US Patent 10,080,733: Diroximel Fumarate Crystal Form Scope, Expiration, and Patent Landscape

US Patent 10,080,733 protects a specific crystalline form of diroximel fumarate, the active ingredient in Vumerity. Its principal value is solid-form protection rather than broad protection for the diroximel fumarate molecule. The patent also covers pharmaceutical compositions containing that crystal and methods of treating multiple sclerosis with the crystal or composition.

The patent issued September 25, 2018, from an application claiming priority to a November 6, 2014 filing. Its expected patent-term expiration is November 6, 2035, subject to any applicable patent-term adjustment or extension recorded by the USPTO or FDA.

What drug and crystalline form does US Patent 10,080,733 protect?

US Patent 10,080,733 covers diroximel fumarate, marketed by Alkermes as Vumerity. Diroximel fumarate is an orally administered fumarate prodrug that is converted to monomethyl fumarate, the pharmacologically active metabolite also associated with dimethyl fumarate products.

The patent’s independent product claim is defined by X-ray powder diffraction rather than by a manufacturing process or a complete list of physical properties.

Patent	Drug	Patent type	Issue date	Expected expiration
US 10,080,733 B2	Diroximel fumarate	Crystalline form, composition, and MS treatment	September 25, 2018	November 6, 2035, before any adjustment

The claim language supplied identifies the protected form by peaks at the following diffraction angles:

Peak	2-theta position
1	11.6°
2	21.0°
3	24.3°
4	27.4°
5	27.9°

Each position is subject to a tolerance of plus or minus 0.2 degrees using a copper X-ray source.

What does claim 1 of US Patent 10,080,733 cover?

Claim 1 covers a crystalline form of diroximel fumarate having an XRPD pattern that includes the five specified peaks.

The claim has four important limitations:

The material must be crystalline.
It must be the claimed compound, diroximel fumarate.
Its XRPD pattern must contain peaks at 11.6°, 21.0°, 24.3°, 27.4°, and 27.9°.
The measurements must fall within the stated 0.2-degree tolerance using a Cu X-ray source.

The word “comprising” is significant. It normally permits the claimed form to have additional XRPD peaks, provided that the five recited peaks are present within the stated tolerances. Claim 1 therefore does not require the pattern to contain only those five peaks.

The claim is narrower than a claim covering all forms of diroximel fumarate. A different polymorph, amorphous form, solvate, hydrate, or physical form that does not produce the claimed five-peak pattern may fall outside claim 1, subject to the doctrine of equivalents and the actual analytical evidence.

How would infringement of claim 1 be assessed?

An infringement analysis would generally compare the accused product’s solid material with the claimed XRPD signature. Relevant evidence could include:

XRPD testing using a copper source;
peak positions and tolerances;
polymorph stability data;
crystallization and drying conditions;
hydrate or solvate content;
batch-to-batch solid-state characterization;
whether the tested material is the commercial drug substance or a formulation component.

A generic applicant could attempt to avoid literal infringement by producing a different polymorph or an amorphous form. That strategy would create formulation, stability, dissolution, and regulatory risks. A product that converts into the patented form during storage or processing could also create a more complex infringement analysis.

What does claim 2 protect?

Claim 2 covers a pharmaceutical composition containing the crystalline form of claim 1 and a pharmaceutically acceptable carrier.

The claim reaches formulations in which the patented crystal is combined with conventional excipients. Those excipients can include diluents, binders, disintegrants, lubricants, coatings, stabilizers, and other pharmaceutically acceptable formulation materials.

Claim 2 does not appear to be limited to a particular capsule, tablet, dose strength, excipient combination, or release profile based on the language supplied. Its scope therefore depends primarily on whether the composition contains the crystalline form defined in claim 1.

A composition containing diroximel fumarate in a different solid form would not literally satisfy claim 2 unless the composition also contains the claimed crystalline form.

What do claims 3 and 4 protect?

Claims 3 and 4 are method-of-use claims for treating multiple sclerosis.

Claim	Protected subject matter	Key limitation
3	Treatment of multiple sclerosis	Administering a therapeutically effective amount of the claim 1 crystalline form
4	Treatment of multiple sclerosis	Administering a therapeutically effective amount of the claim 2 composition

These claims do not cover every use of diroximel fumarate. They are directed to administration for multiple sclerosis. The claims may be relevant to direct infringement by an operator administering the drug and to induced infringement theories involving a manufacturer’s labeling, promotional materials, or instructions.

The method claims provide a separate enforcement route from the solid-form claim. Even if a generic applicant disputes the validity or scope of claim 1, a label that instructs treatment of multiple sclerosis with the patented form could create method-of-use exposure.

When does US Patent 10,080,733 lose exclusivity?

The ordinary patent term is expected to end on November 6, 2035, calculated from the earliest effective nonprovisional filing date identified for the patent family. The actual expiration date should be confirmed against the USPTO patent-term record and any Orange Book listing.

Exclusivity layer	Relevant date or status
FDA approval of Vumerity	October 30, 2019
Patent issue	September 25, 2018
US 10,080,733 expected expiration	November 6, 2035
FDA regulatory exclusivity	Separate from patent term
Patent-term adjustment	Must be confirmed in the USPTO record
Patent-term extension	No extension is assumed in this analysis

FDA regulatory exclusivity and patent exclusivity operate independently. FDA exclusivity can restrict approval of a competing application for a defined period, while the patent can block commercial manufacture, sale, or use through its expiration date.

Vumerity’s regulatory exclusivity does not extend to 2035. The principal long-term barrier is the patent estate, including this crystal-form patent and any additional listed patents.

What is the Orange Book status of US Patent 10,080,733?

US Patent 10,080,733 has been associated with Vumerity’s patent protection and is relevant to FDA patent-certification analysis for an abbreviated new drug application.

For a generic applicant, the most important question is whether the patent is listed for the proposed Vumerity reference product and what use or product information accompanies the listing. An ANDA applicant generally must address listed patents through one of four certifications:

Paragraph I: no patent information is listed;
Paragraph II: the patent has expired;
Paragraph III: the applicant will wait until patent expiration;
Paragraph IV: the patent is invalid, unenforceable, or will not be infringed.

A Paragraph IV certification concerning US 10,080,733 could trigger patent litigation if the patent holder files suit within the statutory period. The litigation would likely focus on claim construction, polymorph identity, XRPD methodology, anticipation, obviousness, enablement, written description, and patent-term issues.

What Paragraph IV challenges could target this patent?

A Paragraph IV challenger would have several potential theories.

Non-infringement

The applicant could argue that its product does not contain the claimed crystalline form. The strongest factual position would be a different polymorph, an amorphous material, or a formulation in which the accused form is absent.

The applicant would need to control crystallization, milling, drying, storage, and formulation conditions. Solid-form interconversion can weaken a non-infringement position.

Anticipation

The challenger could argue that a single earlier reference disclosed the same crystalline form and the required XRPD peaks. General disclosure of diroximel fumarate would not necessarily anticipate a later-defined polymorph. The prior art would need to disclose the claimed form, either expressly or inherently.

Obviousness

The challenger could argue that identifying and isolating the claimed crystal was predictable from known diroximel fumarate solid-state work. The patent holder would likely rely on unexpected properties such as stability, purity, manufacturability, dissolution, or reduced hygroscopicity.

Indefiniteness and written description

The peak positions are numerically defined and include a tolerance. A dispute could address whether the claim adequately identifies the form and whether the specification supports the full range covered by the peaks.

Enablement

The challenger could contend that the patent does not enable the full scope of the claimed XRPD-defined form without undue experimentation. This issue would depend on the number of crystallization variables and the reproducibility of the disclosed methods.

What other patents cover diroximel fumarate and Vumerity?

US 10,080,733 should be analyzed as one component of a layered estate.

Protection category	Commercial significance
Compound or prodrug patents	Can cover diroximel fumarate itself or related fumarate esters
Crystalline-form patents	Can block manufacture or sale of a specific polymorph
Pharmaceutical-composition patents	Can cover a formulation containing the patented form
Method-of-use patents	Can cover treatment of multiple sclerosis
Manufacturing patents	Can restrict synthesis, purification, crystallization, or isolation
Regulatory listings	Determine the patent certifications an ANDA applicant must make

The earliest compound-level patents may expire before the 2035 crystal-form patent. That creates a standard “base patent plus late solid-form patent” structure. Even when broad chemical claims have expired or face validity risk, a later-issued polymorph patent can delay practical generic substitution if the commercial product uses the patented form.

The patent landscape should be separated into:

patents covering the active compound;
patents covering the marketed crystal;
patents covering the dosage form;
patents covering MS treatment;
patents covering manufacturing;
patents listed in the Orange Book.

A patent outside the Orange Book may still create commercial or litigation risk, particularly for manufacturing or method-of-use activity.

How strong is the patent estate for Vumerity?

US 10,080,733 is potentially strong against a generic that reproduces the commercial crystalline form. Its strength comes from the objective XRPD limitations and the practical difficulty of proving that a commercial drug substance lacks the claimed form.

Its scope is narrower than a compound patent. The patent does not, based on the supplied claims, cover:

every diroximel fumarate polymorph;
every amorphous form;
every salt or solvate;
every diroximel fumarate formulation;
every use of diroximel fumarate;
every process for making diroximel fumarate.

The patent’s commercial strength depends on whether Vumerity’s approved drug substance consistently exhibits the claimed XRPD pattern and whether alternative forms can satisfy FDA quality, stability, dissolution, and bioequivalence requirements.

Strength factor	Assessment
Objective product definition	Stronger than purely functional identification
Narrow polymorph scope	Limits reach to the claimed solid form
Composition claim	Extends protection into formulated products
MS method claims	Adds labeling and use-based enforcement risk
Design-around potential	Exists through alternative solid forms
Analytical dispute risk	Material because XRPD conditions affect results
Expiration timing	Long-dated protection through approximately 2035

What generic launch scenarios exist?

Scenario 1: Paragraph III delay

A generic applicant accepts the patent and waits until expiration. This is the lowest litigation-risk path but delays launch until after the patent term, unless another lawful entry route applies.

Scenario 2: Paragraph IV challenge with alternative polymorph

The applicant argues that its drug substance does not contain the patented crystal. This requires robust solid-state controls and evidence that the marketed product will not convert to the patented form.

Scenario 3: Paragraph IV challenge against validity

The applicant attacks the patent while preparing to launch a product that may contain the claimed form. The principal risks are an injunction, damages, an at-risk launch, and loss of market access if the patent survives.

Scenario 4: Carve-out or limited label

If the patent claims only a method of treating multiple sclerosis, a generic may attempt a section viii label carve-out. That strategy is less useful where the patent also covers the drug substance or composition, as claims 1 and 2 do here.

Scenario 5: Licensed entry

The patent holder may authorize entry before patent expiration through a settlement or license. No settlement terms should be assumed without a filed agreement, court order, or regulatory disclosure.

What patent litigation affects US 10,080,733?

The patent number alone does not establish whether a specific ANDA litigation matter has been filed, settled, dismissed, or resolved. Any litigation assessment must distinguish:

a Paragraph IV notice letter;
a complaint filed under the Hatch-Waxman statute;
a preliminary injunction or temporary restraining order;
a final judgment;
a settlement agreement;
a consent judgment;
an appeal;
an FDA approval decision.

For transaction or investment diligence, the critical litigation questions are whether Alkermes has sued an ANDA applicant within the statutory window, whether a 30-month stay applies, whether the case includes other Vumerity patents, and whether any settlement permits an authorized or independent generic launch before November 2035.

How does the Vumerity patent estate compare with Tecfidera?

Vumerity and Tecfidera both belong to the fumarate multiple-sclerosis market, but their patent risks differ.

Issue	Vumerity	Tecfidera
Active drug	Diroximel fumarate	Dimethyl fumarate
Active metabolite	Monomethyl fumarate	Monomethyl fumarate
Key solid-form issue	Diroximel fumarate crystalline form	Dimethyl fumarate product and formulation patents
Commercial company	Alkermes	Biogen
Patent 10,080,733 relevance	Direct crystal-form protection	Not applicable
Generic substitution	Requires separate FDA approval	Cannot automatically substitute for Vumerity
Main regulatory pathway	ANDA or 505(b)(2), depending on product	ANDA or other applicable pathway

A generic dimethyl fumarate product does not automatically avoid Vumerity’s patent estate because it is a different active ingredient. Conversely, a diroximel fumarate product must address the Vumerity-specific product and formulation patents.

Does biosimilar risk apply to Vumerity?

No. Vumerity is a small-molecule drug, not a biologic. Biosimilar approval under the Biologics Price Competition and Innovation Act is not the relevant pathway.

Competitive entrants would generally pursue an ANDA or, depending on the product’s differences, a 505(b)(2) application. The key barriers are pharmaceutical equivalence, bioequivalence, solid-form control, patent certification, and FDA product-quality requirements.

What manufacturing and IP barriers are most important?

The main manufacturing barrier is control of the crystalline form. A generic manufacturer must be able to:

reproduce the target form at commercial scale;
avoid formation of competing polymorphs;
maintain the XRPD profile during drying and milling;
control moisture and temperature;
demonstrate stability through the proposed shelf life;
manufacture a dosage form meeting dissolution and bioequivalence requirements.

The patent does not appear, from the supplied claims, to claim a specific crystallization process. That distinction matters. A manufacturer could potentially use a different process and still infringe if the resulting product is the claimed crystal. Conversely, using the patented process would create separate process-patent exposure even if the final product were not covered by claim 1.

Key Takeaways

US 10,080,733 protects a defined crystalline form of diroximel fumarate, the active ingredient in Vumerity.
Claim 1 is an XRPD product claim requiring peaks at 11.6°, 21.0°, 24.3°, 27.4°, and 27.9°, each within plus or minus 0.2 degrees.
Claim 2 extends protection to pharmaceutical compositions containing the claimed crystal.
Claims 3 and 4 cover treatment of multiple sclerosis using the crystal or composition.
The expected patent expiration is November 6, 2035, before any applicable patent-term adjustment.
The patent is narrower than a compound patent but can be commercially effective against a generic reproducing Vumerity’s solid form.
A Paragraph IV challenge would likely focus on non-infringement, polymorph identity, anticipation, obviousness, written description, and enablement.
Vumerity has no biosimilar pathway because it is a small-molecule drug.
Generic entry is most likely to depend on an alternative polymorph, a successful validity challenge, a license or settlement, or post-expiration launch.
Patent, Orange Book, FDA, and court records must be reviewed together because no single record establishes the complete Vumerity exclusivity position.

FAQs

What is the active ingredient protected by US Patent 10,080,733?

The patent protects a crystalline form of diroximel fumarate, marketed as Vumerity for multiple sclerosis.

Does US 10,080,733 cover all diroximel fumarate products?

No. The supplied claims are directed to a specific XRPD-defined crystalline form, compositions containing that form, and MS treatment using that form or composition.

Can a generic avoid US 10,080,733 by using amorphous diroximel fumarate?

Potentially, if the commercial product does not contain the claimed crystalline form and does not convert to it during manufacture, storage, or use. FDA quality and bioequivalence requirements remain separate obstacles.

Is Vumerity interchangeable with Tecfidera?

No. Vumerity contains diroximel fumarate, while Tecfidera contains dimethyl fumarate. They share monomethyl fumarate as an active metabolite but are not automatically substitutable products.

What is the key evidence in a Vumerity crystal-form patent dispute?

The central evidence would likely include XRPD data, solid-form characterization, crystallization records, stability data, formulation samples, and expert analysis of whether the accused material satisfies each claim limitation.

References

U.S. Patent and Trademark Office. (2018). U.S. Patent No. 10,080,733 B2: Crystalline forms of diroximel fumarate.
U.S. Food and Drug Administration. (2019). Vumerity (diroximel fumarate) prescribing information. Alkermes, Inc.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. Center for Drug Evaluation and Research.
U.S. Food and Drug Administration. (2024). Orange Book: Approved drug products with therapeutic equivalence evaluations.
U.S. Food and Drug Administration. (2024). Small-molecule drug development and abbreviated new drug applications. 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
Biogen	VUMERITY	diroximel fumarate	CAPSULE, DELAYED RELEASE;ORAL	211855-001	Oct 29, 2019	AB	RX	Yes	Yes	10,080,733	⤷ Start Trial	Y	Y		METHOD OF TREATING MULTIPLE SCLEROSIS	⤷ 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

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2970101	⤷ Start Trial	301165	Netherlands	⤷ Start Trial
European Patent Office	2970101	⤷ Start Trial	PA2022003	Lithuania	⤷ Start Trial
European Patent Office	2970101	⤷ Start Trial	2022C/507	Belgium	⤷ Start Trial
European Patent Office	2970101	⤷ Start Trial	LUC00251	Luxembourg	⤷ Start Trial
European Patent Office	2970101	⤷ Start Trial	CA 2022 00010	Denmark	⤷ Start Trial
European Patent Office	2970101	⤷ Start Trial	122022000014	Germany	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 10,080,733

Which drugs does patent 10,080,733 protect, and when does it expire?

Summary for Patent: 10,080,733