for determination of patent listing. FDA. https://www.fda.gov/drugs/abbreviated-new-drug-application-anda/abbreviated-new-drug-application-anda-forms-and-instructions

Drugs Protected by US Patent 5,721,275

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate

Foreign Priority and PCT Information for Patent: 5,721,275

PCT Information
PCT Filed	June 07, 1990	PCT Application Number:	PCT/US90/03219
PCT Publication Date:	December 13, 1990	PCT Publication Number:	WO90/14833

International Family Members for US Patent 5,721,275

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Canada	2063576
Germany	69029804
European Patent Office	0481007
World Intellectual Property Organization (WIPO)	9014833