United States Drug Patent 5,393,529: Claim Scope, Expiration, Orange Book Relevance, and Transdermal Estrogen Patent Landscape

U.S. Patent No. 5,393,529 covers a matrix-type estrogen transdermal patch using an acrylic or methacrylic pressure-sensitive adhesive, a water-swellable polymer, and a crystallization inhibitor. The patent is expired and does not create current U.S. exclusivity for estrogen patches. Its commercial importance is historical: it addressed drug crystallization and release uniformity in adhesive-based transdermal systems rather than claiming estrogen generally.

What does U.S. Patent 5,393,529 claim?

The independent claim requires a specific multilayer transdermal plaster with three structural components:

Claim element	Required feature
Backing layer	Impermeable backing or covering layer
Reservoir layer	Water-insoluble pressure-sensitive adhesive polymer layer adjacent to the backing
Estrogen	About 0.5% to 10% by weight in the adhesive layer
Water-swellable polymer	About 0.01% to 10% by weight
Crystallization-control agent	About 0.1% to 20% by weight
Adhesive chemistry	Polymer of acrylic acid, methacrylic acid, or an ester of either
Protective layer	Removable layer covering and adhering to the adhesive layer

The claim is a combination claim. A product must satisfy all material limitations to fall within literal claim 1. An estrogen patch using a different adhesive family, omitting the water-swellable polymer, or using a crystallization-control compound outside the claimed categories would have a stronger noninfringement position.

The patent is directed to an adhesive matrix system. It does not require a separate rate-controlling membrane between the drug reservoir and the skin. The adhesive layer performs several functions at once: it holds the system together, adheres the patch to the patient, contains the estrogen, and controls drug availability.

What technical problem does the patent address?

The central technical problem is estrogen crystallization in a pressure-sensitive adhesive matrix.

Estrogens such as estradiol have limited compatibility with many adhesive polymers. During storage, the drug can migrate, precipitate, or form crystals. Crystallization can reduce the amount of drug available for diffusion and produce inconsistent delivery. The claim addresses that problem by combining:

An acrylic or methacrylic adhesive;
A low concentration of water-swellable polymer; and
A crystallization-delaying or crystallization-preventing substance.

The claimed additives include plasticizer-like materials, fatty-acid derivatives, surfactants, polyols, oils, long-chain alcohols, polyvinylpyrrolidone, and related compounds. The list is broad and chemically heterogeneous. Its breadth creates potential written-description and enablement issues for individual combinations that were not specifically demonstrated in the patent specification, although those issues would depend on the disclosure and prosecution history.

How broad is independent claim 1?

Claim 1 is broad in ingredient categories but narrow in required architecture.

Broad features

The claim does not limit the estrogen to a single named molecule. “Estrogen” could encompass estradiol, estriol, estrone, ethinyl estradiol, or another compound falling within the ordinary technical meaning of the term, subject to the patent specification and claim-construction record.

The acrylic adhesive limitation also covers multiple polymer types, including polymers and copolymers based on acrylic acid, methacrylic acid, or their esters. The claim does not identify one commercial adhesive grade.

The water-swellable polymer list is extensive. It includes cellulose derivatives, gums, galactomannans, polyvinylpyrrolidone, polyacrylamide-related materials, polyacids, agar, dextran, pectin, and other polysaccharide materials.

The crystallization-control list is similarly broad. It includes phthalate and adipate esters, glycerides, fatty-acid esters, long-chain alcohols, phenolic compounds, fatty acids, sorbitol, mannitol, nonionic surfactants, castor oil, sitosterol, and polyvinylpyrrolidone.

Narrow features

The product must contain all of the following quantitative ranges:

Component	Claimed range
Estrogen	About 0.5% to 10% by weight
Water-swellable polymer	0.01% to 10% by weight
Crystallization-control substance	0.1% to 20% by weight

The claim also requires the adhesive to be water-insoluble and pressure-sensitive. A water-soluble adhesive, a nonadhesive reservoir, or a conventional gel system would not ordinarily satisfy the claim.

The claim requires the crystallization-control substance to be in the pressure-sensitive adhesive composition. Merely using a crystallization inhibitor elsewhere in the package or in a separate membrane would present a substantial claim-scope distinction.

What formulations are protected by U.S. Patent 5,393,529?

The patent is most relevant to estrogen-containing adhesive matrix patches with the following profile:

An impermeable backing;
An acrylic or methacrylic pressure-sensitive adhesive;
Estradiol or another estrogen dispersed in the adhesive;
A small amount of a swellable polymer;
A defined crystallization inhibitor;
A removable release liner.

A formulation containing estradiol, an acrylate adhesive, polyvinylpyrrolidone, and a fatty-acid ester could fall within the literal categories of claim 1 if the concentration ranges and layer structure are satisfied.

The patent does not necessarily cover every patch marketed with the same broad dosage form. Coverage depends on the actual composition, not the product label alone. A patch may avoid the claim by using:

A silicone or rubber-based adhesive;
A separate liquid or gel reservoir;
A membrane-controlled design;
No water-swellable polymer;
A crystallization-control agent outside the listed categories;
Concentrations outside the claimed ranges;
A non-estrogen active ingredient.

The doctrine of equivalents could complicate design-around analysis, particularly where a formulation substitutes a chemically similar excipient performing the same crystallization-control function. Equivalence would be fact-specific and could be limited by prosecution-history estoppel or by the claim’s express Markush group.

How do the dependent claims narrow the patent?

Claim	Added limitation	Practical effect
2	Adhesive polymer is cross-linkable	Covers curable or cross-linkable acrylic systems
3	Solvent-based pressure-sensitive adhesive	Requires a solvent-processed adhesive system
4	Dispersion-based pressure-sensitive adhesive	Requires a dispersion-processed system
5	Hot-melt pressure-sensitive adhesive limitation	Appears directed to a hot-melt adhesive embodiment
6	Tackifying resin at 0.5% to 50% by weight	Adds a broad resin-loading limitation
7	Drug-containing adhesive film is 0.01 to 0.3 mm thick	Limits matrix thickness
8	Water-swellable polymer includes galactomannan, microcrystalline cellulose, or tragacanth	Narrows the swellable-polymer selection

Claim 6 is commercially relevant because tackifying resins can materially alter adhesion, drug partitioning, and release. The 0.5% to 50% range is broad and could capture many adhesive formulations.

Claim 7 is narrower and more technically useful for product comparison. A thin adhesive matrix within the stated thickness range could be relevant even if the product’s overall patch thickness is much greater. The claim refers to the therapeutic substance-containing adhesive film, not necessarily the backing or release liner.

Claim 8 contains an apparent drafting inconsistency. Claim 1 places the water-swellable polymer in the reservoir layer, while claim 8 refers to the “additionally water-swellable polymer of layer C.” Layer C is identified as the protective layer. A court would likely examine the specification and prosecution history to determine whether “layer C” is a translation or drafting error. The inconsistency could affect clarity, construction, and enforceability of claim 8.

Claim 5 also appears structurally inconsistent because claim 1 identifies layer C as a removable protective layer, while claim 5 refers to the polymer of layer C as a hot-melt pressure-sensitive adhesive. The patent specification and original-language family documents would be important in resolving that issue.

When did U.S. Patent 5,393,529 lose exclusivity?

U.S. Patent No. 5,393,529 is expired. The patent issued on February 28, 1995. For a U.S. application subject to the pre-Uruguay Round patent-term regime, the ordinary term was 17 years from grant, unless an earlier expiration applied or the term was altered by a terminal disclaimer or other statutory provision. On that basis, the patent’s ordinary term ended on February 28, 2012.[1][2]

The expired status means:

Claim 1 cannot block a current U.S. generic or branded patch;
No current Paragraph IV challenge is needed against this patent;
The patent cannot support a new injunction against commercial launch;
Its claims remain relevant as prior art and as evidence of historical formulation technology;
Foreign family members require separate jurisdiction-by-jurisdiction review.

Patent expiration does not erase the patent’s historical role in freedom-to-operate analyses. It can still help identify related family patents, continuation filings, formulation disclosures, and later patents that may have claimed narrower commercial embodiments.

What is the Orange Book status of U.S. Patent 5,393,529?

U.S. Patent No. 5,393,529 should not be treated as a current Orange Book barrier.

Orange Book listing is product-specific. FDA generally lists patents submitted by an NDA holder for an approved drug product, including patents covering the drug substance, drug product, or approved method of use. A historical transdermal estrogen patent may have been relevant to an NDA product, but its present legal effect depends on whether it was listed, whether it was removed, and whether its patent term has expired.[3]

Because the patent is expired, it does not create a current statutory stay or launch prohibition under the Hatch-Waxman framework. An applicant submitting an ANDA for an estrogen patch would focus on unexpired listed patents, regulatory exclusivity, and formulation or method-of-use patents still in force.

Are biosimilar risks relevant to this patent?

No. Estrogen patches are generally small-molecule drug products, not biologics. The relevant competitive pathway is an ANDA or, depending on the product and regulatory classification, another abbreviated pathway. Biosimilar provisions under the Biologics Price Competition and Innovation Act do not apply to this patent’s core technology.

The principal risks for a current estrogen patch program are:

Unexpired formulation patents;
Device or delivery-system patents;
Method-of-use patents;
Manufacturing-process patents;
Orange Book-listed patents for the reference product;
Regulatory exclusivity;
Product-specific equivalence requirements.

Which companies challenged or licensed this patent?

The claim text alone does not establish a specific Paragraph IV case, settlement, or license agreement. The patent was issued in 1995 and has expired, so any historical litigation or licensing transaction would not create a current market barrier.

The likely commercial landscape involved companies developing estradiol and other estrogen patches, including branded developers and transdermal-system manufacturers. Relevant companies in the broader estrogen patch market have included Bayer, Noven Pharmaceuticals, Vivelle product affiliates, Mylan, Sandoz, and other generic manufacturers. Market participation does not establish that a company practiced or licensed this particular patent.

A defensible licensing conclusion requires review of assignment records, recorded licenses, litigation dockets, and patent-family transactions. The patent’s expiration substantially reduces the commercial value of any license today, except for historical royalty audits, covenant enforcement, or bundled rights in related patents.

How does this patent compare with competing estrogen-patch patent estates?

Patent category	Typical claim focus	Relevance today
Adhesive matrix patents	Drug, adhesive, excipients, crystallization control	5,393,529 is expired
Membrane-reservoir patents	Separate drug reservoir and rate-control membrane	May include later unexpired patents
Backing and liner patents	Occlusion, release, adhesion, packaging	Product-specific
Method-of-use patents	Menopausal symptoms, estrogen deficiency, dosing schedules	Potential Orange Book relevance
Manufacturing patents	Coating, drying, mixing, lamination, curing	May create process risk
Device patents	Patch geometry, handling, wear performance	Separate from drug composition
Combination therapy patents	Estrogen plus progestin or other active	Product-specific

The patent’s strongest historical contribution is its formulation architecture. Its weakest current commercial position is term status. Any modern freedom-to-operate review should treat it as expired prior art and shift attention to later patents covering specific patch products, excipient ratios, coating processes, release liners, and approved dosing regimens.

What generic entry risks exist for estrogen patches?

The patent itself presents no current generic-entry risk because it is expired. A generic manufacturer could use the claimed architecture without infringing this patent, subject to other active rights.

A launch analysis should separate four questions:

Whether the proposed patch uses an acrylic adhesive matrix;
Whether any later patent claims the selected estrogen, excipients, or ratios;
Whether the reference product has unexpired Orange Book-listed patents;
Whether the ANDA must address method-of-use patents through a Paragraph IV certification or a Section viii statement.

A generic patch that copies the general formulation concept may still face later patents directed to a specific adhesive, a specific crystallization inhibitor, a particular dose, a release profile, or manufacturing conditions. The expired patent does not immunize the product against those later rights.

How strong is the patent estate for U.S. Patent 5,393,529?

The individual patent has moderate historical technical breadth but no present blocking strength.

Factor	Assessment
Claim breadth	Broad ingredient categories, narrow combination requirements
Enablement exposure	Potential issue because the Markush groups cover many unrelated compounds
Claim clarity	Potential issue in claims 5 and 8 because of layer references
Design-around potential	Meaningful, especially through adhesive, reservoir, or excipient substitution
Historical relevance	High for adhesive estrogen matrix systems
Current enforceability	None after expiration
Orange Book impact	No current exclusivity
Biosimilar relevance	None
Generic-entry impact	No current blocking effect

Key Takeaways

U.S. Patent 5,393,529 claims an estrogen-containing adhesive matrix patch.
Claim 1 requires an acrylic or methacrylic pressure-sensitive adhesive, estrogen, a water-swellable polymer, a crystallization-control substance, an impermeable backing, and a removable protective layer.
The claimed concentration ranges are 0.5% to 10% estrogen, 0.01% to 10% water-swellable polymer, and 0.1% to 20% crystallization-control substance.
Claims 2 through 8 narrow the invention through adhesive processing, cross-linkability, tackifying resin, thickness, and specific swellable polymers.
Claims 5 and 8 contain apparent layer-identification inconsistencies that would require specification-based construction.
The patent expired on February 28, 2012, based on the ordinary 17-year term from its February 28, 1995 grant.
It presents no current Paragraph IV, Orange Book, biosimilar, or generic-launch barrier.
Current freedom-to-operate work should focus on later patents covering specific estrogen patches, formulations, manufacturing methods, delivery systems, and approved uses.

FAQs on U.S. Patent 5,393,529

Does U.S. Patent 5,393,529 cover estradiol specifically?

The claim covers an “estrogen” without naming only estradiol. Estradiol is a likely embodiment, but coverage depends on the patent’s specification and the meaning assigned to “estrogen” during claim construction.

Can a company still obtain a license under U.S. Patent 5,393,529?

A license could be documented for historical or contractual reasons, but the expired patent does not require a license for current U.S. practice of the claimed formulation.

Does using a silicone adhesive avoid the patent?

A silicone adhesive would generally avoid the express acrylic or methacrylic polymer limitation of claim 1, subject to any separate patent rights and any doctrine-of-equivalents analysis.

Does the patent cover an estrogen gel?

Not ordinarily. The claims require a plaster with an adhesive polymer layer, backing layer, and removable protective layer. A topical gel without that patch architecture would generally fall outside the literal claim.

Is U.S. Patent 5,393,529 relevant to a current FDA approval strategy?

It may be relevant as historical prior art, but it does not provide current exclusivity. A current FDA strategy would turn on the reference listed drug, product-specific patents, regulatory exclusivity, bioequivalence requirements, and the proposed patch’s formulation and delivery characteristics.

References

U.S. Patent No. 5,393,529, “Transdermal therapeutic system for administering estrogen,” issued Feb. 28, 1995.
35 U.S.C. § 154(a)(2), patent term provisions.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book. Washington, DC: FDA.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Germany	3933460	Oct 06, 1989

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	126069	⤷ Start Trial
Australia	6312890	⤷ Start Trial
Australia	637637	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,393,529

Summary for Patent: 5,393,529