Details for Patent: 8,957,054

« Back to Dashboard

Which drugs does patent 8,957,054 protect, and when does it expire?

Patent 8,957,054 protects INTRAROSA and is included in one NDA.

This patent has fifty-nine patent family members in thirty-two countries.

Summary for Patent: 8,957,054

Title:	Pharmaceutical compositions
Abstract:	Novel methods for treating or reducing the likelihood of acquiring symptoms or diseases due to the menopause, in postmenopausal women, particularly osteoporosis, vaginal atrophy and dryness, hypogonadism, diminished libido, skin atrophy, connective tissue disease, urinary incontinence, breast, endometrial, ovarian and uterine cancers, hot flashes, loss of muscle mass, insulin resistance, fatigue, loss of energy, aging, physical symptoms of menopause, in susceptible warm-blooded animals including humans involving administration of a sex steroid precursor are disclosed. Said method comprising novel ways of administering and dosing dehydroepiandrosterone (DHEA) in order to take advantage of positive androgenic effects in the vaginal layers lamina propia and/or the layer muscularis, without undesirably causing systemic estrogenic effects in order to avoid the risk of breast and uterine cancer. Pharmaceutical compositions for delivery of active ingredient(s) useful to the invention are also disclosed.
Inventor(s):	Fernand Labrie
Assignee:	Myriel Pharmaceuticals LLC
Application Number:	US13/544,407
Patent Claim Types: see list of patent claims	Use; Formulation; Dosage form;

US Patent 8,957,054: Scope, Claims, Expiration, and Prasterone Patent Landscape

US Patent 8,957,054 protects low-dose intravaginal administration of dehydroepiandrosterone, or DHEA, and related sex-steroid precursors for treating or reducing the risk of postmenopausal vaginal atrophy and related conditions. Its commercial relevance is concentrated in 6.5 mg daily prasterone vaginal inserts, including the product marketed as Intrarosa. The patent is a method-of-treatment patent, not a broad composition-of-matter patent. A generic applicant could therefore avoid infringement only by avoiding the claimed active ingredient, route, patient population, dosage range, formulation, or treatment indication.

The patent's base statutory term runs to approximately January 2029, subject to any applicable patent-term adjustment or terminal-disclaimer effects. FDA-approved prasterone is a small-molecule product subject to an ANDA and Paragraph IV challenge framework, not a biosimilar pathway.

What does US Patent 8,957,054 protect?

The patent protects intravaginal administration of a sex-steroid precursor at a daily therapeutic amount of 13 mg or less to postmenopausal women for specified vulvovaginal conditions.

The principal elements are:

Claim element	Scope
Patient	Human postmenopausal female
Route	Intravaginal administration
Active ingredient	DHEA, DHEA sulfate, androst-5-ene-3β,17β-diol, or 4-androstene-3,17-dione
Dose	13 mg per day or less
Conditions	Vaginal atrophy, atrophic vaginitis, vaginal dryness, dyspareunia, or sexual dysfunction
Pharmacology	Certain claims require no increase in circulating androgen metabolites and no increase in estradiol above normal postmenopausal levels
Formulation	Cream, lotion, gel, ointment, ovule, suppository, or vaginal ring
Narrowest commercial embodiment	Vaginal suppository containing 3 to 13 mg of DHEA

The independent claims are claims 1 and 27. Claim 28 is also independently important in practical infringement analysis because it expressly covers a vaginal suppository containing 3 to 13 mg of DHEA.

How do the independent claims differ?

Claim 1: broad low-dose method claim

Claim 1 covers treatment or prophylactic reduction of the listed conditions using any of four sex-steroid precursors:

1. Dehydroepiandrosterone;
2. Dehydroepiandrosterone sulfate;
3. Androst-5-ene-3β,17β-diol; or
4. 4-androstene-3,17-dione.

The dose must be 13 mg per day or less, and administration must be intravaginal. The claim reaches both treatment and reduction of the likelihood of acquiring a condition.

The claim does not require a suppository. A cream, gel, ring, ovule, or other intravaginal delivery system can fall within its literal scope if the dosage and patient limitations are met.

Claim 27: DHEA suppository claim

Claim 27 narrows the active ingredient to DHEA and the dosage form to a vaginal suppository. It retains the upper dose limit of 13 mg or less but does not expressly require the 3 mg lower limit used in claim 28.

Claim 28: 3 to 13 mg DHEA suppository claim

Claim 28 is narrower than claim 27 because it requires 3 to 13 mg of DHEA in a vaginal suppository. A 6.5 mg daily insert is squarely within this range.

This claim is commercially significant because the approved Intrarosa product contains 6.5 mg of prasterone, the pharmaceutical name for DHEA, in a vaginal insert administered once daily.[1]

What dosage ranges are covered by the patent?

Claims 1 through 12 create a nested dosage structure:

Claims	Dose limitation
1-3	13 mg per day or less
4-6	3 to 13 mg per day
7-9	6.5 mg per day or less
10-12	3.25 mg per day or less
27	13 mg or less in a DHEA vaginal suppository
28	3 to 13 mg in a DHEA vaginal suppository

Claims 10 through 12 state "3.25 per day or less" without repeating the unit in the supplied text. In the context of the patent, the limitation is understood as a daily amount of 3.25 mg or less.

The 6.5 mg level is the principal commercial target. A product administered at 6.5 mg daily would generally satisfy the numerical limitation in claims 1, 4, 7, 13-24, 27, and 28 if the remaining limitations are met.

A product delivering more than 13 mg per day would fall outside the express dosage limitation of claims 1 through 9 and 27. It could still implicate other patents or unasserted patent claims in the same family.

What formulation patents and delivery systems are relevant?

US 8,957,054 claims the method of using an intravaginal formulation but does not broadly claim every composition containing DHEA. Claim 25 identifies the permitted formulation categories:

• Cream;
• Lotion;
• Gel;
• Ointment;
• Ovule;
• Suppository; and
• Vaginal ring.

Claim 26 narrows the formulation to a vaginal suppository. Claims 27 and 28 further combine the suppository limitation with DHEA and specified dose ranges.

The patent therefore creates two infringement pathways:

1. Use-based infringement: administering low-dose DHEA intravaginally to the specified postmenopausal population.
2. Product-use combination: administering a DHEA vaginal suppository within the claimed dosage range.

A manufacturer may face infringement exposure even if its formulation excipients, manufacturing process, device design, or packaging differ from the reference product. The claims focus primarily on the active ingredient, route, dose, patient population, condition, and formulation category.

Separate patents in the broader prasterone estate may protect insert composition, excipient selection, manufacturing processes, release characteristics, or particular dosing regimens. Those patents must be analyzed independently because design-around of US 8,957,054 does not eliminate exposure under other family members.

What are the most important dependent claims?

Claims 2, 3, and 5, 6, 8, 9, 11, and 12 add pharmacokinetic limitations.

Claim 2 requires that the therapeutic amount:

• Not increase circulating androgen metabolites; and
• Not increase circulating estradiol above levels found in normal postmenopausal women.

Claim 3 adds an average 24-hour circulating estradiol level below 10 pg/mL.

These limitations reflect the patent's safety and local-conversion theory: DHEA is administered locally, converted within vaginal tissue into active sex steroids, and does not materially raise systemic estrogen exposure.

The limitations may strengthen validity by narrowing the claims to a defined pharmacological result. They can also complicate enforcement because infringement may depend on clinical or pharmacokinetic evidence. A patent owner would need to establish that the accused regimen produces the claimed hormone profile, particularly for claims 2, 3, 5, 6, 8, 9, 11, and 12.

The dependent DHEA claims, claims 13 through 24, remove the alternative precursors and focus on the commercial active ingredient. Claims 16 through 24 combine DHEA with the narrower dose and estradiol limitations.

When does US Patent 8,957,054 expire?

The patent's base term is projected to expire around January 2029, calculated from the earliest effective nonprovisional priority date under the 20-year patent term framework.[2] The operative expiration date must be taken from the USPTO Patent Examination Data System and the patent's term-adjustment calculation.

The expiration analysis should distinguish among:

Term category	Relevance
Base patent term	Approximately January 2029
Patent-term adjustment	Could extend the base term for qualifying USPTO delay
Patent-term extension	Potentially available for regulatory review, although applicability depends on the specific product and statutory requirements
Terminal disclaimer	Could shorten the term if one was filed against a related patent
Orange Book listing	Does not itself extend patent term

The patent was issued in 2015. FDA approval of the related prasterone product occurred in 2016. Any regulatory exclusivity associated with the NDA is separate from the patent term and does not replace patent protection.

What is the FDA and Orange Book status of the related prasterone product?

The FDA approved prasterone vaginal inserts under NDA 208470 for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause.[1] The approved product is a 6.5 mg vaginal insert administered once daily at bedtime.

Prasterone is a locally administered steroid precursor. It is not an estrogen product, and its FDA labeling describes local conversion to estrogens and androgens in vaginal tissues.[1]

The Orange Book is the controlling FDA source for listed patents and regulatory exclusivity associated with an approved drug product.[3] For commercial diligence, the following points matter:

• The product is a small molecule, so ANDA applicants may rely on the reference product's safety and efficacy findings.
• An ANDA applicant must address listed patents through certification under section 505(j)(2)(A)(vii).
• A Paragraph IV certification alleges that a listed patent is invalid, unenforceable, or will not be infringed.
• A timely Paragraph IV notice can trigger patent litigation and a 30-month stay of approval under the Hatch-Waxman Act.
• A successful Paragraph IV challenge can support an earlier generic launch.
• FDA approval does not authorize launch during an enforceable injunction or a valid settlement-restricted period.

Orange Book listings should be reviewed by NDA number and product strength because listing status can change through patent-listing updates, delisting requests, court decisions, and expiration events.

What Paragraph IV risks apply to a prasterone generic?

A 6.5 mg generic vaginal insert would be a direct target for a Paragraph IV challenge because it would likely practice the central commercial embodiment of the patent:

• Postmenopausal women;
• Intravaginal administration;
• DHEA;
• 6.5 mg daily;
• Treatment of vaginal atrophy-related symptoms; and
• Vaginal insert or suppository dosage form.

The principal generic strategies would include:

Noninfringement arguments

A generic applicant could argue that:

• Its label does not induce treatment of a claimed condition;
• Its proposed use is outside the postmenopausal population;
• Its product is not a "suppository" under the claim construction;
• Its dosage differs from the claimed amount;
• Its label omits a claimed method of treatment; or
• The product is not administered at the frequency required by the claim.

Method-of-use infringement may turn on the content of the proposed label and the degree to which physicians are expected to use the product for the patented indication.

Invalidity arguments

The principal validity attacks would likely involve:

• Anticipation by earlier intravaginal DHEA references;
• Obviousness based on prior vaginal DHEA studies and known local steroid conversion;
• Written-description support for the broad precursor genus;
• Enablement across all claimed formulations and doses;
• Indefiniteness of functional pharmacokinetic limitations; and
• Lack of support for prophylactic treatment or "reducing the likelihood of acquiring" a condition.

The claims are vulnerable to obviousness arguments because DHEA, vaginal atrophy, local steroid therapy, and intravaginal delivery were individually known concepts. The patent owner's strongest response is the claimed low-dose regimen combined with controlled systemic exposure and clinical benefit.

Label carve-out

A Section viii statement may be possible for an unpatented use, but it is less effective where the product's principal approved use overlaps with the claimed method. The FDA labeling for prasterone is directed to dyspareunia due to vulvar and vaginal atrophy, which overlaps materially with the patent's claim language.

Which companies challenge or compete with prasterone?

The competitive landscape contains both direct generic risk and therapeutic substitutes.

Product or company category	Active ingredient or modality	Relationship to US 8,957,054
Prasterone vaginal insert	DHEA	Direct patent and ANDA exposure
Estradiol vaginal tablets or inserts	Estradiol	Usually outside DHEA-specific claims
Estradiol vaginal softgel inserts	Estradiol	Competes clinically, not ordinarily within DHEA claims
Estradiol vaginal ring	Estradiol	Alternative local estrogen therapy
Conjugated estrogen cream	Conjugated estrogens	Different active ingredient and formulation
Ospemifene	Selective estrogen receptor modulator	Oral alternative for dyspareunia
Nonhormonal moisturizers and lubricants	Nonhormonal	Symptom-management substitutes

Generic manufacturers with approved or pending prasterone products would present the most direct competitive threat. Estradiol generics create commercial pressure but generally do not practice the DHEA-specific claims.

There is no biosimilar pathway for prasterone. Biosimilar risk applies to biological products under section 351(k) of the Public Health Service Act, while prasterone is regulated as a chemically synthesized small molecule under the ANDA pathway.[4]

How strong is the patent estate?

US 8,957,054 has meaningful commercial strength against a same-label 6.5 mg DHEA vaginal insert, but its strength is narrower than a composition-of-matter patent.

Strengths

• The claims map directly onto the approved 6.5 mg vaginal insert.
• Claims 27 and 28 specifically target DHEA suppositories.
• The claims cover multiple vaginal dosage forms.
• The claims cover both treatment and, in claim 1, risk reduction.
• The low-dose limitation distinguishes the patent from higher-dose systemic DHEA therapy.
• Dependent claims provide fallback positions at 6.5 mg and 3.25 mg.

Weaknesses

• The patent does not claim DHEA as a chemical compound.
• A competitor can potentially avoid the claims through a different active ingredient or route.
• The broad precursor group may face written-description and obviousness scrutiny.
• The pharmacokinetic limitations require measurable evidence and may create claim-construction disputes.
• Claims 27 and 28 depend heavily on how "vaginal suppository" is construed.
• Generic label design and treatment-indication language can determine induced-infringement exposure.

The estate is strongest against a product that copies the reference product's active ingredient, dose, route, dosage form, patient population, and indication. It is weaker against non-DHEA local therapies and products marketed for a materially different indication.

What patent litigation and settlement issues affect generic launch?

A Paragraph IV notice involving a listed prasterone patent can produce:

1. Patent litigation in federal district court;
2. A potential 30-month FDA approval stay;
3. Discovery concerning formulation, bioequivalence, labeling, and intended use;
4. Claim-construction proceedings;
5. Settlement negotiations involving a licensed launch date; and
6. Potential acceleration through invalidity or noninfringement judgment.

Settlement terms may include an agreed generic entry date, a license, a covenant not to sue, or restrictions on the generic label. A settlement can also address patents not asserted in the initial litigation if the parties seek comprehensive market certainty.

The key diligence point is that patent expiration, FDA approval, and commercial launch are separate events. A generic may receive tentative approval before patent expiry but remain unable to launch until the patent barrier, regulatory exclusivity, court injunction, or settlement restriction ends.

What generic launch scenarios exist?

Scenario	Commercial consequence
Patent upheld and no license granted	Generic launch delayed until enforceable patent protection ends
Patent invalidated	FDA approval and launch can proceed subject to remaining patents and exclusivity
Noninfringement judgment	Same-label or narrow-label launch may proceed
Settlement with licensed entry	Launch occurs on the negotiated date
Label carve-out accepted	Launch may proceed for noninfringing uses
Alternative DHEA formulation	May reduce exposure under suppository claims but remains subject to claims 1 and 25
Non-DHEA local therapy	Generally outside this patent but competes commercially

Key Takeaways

• US Patent 8,957,054 is a low-dose intravaginal DHEA method patent.
• Its core commercial target is a 6.5 mg daily prasterone vaginal insert.
• Claims 27 and 28 are the most product-relevant claims because they expressly cover DHEA vaginal suppositories.
• The patent covers doses of 13 mg or less, with narrower fallbacks at 6.5 mg or less and 3.25 mg or less.
• It does not broadly claim DHEA as a molecule or every DHEA formulation.
• The patent's base term is approximately January 2029, subject to patent-term adjustments and related legal effects.
• Generic prasterone exposure is principally an ANDA and Paragraph IV issue.
• Biosimilar competition does not apply because prasterone is a small molecule.
• The strongest design-around routes involve a different active ingredient, different route, different indication, or a dosage and formulation outside the claim limitations.
• The patent estate is commercially meaningful but narrower than a composition-of-matter estate.

FAQs About US Patent 8,957,054 and Prasterone

Does a 6.5 mg prasterone vaginal insert fall within US Patent 8,957,054?

Yes. A 6.5 mg daily intravaginal DHEA insert fits the central dosage, active-ingredient, route, patient, condition, and formulation limitations described in the patent.

Does an estradiol vaginal insert infringe this patent?

Ordinarily no. The claims require DHEA or one of the specifically listed sex-steroid precursors. Estradiol is not one of the claimed active ingredients.

Can a DHEA cream avoid the patent?

Not necessarily. Claim 25 expressly identifies cream as a covered intravaginal formulation, and claim 1 is not limited to suppositories. A DHEA cream could remain within the patent if the dose, route, population, and indication satisfy the claims.

Is prasterone subject to biosimilar competition?

No. Prasterone is a chemically synthesized small molecule. Competition proceeds through the ANDA pathway rather than the biosimilar pathway.

What is the most important patent claim for a generic prasterone manufacturer?

Claim 28 is one of the most commercially important claims because it directly covers treatment using a vaginal suppository containing 3 to 13 mg of DHEA. Claims 1 and 27 provide broader or alternative infringement theories.

References

1. U.S. Food and Drug Administration. (2016). Intrarosa (prasterone) vaginal inserts, 6.5 mg: Prescribing information. FDA.

2. United States Patent and Trademark Office. (2015). U.S. Patent No. 8,957,054, Use of a low dose of dehydroepiandrosterone for the treatment of vaginal atrophy. USPTO.

3. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.

4. U.S. Food and Drug Administration. (2024). Biosimilar and interchangeable biosimilar products. FDA.

5. Drug Price Competition and Patent Term Restoration Act of 1984, 21 U.S.C. § 355(j).

Drugs Protected by US Patent 8,957,054

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Millicent	INTRAROSA	prasterone	INSERT;VAGINAL	208470-001	Nov 16, 2016		RX	Yes	Yes						INTRAVAGINAL PRASTERONE (DEHYDROEPIANDROSTERONE) AT A DAILY DOSE OF 6.5MG FOR THE TREATMENT OF DYSPAREUNIA, A SYMPTOM OF VULVAR AND VAGINAL ATROPHY, DUE TO MENOPAUSE

International Family Members for US Patent 8,957,054

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2185157		C02185157/01	Switzerland
Argentina	068702
Argentina	104577
Argentina	114051
Australia	2008286651
Brazil	PI0815353
Canada	2696127