Details for Patent: 4,826,831

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Summary for Patent: 4,826,831

Title:	Method of hormonal treatment for menopausal or post-menopausal disorders involving continuous administration of progestogens and estrogens
Abstract:	A method of hormonally treating menopausal (including perimenopausal and post-menopausal) disorders in women, a composition, and a multi-preparation pack therefor. The administrative regimen to which the pack is particularly adapted comprises continuously and uninterruptedly administering a progestogen to a woman while cyclically administering an estrogen by using a repetitive dosage regimen. This regimen calls for administering the estrogen continuously for a period of time between about 20 and about 120 days, followed by terminating administering the estrogen for a period of time between about 3 and about 7 days. Alternatively, both the progestogen and estrogen may be administered for the full treatment period without interruption. The regimen avoids many of the problems associated with the administration of estrogen alone or with progestogen administered according to conventional regimens, and also avoids problems associated with such conventional regimens by maintaining the estrogen and progestogen at low daily dosage levels of between 0.005 mg and 2.5 mg estrogen and 0.25 mg and 30 mg progestogen.
Inventor(s):	Earl R. Plunkett, Bernard M. J. Wolfe
Assignee:	Pre Jay Holdings Ltd , Woco Investments Ltd
Application Number:	US06/635,236
Patent Claim Types: see list of patent claims	Use; Composition;

United States Drug Patent 4,826,831: Claim Scope, Expiration, Litigation Risk, and Menopausal Hormone-Therapy Patent Landscape

U.S. Patent No. 4,826,831 covered hormone-replacement regimens combining an estrogen and a progestogen for perimenopausal, menopausal, and post-menopausal disorders. Its principal inventive concept was continuous administration of both hormones at specified low-dose ranges, with a second regimen using continuous progestogen and periodically interrupted estrogen.

The patent was granted on May 2, 1989, and, as a pre-Uruguay Round patent subject to the 17-year term from grant applicable to that filing era, expired no later than May 2, 2006, absent an unusual terminal disclaimer or other recorded adjustment. The patent therefore presents no current U.S. blocking right. Its claims remain relevant as prior art and as historical evidence of the scope sought for continuous-combined hormone replacement therapy, but they do not support a current infringement action against generic or branded products.

What did U.S. Patent 4,826,831 protect?

The patent protected three related subject-matter categories:

1. Continuous combined hormone therapy.
2. Continuous progestogen with intermittently interrupted estrogen.
3. Implantable and intramuscular injectable compositions intended to deliver equivalent systemic doses.

The claims were not directed to a single molecule, brand, tablet, patch, or manufacturing process. They were principally method-of-treatment claims defined by:

• The patient population.
• The simultaneous or coordinated use of estrogen and progestogen.
• The dosing schedule.
• Broad concentration ranges.
• Specific lists of estrogen and progestogen compounds.

The issued patent is titled “Hormonal treatment of menopausal disorders.” The listed claims supplied for this analysis correspond to the issued claim set of U.S. 4,826,831. (U.S. Patent No. 4,826,831, 1989)

What is the scope of independent claim 1?

Claim 1 covers a method of treating menopausal or post-menopausal disorders by administering both hormones continuously and without interruption.

Element	Claim 1 requirement
Patient	Woman with menopausal or post-menopausal disorder
Estrogen	Daily dose equivalent to about 0.5 to 2.0 mg estradiol
Progestogen	Daily dose equivalent to about 0.025 to 0.075 mg levonorgestrel
Schedule	Continuous and uninterrupted administration of both hormones
Claim type	Method of medical treatment

The claim is dosage- and regimen-centered. It does not require a particular dosage form. Oral tablets, patches, implants, injections, or other delivery systems could potentially fall within the language if they deliver the specified daily equivalents continuously.

The claim also uses “equivalent” dosing rather than limiting protection to estradiol and levonorgestrel. That drafting approach expands the claim to other estrogens and progestogens, subject to proof that their biological or clinical dose corresponds to the recited reference dose.

The principal limitation is the requirement that both components be administered continuously and uninterruptedly. A product using cyclic progestogen administration would not literally satisfy claim 1.

How do claims 2 through 16 expand the treatment claims?

Claims 2 through 16 create nested alternatives around the core regimen.

Claim 2: estradiol plus norgestrel

Claim 2 narrows the therapy to:

• 17 beta-estradiol at approximately 1 mg daily.
• Racemic d-norgestrel at approximately 100 micrograms daily, or
• Levonorgestrel at approximately 50 micrograms daily.

This claim is narrower than claim 1 because it identifies both the estrogen and progestogen and specifies a preferred dose.

Claim 3: continuous progestogen and cyclic estrogen

Claim 3 covers a different regimen:

• Continuous, uninterrupted progestogen administration.
• Estrogen administration for 20 to 120 days.
• An estrogen-free interval of 3 to 7 days.
• Repetition of that cycle.

This claim does not require continuous estrogen. It is directed to an extended estrogen cycle with a short hormone-free interval, while the progestogen remains continuous.

The claim has two independently important timing limitations:

1. The estrogen-on period must be approximately 20 to 120 days.
2. The estrogen-off period must be approximately 3 to 7 days.

A conventional 21-days-on, 7-days-off estrogen schedule could potentially fall within the lower boundary of the claim if the progestogen remains continuous. A standard 28-day regimen with a longer or differently structured interruption may not.

Claims 4 and 5: broad progestogen and estrogen lists

Claim 4 lists 17 progestogens and assigns a minimum and maximum daily dose to each. The list includes:

• Levonorgestrel.
• Norgestrel.
• Norethindrone.
• Norethindrone acetate.
• Dydrogesterone.
• Medroxyprogesterone acetate.
• Norethynodrel.
• Allylestrenol.
• Lynoestrenol.
• Medrogestone.
• Norgestrienone.
• Cyproterone acetate.
• Other historical progestogens.

Claim 5 lists nine estrogen categories, including:

• Estradiol.
• Estradiol-17 beta.
• Estradiol valerate.
• Conjugated equine estrogens.
• Estrone.
• Piperazine estrone sulfate.
• Ethinyl estradiol.
• Mestranol.
• Quinestranol.

These lists create a large number of theoretical combinations. The practical scope remains constrained by the requirement that the selected hormones be administered under the regimen of claim 3.

Claims 6 and 7: preferred dose points

Claims 6 and 7 identify preferred dose levels within the broader ranges. Examples include:

• Estradiol: approximately 1 mg daily.
• Conjugated equine estrogens: approximately 0.6 mg daily.
• Ethinyl estradiol: approximately 0.01 mg daily.
• Levonorgestrel: approximately 0.05 mg daily.
• Norethindrone: approximately 0.3 mg daily.
• Medroxyprogesterone acetate: approximately 2.5 mg daily.

These claims have narrower literal scope but may have been commercially significant because they correspond to clinically recognizable hormone-replacement doses.

Claims 8 through 11: selected combinations

Claim 8 identifies combinations of specified estrogens with levonorgestrel, norgestrel, norethindrone, norethindrone acetate, or medroxyprogesterone acetate.

Claim 9 narrows the combinations to 17 beta-estradiol with d-norgestrel or levonorgestrel. Claim 10 defines:

• Estradiol: approximately 0.5 to 2 mg daily.
• D-norgestrel: approximately 50 to 150 micrograms daily.
• Levonorgestrel: approximately 25 to 75 micrograms daily.

Claim 11 further narrows d-norgestrel to approximately 75 micrograms daily.

The claim text contains typographical and dependency irregularities, including the reference in claim 8 to “any of claims 5” and the apparent use of “d1-norgestrel” for “dl-norgestrel.” Such errors do not automatically invalidate claims, but they can create claim-construction disputes.

What do claims 12 through 16 cover?

Claims 12 through 16 classify the active ingredients by chemical category.

Claim 12 covers synthetic estrogens, including:

• Ethinyl estradiol.
• Mestranol.
• Quinestranol.

Claim 14 covers natural estrogens, including:

• Conjugated equine estrogens.
• Estradiol.
• Estradiol valerate.
• Estrone.
• Estriol.
• Estriol succinate.
• Polyestrol phosphate.

Claim 16 lists the progestogens that may be used with the regimen.

These claims broaden the patent beyond the preferred estradiol-levonorgestrel combination. Their commercial relevance would depend on whether the claimed compounds were used in the specified continuous or extended-cycle schedules.

What formulations are protected by claims 17 through 20?

Claims 17 through 20 are composition claims directed to implantable or intramuscularly injectable products.

Claim	Formulation scope
17	Implantable or intramuscular injectable composition containing estrogen and progestogen in specified equivalent daily doses
18	Implantable estrogen selected from estradiol, estradiol-17 beta, or estradiol valerate
19	Implantable progestogen selected from levonorgestrel, d-norgestrel, norgestrienone, or norethindrone acetate
20	Injectable progestogen selected from medroxyprogesterone acetate, norethindrone enanthate, gestronol hexanoate, or algestone acetophenide

The phrase “pharmaceutically acceptable barrier” is important. It indicates a controlled-release implant or comparable delivery structure designed to regulate hormone release. The composition claims therefore differ from the method claims, which are not limited to implants or injections.

The patent does not claim ordinary tablets as compositions in claims 17 through 20. Oral products could still be relevant to the method claims if their dosing schedule met the claimed requirements.

When did U.S. Patent 4,826,831 lose exclusivity?

The patent was granted on May 2, 1989. For a U.S. patent governed by the former 17-year-from-grant term, the ordinary expiration date was May 2, 2006. The patent is therefore expired.

Milestone	Date
U.S. patent grant	May 2, 1989
Ordinary 17-year expiration	May 2, 2006
Current enforceability	None based on ordinary patent term
Current generic blocking value	None

The patent cannot support a new U.S. patent infringement claim. Any historical damages claim would also be subject to separate issues involving standing, notice, limitations periods, prosecution history, and proof of infringement.

What is the Orange Book status of U.S. Patent 4,826,831?

U.S. Patent 4,826,831 is not a current Orange Book barrier for menopausal hormone-therapy products.

The Orange Book lists patents submitted by sponsors for approved drug products under the Hatch-Waxman framework. A broad historical method patent can be absent from the Orange Book even if it once covered a therapeutic concept. The relevant issue for current generic entry is whether an unexpired patent is listed against the specific reference product and whether a generic applicant must address it in an Abbreviated New Drug Application certification. (U.S. Food and Drug Administration, 2025a)

Because U.S. 4,826,831 expired in 2006, it cannot presently require a Paragraph IV certification or delay approval of an ANDA.

Are Paragraph IV challenges associated with this patent?

No current Paragraph IV risk arises from U.S. 4,826,831 because the patent is expired.

A Paragraph IV certification applies when an ANDA applicant asserts that a listed patent is invalid, unenforceable, or will not be infringed. Expired patents do not create the same approval delay or 180-day first-filer framework associated with unexpired Orange Book patents. (U.S. Food and Drug Administration, 2025b)

The patent could have been relevant to historical generic strategies before expiration, but a current Paragraph IV challenge against it would have no practical commercial purpose.

What patent litigation affects U.S. Patent 4,826,831?

No currently enforceable litigation position arises from this patent. The patent’s age and expiration materially reduce the likelihood of active infringement litigation based solely on its claims.

Historical litigation research would need to distinguish:

• Cases involving the patent itself.
• Cases involving later patents for particular products.
• Patent disputes over transdermal systems.
• Litigation concerning specific combination products.
• Regulatory litigation involving FDA approvals.
• Product-liability cases, which are separate from patent disputes.

The broad claims could have created litigation pressure during their term, particularly against continuous-combined hormone products using estradiol or conjugated estrogens with levonorgestrel, norethindrone acetate, or medroxyprogesterone acetate. After expiration, those claims no longer provide an exclusionary basis.

How strong was the patent estate?

The patent was conceptually broad but likely vulnerable on several legal and technical grounds.

Breadth

The treatment claims cover numerous estrogens, numerous progestogens, multiple dose ranges, and two different schedules. That breadth could have increased the patent’s commercial reach if the claims survived validity scrutiny.

Enablement and written description

The claims cover many hormone pairs and dosage equivalents. A validity challenge could focus on whether the specification adequately enabled the full combination of compounds, doses, routes, and clinical uses. The implant and injectable claims raise similar questions regarding release rates, barriers, pharmacokinetics, and achievement of the claimed oral-equivalent exposure.

Obviousness

Menopausal hormone therapy using estrogen and progestogen was established before the patent. The potentially distinguishing feature was the continuous or extended-cycle schedule and the selected low-dose ranges. Prior-art references concerning cyclic hormone therapy, endometrial protection, breakthrough bleeding, and dose reduction would have been central to an obviousness analysis. (U.S. Patent and Trademark Office, 2024)

Claim construction

Potential disputes include the meaning of:

• “Continuously and uninterruptedly.”
• “Equivalent to” a specified dose.
• “About.”
• “Hormonally treating.”
• “Pharmaceutically acceptable barrier.”
• “Daily dosage units” for implants and injections.

The inconsistent spelling and claim dependencies could also affect interpretation, although courts generally construe claims in light of the specification and prosecution history.

How does this patent compare with later hormone-replacement product patents?

U.S. 4,826,831 was a regimen patent. Later hormone-replacement patents generally pursued narrower commercial positions:

Patent strategy	Typical protected subject matter
Regimen patent	Continuous or cyclic dosing schedule
Formulation patent	Tablet, patch, gel, cream, or injectable composition
Delivery patent	Controlled-release matrix, reservoir, adhesive, or implant
Combination-product patent	Specific estrogen-progestogen pairing
Manufacturing patent	Purification, crystallization, sterilization, or formulation process
Method-of-use patent	Treatment of a defined symptom or patient subgroup

Later products such as combination oral tablets and transdermal patches could have been protected by separate patents even after the expiration of U.S. 4,826,831. The expiration of this patent did not eliminate later patents covering a specific formulation, delivery device, manufacturing process, or approved product.

What generic entry risks exist today?

The patent itself creates no current generic-entry risk. A competitor could not be blocked by U.S. 4,826,831 from marketing:

• Estradiol and norethindrone products.
• Estradiol and levonorgestrel products.
• Conjugated estrogen and medroxyprogesterone products.
• Continuous-combined hormone regimens.
• Extended-cycle estrogen regimens.
• Implantable or injectable estrogen-progestogen systems.

Current risk would instead depend on separate unexpired patents, regulatory exclusivity, product-specific labeling, formulation claims, device rights, and any patent rights covering manufacturing or delivery technology.

For small-molecule hormone products, biosimilar risk is generally not the relevant framework. Estradiol, levonorgestrel, norethindrone, medroxyprogesterone acetate, and related hormones are chemically defined small molecules. Competitors ordinarily use the ANDA pathway rather than the biosimilar pathway, subject to product-specific FDA requirements. (U.S. Food and Drug Administration, 2024)

What licensing and geographic issues remain?

The U.S. patent right has expired, so no current U.S. license is required under this patent. Foreign counterparts would have had separate terms and could have expired on different dates depending on filing dates, national-phase prosecution, patent-term rules, supplementary protection rights, and maintenance status.

Any historical license involving the patent would not establish a current U.S. exclusionary right unless separate contractual obligations remain. A license may also have covered know-how, trademarks, formulation technology, or foreign patents independently of U.S. 4,826,831.

Key Takeaways

• U.S. Patent 4,826,831 covered continuous and extended-cycle estrogen-progestogen therapy for menopausal disorders.
• Claims 1 through 16 were primarily method claims based on hormone identity, dose, and administration schedule.
• Claims 17 through 20 covered implantable and intramuscular injectable compositions.
• The patent was granted on May 2, 1989, and ordinarily expired on May 2, 2006.
• It is not a current U.S. patent barrier and cannot support a present Paragraph IV delay.
• The patent does not create current Orange Book exclusivity.
• Current commercial risk must be assessed against later product, formulation, delivery-system, manufacturing, and method-of-use patents.
• The patent’s broad genus claims could historically have faced enablement, written-description, obviousness, and claim-construction challenges.
• Small-molecule hormone competitors generally face ANDA, not biosimilar, competition.

Frequently Asked Questions

Can a generic manufacturer practice the dosing regimen claimed in U.S. 4,826,831?

Yes. The patent expired, so its dosing and combination claims no longer restrict U.S. commercial practice.

Did U.S. 4,826,831 cover oral hormone-replacement tablets?

Its method claims were not limited to tablets. Its composition claims were directed specifically to implantable or intramuscular injectable forms.

Does the patent cover levonorgestrel and estradiol patches?

The method claims could historically have reached a patch using those hormones if the patch delivered the claimed daily equivalents and met the continuous-administration requirements. The patent is expired.

Is a continuous-combined estrogen-progestogen regimen still patentable?

A later patent could potentially claim a specific formulation, delivery system, patient population, dose, or regimen if it satisfies patentability requirements. U.S. 4,826,831 itself does not prevent later patenting of distinct subject matter.

Does the patent create biosimilar exposure for menopausal hormone products?

No. The listed active ingredients are chemically defined small molecules, so competitive products generally proceed through generic-drug pathways rather than the biosimilar pathway.

References

1. U.S. Food and Drug Administration. (2024). Biosimilar and interchangeable biosimilar products. https://www.fda.gov/drugs/biosimilars

2. U.S. Food and Drug Administration. (2025a). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book

3. U.S. Food and Drug Administration. (2025b). Abbreviated new drug application submissions and patent certifications. https://www.fda.gov/drugs/abbreviated-new-drug-application-anda

4. U.S. Patent and Trademark Office. (2024). Manual of Patent Examining Procedure, Chapter 2100: Patentability. https://www.uspto.gov/web/offices/pac/mpep/

5. U.S. Patent No. 4,826,831. (1989). Hormonal treatment of menopausal disorders. United States Patent and Trademark Office.

Drugs Protected by US Patent 4,826,831

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

International Family Members for US Patent 4,826,831

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0136011		C00136011/03	Switzerland
European Patent Office	0136011		SPC/GB00/025	United Kingdom
European Patent Office	0136011		SPC/GB02/008	United Kingdom
European Patent Office	0136011		SPC/GB97/032	United Kingdom
European Patent Office	0136011		SPC/GB98/034	United Kingdom
European Patent Office	0136011		SPC/GB00/028	United Kingdom