Details for Patent: 8,399,514

Which drugs does patent 8,399,514 protect, and when does it expire?

Patent 8,399,514 protects TECFIDERA and is included in one NDA.

This patent has forty-five patent family members in eighteen countries.

Summary for Patent: 8,399,514

Title:	Treatment for multiple sclerosis
Abstract:	Provided are certain methods of screening, identifying, and evaluating neuroprotective compounds useful for treatment of neurological diseases, such as, e.g., multiple sclerosis (MS). The compounds described upregulate the cellular cytoprotective pathway regulated by Nrf2. Also provided are certain methods of utilizing such compounds in therapy for neurological disease, particularly, for slowing or reducing demyelination, axonal loss, or neuronal and oligodendrocyte death.
Inventor(s):	Matvey E. LUKASHEV, Gilmore O'Neill
Assignee:	Biogen MA Inc
Application Number:	US13/372,426
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,399,514
Patent Claim Types: see list of patent claims	Use; Composition; Dosage form;

United States Patent 8,399,514: Claim Scope, Tecfidera Exclusivity and Patent Landscape

US Patent No. 8,399,514 covers methods of treating multiple sclerosis with approximately 480 mg per day of dimethyl fumarate, monomethyl fumarate, or both. Its commercial target was Biogen’s Tecfidera delayed-release dimethyl fumarate product. The patent has a nominal Orange Book expiration date in 2028, but the asserted claims were held invalid as obvious in litigation brought against Mylan. The Federal Circuit affirmed that judgment, materially reducing the patent’s practical exclusionary value.[1,2]

What does US Patent 8,399,514 protect?

The patent protects a dosing regimen rather than a new chemical entity, tablet technology, or manufacturing process. Its central limitation is the administration of approximately 480 mg per day of dimethyl fumarate, monomethyl fumarate, or a combination of the two to treat multiple sclerosis.

Patent element	Scope under the claims
Active ingredient	Dimethyl fumarate, monomethyl fumarate, or both
Daily amount	About 480 mg per day
Disease	Multiple sclerosis
Route	Oral administration in most principal claims
Dosage forms	Tablet, suspension, or capsule under claim 2
Administration schedule	Two, three, four, or six equal doses under claim 3
Preferred schedule	Two equal doses under claims 4, 9, 10, 13 and 16
Duration	At least 12 weeks under claims 8 and 10
Composition	Active ingredient plus one or more pharmaceutically acceptable excipients
Biomarker limitation	Elevated NQO1 expression under claims 17 to 19

The commercially relevant regimen is 240 mg twice daily, which totals 480 mg per day. That corresponds to the approved Tecfidera maintenance dose.[3]

How are the independent claims structured?

The independent claims divide into four principal categories.

Claim 1: Composition-based treatment method

Claim 1 requires:

1. A subject needing treatment for multiple sclerosis.
2. Oral administration.
3. A pharmaceutical composition.
4. Dimethyl fumarate, monomethyl fumarate, or both.
5. One or more pharmaceutically acceptable excipients.
6. Approximately 480 mg per day of the active fumarate.

The phrase “consisting essentially of” limits the composition to the listed fumarate active ingredient or ingredients and excipients, while permitting additional components that do not materially affect the claimed invention. This is narrower than an “open” comprising formulation claim but broader than a claim limited to a specific marketed formulation.

Claim 1 does not require:

• A particular tablet coating.
• A delayed-release mechanism.
• A particular excipient.
• A specific patient population, such as relapsing-remitting MS.
• A specific clinical endpoint.
• A particular treatment duration unless claim 8 is invoked.

Claim 11: Active-ingredient dosing method

Claim 11 is broader in formulation terms. It covers treating multiple sclerosis by administering approximately 480 mg per day of dimethyl fumarate, monomethyl fumarate, or both. It does not expressly require a pharmaceutical composition containing excipients.

The claim remains method-of-treatment focused. It does not claim the fumarate molecule itself, a composition as a product, or a manufacturing process.

Claim 15: Dimethyl fumarate composition method

Claim 15 narrows the active ingredient to dimethyl fumarate and requires oral administration of a composition consisting essentially of dimethyl fumarate and pharmaceutically acceptable excipients at approximately 480 mg per day.

This is the claim most directly aligned with Tecfidera’s active ingredient and commercial dosing regimen.

Claim 20: Broad treatment method

Claim 20 covers treatment of multiple sclerosis with a therapeutically effective amount of dimethyl fumarate, monomethyl fumarate, or both, where the amount is approximately 480 mg per day.

Unlike claims 1 and 15, claim 20 does not expressly require oral administration or a defined pharmaceutical composition. Its broader language creates potential claim-construction issues, although the patent’s specification, prosecution history and the litigation record remain relevant to its interpretation.

What do the dependent claims add?

The dependent claims add administration, duration, active-ingredient and biomarker limitations.

Claims	Added limitation	Commercial relevance
2	Tablet, suspension or capsule	Captures conventional oral dosage forms
3	Two, three, four or six equal doses	Covers multiple daily dosing schedules
4	Two equal doses	Maps to 240 mg twice daily
5	Three equal doses	Covers 160 mg three times daily
6	Dimethyl fumarate-only composition	Aligns with Tecfidera
7	Monomethyl fumarate-only composition	Potentially relevant to MMF products
8	Treatment for at least 12 weeks	Adds a treatment-duration requirement
9	Dimethyl fumarate in two equal doses	Directly captures 240 mg twice daily
10	Claims 9 regimen for at least 12 weeks	Dosing plus duration
12	Approximately 480 mg/day dimethyl fumarate	Narrows claim 11
13	Dimethyl fumarate in two equal doses	Tecfidera maintenance regimen
14	Dimethyl fumarate in three equal doses	Alternative schedule
16	Claim 15 composition in two equal doses	Composition and regimen combination
17-19	Elevated NQO1 expression after treatment	Biomarker-limited treatment claims

The two-dose limitations are commercially important because Tecfidera is administered as 240 mg twice daily after the initial titration period. A generic product using the same active ingredient and labeled maintenance dose would have been exposed to the core regimen claims absent a successful invalidity or noninfringement position.

What is the role of the NQO1 limitations?

Claims 17, 18 and 19 require that NQO1 expression in the subject be elevated after administration.

NQO1, or NAD(P)H quinone dehydrogenase 1, is associated with cellular oxidative-stress response pathways. These claims attempt to add a biological-response limitation to the dosing method. They do not require:

• Measurement of NQO1 before treatment.
• A specified testing method.
• A minimum numerical increase.
• Patient selection based on a pre-treatment NQO1 level.
• A particular clinical response.

The claims therefore raise questions about proof of infringement and claim definiteness. A product label generally will not instruct physicians to measure post-treatment NQO1 expression. A patent owner would likely need patient-specific evidence or clinical-study evidence to establish that the claimed response occurred.

The NQO1 claims are narrower than the basic 480 mg/day claims. Their practical enforcement value is consequently lower unless the patent owner can identify a testing protocol, a label instruction, or reliable evidence that treatment predictably produces the claimed elevation.

When does US Patent 8,399,514 expire?

The Orange Book-listed expiration date for US Patent 8,399,514 is June 1, 2028.[4] That date reflects the patent term recorded for the listed patent and does not eliminate earlier statutory or judicial barriers to enforcement.

Milestone	Date or status
Patent	US 8,399,514
Grant	March 26, 2013
Listed product	Tecfidera delayed-release capsules
NDA holder	Biogen
FDA approval of Tecfidera	March 27, 2013
Orange Book expiration	June 1, 2028
Main asserted generic challenger	Mylan
District court result	Claims held obvious
Federal Circuit result	Invalidity judgment affirmed
Practical status	Patent remains recorded, but asserted claims were judicially invalidated

A patent’s expiration date is not the same as its enforceability. A final judgment that asserted claims are invalid prevents those claims from supporting an infringement injunction against the adjudicated challenger. The patent may continue to appear in USPTO and Orange Book records unless removed, expired, or otherwise administratively changed.

What is the Orange Book status of Tecfidera?

Tecfidera was approved by FDA as delayed-release dimethyl fumarate capsules under NDA 204063.[3] The Orange Book listed multiple Biogen patents associated with Tecfidera, including patents directed to fumarate treatment regimens and related subject matter.[4]

The key distinction is between:

• Patents directed to the active compound or broad fumarate use.
• Patents directed to specific dosing regimens.
• Patents directed to formulations or release characteristics.
• Regulatory exclusivity.
• Judicially enforceable patent rights.

US 8,399,514 is primarily a method-of-use and dosing patent. It is not a conventional formulation patent because the claims do not require Tecfidera’s specific enteric or delayed-release construction.

FDA approval and Orange Book listing do not establish that the claims are valid. FDA’s role is to identify listed patents and process ANDA certifications. Patent validity is determined through litigation or USPTO proceedings.

Which companies challenged the Tecfidera patent?

Mylan filed an abbreviated new drug application seeking approval for generic dimethyl fumarate delayed-release capsules. The resulting litigation centered on US 8,399,514 and the obviousness of its 480 mg/day dosing claims.

The Federal Circuit upheld the district court’s determination that the asserted claims were obvious.[1,2] The court’s reasoning focused on the prior-art record, including disclosures supporting fumarate treatment of multiple sclerosis and clinical information associated with the 480 mg/day regimen.

The case established a critical distinction:

• A regimen can be clinically successful and commercially important.
• Those facts do not necessarily establish nonobviousness.
• Where prior art points toward the claimed dose and provides a reasonable expectation of success, secondary considerations may not save the claims.

Generic applicants could use Paragraph IV certifications against listed patents. Under the Hatch-Waxman framework, a Paragraph IV notice alleges that a listed patent is invalid, unenforceable or not infringed.[5] Litigation can trigger a 30-month FDA approval stay, but that stay does not guarantee patent validity or block launch after an adverse judgment.

How did the invalidity ruling affect generic launch risk?

Before the invalidity ruling, the 2028 Orange Book date created a potentially long period of patent-based delay for generic dimethyl fumarate. After the ruling, the risk profile changed materially.

Generic scenario	Effect of US 8,399,514
Generic label includes 480 mg/day	High theoretical exposure before invalidity judgment
Generic label uses 240 mg twice daily	Direct overlap with claims 4, 9, 13 and 16
Generic uses a different daily dose	May avoid literal infringement but must remain therapeutically and regulatorily viable
Generic uses dimethyl fumarate with excipients	Direct relevance of claims 1, 6 and 15
Generic omits treatment-duration instructions	May avoid claims requiring at least 12 weeks, but not claims without that limitation
Generic relies on a Paragraph IV certification	Litigation risk depends on all listed patents, not this patent alone
Generic launches after final invalidity ruling	US 8,399,514 is substantially weakened as a blocking patent

The invalidity judgment does not automatically resolve every other Tecfidera patent. A generic applicant must assess each Orange Book-listed patent separately, including formulation, release-profile and method-of-use patents.

What patents and IP rights compete with US 8,399,514?

The Tecfidera estate included earlier patents associated with fumaric acid esters and later patents directed to treatment and product-specific subject matter.

Earlier fumarate patents

US Patent No. 6,509,376 and US Patent No. 7,320,999 were associated with fumaric acid ester treatments and related use claims. Their terms were substantially earlier than the 2028 date associated with US 8,399,514.[4]

These patents were important historically because they supported the initial product and treatment platform. They were less effective as long-term barriers once their terms expired.

Later method-of-use patents

Biogen also pursued related patents covering fumarate treatment methods, dosing and biological effects. A patent landscape review should separate continuations and divisionals from genuinely distinct inventions. Multiple patent numbers may share overlapping disclosure and priority claims while presenting different enforceability profiles.

Formulation and manufacturing rights

US 8,399,514 does not materially protect:

• A specific enteric polymer.
• A defined dissolution profile.
• A particular particle-size distribution.
• A manufacturing sequence.
• A capsule shell.
• A specific impurity specification.
• A commercial-scale production process.

Those barriers, if present in related patents, must be analyzed independently. A generic can avoid a formulation claim through a noninfringing release design while still infringing a dose-based method claim, or it can face the reverse situation.

How strong is the patent estate for dimethyl fumarate?

The estate was commercially strong before the Mylan decision because the 480 mg/day dose is central to Tecfidera’s label and difficult to avoid while maintaining an equivalent generic label. Its weaknesses were structural.

Strengths

• The claims align with the approved maintenance regimen.
• Claims 4, 9, 13 and 16 target two equal daily doses.
• Claims 6 and 15 focus specifically on dimethyl fumarate.
• The 2028 nominal expiration date extended well beyond the earlier fumarate patents.
• The claims could support a direct infringement theory based on the generic label.

Weaknesses

• The claimed dose was vulnerable to an obviousness challenge.
• The claims did not require a technically complex formulation.
• The active ingredient and therapeutic area were known.
• The commercial regimen was disclosed in the clinical and prior-art record.
• NQO1 claims may be difficult to enforce without patient-level evidence.
• “About 480 mg” creates potential claim-construction and dose-equivalence disputes.

The final invalidity determination is the controlling commercial fact. The patent’s formal term does not restore exclusivity for claims held invalid.

What licensing deals affect this patent landscape?

Biogen’s fumarate franchise originated from technology and commercial rights associated with Fumapharm and related fumaric acid ester development. Biogen acquired or consolidated rights to the fumarate program before Tecfidera’s FDA approval.[6]

Those transactions are relevant to ownership, prosecution and enforcement history. They do not change the claim scope of US 8,399,514. No license can convert an invalid claim into an enforceable one, although contractual rights may govern royalties, settlement payments or technology access.

Later fumarate products, including Vumerity, also affect the competitive landscape. Vumerity contains diroximel fumarate, a prodrug that generates monomethyl fumarate. Its separate product profile and patent estate should not be treated as identical to Tecfidera’s dimethyl fumarate estate.

What revenue was exposed to this patent?

Tecfidera generated approximately $4.4 billion in annual revenue at its peak before generic erosion.[7] Because US 8,399,514 targeted the labeled 480 mg/day regimen, it was one of the patents with direct potential exposure to the product’s core revenue stream.

The economic value of the patent was higher before:

1. Generic filing and Paragraph IV litigation.
2. The district court invalidity ruling.
3. Federal Circuit affirmance.
4. Commercial generic entry.
5. Erosion of Tecfidera pricing and volume.

The patent’s remaining value is primarily historical, defensive or settlement-related. Its nominal 2028 expiration date should not be used as a standalone forecast for Tecfidera exclusivity.

Key Takeaways

• US 8,399,514 covers treatment of multiple sclerosis with approximately 480 mg/day of dimethyl fumarate, monomethyl fumarate or both.
• Claims 4, 9, 13 and 16 most directly capture Tecfidera’s 240 mg twice-daily maintenance regimen.
• Claims 1 and 15 require a composition containing active fumarate and excipients; claim 11 is broader in composition terms.
• Claims 17 to 19 add elevated NQO1 expression but create significant proof and enforcement issues.
• The Orange Book-listed expiration date is June 1, 2028.
• The asserted claims were held invalid as obvious in Biogen’s litigation against Mylan, and the Federal Circuit affirmed.
• The patent is not a formulation or manufacturing patent. Related Tecfidera patents must be analyzed separately.
• Tecfidera’s peak annual revenue was approximately $4.4 billion, making the patent commercially significant before generic entry.
• The 2028 expiration date does not represent effective exclusivity after the final invalidity judgment.

FAQs About US Patent 8,399,514

Does US 8,399,514 cover Tecfidera itself?

No. It covers methods of treating multiple sclerosis using approximately 480 mg/day of fumarate active ingredient. It does not claim Tecfidera as a composition of matter.

Is 240 mg twice daily covered by US 8,399,514?

Yes. The 240 mg twice-daily regimen totals approximately 480 mg/day and is expressly captured by dependent claims requiring two equal administrations.

Does the patent cover Vumerity?

Not automatically. Vumerity contains diroximel fumarate, a different active pharmaceutical ingredient from dimethyl fumarate. Coverage requires a separate analysis of the claim language, product conversion, labeling and related patents.

Can a generic avoid US 8,399,514 by using a different capsule formulation?

A different formulation may avoid formulation-specific claims in other patents, but it would not necessarily avoid the dose-based claims in US 8,399,514. The principal issue for this patent is the active ingredient, treatment indication and daily dose.

Is US 8,399,514 still a meaningful barrier after the Mylan case?

Its practical blocking value is substantially reduced because the asserted claims were held invalid as obvious and that result was affirmed on appeal. The patent’s formal Orange Book listing and 2028 expiration date do not negate the final judicial invalidity ruling.

References

1. Biogen International GmbH v. Mylan Pharmaceuticals Inc., 18-1165, United States Court of Appeals for the Federal Circuit (2020).

2. United States District Court for the District of Delaware. Biogen International GmbH v. Mylan Pharmaceuticals Inc., litigation concerning US Patent No. 8,399,514.

3. U.S. Food and Drug Administration. (2013). Tecfidera (dimethyl fumarate) delayed-release capsules, NDA 204063: Approval letter and prescribing information.

4. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, Orange Book: Tecfidera patent listings.

5. U.S. Food and Drug Administration. (2024). Guidance for industry: 180-day exclusivity: Questions and answers.

6. Biogen Inc. (2006). Annual report and corporate disclosures concerning fumaric acid ester technology and Fumapharm-related transactions.

7. Biogen Inc. (2020). Annual report: Tecfidera product revenue and generic competition.

Drugs Protected by US Patent 8,399,514

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	TECFIDERA	dimethyl fumarate	CAPSULE, DELAYED RELEASE;ORAL	204063-001	Mar 27, 2013	AB	RX	Yes	No	8,399,514					METHOD OF TREATING MULTIPLE SCLEROSIS
Biogen	TECFIDERA	dimethyl fumarate	CAPSULE, DELAYED RELEASE;ORAL	204063-002	Mar 27, 2013	AB	RX	Yes	Yes	8,399,514					METHOD OF TREATING MULTIPLE SCLEROSIS

International Family Members for US Patent 8,399,514

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	2137537		C300674	Netherlands
European Patent Office	2137537		CA 2014 00035	Denmark
European Patent Office	2137537		PA2014024	Lithuania
European Patent Office	2137537		1490038-5	Sweden