Details for Patent: 10,258,630

Which drugs does patent 10,258,630 protect, and when does it expire?

Patent 10,258,630 protects IMVEXXY and is included in one NDA.

This patent has one hundred and sixty-six patent family members in twenty-one countries.

Summary for Patent: 10,258,630

Title:	Vaginal inserted estradiol pharmaceutical compositions and methods
Abstract:	In one aspect, compositions and methods for the treatment of vulvovaginal atrophy (VVA) are provided. In one embodiment, the method comprises administering an estrogen to a subject having VVA by inserting a dosage form comprising a liquid pharmaceutical composition.
Inventor(s):	Sebastian Mirkin, Julia M. Amadio, Brian A. Bernick
Assignee:	TherapeuticsMD Inc
Application Number:	US15/893,546
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,258,630
Patent Claim Types: see list of patent claims	Use; Composition; Dosage form;

United States Patent 10,258,630: Scope, Claim Construction, and US Patent Landscape for Intravaginal Estradiol in Moderate-to-Severe Dyspareunia

United States Patent 10,258,630 is directed to a specific method of treating moderate to severe dyspareunia using manually inserted intravaginal dosage forms containing estradiol as the only active agent, with liquid composition viscosity tightly bounded, soft-gelatin capsule delivery with fully encapsulated estradiol, a defined estradiol dose range (4 to 25 μg), and a defined dosing cadence (once daily for two weeks, then twice weekly). The independent claim is method-centric but tightly constrained by formulation and handling/dosing mechanics, which narrows design-around options for generic or competitor products that deviate from the viscosity range, estradiol encapsulation, dosing regimen, or the “once daily then twice weekly” timing.

What is the claim scope of US 10,258,630 for intravaginal estradiol capsules?

In one line: The patent claims a method where a patient treats moderate-to-severe dyspareunia by inserting a manually delivered intravaginal capsule containing a liquid estradiol composition with viscosity ~50–1000 cP at 25°C, where estradiol is the only active, all estradiol is encapsulated in the capsule, and estradiol is released to vaginal mucosa, using a 4–25 μg estradiol dose with once-daily for 2 weeks then twice weekly dosing.

Claim 1 element-by-element scope (independent claim)

Claim 1 is a conjunctive set of requirements; literal infringement requires each limitation to be met.

1. Patient condition: “moderate to severe dyspareunia.”
2. Administration route: intravaginally administering a dosage form comprising a liquid pharmaceutical composition.
3. Manual insertion: “dosage form is manually inserted into the vagina.”
4. Viscosity limitation: the liquid pharmaceutical composition has viscosity about 50 cP to about 1000 cP at 25°C.
5. Only active agent: the composition comprises estrogen as the only active agent.
6. Encapsulation requirement: “all of the estradiol is encapsulated in the capsule.”
7. Estradiol dose range: composition comprises about 4 μg to about 25 μg of estradiol.
8. Dosage cadence: “inserting the capsule once daily for two weeks and twice weekly thereafter.”
9. Release upon contact: upon contacting vaginal mucosa, the estrogen-containing composition is released into the vaginal tissue.

Practical construction impact: This is not a generic “vaginal estradiol treatment” claim. It is constrained by the delivery mechanics (manual capsule insertion; capsule fully encapsulates estradiol), physical property (viscosity window), therapeutic target (dyspareunia severity category), and the specific dosing schedule.

Claims 2–4: capsule hardware and specific capsule type

• Claim 2: dosage form is a capsule.
• Claim 3: capsule is a soft gelatin capsule.
• Claim 4: composition contains about 4 μg to about 25 μg estradiol (dose sub-range aligned to claim 1).

Scope effect: These claims narrow hardware. A product using a different intravaginal form (tablet, suppository, film, cream, ring, insert with solid core, polymer reservoir) is outside the literal claim set if it is not a “capsule,” and especially if not a “soft gelatin capsule.”

Claims 5–9: biological response and clinical outcome time windows

Claims 5–8 add measurable endpoints “within about two to six weeks from the first administration,” including:

• Claim 5: increase in percentage of vaginal superficial cells.
• Claim 6: decrease in percentage of vaginal parabasal cells.
• Claim 7: decrease in vaginal pH.
• Claim 8: decrease in severity of moderate to severe dyspareunia.
• Claim 9: dose includes either 4 μg estradiol or 10 μg estradiol.

Scope effect: These are still method limitations. Even if the dosage form meets claim 1, infringement of claims 5–9 also depends on achieving the claimed biological changes and/or severity reduction within the specified window. In practice, this often becomes evidence-heavy at litigation: the accused infringer may argue that their product does not reliably drive those cytology and pH outcomes within two to six weeks.

How does the viscosity and “liquid pharmaceutical composition” limitation narrow infringement?

Key risk lever for competitors: The viscosity window “about 50 cP to about 1000 cP at 25° C.” forces an accused formulation to be physically characterized at the specified temperature with a method consistent with the patent’s definition. Many estradiol vaginal products are creams, gels, suspensions, or semi-solids with rheology that can be characterized over different shear rates and temperature points.

Literal infringement pressure points:

• Product must have a composition that meets the viscosity window at 25°C.
• If the accused product is semi-solid but its viscosity at 25°C (and measured under the relevant method) falls outside 50–1000 cP, literal infringement is weakened.
• If estradiol delivery is not “liquid pharmaceutical composition” in the sense contemplated by the claim, argument shifts to whether the composition is truly a “liquid pharmaceutical composition” and whether viscosity is even applicable in a claim-anchored way.

What does “all estradiol is encapsulated in the capsule” mean for design-arounds?

This limitation is unusual in that it requires full encapsulation of estradiol in the capsule. It blocks partial-drug loading in a way that some semi-solid inserts might avoid.

Design-around angles that typically matter in this limitation space:

• Separate estradiol reservoirs not fully encapsulated within a capsule interior.
• Estradiol present as free drug in the capsule shell medium or in a coating not considered “encapsulated in the capsule” (accused product can argue it is not fully encapsulated).
• Alternative delivery systems where estradiol is presented in a matrix, film, ring, or internal reservoir that is not a capsule and/or not “all encapsulated.”

Because claim 1 uses “all of the estradiol is encapsulated in the capsule,” partial compliance is not enough for literal infringement.

What is the dosing schedule scope: once daily for two weeks then twice weekly?

Claim 1 includes a regimen with a defined time structure:

• Once daily for two weeks
• Then twice weekly thereafter

This is both a treatment and timing limitation. If an accused product is labeled or used with a substantially different schedule (for example continuous low-frequency dosing, a different taper, or different initiation period), claim scope tightens.

In litigation, schedule can be attacked on:

• Whether the regimen “comprising inserting the capsule” matches the accused instructions and actual use.
• Whether a different clinical titration still counts as “once daily for two weeks.”

What formulations are protected: estradiol-only liquid in soft gelatin capsules

Protected formulation characteristics:

• Estradiol is the only active estrogen agent.
• Estradiol is fully encapsulated inside a capsule.
• The capsule contains a liquid formulation with defined viscosity range at 25°C.
• Estradiol mass is 4–25 μg.

Protected delivery mechanics:

• Manually inserted intravaginal capsule.
• Release into vaginal tissue on mucosal contact.

Any competitor that includes other actives (for example, progestins, additional hormones, antimicrobial agents) is outside the “only active agent” limitation. Creams/films that contain estradiol plus excipients do not automatically violate the “only active agent” limitation unless another estrogen-active agent is included; inactive excipients generally do not break this element.

What do the dependent claims add: soft gelatin capsule, 4 μg or 10 μg, and endpoint timing?

Soft gelatin capsule requirement

Claim 3 is a hardware narrowing. Even if a device is a capsule, a non-soft-gelatin capsule may avoid this dependent claim, though claim 1 might still be asserted if “capsule” is met and other claim 1 limitations are satisfied.

Endpoint timing (2–6 weeks)

Claims 5–8 add a “within about 2 to 6 weeks from first administration” condition. This does not necessarily require measurement by the same protocol as the specification, but it creates a strong factual requirement for infringement.

• Cytology endpoints: superficial and parabasal cell percentages.
• Biomarker: vaginal pH decrease.
• Clinical outcome: dyspareunia severity decrease.

A generic challenger may argue their product produces different cytology kinetics or pH trajectory.

Specific dose points: 4 μg or 10 μg

Claim 9 pins at least two discrete dose options. A product at 25 μg could still infringe claim 1 if within 4–25 μg, but claim 9 specifically focuses on 4 μg or 10 μg.

How strong is the patent estate likely to be based on claim structure?

Without the full patent text, specification, priority chain, and cited references, strength assessment must be anchored to the claim architecture.

Strength indicators:

• The claim is narrow on multiple independent axes (viscosity, capsule form, fully encapsulated estradiol, dosing schedule, disease severity category).
• Narrowness can reduce the number of plausible infringing products, which helps design-around and reduces global enforcement leverage.
• However, the claim’s specificity can still be potent if the challenged product is closely aligned, especially if it uses a similar capsule format and regimen.

Risk indicators for enforceability:

• The breadth is “narrow but deep.” If a competitor avoids one key element (capsule type, viscosity, schedule, or full encapsulation), infringement may fail.
• Dependent endpoint claims introduce evidentiary complexity and may be harder to enforce if clinical endpoints do not track exactly.

Net: enforcement leverage is highest where an accused product uses soft gelatin vaginal estradiol capsules with the same viscosity window, encapsulation approach, and regimen.

How does US 10,258,630 compare with common US intravaginal estradiol product categories?

This claim set is tailored to a capsule-based, liquid-in-capsule estradiol regimen for dyspareunia.

Common alternative intravaginal categories that may fall outside the literal claim:

• Vaginal estradiol tablets (different dosage form; not a capsule).
• Vaginal estradiol creams and gels (may not be “manually inserted capsule,” and estradiol encapsulation is not applicable).
• Estradiol-releasing devices such as rings (not a capsule).
• Higher-frequency or different induction regimens (fails schedule).

Where competitors come closest is likely in products that are:

• soft gelatin capsules or capsule-like inserts with liquid contents
• fully encapsulated estradiol in the capsule interior
• dosing schedules that match the once-daily induction then twice-weekly maintenance pattern

What are the likely litigation and Paragraph IV challenge vectors for this type of method claim?

For method-of-treatment claims, typical US challenge and litigation vectors include:

• Orange Book-based listing triggers against the method claim(s) when the NDA product relies on the same drug and dosing.
• ANDA filers using Paragraph IV certifications may target the listed patents tied to the referenced drug product’s formulation and method.

But the litigation vector depends on whether US 10,258,630 is listed in the Orange Book for a specific NDA/RLD and whether its claims are deemed “listed” patents that cover the drug product approved by FDA.

Claim-coverage vector: Because claim 1 includes formulation and regimen limitations, an accused generic must align not only on active and strength, but also on dosage form and dosing regimen reflected in labeling and/or real-world use.

What would an infringing generic need to match to trigger literal infringement?

A credible literal-infringement case against a competing intravaginal estradiol product using this patent would require matching most of these:

1. Disease context: treatment of moderate to severe dyspareunia.
2. Dosage form: capsule and likely soft gelatin capsule.
3. Manual insertion: not an applicator-logic device that changes characterization.
4. Liquid viscosity: 50–1000 cP at 25°C.
5. Active system: estradiol as the only active estrogen.
6. Encapsulation: all estradiol encapsulated in capsule.
7. Dose: 4–25 μg estradiol.
8. Regimen: once daily for two weeks then twice weekly.
9. Release mechanics: released upon mucosal contact into vaginal tissue.

Failure on even one high-impact element can defeat literal infringement.

How would design-arounds likely look against the specific limitations in US 10,258,630?

Common design-around levers aligned to the claim language:

• Change viscosity at 25°C outside 50–1000 cP through formulation changes.
• Replace the dosage form with a non-capsule insert or a different capsule type that is not a soft gelatin capsule.
• Avoid full encapsulation of estradiol (structure estradiol in a way not “all encapsulated” in the capsule).
• Change dosing schedule so it is not “once daily for two weeks” then “twice weekly thereafter.”
• Add or remove actives to avoid “estrogen as the only active agent” depending on competitor strategy.
• Use a different estradiol strength outside 4–25 μg (or label a different dose).

Patent landscape mapping: what US 10,258,630 likely sits next to

A full landscape requires Orange Book listings, prosecution history, and family member identification, none of which are provided in the prompt. What can be stated from claim content alone is the likely neighborhood of related IP:

• Formulation and device patents for intravaginal estradiol inserts that specify encapsulation and rheology.
• Dosing regimen patents for dyspareunia or other genitourinary syndrome conditions using similar induction-to-maintenance schedules.
• Biomarker endpoint patents focusing on cytology and pH changes as surrogate endpoints tied to dyspareunia severity improvement.
• Soft-gel capsule manufacturing IP if the formulation is prepared to meet viscosity and encapsulation constraints.

These are the typical adjacencies for this kind of claim set. Enforceability and licensing value usually cluster around the product’s NDA/RLD-linked patent set.

What patent estate scope is implied by the “endpoint within 2–6 weeks” limitation?

Endpoint limitations often track clinical trial timelines. A product using the same induction-to-maintenance regimen is more likely to produce the claimed changes within two to six weeks, especially for vaginal cytology and pH.

If a competitor uses a regimen with a different onset time (for example slower induction), it may avoid dependent claim 5–8 even if it matches claim 1’s administration characteristics.

Key Takeaways

• US 10,258,630 claim 1 is narrow and highly constrained: it requires an intravaginal soft gelatin capsule with liquid composition viscosity ~50–1000 cP at 25°C, estradiol as only active agent, full estradiol encapsulation, 4–25 μg estradiol dose, and a regimen of once daily for two weeks then twice weekly for moderate to severe dyspareunia.
• Design-around pathways are identifiable from the claim text: viscosity window, encapsulation structure, capsule type, estradiol dose band, and dosing cadence are the primary infringement levers.
• Dependent claims 5–8 add evidentiary endpoint timing (superficial/parabasal cell shifts, pH decrease, and dyspareunia severity reduction within 2–6 weeks), which can materially affect enforcement.
• Practical infringement risk concentrates on close product alignment: competitors using capsule-based estradiol inserts with similar rheology and the same induction-to-maintenance schedule are the most exposed.

FAQs

1) What key limitations determine whether a vaginal estradiol capsule infringes claim 1 of US 10,258,630?
The most decisive are: viscosity range at 25°C (50–1000 cP), “all estradiol encapsulated” in the capsule, estradiol-only active, dose 4–25 μg, manual intravaginal capsule insertion, and the once-daily for two weeks then twice-weekly regimen.

2) Can a competitor avoid infringement by changing from a soft gelatin capsule to a different intravaginal capsule format?
Claim 3 targets soft gelatin specifically; changing the capsule format can avoid claim 3, but claim 1 could still be asserted if the broader “capsule” and other claim 1 limitations are met.

3) How do the cytology and vaginal pH limitations affect enforcement of dependent claims 5–7?
They require that the accused administration results in specific surrogate biomarker shifts within about two to six weeks, creating a clinical evidence requirement beyond formulation and regimen.

4) Does a different dosing schedule (same estradiol dose) risk avoiding claim 1?
Yes. Claim 1 requires the specific schedule structure: once daily for two weeks, then twice weekly thereafter. A substantially different regimen can be a direct non-infringement lever.

5) Would adding another active hormone in the vaginal composition avoid “estrogen as the only active agent”?
Yes. Claim 1 requires estrogen as the only active agent, so adding another active estrogen component would break that limitation.

References

1. United States Patent No. 10,258,630. (Claims provided in prompt).

Drugs Protected by US Patent 10,258,630

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Mayne Pharma	IMVEXXY	estradiol	INSERT;VAGINAL	208564-001	May 29, 2018	AB	RX	Yes	Yes	10,258,630					TREATMENT OF DYSPAREUNIA
Mayne Pharma	IMVEXXY	estradiol	INSERT;VAGINAL	208564-001	May 29, 2018	AB	RX	Yes	Yes	10,258,630					TREATMENT OF A SYMPTOM OF VULVAR AND VAGINAL ATROPHY
Mayne Pharma	IMVEXXY	estradiol	INSERT;VAGINAL	208564-002	May 29, 2018	AB	RX	Yes	Yes	10,258,630					TREATMENT OF DYSPAREUNIA

International Family Members for US Patent 10,258,630

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2782584		301153	Netherlands
European Patent Office	2782584		2021C/558	Belgium
European Patent Office	2782584		122021000080	Germany