Details for Patent: 10,052,386

Which drugs does patent 10,052,386 protect, and when does it expire?

Patent 10,052,386 protects BIJUVA and is included in one NDA.

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

Summary for Patent: 10,052,386

Title:	Progesterone formulations
Abstract:	Various pharmaceutical formulations are disclosed herein. For example, a pharmaceutical formulation is disclosed comprising ultra-micronized progesterone.
Inventor(s):	Brian A. Bernick, Julia M. Amadio, Peter H. R. Persicaner, Janice Louise Cacace, Thorsteinn Thorsteinsson, Frederick D. Sancilio
Assignee:	TherapeuticsMD Inc
Application Number:	US14/125,547
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,052,386
Patent Claim Types: see list of patent claims	Composition; Formulation; Dosage form;

United States Patent 10,052,386: Progesterone Formulation Claims, Patent Scope, and Competitive Landscape

US Patent 10,052,386 protects oral pharmaceutical compositions containing a high concentration of progesterone, a medium-chain oil, and a nonionic surfactant. The claims focus on ultra-micronized progesterone, partial solubilization and suspension, MIGLYOL 812, specific surfactants, gelatin capsules, and comparative bioavailability against progesterone suspended in peanut oil.

The patent has three independent composition claims directed to general progesterone formulations, 75-mg formulations, and 150-mg formulations. Claim 40 is the narrowest and commercially most specific claim because it requires MIGLYOL 812, lauroyl polyoxyl-32 glycerides, and increased bioavailability relative to an equivalent peanut-oil formulation.

What does US Patent 10,052,386 protect?

The patent protects a formulation architecture rather than progesterone as a molecule. Its core combination requires:

1. Progesterone.
2. A medium-chain oil.
3. A nonionic surfactant.
4. Progesterone representing approximately 20% to 50% by weight of the total composition.

The claims do not require estradiol, another hormone, or a therapeutic indication. Claims 8, 21, and 34 expressly require progesterone to be the sole active ingredient.

The principal technical concept is a self-emulsifying or partially solubilizing lipid formulation intended to improve oral progesterone exposure compared with conventional micronized progesterone suspended in peanut oil.

Patent identification

Field	Information
Patent	US 10,052,386 B2
Issue date	August 21, 2018
Claim type	Pharmaceutical composition
Active ingredient	Progesterone
Dosage strengths expressly claimed	General composition, 75 mg, and 150 mg
Key oil	Medium-chain triglyceride oil, including MIGLYOL 812
Key surfactants	Lauroyl macrogol-32 glycerides, lauroyl polyoxyl-32 glycerides, and caprylocaproyl macrogol-8 glycerides
Dosage form	Gelatin capsule is expressly claimed
Core comparator	Micronized progesterone suspended in peanut oil
Independent claims	Claims 1, 14, and 27
Narrow species claim	Claim 40

The patent number, claims, and issue date are taken from the issued patent record. Ownership, maintenance, terminal-disclaimer, patent-term-adjustment, and current legal-status determinations must be taken from the USPTO Patent Center and assignment records rather than inferred from the claims.[1]

How are the independent claims structured?

Claim 1: broad composition claim

Claim 1 requires progesterone, a medium-chain oil, and a nonionic surfactant, with progesterone at approximately 20% to 50% by weight.

This is the broadest independent claim. It does not require:

• Ultra-micronized progesterone.
• A particular surfactant.
• MIGLYOL 812.
• A 75-mg or 150-mg dose.
• A gelatin capsule.
• A particular release profile.
• A specific indication.
• A demonstrated bioavailability improvement.

A competing product could fall within claim 1 even if it uses a different medium-chain oil or a different nonionic surfactant, provided the composition satisfies the weight-percent limitation.

Claim 14: 75-mg formulation

Claim 14 repeats the claim 1 structure but requires 75 mg of progesterone. The formulation must still contain 20% to 50% progesterone by weight.

At a 20% concentration, 75 mg of progesterone implies a total fill weight of approximately 375 mg. At a 50% concentration, the total fill weight would be approximately 150 mg. The actual formulation may contain additional excipients, but the weight-percent range constrains the total composition.

Claim 27: 150-mg formulation

Claim 27 requires 150 mg of progesterone, the same medium-chain oil and nonionic surfactant combination, and the 20% to 50% progesterone concentration.

At a 20% concentration, the total fill weight would be approximately 750 mg. At a 50% concentration, the total fill weight would be approximately 300 mg.

The 150-mg claim can be commercially significant because conventional oral micronized progesterone products commonly use 100-mg and 200-mg strengths. A 150-mg product may have a distinct formulation and dosing profile, but the claim itself does not require a particular clinical indication.

What limitations are added by the dependent claims?

The 39 dependent claims narrow the three independent claims through repeated technical limitations.

Particle-size limitations

Claims 2, 15, and 28 require ultra-micronized progesterone with an X50 of no more than 15 microns.

Claims 3, 16, and 29 add an X90 of less than approximately 25 microns.

These limitations concern the particle-size distribution rather than merely the average particle size. A product may need to satisfy both the median-size and upper-tail-size requirements. Testing methodology, sample preparation, agglomeration, and measurement technique could affect infringement analysis.

The claims do not define the analytical instrument or measurement method in the claim text supplied. That issue can become important in a dispute involving laser diffraction, dynamic image analysis, or another particle-size technique.

Solubilized and suspended progesterone

Claims 4, 17, and 30 require a formulation in which part of the progesterone is solubilized and part is suspended.

This limitation distinguishes a fully dissolved formulation and a formulation in which all progesterone remains as solid particles. It creates a mixed physical state. The formulation may require analytical evidence showing:

• The amount of progesterone dissolved in the vehicle.
• The amount remaining as suspended solid.
• The state of the formulation at manufacture, storage, or administration.
• Whether the distinction changes over time or with temperature.

This is a potentially valuable limitation for technical differentiation but a potentially difficult one for routine product screening.

Nonionic surfactant limitations

Claims 5, 18, and 31 identify three surfactant categories:

• Lauroyl macrogol-32 glycerides EP.
• Lauroyl polyoxyl-32 glycerides.
• Caprylocaproyl macrogol-8 glycerides EP.

The nomenclature may cover overlapping or substantially equivalent excipient descriptions. A product specification, certificate of analysis, supplier identity, and pharmacopoeial designation would be relevant to determining whether a formulation uses a claimed surfactant.

A formulation using a different nonionic surfactant may avoid these dependent claims while remaining exposed under claim 1 if the alternative surfactant and oil satisfy the broader language.

Gelatin capsule limitation

Claims 6, 19, and 32 require a gelatin capsule. This limitation does not appear in the independent claims. A softgel or hard gelatin capsule could satisfy the limitation depending on the product construction. A non-gelatin capsule may avoid these dependent claims but would not avoid claims 1, 14, or 27.

Bioavailability limitation

Claims 7, 20, and 33 require increased bioavailability compared with micronized progesterone suspended in peanut oil.

Claim 40 includes a more specific version of the same concept, requiring:

• MIGLYOL 812.
• Lauroyl polyoxyl-32 glycerides.
• Increased progesterone bioavailability.
• Comparison with an equivalent amount of micronized progesterone suspended in peanut oil.

This is a functional limitation. The relevant comparison may depend on the protocol, dose normalization, pharmacokinetic endpoints, fed or fasted state, and statistical analysis. A generic developer would likely evaluate this limitation through formulation characterization and comparative pharmacokinetic studies.

Medium-chain oil limitations

Claims 9, 22, and 35 define the oil by chemical structure. The covered oils include C6-C14 fatty-acid mono-, di-, or tri-esters of glycerol, and mono- or di-esters of a glycol.

Claims 10, 23, and 36 narrow the oil to a C8 fatty-acid glycerol ester.

Claims 11, 24, and 37 require a second C6-C14 fatty-acid glycerol ester.

Claims 12, 25, and 38 specify a C10 fatty-acid glycerol ester as the second ester.

Claims 13, 26, and 39 identify MIGLYOL 812 as the medium-chain oil. MIGLYOL 812 is generally understood as a medium-chain triglyceride product containing predominantly caprylic and capric triglycerides. Commercial composition specifications should be reviewed because supplier grades and compendial descriptions can vary.

How broad is the patent’s claim scope?

The practical claim hierarchy is:

Scope level	Representative claims	Required limitations
Broadest	1, 14, 27	Progesterone, medium-chain oil, nonionic surfactant, 20%-50% progesterone
Particle-size	2-3, 15-16, 28-29	Ultra-micronized progesterone, X50 and X90 limits
Physical-state	4, 17, 30	Partly solubilized and partly suspended progesterone
Surfactant-specific	5, 18, 31	One of three identified surfactant classes
Dosage-form-specific	6, 19, 32	Gelatin capsule
Bioavailability-specific	7, 20, 33	Increased bioavailability versus peanut-oil suspension
Oil-specific	9-13, 22-26, 35-39	C8/C10 glycerol esters or MIGLYOL 812
Narrow commercial species	40	150-mg formulation, MIGLYOL 812, lauroyl polyoxyl-32 glycerides, increased bioavailability

The strongest commercial coverage is likely concentrated in claims 1, 14, 27, and 40. The broad independent claims create the primary blocking position. Claim 40 provides a concrete species that may be easier to map against a commercial formulation but is more vulnerable to design-around strategies.

What formulations are protected by US 10,052,386?

A formulation is most directly exposed when it contains all of the following:

• Progesterone as the only active ingredient.
• Approximately 20% to 50% progesterone by weight.
• Ultra-micronized progesterone with an X50 of 15 microns or less.
• An X90 below approximately 25 microns.
• MIGLYOL 812.
• Lauroyl polyoxyl-32 glycerides.
• A mixture of solubilized and suspended progesterone.
• A gelatin capsule.
• A 75-mg or 150-mg dose.

A product does not need to satisfy every dependent limitation to infringe an independent claim. For example, a product without ultra-micronized progesterone could still fall within claim 1 if it has the required active, oil, surfactant, and concentration.

Conversely, a product using progesterone below 20% by weight would have a substantial noninfringement position against the supplied claims, subject to claim construction and possible prosecution-history issues.

What are the principal design-around strategies?

Potential formulation design-arounds include:

1. Use a progesterone concentration below 20% or above 50%.
2. Replace the medium-chain oil with a non-covered vehicle.
3. Use a surfactant outside the claimed nonionic-surfactant language.
4. Use a fully dissolved formulation without suspended progesterone.
5. Use a non-gelatin dosage form.
6. Use particle sizes outside the claimed X50 and X90 thresholds.
7. Use a different progesterone dose that does not satisfy claims 14 or 27.
8. Use a combination product, although combination therapy alone may not avoid claims 1, 14, or 27 because those claims do not require progesterone to be the sole active ingredient.
9. Use a different formulation that does not demonstrate increased bioavailability against the specified peanut-oil comparator.

The most difficult limitation to design around may be the 20% to 50% progesterone concentration if the desired product requires a compact softgel. The most straightforward changes may involve the surfactant, capsule shell, or oil system.

What prior-art issues affect patent strength?

The patent’s validity will likely turn on whether the claimed combination was obvious in view of earlier progesterone formulations and lipid-based drug-delivery technology.

Likely prior-art categories

Relevant prior art would include:

• Micronized progesterone in peanut oil.
• Oral progesterone softgels.
• Medium-chain triglyceride vehicles.
• Nonionic surfactants used to improve dissolution or absorption.
• Self-emulsifying drug-delivery systems.
• Gelatin capsules containing lipid formulations.
• Progesterone particle-size reduction.
• Formulations containing caprylic and capric triglycerides.
• Comparative pharmacokinetic studies showing improved exposure.

A challenger would likely argue that the formulation combines known excipient classes for their conventional functions: solubilization, wetting, dispersion, and improved intestinal absorption. The patent holder would respond that the particular concentration range, mixed solubilized/suspended state, particle-size distribution, and bioavailability result were not predictable from the prior art.

Potential validity pressure points

The supplied claims present several potential attack points:

• Obviousness based on combining known progesterone and lipid-formulation teachings.
• Lack of written description for the full breadth of all C6-C14 ester combinations.
• Enablement across the full 20%-50% concentration range.
• Ambiguity in measuring "increased bioavailability."
• Ambiguity in determining when progesterone is partly solubilized and partly suspended.
• Uncertainty over the analytical method for X50 and X90.
• Anticipation by a prior formulation containing the same oil and surfactant combination.

The narrow claim 40 may have stronger technical specificity but could face a direct anticipation or obviousness challenge if the exact MIGLYOL 812 and lauroyl polyoxyl-32 glycerides combination was disclosed before the relevant priority date.

When does US 10,052,386 lose exclusivity?

The supplied claim set does not establish the patent’s earliest effective nonprovisional filing date, patent-term adjustment, terminal disclaimer, or any patent-term extension. The ordinary statutory term is generally 20 years from the earliest effective nonprovisional filing date, subject to adjustments and disclaimers under 35 U.S.C. §§ 154 and 156.[2]

The patent issued in 2018. Its expiration therefore cannot be reliably calculated from the issue date alone. Patent-term information should be taken from the USPTO continuity data and the patent-term calculation record.[1]

FDA regulatory exclusivity is separate from patent exclusivity. A patent may remain in force after FDA marketing exclusivity ends, and an FDA-listed patent may be challenged through a Paragraph IV certification under the Hatch-Waxman framework.[3]

What is the Orange Book status of the patent?

A patent number is not automatically an Orange Book-listed patent. Listing depends on whether the patent is submitted by an NDA holder, whether it claims the approved drug or an approved method of use, and whether FDA accepts it for publication under its patent-listing standards.[4]

The supplied claims are composition claims. They do not recite a disease indication, dosing regimen, or method of treatment. If the patent were listed for an approved progesterone product, its relevance would primarily concern the formulation and dosage form rather than a method-of-use block.

The Orange Book should be checked by approved product, NDA, active ingredient, and patent number. A failure to appear in the Orange Book would not eliminate ordinary patent-infringement risk, but it could affect the availability and timing of Hatch-Waxman litigation.

Which companies are challenging the patent?

No challenger, Paragraph IV certification, district-court case, or settlement agreement is established by the claim text supplied. A reliable answer requires a current review of USPTO Patent Center, PACER, district-court dockets, the Federal Circuit docket, FDA Orange Book updates, and any public licensing disclosures.

The patent should not be treated as litigated or settled solely because it covers a commercially relevant formulation.

What generic entry risks exist?

A generic applicant could pursue several pathways:

Launch strategy	Principal exposure
Same 75-mg or 150-mg lipid formulation	High risk under claims 14 or 27
Same MIGLYOL 812 and lauroyl polyoxyl-32 glycerides	Potential claim 40 exposure
Peanut-oil suspension	More likely outside the core formulation combination, subject to other patents
Different medium-chain oil	May avoid oil-specific claims but not necessarily claim 1
Different surfactant	May avoid claims 5, 18, 31, and 40, but not necessarily claim 1
Fully solubilized formulation	May avoid claims requiring mixed physical state
Non-gelatin capsule	Avoids capsule-dependent claims only
Concentration below 20%	Potentially avoids all supplied claims

The most important due-diligence document for a generic applicant would be the formulation’s quantitative composition, excipient identity, particle-size specification, and physical-state data. A label comparison alone would not resolve all limitations.

How does this patent compare with conventional progesterone products?

Attribute	Conventional peanut-oil progesterone	Claimed formulation
Active	Micronized progesterone	Progesterone, including ultra-micronized material
Vehicle	Peanut oil	Medium-chain oil
Surfactant	Not necessarily present	Required by independent claims
Physical state	Primarily suspended	May be partly solubilized and partly suspended
Particle-size limitation	Not necessarily claimed	X50 and X90 limits in dependent claims
Dosage form	Often soft gelatin capsule	Gelatin capsule expressly claimed in dependent claims
Bioavailability comparison	Baseline comparator	Increased exposure is claimed in selected claims
Dose claims	Product-dependent	75 mg and 150 mg expressly claimed

The patent is therefore directed to a formulation improvement over conventional suspended progesterone, not to a new progesterone molecule or a new hormone indication.

How strong is the patent estate?

Based only on the supplied patent and claims, the estate appears concentrated rather than diversified.

Strengths

• Three independent claims cover general, 75-mg, and 150-mg formulations.
• The independent claims do not require the narrow particle-size, gelatin-capsule, or MIGLYOL limitations.
• The claims cover both formulation composition and selected functional performance.
• The 20%-50% progesterone range may capture compact oral dosage forms.

Weaknesses

• All supplied claims are composition claims.
• There are no separate manufacturing, treatment-method, dosing-regimen, crystalline-form, or formulation-process claims in the claim set provided.
• Alternative excipients and vehicles may support design-around strategies.
• Bioavailability and mixed physical-state limitations may create factual disputes.
• The patent’s commercial blocking value depends heavily on the formulation of the approved or proposed product.

The patent may provide meaningful formulation protection, but it does not by itself establish a broad exclusivity position over all oral progesterone products.

What is the likely commercial exposure?

Commercial exposure depends on whether the protected formulation is linked to a marketed product, an approved NDA, or a development program. The claims could affect:

• Oral progesterone softgels.
• Hormone-replacement products containing progesterone as the only active ingredient.
• 75-mg and 150-mg progesterone products.
• Lipid-based progesterone products using MIGLYOL 812.
• Products using lauroyl polyoxyl-32 glycerides or related glyceride surfactants.

The patent is less relevant to transdermal progesterone, vaginal progesterone, implants, injectables, or conventional peanut-oil formulations unless those products use the claimed composition elements.

Key Takeaways

• US 10,052,386 is a formulation patent covering progesterone with a medium-chain oil and nonionic surfactant.
• Claims 1, 14, and 27 are the primary blocking claims.
• Claims 14 and 27 specifically target 75-mg and 150-mg formulations.
• Claim 40 is the narrow commercial species requiring MIGLYOL 812, lauroyl polyoxyl-32 glycerides, and increased bioavailability.
• Ultra-micronized particle-size limits, mixed solubilized/suspended progesterone, and the peanut-oil bioavailability comparison are important dependent limitations.
• The patent does not claim progesterone itself, a broad therapeutic indication, or a general method of treatment.
• Design-around options include changing the oil, surfactant, concentration, particle-size distribution, physical state, or capsule material.
• The exact expiration date, Orange Book listing, Paragraph IV activity, litigation record, and settlement status require current official-record verification.
• The patent’s commercial strength depends on whether a marketed or pipeline product practices the broad independent claims.

FAQs

Does US 10,052,386 cover Prometrium?

Not necessarily. A conventional peanut-oil progesterone product may avoid the claimed medium-chain-oil and nonionic-surfactant combination. Product-specific formulation data and any separate patents must be reviewed.

Does adding estradiol avoid US 10,052,386?

No. The independent claims do not require progesterone to be the only active ingredient. Adding estradiol alone would not necessarily avoid infringement.

Does a 100-mg progesterone product avoid the patent?

It may avoid the 75-mg and 150-mg claims, but it could still fall within claim 1 if it contains the required oil, surfactant, and 20%-50% progesterone concentration.

Can a formulation using MIGLYOL 812 avoid claim 40?

Yes, potentially. Claim 40 also requires lauroyl polyoxyl-32 glycerides and the specified increased-bioavailability limitation. MIGLYOL 812 alone does not satisfy the complete claim.

Are biosimilars relevant to this progesterone patent?

No. Progesterone is a chemically synthesized small molecule, so the relevant competitive pathway is generally generic drug approval under Hatch-Waxman, not biosimilar approval under the Biologics Price Competition and Innovation Act.

References

1. United States Patent and Trademark Office. (n.d.). Patent Center and patent-term information. https://patentcenter.uspto.gov/
2. 35 U.S.C. §§ 154, 156.
3. Food and Drug Administration. (2023). Approved drug products with therapeutic equivalence evaluations. U.S. Department of Health and Human Services. https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book-data-files
4. Food and Drug Administration. (n.d.). Guidance for industry: Submitting patent information and exclusivity information for listing in the Orange Book. U.S. Department of Health and Human Services. https://www.fda.gov/regulatory-information/search-fda-guidance-documents/submitting-patent-and-nonpatent-exclusivity-information-drugs-approved-under-section-505-federal

Drugs Protected by US Patent 10,052,386

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	BIJUVA	estradiol; progesterone	CAPSULE;ORAL	210132-002	Dec 28, 2021		RX	Yes	No	10,052,386		Y
Mayne Pharma	BIJUVA	estradiol; progesterone	CAPSULE;ORAL	210132-001	Oct 28, 2018		RX	Yes	Yes	10,052,386		Y

Foreign Priority and PCT Information for Patent: 10,052,386

PCT Information
PCT Filed	June 18, 2013	PCT Application Number:	PCT/US2013/046442
PCT Publication Date:	December 27, 2013	PCT Publication Number:	WO2013/192248

International Family Members for US Patent 10,052,386

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
European Patent Office	2782584		LUC00245	Luxembourg
European Patent Office	2782584		132021000000197	Italy
European Patent Office	2782584		C202130068	Spain