US Patent 9,107,827: Megestrol Acetate Nanoparticle Claims, Expiration, and Patent Landscape

US Patent 9,107,827 covers a once-daily oral megestrol acetate suspension for anorexia, cachexia, or loss of body mass. The central limitation is a nanoparticulate formulation containing particles predominantly in the 50-250 nm range, combined with a surface stabilizer and a reduced food effect on megestrol exposure.

The patent is directed to the product-performance profile associated with Megace ES rather than to megestrol acetate as a molecule. Its commercial relevance depends on whether a competing product reproduces all elements of the claimed formulation, dosing regimen, patient population, and pharmacokinetic behavior.

What does US Patent 9,107,827 claim?

Claim 1 is an active method-of-treatment claim with five principal limitations:

Claim element	Requirement
Patient	Human patient with anorexia, cachexia, or loss of body mass
Disease context	General claim; dependent claims specify HIV/AIDS or cancer
Drug	Megestrol acetate
Dosage form	About 40 mg to about 800 mg in approximately 5 mL of oral suspension
Particle size	About 80% of particles between approximately 50 nm and 250 nm
Stabilization	At least one surface stabilizer associated with particle surfaces
Administration	Once daily
Food effect	Fed-versus-fasted Cmax difference less than about 100% after a single dose

The claim combines structural, clinical, dosing, and pharmacokinetic requirements. A competing suspension that uses nanoparticles but lacks the claimed food-effect profile may not satisfy claim 1. Conversely, a product with a comparable PK profile but a materially different particle-size distribution or stabilizer may avoid literal infringement.

What is the scope of the nanoparticle limitation?

The particle-size limitation is the core formulation restriction. Claim 1 requires that approximately 80% of the megestrol acetate particles fall between about 250 nm and about 50 nm. Claim 2 narrows the range to approximately 230 nm to 70 nm.

The wording does not require every particle to fall within the specified range. It requires a population distribution in which approximately 80% of particles meet the stated size boundaries. The claim therefore reaches formulations with a minority of particles outside the range, subject to the meaning assigned to “about,” the measurement method, and the relevant particle-size metric.

How do claims 1 and 2 differ?

Claim 2 is narrower because it excludes particles below approximately 70 nm and above approximately 230 nm from the defined 80% population. A formulation satisfying claim 2 should also satisfy the broader size limitation in claim 1, assuming the same measurement methodology.

The particle-size range must be assessed using the method disclosed in the patent and the applicable construction of terms such as “about,” “equivalent to,” and “80%.” Dynamic light scattering, laser diffraction, electron microscopy, and other techniques can produce different apparent distributions. Particle-size testing is therefore a likely technical dispute in litigation.

Which dependent claims create the strongest infringement positions?

Claims 5 through 13 progressively narrow the allowed fed-versus-fasted Cmax difference:

Claim	Fed-versus-fasted Cmax difference
1	Less than about 100%
5	Less than about 90%, 80%, 70%, or 60%
6	Less than about 50%
7	Less than about 40%
8	Less than about 30%
9	Less than about 20%
10	Less than about 15%
11	Less than about 10%
12	Less than about 5%
13	Less than about 3%

These claims are useful only if the relevant PK comparison is measured under the specified conditions. The claim defines fasting as no food for at least 10 hours before dosing and feeding as a high-calorie meal within approximately 30 minutes of dosing.

The dependent claims do not merely describe a preferred formulation. They impose post-administration performance requirements. A product may be structurally similar but fall outside claims 6-13 if its fed-versus-fasted Cmax difference is too large.

What pharmacokinetic properties are protected?

Claims 14 through 21 protect additional performance characteristics.

Fed-versus-fasted Tmax

Claim 14 covers a difference in mean Tmax of less than approximately 100%, with dependent thresholds extending to less than approximately 3%. Tmax is more variable than Cmax and can be affected by sampling intervals, subject variability, gastric emptying, and meal composition.

Cmax improvement over conventional megestrol

Claim 15 compares the claimed formulation with a standard commercial, non-nanoparticulate megestrol composition administered at the same dosage. The claimed mean Cmax may be greater by thresholds ranging from approximately 5% to 150%.

This limitation creates several potential claim-construction issues:

The identity of the “standard commercial” comparator.
Whether the comparison must use the same subjects or a separate clinical study.
Whether the comparison must be statistically significant.
Whether “same dosage” means the same milligram dose, volume, or active-ingredient exposure.
The relevant fed or fasted condition.

AUC and absorption

Claim 16 covers a fed-versus-fasted AUC difference of less than approximately 35%, with narrower alternatives down to less than approximately 3%.

AUC is generally a more stable exposure measure than Cmax, but it still depends on sampling duration, assay sensitivity, dose administration, and statistical treatment. A product could fall within the Cmax claims while failing the AUC limitation, or the reverse.

Time to peak concentration and plasma concentration

Claims 17 through 21 cover:

Maximum plasma concentration reached in approximately one hour or less in fasting subjects.
Maximum megestrol concentration of at least approximately 700 ng/mL.
At least approximately 700 ng/mL reached in less than five hours.
At least approximately 400 ng/mL reached in less than five hours.
Mean fasted-state Cmax between approximately 300 ng/mL and 2,000 ng/mL.

These limitations make the patent partly dependent on clinical and bioanalytical evidence. In a Hatch-Waxman dispute, the applicant’s ANDA product testing, formulation records, batch data, and bioequivalence studies would be central to infringement analysis.

What surface stabilizers are covered?

Claim 22 broadly identifies four stabilizer classes:

Nonionic surfactants
Cationic surfactants
Ionic surfactants
Zwitterionic surfactants

Claim 23 lists specific stabilizers, including:

Hydroxypropyl methylcellulose
Hydroxypropylcellulose
Polyvinylpyrrolidone
Sodium lauryl sulfate
Dioctylsulfosuccinate
Polyoxyethylene alkyl ethers
Polyoxyethylene sorbitan fatty acid esters
Tetramethylbutylphenol ethoxylate polymers
Lysozyme
Random copolymers of vinylpyrrolidone and vinyl acetate

Claim 24 narrows the stabilizer to hydroxypropyl methylcellulose, dioctylsulfosuccinate, or a combination of the two.

The stabilizer must be “associated with the surface” of the megestrol acetate particles. That language may require more than simply showing the stabilizer elsewhere in the suspension. Formulation records, adsorption data, surface characterization, manufacturing conditions, and excipient ratios may be relevant.

How does US 9,107,827 compare with conventional Megace products?

Megestrol acetate has long been available in tablets and conventional oral suspensions. The patent does not broadly cover those products. It targets a nanoparticulate suspension designed to improve dissolution and reduce the strong food effect associated with conventional megestrol formulations.

Attribute	Conventional megestrol suspension	Nanoparticulate formulation covered by US 9,107,827
Active ingredient	Megestrol acetate	Megestrol acetate
Particle architecture	Conventional-size particles	Predominantly approximately 50-250 nm particles
Dosing	Product-specific	Once daily under claim 1
Food effect	May be substantial	Claimed fed-versus-fasted Cmax reduction
Dose volume	Product-specific	Approximately 5 mL in claim 1
PK requirement	No specific claimed profile	Cmax, Tmax, AUC, and concentration limitations
Commercial reference	Generic megestrol products and older Megace products	Megace ES-type nanoparticulate suspension

The patent therefore distinguishes the claimed product from megestrol acetate based on formulation engineering and pharmacokinetic behavior, not active-ingredient novelty.

What is the FDA and Orange Book relevance?

Megace ES is an FDA-approved megestrol acetate oral suspension associated with the nanoparticulate formulation technology. The FDA-approved indication is anorexia, cachexia, or significant unexplained weight loss in patients with AIDS. The product is administered as a concentrated oral suspension, historically at 625 mg per 5 mL.[1]

For an ANDA applicant, relevant regulatory issues include:

Whether the reference listed drug is Megace ES or another megestrol acetate product.
Whether the proposed product uses the same dosage form and strength.
Whether the application must address listed patents through Paragraph IV certification.
Whether the patent is listed against the reference product in the Orange Book.
Whether the patent claims are directed to an approved method of use or a formulation-performance profile.

Orange Book listing status must be evaluated by product and NDA rather than by patent number alone. The FDA’s electronic Orange Book is the controlling source for current listing, delisting, and patent-use-code information.[2]

A patent directed to a formulation or method of treatment can create an ANDA certification issue if it is properly listed for the reference product. A Paragraph IV certification would state that the patent is invalid, unenforceable, or not infringed. The patent owner or NDA holder could then bring an action under 35 U.S.C. § 271(e)(2), potentially triggering a 30-month stay under the Hatch-Waxman framework.[3]

When does US Patent 9,107,827 lose exclusivity?

US Patent 9,107,827 issued on August 18, 2015. Patent expiration is not calculated from the issue date. For a utility patent, the relevant term generally runs 20 years from the earliest effective nonprovisional U.S. filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and any applicable priority-chain rules.[4]

The patent’s enforceability period must therefore be confirmed against the USPTO patent term record and any related patent-term adjustment or extension information. The issuance of a continuation patent does not ordinarily restart the 20-year term.

For commercial planning, the critical distinction is between:

Patent expiration, which ends enforceable patent rights after applicable adjustments.
FDA regulatory exclusivity, which is separate from patent term.
Orange Book listing, which does not itself extend the patent term.
Litigation settlement dates, which may create an earlier or later commercial-entry date than the nominal patent expiration.

What generic entry risks exist?

A generic applicant can pursue several noninfringement strategies.

Avoid the nanoparticle range

The applicant may use conventional-size megestrol acetate particles or a particle distribution outside the claimed 80% range. This approach may avoid claims 1 and 2, but it could produce a different dissolution profile or require a different regulatory pathway.

Use a different stabilization system

A formulation may use an excipient that does not fall within claims 22-24. That strategy is less useful against claim 1, which broadly requires only “at least one surface stabilizer,” unless the applicant can show that its excipient is not associated with the particle surface.

Avoid the once-daily limitation

A twice-daily product could avoid the express once-daily limitation in claim 1. Regulatory approval, labeling, dose equivalence, and commercial positioning would determine whether that approach is viable.

Fail the PK limitations

The applicant may develop a product that does not meet the specified fed-versus-fasted Cmax, AUC, Tmax, or plasma-concentration thresholds. This strategy depends on whether those parameters are inherent in the product and whether the patent owner can prove them from testing.

Challenge validity

Potential validity issues include:

Lack of written description for the full breadth of particle-size and PK ranges.
Enablement across all stabilizers, doses, particle distributions, and clinical populations.
Obviousness based on prior nanoparticulate drug-delivery technology and existing megestrol products.
Indefiniteness of terms such as “about,” “equivalent to,” “associated with,” and “high-calorie meal.”
Inherency and reproducibility of the fed-versus-fasted PK limitations.

The validity analysis would depend heavily on the patent specification, prosecution history, cited prior art, and the clinical data relied on during examination.

Which companies are relevant to the patent landscape?

The principal commercial parties are:

Entity	Relevance
FDA	Approved Megace ES and maintains Orange Book records
NDA holder or sponsor	Controls the branded reference product and may enforce listed patents
Patent owner or exclusive licensee	Holds or exercises rights under the nanoparticulate formulation patent
Generic applicants	May file ANDAs for megestrol acetate suspension products
Nanoparticle technology licensors	May control underlying particle-size reduction or stabilization technology

The commercial landscape includes branded Megace ES, conventional megestrol acetate oral suspensions, tablets, and potential generic versions of the concentrated suspension. Biosimilar risk is not material because megestrol acetate is a small-molecule drug, not a biologic. The relevant competitive threats are ANDA generics and alternative megestrol formulations.

What manufacturing and intellectual-property barriers remain?

The formulation may require controlled wet milling, homogenization, precipitation, or another particle-size reduction process capable of maintaining a reproducible nanoscale distribution. Manufacturing barriers include:

Maintaining the 80% particle-size requirement across commercial batches.
Preventing particle growth during storage.
Controlling sedimentation and redispersibility.
Achieving uniform dose delivery in a concentrated suspension.
Preserving surface-stabilizer coverage.
Demonstrating consistent dissolution and PK performance.
Supporting shelf life under FDA stability requirements.

Process patents, equipment know-how, formulation specifications, analytical methods, and trade secrets can remain commercially important even after a product patent expires. Those rights may affect launch timing but do not automatically prevent an otherwise lawful generic product from entering the market.

How strong is the patent estate for Megace ES?

US 9,107,827 is strongest against a product that reproduces the full combination of:

Nanoparticulate megestrol acetate.
A claimed particle-size distribution.
A surface stabilizer.
Approximately 5 mL oral suspension dosing.
Once-daily administration.
A reduced fed-versus-fasted Cmax difference.

Its principal weakness is claim complexity. Each additional limitation creates another potential noninfringement pathway. The PK limitations also introduce evidentiary and reproducibility issues that are less common in conventional formulation claims.

The patent does not block every megestrol acetate product. It is most relevant to a Megace ES-type concentrated nanoparticulate suspension used according to the claimed regimen.

Key Takeaways

US 9,107,827 is a method patent covering nanoparticulate megestrol acetate oral suspension treatment.
Claim 1 requires a specific dose range, approximately 5 mL suspension, 50-250 nm particle distribution, surface stabilization, once-daily administration, and reduced food effect.
Claims 5-21 add narrower Cmax, Tmax, AUC, and plasma-concentration requirements.
Claims 22-24 identify broad and specific surface-stabilizer options.
The patent does not broadly cover conventional megestrol acetate tablets or non-nanoparticulate suspensions.
Generic risk is highest for products designed as Megace ES substitutes.
The patent’s enforceability depends on its current term, patent-term adjustment, Orange Book listing, and any litigation or settlement history.
Biosimilar competition is not relevant because megestrol acetate is a small molecule.
Particle-size testing, surface association, fed-versus-fasted PK testing, and the meaning of “about” are likely dispute points.
A complete launch analysis requires reviewing the live USPTO term record, FDA Orange Book listing, prosecution history, related family members, and any Paragraph IV litigation.

FAQs About US Patent 9,107,827

Does US 9,107,827 cover all megestrol acetate products?

No. It targets a nanoparticulate oral suspension with defined particle-size, stabilization, dosing, and pharmacokinetic characteristics.

Is Megace ES a biologic subject to biosimilar competition?

No. Megace ES contains megestrol acetate, a small-molecule active ingredient. Competition would proceed primarily through the ANDA generic-drug pathway.

Can a generic avoid the patent by using larger megestrol particles?

Potentially. A product outside the claimed particle-size distribution may avoid literal infringement, but the full formulation and method claims must be assessed element by element.

Why do the claims include fed-versus-fasted Cmax limitations?

The limitations distinguish the nanoparticulate formulation from conventional megestrol products that can show substantial food-dependent changes in exposure.

Does Orange Book listing automatically extend patent protection?

No. Listing affects ANDA certification and potential Hatch-Waxman litigation. It does not extend the underlying patent term.

References

U.S. Food and Drug Administration. (2005). Megace ES (megestrol acetate) oral suspension prescribing information.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Electronic Orange Book.
Hatch-Waxman Amendments, 21 U.S.C. § 355(j); 35 U.S.C. § 271(e)(2).
United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term calculation guidance.
U.S. Patent No. 9,107,827. (2015). Methods of treating anorexia, cachexia or loss of body mass using megestrol acetate formulations.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	539737	⤷ Start Trial
Australia	2003230885	⤷ Start Trial
Australia	2003231071	⤷ Start Trial
Australia	2006262144	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 9,107,827

Summary for Patent: 9,107,827