United States Drug Patent 5,188,835: Claim Scope, Expiration, Estring Coverage, and Patent Landscape

U.S. Patent No. 5,188,835 covers an intravaginal elastomeric device that continuously releases 17 beta-estradiol at a substantially constant rate for at least one month, together with methods of treating hypoestrogenic symptoms using that device. The patent issued on February 23, 1993, and its enforceable term expired on February 23, 2010, assuming the standard pre-URAA 17-year term from issuance. The patent therefore has no current blocking effect against generic or competing products. Its principal commercial relevance was its historical relationship to the Estring estradiol vaginal ring.

What does U.S. Patent 5,188,835 cover?

The patent has six claims divided into two categories:

Claim category	Claims	Core subject matter
Device claims	1-3	An intravaginal elastomeric device containing 17 beta-estradiol
Method claims	4-6	Treating hypoestrogenic symptoms by positioning the device intravaginally

The independent device claim, claim 1, requires each of the following elements:

An intravaginal device.
Intended for use by hypoestrogenic women.
17 beta-estradiol incorporated within a supporting elastomeric matrix.
Continuous release for at least one month.
An essentially constant release rate.
A release rate of approximately 0.5 to 25 micrograms per 24 hours.

Claim 4 contains substantially the same technical limitations but applies them to a treatment method.

The dependent claims narrow the release-rate range:

Claim	Release rate	Claim type
1	About 0.5-25 micrograms per 24 hours	Independent device
2	About 1-10 micrograms per 24 hours	Dependent device
3	About 4-8 micrograms per 24 hours	Dependent device
4	About 0.5-25 micrograms per 24 hours	Independent method
5	About 1-10 micrograms per 24 hours	Dependent method
6	About 4-8 micrograms per 24 hours	Dependent method

The claims are directed to sustained local estrogen delivery. They do not claim 17 beta-estradiol generally, vaginal estrogen therapy generally, or every estradiol-containing vaginal dosage form.

How should the key claim limitations be interpreted?

“Intravaginal device”

The claims require a device positioned inside the vagina. A tablet, cream, gel, insert, or other dosage form that does not operate as an intravaginal device would not literally satisfy this limitation.

The term is broad as to physical configuration. Claim 1 does not expressly require a ring, torus, core-and-coating structure, particular dimensions, or a specified polymer. The claim could therefore encompass multiple device geometries if the remaining limitations are met.

“17 beta-estradiol”

The claimed active ingredient is 17 beta-estradiol, commonly called estradiol. The claim is narrower than claims directed to estrogen compounds generally. Products using ethinyl estradiol, estriol, conjugated estrogens, or another estrogen would not literally meet this limitation.

The claim also focuses on the active pharmaceutical ingredient rather than a particular salt, excipient, stabilizer, or manufacturing process.

“Supporting elastomeric matrix”

The estradiol must be incorporated within an elastomeric matrix. This limitation distinguishes the claimed device from a simple vaginal tablet or a non-elastomeric reservoir.

The patent does not limit the claims to one named elastomer. The scope therefore depends on whether the drug-containing structure is properly characterized as an elastomeric matrix. A device with estradiol merely deposited on a surface, suspended in a non-elastomeric solid, or contained only in a separate liquid reservoir would present a stronger non-infringement position.

The matrix limitation is likely the principal structural boundary of the claims.

“For at least a month”

The device must release estradiol continuously for at least one month. A product designed for a shorter treatment period would fall outside the literal duration requirement.

The phrase does not require a specific 30-day replacement schedule, provided the release period reaches at least one month. A 90-day device can satisfy the duration limitation if it maintains the claimed release profile.

“Essentially constant rate”

This is a functional performance limitation. The claims do not require zero variation. They require a release profile that is sufficiently stable to qualify as essentially constant over the claimed period.

The limitation would generally be evaluated using release testing, analytical data, product specifications, and the patent’s technical disclosure. A device with a large initial burst, rapid decline, or highly variable release profile would have a stronger argument that it does not satisfy this limitation.

Release-rate ranges

The ranges are nested:

Claim 1 covers approximately 0.5-25 micrograms per 24 hours.
Claim 2 narrows the range to approximately 1-10 micrograms per 24 hours.
Claim 3 narrows it further to approximately 4-8 micrograms per 24 hours.

Claims 2 and 3 do not expand the scope of claim 1. They provide narrower fallback positions. The same structure applies to method claims 4-6.

What products were historically associated with U.S. Patent 5,188,835?

The patent is closely associated with Estring, Pfizer’s estradiol vaginal ring. Estring is a silicone elastomer vaginal ring designed to release approximately 7.5 micrograms of estradiol per day over a 90-day period. That commercial profile falls within the ranges in claims 1, 2, and 3.

Estring attribute	Relationship to U.S. 5,188,835
Active ingredient	17 beta-estradiol
Route	Intravaginal
Device type	Elastomeric vaginal ring
Nominal release	Approximately 7.5 micrograms per day
Duration	Approximately 90 days
Claim range	Within claims 1, 2, and 3
Therapeutic use	Symptoms associated with vaginal atrophy and hypoestrogenism

FDA labeling identifies Estring as a vaginal ring containing estradiol and describes continuous delivery over a 90-day period. The product’s approximately 7.5 microgram daily delivery rate is within the 4-8 microgram range recited in claims 3 and 6. [2]

The patent does not, however, claim the Estring brand name, Pfizer’s specific commercial specifications, or every element of the Estring manufacturing process.

When did U.S. Patent 5,188,835 expire?

U.S. Patent 5,188,835 issued on February 23, 1993. For a patent subject to the pre-June 8, 1995 patent-term rules, the basic term was 17 years from issuance. On that basis, the patent expired on February 23, 2010. [1][3]

Event	Date
Patent issued	February 23, 1993
Standard term	17 years from issuance
Estimated expiration	February 23, 2010
Current enforceability	Expired

Any patent-term adjustment, patent-term extension, terminal disclaimer, or other recorded event would need to be reflected in the official USPTO patent record. The standard term calculation places the patent’s expiration in 2010, and the patent is no longer an enforceable barrier to market entry.

The expiration of the patent does not eliminate separate rights in later patents covering formulations, manufacturing processes, packaging, or other product attributes.

What was the Orange Book status of the patent?

U.S. Patent 5,188,835 was historically associated with Estring and its FDA regulatory exclusivity record. Orange Book patent listings are product-specific and do not mean that every claim in the patent is currently enforceable. Once the listed patent expires, it no longer provides an active patent barrier to an ANDA applicant.

For an ANDA applicant, an expired listed patent generally does not require a Paragraph IV certification. A certification addressing an unexpired patent would be relevant only while the patent remained within its enforceable term. The patent’s 2010 expiration therefore eliminates the principal Paragraph IV timing issue associated with this patent.

Orange Book status should be distinguished from FDA approval status:

FDA approval concerns whether a product may be marketed.
Orange Book listing concerns patents submitted by the NDA holder.
Patent expiration concerns enforceability under patent law.
Regulatory exclusivity may expire on a different date from the patent.

The patent’s expiration does not itself establish that a particular generic product has FDA approval. It establishes only that this patent is no longer an enforceable patent obstacle.

How strong are the device claims?

The original claims were commercially meaningful because they combined composition, device structure, release performance, and therapeutic duration. Their strength during the patent term came from the combination of limitations rather than from broad ownership of estradiol therapy.

Strengths

The claims had several features that could support infringement allegations:

They covered both the device and treatment method.
The release-rate ranges aligned with the commercial Estring profile.
The claims covered a broad range of elastomeric structures.
The duration requirement captured monthly and longer-acting products.
The method claims could reach clinical use of a qualifying device.

Limitations

The claims also had material boundaries:

The device had to use 17 beta-estradiol.
The drug had to be incorporated in an elastomeric matrix.
The product had to release continuously for at least one month.
The release had to be essentially constant.
The rate had to fall within the stated range.
A product outside the claimed rate or duration could avoid literal infringement.

The claims are therefore narrower than a general claim to vaginal estrogen delivery. They are strongest against products that replicate the same long-acting elastomeric diffusion platform.

What formulations and technologies fall outside the claims?

The following product categories could avoid literal infringement of the issued claims, depending on their actual design and performance:

Product or technology	Likely claim issue
Vaginal estradiol tablet	No elastomeric matrix or device structure
Estradiol cream	No supporting elastomeric matrix; usually non-device dosage form
Estradiol gel	No claimed elastomeric device
Short-duration vaginal insert	May fail the one-month requirement
Estradiol ring releasing below 0.5 micrograms per day	Outside claim 1’s stated range
Estradiol device releasing above 25 micrograms per day	Outside claim 1’s stated range
Device using another estrogen	Does not contain 17 beta-estradiol
Non-elastomeric polymer system	May fail the matrix limitation
Device with materially nonconstant release	May fail the release-profile limitation
System delivering estradiol systemically through another route	Not intravaginal

A competing vaginal ring could still face technical and regulatory scrutiny even if it avoids the patent. The key questions would include drug loading, elastomer selection, diffusion control, release uniformity, sterilization, extractables, stability, and clinical comparability.

What patent landscape surrounded Estring and vaginal estradiol rings?

The relevant patent estate was broader than U.S. Patent 5,188,835. Commercial protection for Estring-type products could include separate patents or applications directed to:

The general intravaginal estradiol device.
Ring geometry and drug distribution.
Silicone elastomer composition.
Drug-release control.
Manufacturing and curing methods.
Packaging and storage.
Manufacturing specifications.
Later improvements or continuation applications.

The existence of a later patent does not extend the term of U.S. Patent 5,188,835. Each patent must be analyzed separately by claim scope, priority date, expiration date, and product relevance.

Geographic coverage

U.S. Patent 5,188,835 provided rights only in the United States. Corresponding foreign patents, if granted, would have had separate terms and enforcement histories. A U.S. competitor could not rely on the U.S. expiration to determine freedom to operate in Europe, Canada, Japan, China, or other markets.

Foreign analysis would require review of the relevant national-phase or direct applications, granted claims, maintenance fees, and local patent-term rules.

Were there Paragraph IV challenges or patent litigation?

The available patent record establishes the patent, its claims, and its expiration. The expiration date means that no current Paragraph IV challenge to U.S. Patent 5,188,835 is commercially necessary. A generic applicant entering after expiration can address the patent as expired rather than litigate a live patent dispute.

Historical litigation or settlement activity involving Estring, Pfizer, or generic applicants would need to be tied to a specific later patent or FDA submission. U.S. Patent 5,188,835 itself should not be treated as an active litigation risk after February 23, 2010.

There is no basis to infer that a historical patent listing created a permanent market exclusion. Any settlement agreement involving other Estring-related patents would require separate analysis and would not revive this expired patent.

What is the current generic entry risk?

The current risk from U.S. Patent 5,188,835 is high for the patent holder and low for a competing manufacturer because the patent has expired.

A generic or competing product still must address:

FDA approval requirements.
Pharmaceutical equivalence or clinical requirements.
Device performance.
Sterility and microbiological controls.
Manufacturing consistency.
Stability and shelf life.
Bioequivalence or other applicable regulatory evidence.
Any unexpired patents covering the product or process.
Trade dress, trademark, and contractual restrictions.

The expired patent removes one legal barrier. It does not guarantee FDA approval or commercial success.

Generic launch scenarios

Scenario	Patent impact
Estradiol vaginal tablet	U.S. 5,188,835 is not relevant
Estradiol cream or gel	U.S. 5,188,835 is not relevant
One-month elastomeric estradiol ring	Patent expired; no current blocking effect
90-day estradiol vaginal ring	Patent expired; later patents must be checked
Non-estradiol vaginal ring	Outside the literal active-ingredient limitation
New delivery system with different polymer	Likely outside literal scope, subject to full claim analysis

What commercial exposure did the patent create?

The patent likely had high strategic value while active because it aligned closely with the central architecture of a long-acting estradiol vaginal ring. Its commercial exposure was concentrated in products that combined:

17 beta-estradiol;
an elastomeric vaginal matrix;
a release period of at least one month;
a daily release rate between 0.5 and 25 micrograms.

The patent did not cover the entire vaginal estrogen market. Revenue from creams, tablets, inserts, gels, and other estrogen products would not necessarily have depended on this patent.

No reliable revenue amount can be attributed solely to U.S. Patent 5,188,835 without product-level sales data and an analysis of the patent’s contribution to Estring’s market exclusivity.

What manufacturing barriers remain after patent expiration?

Patent expiration leaves several non-patent barriers:

Reproducing a stable elastomer formulation.
Achieving a predictable 90-day release profile.
Controlling initial burst release.
Maintaining dose uniformity across batches.
Validating ring dimensions and drug distribution.
Meeting sterilization and packaging requirements.
Controlling extractables and leachables.
Demonstrating stability over the labeled shelf life.
Establishing clinical or bioequivalence support.

These barriers can delay market entry but do not extend the patent term. They may be protected through trade secrets, know-how, quality systems, or regulatory data requirements rather than enforceable claims in U.S. Patent 5,188,835.

How does U.S. Patent 5,188,835 compare with alternative vaginal estrogen products?

Product type	Long-acting device	Elastomeric matrix	Estradiol	Typical patent relationship
Estring-type ring	Yes	Yes	Yes	Historical target of the patent
Vaginal estradiol tablet	No	No	Yes	Generally outside the claims
Vaginal estradiol cream	No	No	Yes	Outside the device claims
Vaginal estradiol insert	Usually no	Usually no	Yes	Depends on structure and release
Estriol vaginal product	May vary	May vary	No	Outside the 17 beta-estradiol limitation
Conjugated estrogen cream	No	No	No	Outside the claims
Estradiol transdermal system	No	May use elastomer	Yes	Outside the intravaginal limitation

Key Takeaways

U.S. Patent 5,188,835 covers an intravaginal elastomeric device containing 17 beta-estradiol.
The device must release estradiol continuously for at least one month at approximately 0.5-25 micrograms per day.
Claims 2 and 3 narrow the release-rate range to 1-10 and 4-8 micrograms per day, respectively.
The corresponding method claims cover treatment of hypoestrogenic symptoms using the claimed device.
Estring’s approximately 7.5 microgram-per-day, 90-day vaginal ring falls within the central claim ranges.
The patent issued February 23, 1993, and its standard 17-year term expired February 23, 2010.
The patent no longer creates a current Paragraph IV or generic-entry barrier.
Later patents, regulatory requirements, manufacturing know-how, trademarks, and trade secrets must be analyzed separately.
The claims do not cover all vaginal estrogen products or all estradiol formulations.
No current enforceable rights should be attributed to this patent.

Frequently Asked Questions

Does U.S. Patent 5,188,835 cover Estring?

Yes. Estring’s estradiol-containing elastomeric vaginal ring, approximately 7.5 microgram-per-day release rate, and 90-day duration fit within the principal device and method claim limitations. The patent has expired.

Can a generic manufacturer launch an estradiol vaginal ring without licensing this patent?

Yes, this patent does not require a license after its expiration. The manufacturer must still address FDA approval requirements and any other unexpired patent rights.

Does the patent cover vaginal estradiol cream?

No. The issued claims require an intravaginal device with 17 beta-estradiol incorporated in a supporting elastomeric matrix. A conventional cream does not meet those limitations.

Does the patent cover a vaginal ring lasting only two weeks?

A two-week device would likely fail the express requirement that estradiol be continuously released for at least one month.

Does patent expiration eliminate all intellectual-property risk for an Estring-type product?

No. It eliminates the blocking effect of U.S. Patent 5,188,835. Separate patents, trademarks, trade secrets, manufacturing claims, regulatory requirements, and contractual restrictions may remain relevant.

References

United States Patent and Trademark Office. (1993). U.S. Patent No. 5,188,835, Intravaginal device for use by hypoestrogenic women.
U.S. Food and Drug Administration. (2022). Estring (estradiol vaginal system) prescribing information.
United States Code. (2023). 35 U.S.C. § 154: Contents and term of patent; provisional rights.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Sweden	8602666-3	Jun 16, 1986

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	68097	⤷ Start Trial
Australia	599988	⤷ Start Trial
Australia	7422287	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,188,835

Summary for Patent: 5,188,835