Details for Patent: RE36247

Summary for Patent: RE36247

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 E. Plunkett, Bernard M. J. Wolfe
Assignee:	Pre Jay Holdings Ltd , Woco Investments Ltd
Application Number:	US08/542,941
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent RE36247
Patent Claim Types: see list of patent claims	Use; Composition; Dosage form;

United States Patent RE36,247: Claim Scope, Validity, Exclusivity, and Menopausal Hormone-Therapy Patent Landscape

United States Patent RE36,247 covers continuous or extended-cycle administration of estrogen and progestogen for perimenopausal, menopausal, and postmenopausal disorders. Its central limitations are fixed daily dosing, specified estrogen and progestogen dose-equivalence ranges, uninterrupted administration, and, in the added claims, reduction of bone demineralization, osteoporosis risk, lipid changes, spotting, and bleeding. The patent is expired and cannot presently block generic or branded products, although its claims remain relevant to historical freedom-to-operate analysis and patent-landscape studies.

What does U.S. Patent RE36,247 protect?

RE36,247 protects treatment regimens rather than a particular chemical compound. The claims focus on the combination of:

1. An estrogen.
2. A progestogen.
3. Continuous and uninterrupted administration, or an extended estrogen cycle with a short estrogen-free interval.
4. Defined daily dosage ranges.
5. Treatment of menopausal or postmenopausal disorders.
6. In later claims, prevention or retardation of bone demineralization and osteoporosis.
7. In several claims, administration in a single dosage form, including a tablet.

The broadest original method claims are claims 1 and 3.

Claim	Principal subject matter	Key limitations
1	Continuous combined hormone therapy	Estrogen and progestogen administered continuously and uninterruptedly
3	Extended-cycle hormone therapy	Progestogen continuous; estrogen administered for 20-120 days, followed by a 3-7 day estrogen-free interval
17	Implantable or injectable composition	Estrogen and progestogen associated with a pharmaceutically acceptable barrier
21	Bone-protection method	Continuous fixed daily estrogen and progestogen; lower levonorgestrel-equivalent range
22	Bone-protection method with combination product	Same as claim 21, with estrogen and progestogen in one dosage form
23-25	Bleeding-minimization regimens	Fixed daily doses intended to minimize spotting or bleeding
27, 36, 43, 48	Long-duration treatment	Treatment period greater than 120 days
28	Osteoporosis	Dosage and duration sufficient to prevent or retard osteoporosis
29, 44, 49	Cardiovascular-risk surrogate	Prevention or retardation of adverse blood-lipid changes
39-43	Premarin-type combination	Conjugated equine estrogens with medroxyprogesterone acetate
45-49	Norethindrone acetate combinations	Estradiol or related estrogen with norethindrone acetate
54	Tablet	Single-dose-form tablet
55	Micronized progestogen	Progestogen in micronized form

The claims use “equivalent to” language. That language expands the claim beyond a single active ingredient, but it also creates a technical infringement issue: the accused product must fall within the stated pharmacologic or dosage equivalence standard.

How broad are the independent claims?

Claim 1: continuous combined therapy

Claim 1 requires:

• A woman with menopausal or postmenopausal disorders.
• Both progestogen and estrogen.
• Continuous and uninterrupted administration.
• Daily progestogen equivalent to 0.025-0.075 mg of levonorgestrel.
• Daily estrogen equivalent to 0.5-2.0 mg of estradiol.

The claim does not require a particular dosage form, route, brand, treatment duration, therapeutic endpoint, or specific estrogen-progestogen pair. A product could therefore fall within claim 1 if it uses oral tablets, patches, implants, or injections, provided the dosing and continuous-administration limitations are met.

Claim 1 is narrower than a generic claim to menopausal hormone replacement because it requires both hormones and specified dose ranges. It is broader than claims directed to a named product, such as estradiol plus levonorgestrel, because it covers multiple estrogen and progestogen choices through dose equivalence.

Claim 3: extended-cycle estrogen administration

Claim 3 uses a different regimen:

• Progestogen is administered continuously and without interruption.
• Estrogen is administered for 20-120 days.
• Estrogen is then stopped for 3-7 days.
• The cycle is repeated.
• Estrogen and progestogen must remain within the claimed dose-equivalence ranges.

This claim can reach products using an extended-cycle or modified continuous regimen, but not a conventional monthly regimen with substantially shorter estrogen exposure or a longer estrogen-free period.

Added claims 21-57

The added claims materially shift the patent toward later-developed commercial and therapeutic concepts:

• Bone-sparing treatment.
• Reduced spotting and bleeding.
• Treatment exceeding 120 days.
• Single-tablet administration.
• Specific combinations involving medroxyprogesterone acetate, norethindrone acetate, conjugated equine estrogens, estradiol, and levonorgestrel.
• Use of minimum effective hormone quantities.

These claims are narrower because they add therapeutic, duration, dosage-form, or ingredient limitations. Their practical scope depends heavily on claim construction of terms such as “minimize spotting and/or bleeding,” “bone-sparing estrogen,” “minimum effective quantities,” and “sufficient to prevent or retard.”

Which active ingredients and products fall within the claimed chemical classes?

The estrogen claims cover natural and synthetic estrogens. The listed compounds include estradiol, estradiol-17β, estradiol valerate, conjugated equine estrogens, estrone, estropipate, ethinyl estradiol, mestranol, and quinestrol.

The progestogen claims list a broad group of compounds, including:

• Levonorgestrel, described in the patent as laevo-norgestrel.
• Racemic norgestrel, described as dl-norgestrel.
• Norethindrone and norethindrone acetate.
• Ethynodiol diacetate.
• Dydrogesterone.
• Medroxyprogesterone acetate.
• Norethynodrel.
• Allylestrenol.
• Lynoestrenol.
• Quingestanol acetate.
• Medrogestone.
• Norgestrienone.
• Dimethisterone.
• Ethisterone.
• Cyproterone acetate.

The combinations expressly identified in claim 8 include estradiol or related estrogens paired with levonorgestrel, norgestrel, norethindrone, norethindrone acetate, or medroxyprogesterone acetate.

The most commercially relevant claim clusters are:

Product concept	Relevant claim cluster
Estradiol plus levonorgestrel	Claims 1, 2, 8-10, 21-27, 33-36, 51
Estradiol plus norethindrone acetate	Claims 8, 16, 45-49
Conjugated equine estrogens plus medroxyprogesterone acetate	Claims 8, 21-24, 37-44
Single-tablet continuous combination	Claims 22, 24, 25, 54
Long-term continuous therapy	Claims 27, 36, 43, 48
Bone-protection indication	Claims 21-44
Implant or injection	Claims 17-20

What formulations are protected by RE36,247?

The formulation coverage is limited compared with a conventional composition patent.

Claims 1-16 are method claims. They do not require a tablet, capsule, patch, implant, or injection. The accused product could therefore be evaluated based on its administration regimen rather than its physical formulation.

Claims 17-20 are composition claims directed to implantable or intramuscularly injectable forms. They require association with a pharmaceutically acceptable “barrier” and sufficient hormone content to provide the claimed oral-dose equivalents. These claims are more technically constrained and would not ordinarily cover a conventional oral tablet unless another claim applies.

Claims 22, 24, 25, and 54 address combination dosage forms. Claim 54 narrows the single dosage form to a tablet. A two-tablet regimen, separately packaged estrogen and progestogen, or a transdermal system would face a different analysis.

The patent does not appear, from the supplied claim text, to claim:

• A specific excipient system.
• A particular dissolution profile.
• A transdermal adhesive matrix.
• A controlled-release polymer.
• A specific manufacturing process.
• A defined particle-size distribution, except the later micronization limitation in claim 55.
• A particular tablet architecture.

Its principal value was regimen protection, not formulation engineering.

When does RE36,247 lose exclusivity?

RE36,247 is expired. The patent’s enforceable term was governed by the term of the underlying patent and the applicable pre- and post-1995 patent-term rules. Reissue does not restart the patent term or create a new full term.

Event	Significance
Original patent filing and priority	Established the underlying term and prior-art position
Reissue application	Corrected or amended the original patent; did not reset patent term
Reissue grant	Produced RE36,247
Patent expiration	Ended enforceable exclusionary rights
Present status	No current patent injunction or damages exposure based solely on RE36,247

Because RE36,247 is expired, a present-day generic manufacturer does not need a Paragraph IV certification against this patent. A product could still have faced a Paragraph IV challenge during the patent’s active term if the patent had been listed for the relevant drug and dosage form.

What is the Orange Book status of RE36,247?

RE36,247 is not a current source of Orange Book exclusivity. Orange Book listing is drug-specific and applies primarily to patents that claim an approved drug substance, drug product, or method of use. A broad hormone-therapy regimen patent would require a qualifying listing tied to an approved product and indication.

The supplied claims do not identify a specific approved New Drug Application, product trade name, or NDA holder. The claims also include many active ingredients and dosage forms, which makes a single-product Orange Book listing less straightforward than a patent directed to one approved tablet formulation.

The key regulatory distinction is:

• A patent may exist in the U.S. patent record without being listed in the Orange Book.
• An expired patent may remain visible in Orange Book historical data without providing current exclusivity.
• Orange Book listing does not determine validity or infringement.
• A method-of-use patent can affect an abbreviated new drug application only if it is properly listed and its use is relevant to the approved product.

FDA approval of a menopausal hormone-therapy product therefore does not establish infringement of RE36,247. The relevant question is whether the approved labeling and actual commercial instructions practice every limitation of an unexpired claim. FDA, Orange Book, and patent status must be analyzed separately. [2][3]

Which companies and products were the likely commercial targets?

The claim set corresponds to the technical field of continuous combined hormone-replacement therapy. Relevant commercial categories included products containing:

• Estradiol and norethindrone acetate.
• Conjugated equine estrogens and medroxyprogesterone acetate.
• Estradiol and levonorgestrel.
• Other continuous or extended-cycle estrogen-progestogen combinations.

Representative U.S. hormone-therapy products historically included Prempro and Premphase, associated with Wyeth and later Pfizer, and Activella, associated with Novo Nordisk. Estradiol/norethindrone acetate products were also marketed by multiple companies, including generic manufacturers after loss of product exclusivity.

Commercial relevance depends on whether a product used:

1. Continuous daily administration of both hormones.
2. A 20-120 day estrogen cycle followed by a 3-7 day estrogen-free interval.
3. A single combined dosage form.
4. A claimed dose-equivalence range.
5. The patented menopausal or bone-protection indication.

A product using cyclic progestogen administration, a different dose outside the claimed range, estrogen-only treatment, or a nonmenopausal indication would have stronger noninfringement positions under the supplied claims.

What generic entry risks existed during the patent term?

During the active term, the principal risk would have been a method-of-use or regimen infringement claim rather than compound infringement.

Generic tablet risk

A generic manufacturer using the same estrogen-progestogen combination and the same continuous regimen could have faced claims 1, 8-10, 21-25, or 51. Claims 22, 24, 25, and 54 would be particularly relevant to a single-tablet product.

Skinny-label risk

A generic applicant could seek to omit patented menopausal, osteoporosis, or cardiovascular-related uses from its labeling under the FDA’s section viii pathway, subject to the drug’s remaining approved uses and the scope of any listed method-of-use patent. The effectiveness of a skinny label would depend on whether the commercial product and labeling still induced the claimed regimen.

Dose-designaround risk

The ranges contain practical designaround opportunities. A product could potentially avoid a literal claim by using:

• Estrogen outside 0.5-2.0 mg estradiol-equivalent daily.
• Progestogen outside the relevant levonorgestrel-equivalent range.
• A noncontinuous progestogen regimen.
• An estrogen-free interval outside 3-7 days.
• Separate dosage forms where a single dosage form is required.
• A treatment duration of 120 days or less where “greater than 120 days” is required.

The doctrine of equivalents could limit some designarounds, but the numerical ranges and regimen intervals would remain central infringement issues.

How strong was the patent estate?

The estate was broad in subject matter but uneven in enforceability.

Strength factor	Assessment
Therapeutic concept	Broad coverage of continuous combined hormone therapy
Chemical scope	Broad list of estrogens and progestogens
Dose scope	Defined ranges create useful commercial targeting but also designaround points
Formulation scope	Narrow outside implantable, injectable, and single-tablet claims
Method-of-use scope	Potentially significant if approved labeling matched the claimed regimen
Bone and lipid claims	Narrower; dependent on proof of treatment effect and claim construction
Manufacturing protection	Minimal based on the supplied claims
Current enforceability	None because the patent has expired
Biosimilar relevance	Limited; the claims concern small-molecule hormone therapy, not biologics

The claim estate’s strongest historical position was against a fixed-dose, continuous combined oral product using a listed estrogen-progestogen pair within the claimed dose ranges. Its weakest position was against products with materially different schedules, routes, doses, or indications.

Did biosimilar risk apply to RE36,247?

No meaningful biosimilar pathway risk applies. The claimed products contain small-molecule estrogens and progestogens. They would generally be regulated through NDA or ANDA pathways, not the Biologics Price Competition and Innovation Act biosimilar pathway.

Conjugated equine estrogens are complex mixtures, but their presence in a hormone-therapy product does not convert RE36,247 into a biologic patent estate. The principal competitive threats were generic substitution, authorized generics, and competing branded hormone-therapy products.

What patent litigation or settlement agreements affected RE36,247?

The supplied materials do not identify litigation captions, ANDA filers, settlement terms, or a specific listed NDA. No litigation or settlement conclusion can be reliably assigned to RE36,247 from the claim text alone.

Because the patent is expired, any historical litigation would now have significance primarily for:

• Claim construction.
• Validity analysis.
• Prior-art development.
• Settlement and launch-timing precedent.
• Interpretation of continuous hormone-therapy claims.

A current freedom-to-operate opinion should not treat RE36,247 as an active blocking right.

How does RE36,247 compare with later hormone-therapy patents?

RE36,247 is principally a regimen patent. Later estates in menopausal hormone therapy generally moved toward narrower and more product-specific protection:

Patent category	Typical protection
Regimen patent	Continuous or extended-cycle dosing
Composition patent	Specific estrogen-progestogen combination
Formulation patent	Release profile, excipients, tablet structure, patch, gel, or ring
Device patent	Applicator, implant, delivery system, or transdermal device
Method-of-use patent	Osteoporosis, vasomotor symptoms, vaginal symptoms, or bleeding control
Manufacturing patent	Purification, conjugation, particle size, or processing

A company commercializing a modern hormone-therapy product should therefore review the full patent family, continuation practice, formulation patents, Orange Book listings, pediatric exclusivity, regulatory exclusivity, and any post-expiration patent claims. RE36,247 alone does not define the current landscape.

What geographic coverage did RE36,247 provide?

The patent provided rights only in the United States. Corresponding foreign rights would require separate national or regional patents and separate expiration analysis. The claim language and U.S. reissue status do not establish protection in Europe, Canada, Japan, Australia, or other markets.

For international commercialization, the relevant comparison is between:

• U.S. reissue and continuation records.
• European Patent Office family members.
• National validation and lapse records.
• Patent-term adjustments or supplementary protection certificates.
• Local regulatory exclusivity.
• Local claim construction for medical-use claims.

No U.S. patent can independently prevent launch outside the United States.

Key Takeaways

• RE36,247 covers continuous or extended-cycle estrogen-progestogen therapy for menopausal and postmenopausal disorders.
• Claims 1 and 3 are the central regimen claims.
• The patent also covers selected implantable, injectable, single-tablet, bone-protection, lipid, and bleeding-minimization embodiments.
• The principal numerical ranges are 0.025-0.075 mg levonorgestrel-equivalent progestogen and 0.5-2.0 mg estradiol-equivalent estrogen.
• The listed combinations include estradiol, conjugated equine estrogens, levonorgestrel, norethindrone acetate, and medroxyprogesterone acetate.
• The patent is expired and does not create current U.S. market exclusivity.
• It is a method and regimen patent, not a modern formulation or manufacturing patent.
• Biosimilar analysis is largely irrelevant because the products are small-molecule hormone therapies.
• Historical generic risk would have centered on fixed-dose continuous combination products and matching menopausal or bone-protection labeling.
• Current commercial diligence requires review of later product-specific patents, Orange Book records, and any remaining formulation or delivery-system rights.

Frequently Asked Questions

Can an expired RE36,247 patent support a current infringement lawsuit?

No. Expiration ends the right to obtain prospective patent injunctions and damages for post-expiration conduct.

Did RE36,247 claim Prempro specifically?

No. The supplied claims do not name Prempro. They cover broader combinations that may include conjugated equine estrogens and medroxyprogesterone acetate within specified regimens and doses.

Does a transdermal estradiol patch automatically avoid RE36,247?

No. The original method claims are not limited to oral administration. A patch could require analysis under the continuous-administration and dose-equivalence limitations, although the single-tablet claims would not apply.

Could a monthly cyclic hormone-therapy product infringe claim 3?

Generally, claim 3 requires continuous progestogen and estrogen administration for 20-120 days followed by only 3-7 days without estrogen. A materially different monthly schedule would have a substantial noninfringement argument.

Is RE36,247 relevant to current ANDA approvals?

Only historically or as background prior art. An expired patent does not independently delay current ANDA approval, although other unexpired patents and applicable Orange Book listings may do so.

References

1. United States Patent and Trademark Office. (1999). U.S. Patent No. RE36,247, Reissue of patent concerning continuous estrogen and progestogen treatment for menopausal disorders. U.S. Department of Commerce.

2. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. Center for Drug Evaluation and Research.

3. U.S. Food and Drug Administration. (2024). Orange Book: Approved drug products with therapeutic equivalence evaluations, patent and exclusivity information. Center for Drug Evaluation and Research.

4. 35 U.S.C. §§ 154, 251, 271, 282. (2024). United States Code.

5. 21 U.S.C. § 355(j)(2)(A)(viii). (2024). United States Code.

Drugs Protected by US Patent RE36247

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 RE36247

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