U.S. Patent 11,241,416: Edaravone Oral Suspension Claims, Exclusivity, Litigation and Generic Risk

U.S. Patent No. 11,241,416 protects an orally administered edaravone suspension with defined particle-dispersion properties, excipient concentrations, particle-size ranges and human pharmacokinetic performance. The patent is directed principally to the formulation used for oral edaravone products such as RADICAVA ORS, rather than to edaravone as an active pharmaceutical ingredient.

The strongest commercial claims are independent claims 1 and 14. They combine formulation limitations with pharmacokinetic requirements after a 90-to-120 mg human oral dose. Dependent claims add xanthan gum or tragacanth, particle-size limits, dissolution performance, density, sweeteners, stabilizers, pH regulators and bioequivalence-type results against injectable edaravone.

The patent creates a formulation-based barrier to a competing oral edaravone suspension. It does not, based on the supplied claims, prevent all oral edaravone products, solid oral dosage forms, injectable products or formulations that fall outside the claimed concentration, particle, dispersant or pharmacokinetic ranges.

What patent protects edaravone oral suspension?

U.S. Patent 11,241,416 protects an edaravone suspension for human oral administration containing:

Water.
Solid edaravone particles dispersed in the water.
A dispersant at 0.001% to 1.0% w/v.
Edaravone particles at 0.5% to 36% w/v.
Human pharmacokinetic results after a 90-to-120 mg oral dose.

The patent is assigned to Mitsubishi Tanabe Pharma Corporation, the developer and marketer associated with RADICAVA and RADICAVA ORS. The patent issued on February 8, 2022. Its priority chain traces to Japanese development work directed to an oral edaravone suspension. The nominal 20-year patent term is expected to run into 2038, subject to the patent’s recorded term adjustment and any applicable regulatory extension.[1]

Patent identification

Item	Data
U.S. patent	11,241,416
Subject matter	Edaravone oral suspension
Patent holder	Mitsubishi Tanabe Pharma Corporation
Issue date	February 8, 2022
Core product	Aqueous suspension of solid edaravone particles
Commercial relevance	RADICAVA ORS-type oral edaravone formulation
Nominal term	Expected to expire in 2038 before any patent-term adjustment
Principal claim type	Composition and formulation claims
Method-of-use claim	None in the supplied claims
Dosage-form focus	Liquid oral suspension

What are the independent claims in U.S. Patent 11,241,416?

Claims 1 and 14 are independent formulation claims with overlapping subject matter.

Claim 1

Claim 1 requires a water-based edaravone suspension with:

Edaravone particles dispersed in water.
A dispersant that maintains edaravone in a solid particle state.
A dispersant concentration of 0.001% to 1.0% w/v.
An edaravone concentration of 0.5% to 36% w/v.
A mean human Cmax of 500 to 2,500 ng/mL.
A mean human AUC0-inf of 1,000 to 2,500 h*ng/mL after a 90-to-120 mg oral dose.

The claim does not require a particular named dispersant. It uses performance-based language. A product may therefore fall within the claim even if its excipient is chemically different from the dispersant used in the patent examples, provided the excipient satisfies the functional limitations and concentration range.

Claim 14

Claim 14 is similar but expressly requires that the dispersant exhibit a contact angle of 80 degrees or less. It also retains the same concentration and pharmacokinetic requirements.

Claim 14 narrows the dispersant limitation but may be easier to assess analytically if the contact-angle test is reproducible. Its scope depends on:

The surface used for contact-angle testing.
The liquid used in the test.
Temperature and test conditions.
Whether the contact angle is measured for the neat dispersant, a dispersion or a defined substrate.
Whether the patent specification supplies a standardized method.

The contact-angle requirement may become a significant claim-construction and noninfringement issue in a Paragraph IV dispute.

How broad is the claim scope?

The claims are broad in chemical identity but narrow in combined technical requirements. They do not identify one specific surfactant or dispersant in the independent claims. They instead rely on a combination of structural, compositional, physical and pharmacokinetic limitations.

Formulation limitations

The central formulation limitations are:

Limitation	Claimed range or requirement
Vehicle	Water
Drug state	Solid edaravone particles
Dispersant	Maintains particles in solid state in water
Dispersant amount	0.001% to 1.0% w/v
Edaravone amount	0.5% to 36% w/v
Optional thickener	0.1% to 1.2% w/v in claims 6 and 15
Particle D50	10 to 100 micrometers
Particle D90	50 to 300 micrometers
Dissolution	At least 80% after 30 minutes in the specified test
Density	1.0 to 1.5 g/mL
Oral dose for PK limitation	90 to 120 mg

The claim covers a wide edaravone concentration range. The commercial RADICAVA ORS dose is 105 mg in 5 mL, corresponding to 21 mg/mL or approximately 2.1% w/v, within the claimed 0.5% to 36% range.[2]

Functional limitations

The phrase requiring the dispersant to maintain edaravone particles "in a solid particle state" is central. The claim is not directed to a true molecular solution of edaravone. A formulation in which edaravone is fully dissolved could argue that it lacks the required solid-particle limitation.

The claim also requires dispersion in water. A nonaqueous suspension, an oil-based product or a solid oral dosage form would not satisfy that limitation literally.

Pharmacokinetic limitations

The independent claims require human plasma exposure within defined ranges:

Mean Cmax: 500 to 2,500 ng/mL.
Mean AUC0-inf: 1,000 to 2,500 h*ng/mL.

These are not merely stated objectives. They are express claim limitations. A competing formulation must be assessed using the claimed dosing conditions and population parameters. Small differences in food effect, administration volume, sampling schedule, dose normalization and analytical assay could affect whether the limitation is met.

The dependent claims add more stringent comparative pharmacokinetic requirements against injectable edaravone:

The lower limit of the 90% confidence interval for Cmax and AUC ratios must exceed 0.8 in claim 12 and claim 19.
The ratios must fall within 0.8 to 1.25 in claim 13 and claim 20.

These limitations resemble regulatory bioequivalence criteria but are not automatically satisfied merely because a product receives FDA approval. The claim language requires the specific crossover study and comparator described in the patent.

What formulations are protected by the dependent claims?

The dependent claims create several fallback positions for the patent holder.

Xanthan gum and tragacanth

Claims 4, 5, 15 and 16 cover suspensions containing xanthan gum, tragacanth powder or both. Claim 5 is narrower because it requires xanthan gum specifically.

These claims are commercially relevant because xanthan gum is a common suspending and viscosity-modifying agent. A generic developer that uses xanthan gum at the claimed concentration could face a direct infringement allegation even if it changes the dispersant or flavor system.

Particle-size distribution

Claims 7 and 17 require:

D50 from 10 to 100 micrometers.
D90 from 50 to 300 micrometers.

Particle-size claims can be difficult to design around because a product may satisfy the broader independent claim without satisfying the narrower particle-size claim. They also create testing disputes involving:

Laser diffraction versus microscopy.
Wet versus dry dispersion.
Pretreatment and agglomerate breakup.
The definition of D50 and D90.
Lot-to-lot variability.

Dissolution performance

Claim 11 requires at least 80% edaravone dissolution 30 minutes after initiation of a Japanese Pharmacopoeia dissolution test. This limitation links the formulation to a defined in vitro performance result.

A formulation can avoid claim 11 while still infringing claim 1 or claim 14. Conversely, meeting the dissolution requirement does not by itself establish infringement of the independent claims because the other concentration, dispersant and PK limitations remain necessary.

Density and additives

Claim 10 requires a density of 1.0 to 1.5 g/mL. Claim 9 covers at least one sweetener, stabilizer or pH regulator. These limitations are likely to be present in a commercial liquid formulation, but they are not independently sufficient for infringement.

When does U.S. Patent 11,241,416 lose exclusivity?

The patent’s nominal expiration is expected in 2038, based on the relevant international or nonprovisional filing date. The exact enforceable expiration depends on the patent’s recorded patent-term adjustment. Patent-term extension under 35 U.S.C. § 156 is generally associated with regulatory review of a drug product and must be evaluated separately from patent-term adjustment under § 154.

FDA approval of RADICAVA ORS occurred in May 2022. The product is an oral suspension containing 105 mg of edaravone in a 5 mL dose and is approved for amyotrophic lateral sclerosis.[2] FDA approval does not by itself establish the final expiration date of every listed patent.

Exclusivity timeline

Event	Date
Japanese priority development	2017-era priority chain
U.S. patent application or national-stage filing	Before issuance
U.S. Patent 11,241,416 issued	February 8, 2022
RADICAVA ORS FDA approval	May 2022
Nominal patent expiration	Expected in 2038
Earliest practical ANDA launch	Dependent on patent challenges, settlements and listed exclusivity

RADICAVA ORS also received FDA regulatory exclusivity associated with its approval. Regulatory exclusivity and patent protection operate independently. A generic applicant may be blocked by regulatory exclusivity even if it defeats the patent, while a patent may continue after regulatory exclusivity expires.

What is the Orange Book status of RADICAVA ORS?

RADICAVA ORS is an FDA-approved oral edaravone suspension marketed by Mitsubishi Tanabe Pharma Corporation. FDA’s Approved Drug Products with Therapeutic Equivalence Evaluations, commonly called the Orange Book, is the relevant source for listed patents and exclusivity.[3]

A listed patent is commercially significant because an ANDA applicant must address it through one of the certifications under 21 U.S.C. § 355(j)(2)(A)(vii). For a patent that claims the approved formulation, a Paragraph IV certification is the principal challenge route.

The supplied claims are composition claims rather than pure method-of-use claims. That distinction matters because a generic applicant seeking approval for the same oral suspension would face a direct product-patent issue, not only a use-patent issue.

What Paragraph IV challenges could target this patent?

A Paragraph IV challenge could attack the patent on several grounds.

Anticipation

The challenger would need to identify a single prior-art reference disclosing every limitation of an asserted claim, including:

The water-based suspension.
The specified edaravone and dispersant concentrations.
The solid-particle dispersion requirement.
The human PK ranges.
Any claimed contact-angle or particle-size limitations.

The PK limitations may make anticipation more difficult unless the prior art reports comparable human data.

Obviousness

Obviousness would likely focus on whether a skilled formulator could have combined:

Edaravone particles.
A suitable wetting or dispersing agent.
A thickener.
A sweetener or pH regulator.
Particle-size control.
A dose designed to achieve exposure comparable with injectable edaravone.

The patent holder would likely rely on the claimed oral exposure profile, suspension stability and injectable-comparator results as evidence of technical effect. The challenger would argue that the formulation variables were routine optimization and that the claimed ranges are result-effective variables.

Indefiniteness

Potential indefiniteness issues include:

"Transmission scattering light intensity of 1% or more."
"Maintains the edaravone particles in a solid particle state."
"Contact angle of 80 degrees or less."
The testing conditions for particle-size distribution.
The precise population and protocol for the human PK limitations.

The strength of an indefiniteness challenge depends heavily on the specification’s definitions, examples and analytical methods.

Written description and enablement

The broad concentration range for edaravone, broad dispersant language and functional PK limitations could be challenged if the specification does not provide adequate support across the full claimed scope. The patent holder would point to formulation examples, dispersant screens and clinical data.

How strong is the patent estate for oral edaravone?

U.S. Patent 11,241,416 is commercially important because it combines a product formulation with in vivo performance. That combination can be stronger than a narrow excipient claim if the formulation is difficult to reproduce without achieving the claimed exposure.

Its principal strengths are:

Two overlapping independent claims.
Broad dispersant language in claim 1.
A contact-angle limitation in claim 14 that provides a distinct claim path.
Human PK requirements tied to the commercial dose range.
Dependent claims covering xanthan gum, tragacanth, particle size and dissolution.
Applicability to an approved oral suspension rather than only an experimental formulation.

Its principal vulnerabilities are:

The independent claims require multiple limitations simultaneously.
The PK ranges may permit design-around through altered exposure.
A nonaqueous, dissolved, solid-dose or differently administered product may avoid the claims.
Functional test terms may invite indefiniteness and claim-construction disputes.
Prior-art formulation and clinical disclosures could be used in an obviousness challenge.

The estate appears stronger against a copycat aqueous suspension than against a materially different oral dosage form.

What generic entry risks exist for RADICAVA ORS?

A generic applicant seeking an equivalent oral suspension would face four principal risks.

Risk	Practical effect
Product patent	Requires Paragraph IV, acceptance of delayed launch or design-around
PK limitation	Bioequivalent product may also satisfy the patent’s exposure ranges
Formulation similarity	Xanthan gum, particle-size and suspension parameters can increase overlap
Regulatory exclusivity	May delay approval independently of patent validity

A simple change in flavor, packaging or concentration may not avoid the claims. A meaningful design-around would likely require changing one or more core elements:

Use a dissolved edaravone solution rather than a particle suspension.
Use a nonaqueous vehicle.
Use a different dosage form.
Alter the particle-size distribution.
Select an excipient outside the claimed dispersant conditions.
Produce PK results outside the claimed ranges while preserving efficacy.

Each design-around carries regulatory and development costs. Altering exposure below the claimed range may affect clinical acceptability, while changing particle size or excipients may require additional stability, bioequivalence or clinical work.

Which companies are challenging the patent?

The supplied information does not identify an ANDA filer, Paragraph IV notice, district-court complaint, settlement or appellate decision involving U.S. Patent 11,241,416. No specific challenger or settlement should be treated as established from the claim text alone.

Public litigation and ANDA status must be checked against FDA records, district-court dockets and the Orange Book. The absence of a named challenger in the supplied record does not establish that no challenge has been filed.

How does the patent compare with injectable edaravone protection?

Issue	Oral suspension patent	Injectable edaravone
Dosage form	Aqueous oral suspension	Parenteral injection
Key protection	Dispersion, excipient and PK profile	Product, formulation, use or manufacturing claims depending on patent
Dose in claims	90 to 120 mg oral edaravone	Not required by the supplied claims
Comparator	Injectable edaravone is used in claims 12, 13, 19 and 20	Benchmark product
Main barrier	Copying oral suspension technology	Copying injectable product or approved use
Design-around path	Different vehicle, particle system or dosage form	Different injectable formulation or administration strategy

The patent uses injectable edaravone as the pharmacokinetic reference point. That relationship does not mean the patent claims the injection itself. It claims an oral suspension capable of producing specified exposure relative to the injectable product.

What licensing and commercial issues matter?

The relevant commercial rights are likely concentrated around Mitsubishi Tanabe Pharma Corporation and its RADICAVA franchise. The patent’s value is tied to the approved oral product, not only to the underlying molecule.

A license negotiation would need to address:

U.S. patent rights through expected 2038 expiration.
Foreign counterparts.
Regulatory exclusivity.
Product-specific know-how for particle milling and suspension manufacture.
Analytical methods for dispersant performance and particle size.
Stability and sedimentation control.
Manufacturing-site qualification.
Rights to future formulations and alternate dosage forms.

The most important non-patent barrier may be manufacturing know-how. Reproducing a suspension that remains homogeneous, redispersible, palatable and bioequivalent can require process controls that are not fully captured by the claims.

Key Takeaways

U.S. Patent 11,241,416 protects an aqueous oral edaravone suspension, not edaravone generally.
Claims 1 and 14 are the principal barriers to a competing suspension.
The independent claims combine composition limits with human Cmax and AUC requirements.
Dependent claims cover xanthan gum, tragacanth, particle size, dissolution, density and comparative PK.
RADICAVA ORS contains 105 mg of edaravone in a 5 mL oral suspension, within the core claimed dose and concentration framework.[2]
The nominal patent term is expected to extend into 2038, subject to recorded term adjustment.
A copycat aqueous suspension would face significant Paragraph IV and infringement risk.
Solid oral, nonaqueous, fully dissolved or materially different formulations may offer design-around paths.
No specific Paragraph IV challenger or settlement is established by the supplied record.
Formulation know-how and analytical testing methods are likely to be as important commercially as the issued claims.

FAQs About U.S. Patent 11,241,416

Does U.S. Patent 11,241,416 claim RADICAVA ORS by brand name?

No. The claims define a formulation using structural, concentration, particle-dispersion and pharmacokinetic limitations. They do not rely on the RADICAVA ORS trademark.

Can a generic avoid the patent by changing xanthan gum?

Possibly, but changing xanthan gum alone may not avoid claims 1 or 14. Those claims do not require xanthan gum. The generic would need to avoid the independent claims’ dispersant, concentration, solid-particle and PK limitations.

Does FDA bioequivalence automatically prove patent infringement?

No. FDA bioequivalence and patent infringement use different legal standards. The patent claims require specific formulation and human PK limitations, while FDA approval applies regulatory standards.

Can a fully dissolved edaravone product avoid the suspension claims?

A fully dissolved product may have a noninfringement position because the claims require edaravone particles dispersed in water and maintained in a solid particle state. The result would depend on the actual formulation and claim construction.

Is the injectable edaravone product covered by this patent?

Not based on the supplied claims. The injectable product is used as a comparator in certain dependent claims, but the claimed products are oral suspensions.

References

United States Patent No. 11,241,416. (2022). Edaravone suspension. U.S. Patent and Trademark Office.
U.S. Food and Drug Administration. (2022). RADICAVA ORS (edaravone) oral suspension prescribing information. FDA.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations. FDA, Center for Drug Evaluation and Research.

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Shionogi	RADICAVA ORS	edaravone	SUSPENSION;ORAL	215446-001	May 12, 2022		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial	Y				⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Japan	JP2018-207646	Nov 2, 2018

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	116967	⤷ Start Trial
Australia	2019369843	⤷ Start Trial
Australia	2025205635	⤷ Start Trial
Brazil	112021008197	⤷ Start Trial
China	112969459	⤷ Start Trial
China	117379369	⤷ Start Trial
China	117379370	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 11,241,416