Details for Patent: 11,129,806

Which drugs does patent 11,129,806 protect, and when does it expire?

Patent 11,129,806 protects TECFIDERA and is included in one NDA.

This patent has thirty-seven patent family members in thirteen countries.

Summary for Patent: 11,129,806

Title:	Methods of treating multiple sclerosis
Abstract:	Provided herein are methods of treating multiple sclerosis with a fumarate, wherein the fumarate is a dialkyl fumarate, a monoalkyl fumarate, a combination of a dialkyl fumarate and a monoalkyl fumarate, a prodrug of monoalkyl fumarate, a deuterated form of any of the foregoing, or a pharmaceutically acceptable salt, clathrate, solvate, tautomer, or stereoisomer of any of the foregoing, or a combination of any of the foregoing. The methods provided herein improve the safety of treatment by informing and monitoring patients undergoing treatment regarding progressive multifocal leukoencephalopathy, and/or by monitoring lymphocyte count.
Inventor(s):	Mark Novas, Rui (Ray) Zhang
Assignee:	Biogen MA Inc
Application Number:	US15/647,016
Patent Claim Types: see list of patent claims	Use; Composition;

U.S. Patent 11,129,806: Scope, Claim Construction, Expiration and Fumarate Patent Landscape

U.S. Patent No. 11,129,806 is a narrow method-of-treatment patent covering the management of multiple sclerosis patients treated with dimethyl fumarate or monomethyl fumarate who develop persistent severe lymphopenia. The central limitation requires blood-count monitoring after six months, continued monitoring every six to 12 months, and treatment interruption when the lymphocyte count remains below 0.5 × 10^9/L for more than six months.

The patent does not broadly claim dimethyl fumarate, monomethyl fumarate, Tecfidera, Bafiertam, or a fumarate formulation as chemical products. Its commercial significance arises from the close correspondence between the claimed monitoring protocol and the FDA-approved Tecfidera labeling.

What does U.S. Patent 11,129,806 cover?

U.S. Patent 11,129,806 covers a clinical management method for MS patients receiving a specified fumarate. The independent claim has four operational components:

1. Administering a pharmaceutical composition containing dimethyl fumarate, monomethyl fumarate, or both.
2. Treating a subpopulation that develops a lymphocyte count below 0.5 × 10^9/L.
3. Obtaining a complete blood count after six months of repeated administration and every six to 12 months thereafter.
4. Interrupting treatment if the low lymphocyte count persists for more than six months.

The claim excludes two categories:

• Fumarate salts.
• Any additional fumarate beyond dimethyl fumarate, monomethyl fumarate, or the combination of those compounds.

The dependent claims add PML surveillance, oral dosing, standard Tecfidera dosing, and total daily fumarate dose limits.

Claim	Principal limitation	Commercial relevance
1	Monitoring and treatment interruption for persistent severe lymphopenia	Core method-of-use claim
2	Monitoring for signs or symptoms suggestive of PML	Safety-monitoring extension
3	Monomethyl fumarate	Directly relevant to Bafiertam
4	Dimethyl fumarate	Directly relevant to Tecfidera and generic dimethyl fumarate
5	Oral administration	Captures approved oral products
6	240 mg dimethyl fumarate twice daily	Standard Tecfidera maintenance dose
7	120 mg twice daily for seven days, followed by 240 mg twice daily	Tecfidera titration regimen
8	No more than 720 mg total fumarates daily	Dose ceiling
9	No more than 480 mg total fumarates daily	Standard 480 mg daily regimen
10	Specified PML symptoms	Clinical surveillance detail
11	Diagnostic evaluation for suspected PML	Escalated PML-management step

How should claim 1 be construed?

Claim 1 is a sequential treatment-management claim, not a general claim to treating MS with fumarates.

The patient subpopulation is outcome-defined

The covered population is not limited to patients known in advance to have lymphopenia. It includes patients who experience a lymphocyte count below 0.5 × 10^9/L while receiving the claimed composition.

That wording creates a potentially important infringement issue. A patient may enter the claimed subpopulation only after treatment begins and laboratory monitoring identifies the low count. The claim therefore combines:

• An administration step;
• A laboratory-monitoring step;
• A persistence determination; and
• A later interruption decision.

The threshold is specific

The claim requires a lymphocyte count of less than 0.5 × 10^9/L. A count exactly equal to 0.5 × 10^9/L is outside the literal wording "less than" unless another claim-construction principle applies.

The claim also requires persistence for more than six months. A temporary low count, or a low count lasting six months or less, does not satisfy the final interruption limitation.

Monitoring timing is mandatory

The complete blood count must be obtained:

• After six months of repeated administration; and
• Every six to 12 months thereafter.

A label or clinical protocol that requires more frequent monitoring generally would still satisfy a "every six to 12 months" minimum interval requirement if the monitoring pattern falls within the claimed range. Monitoring only at baseline and at six months would not satisfy the continuing monitoring limitation.

The treatment interruption must be linked to persistence

The claim requires interruption when the lymphocyte count below the threshold persists for more than six months. Merely recommending interruption, reducing the dose, or discontinuing treatment for another reason may not satisfy the claim.

A product label that directs clinicians to "consider interruption" presents a separate issue. Literal infringement may turn on whether the claimed method requires an actual interruption or whether the administering actor performs the method by following a protocol that directs that action.

Which drugs fall within the claimed fumarate scope?

The claims expressly identify dimethyl fumarate and monomethyl fumarate.

Dimethyl fumarate

Dimethyl fumarate is the active ingredient in:

• Tecfidera;
• Generic dimethyl fumarate delayed-release capsules; and
• Certain other dimethyl fumarate products.

Tecfidera's approved maintenance dose is 240 mg twice daily, matching claim 6. The seven-day 120 mg twice-daily starting regimen in claim 7 also tracks the approved Tecfidera dosing instructions. [2]

A generic dimethyl fumarate product that carries the full MS indication and corresponding lymphocyte-monitoring language has a direct method-of-use exposure under claims 1, 4, 5, 6, 7, 8, and 9.

Monomethyl fumarate

Monomethyl fumarate is the active ingredient in Bafiertam. Claims 1 and 3 expressly cover a composition containing monomethyl fumarate, subject to the exclusion of additional fumarates.

Bafiertam therefore presents a distinct product-specific risk. Its approval and labeling must be assessed separately from Tecfidera because an ANDA applicant for dimethyl fumarate and an NDA holder for monomethyl fumarate face different regulatory and infringement pathways. [3]

Diroximel fumarate

Diroximel fumarate, the active ingredient in Vumerity, is not expressly identified in the claims. It is converted in vivo to monomethyl fumarate, but the claim language requires that "the fumarate in the pharmaceutical composition" be dimethyl fumarate, monomethyl fumarate, or a combination of those compounds.

On the face of the claims, Vumerity does not present the same literal infringement profile as a product whose composition contains dimethyl fumarate or monomethyl fumarate. The distinction between the administered compound and its active metabolite is central.

Product	Active ingredient	Literal claim exposure
Tecfidera	Dimethyl fumarate	High
Generic Tecfidera	Dimethyl fumarate	High
Bafiertam	Monomethyl fumarate	High
Vumerity	Diroximel fumarate	Lower on the composition limitation
Fumarate salt product	Fumarate salt	Expressly excluded

What formulations are protected by U.S. 11,129,806?

The patent does not claim a specific capsule, tablet, enteric coating, excipient system, particle size, or release profile.

The formulation scope is functional and negative:

• The composition must contain dimethyl fumarate, monomethyl fumarate, or both.
• It cannot contain a fumarate salt.
• It cannot contain an additional fumarate outside the expressly permitted compounds.

The patent therefore differs from formulation patents that claim delayed-release capsules, enteric coatings, pharmaceutical compositions, or specific excipient combinations. A manufacturer could avoid literal infringement of the composition limitation by using a different active fumarate, although the method-of-use analysis would still depend on the complete product and treatment protocol.

What are the PML and lymphopenia limitations?

Claims 2, 10, and 11 expand the core lymphopenia protocol to PML surveillance.

The claimed PML signs and symptoms include:

• Progressive weakness on one side of the body;
• Limb clumsiness;
• Visual disturbance;
• Changes in thinking;
• Memory changes;
• Disorientation;
• Confusion; and
• Personality changes.

Claim 11 requires an appropriate diagnostic evaluation for PML when a patient develops a sign or symptom suggestive of the disease.

These limitations are narrower than claim 1. A party could potentially practice claim 1 without practicing claims 2, 10, or 11 if it performs the lymphocyte-monitoring and treatment-interruption steps but does not perform the specified PML surveillance or diagnostic evaluation.

The PML claims also create proof issues. The patent holder would need to establish that the relevant sign or symptom occurred, that it was suggestive of PML, and that an appropriate diagnostic evaluation was performed.

What is the FDA regulatory status and Orange Book significance?

The FDA-approved Tecfidera labeling instructs prescribers to obtain a complete blood count, including lymphocyte count, before treatment, after six months, and every six to 12 months thereafter. The label states that treatment interruption should be considered when lymphocyte counts remain below 0.5 × 10^9/L for more than six months. It also directs monitoring for PML signs and symptoms. [2]

That alignment makes the patent a classic label-overlap method-of-use patent.

Orange Book position

U.S. Patent 11,129,806 is relevant as a use patent rather than a composition-of-matter patent. An Orange Book listing for a method-of-use patent normally identifies a particular approved use through a use code. The effect of the listing depends on:

• Whether the patent was listed for the relevant reference-listed drug;
• The approved indication and use code;
• The date of listing;
• The ANDA filing date; and
• Whether the applicant uses a Paragraph IV certification or a section viii statement.

A use patent does not prevent all generic approval. An ANDA applicant may seek approval with the patented use carved out if the remaining labeling supports approval. The risk increases when the patented monitoring protocol is embedded in the labeling for the only commercially relevant MS indication.

When does U.S. Patent 11,129,806 expire?

The patent issued on September 28, 2021. Its enforceable term is governed by the earliest effective nonprovisional or international application filing date, adjusted for any patent-term adjustment and subject to any terminal disclaimer.

The patent should be analyzed as having a base statutory term extending into the early 2030s rather than expiring with the earlier Tecfidera composition patents. The exact enforceable expiration date must be taken from the USPTO patent-term record because patent-term adjustment and terminal-disclaimer information control the final date. [1]

The patent is therefore potentially relevant after the expiration of earlier fumarate patents covering the active ingredient or basic product formulation.

How does the patent compare with the broader Tecfidera patent estate?

The patent estate around Tecfidera has included several distinct categories:

Patent category	Typical subject matter	Risk to generic launch
Active-ingredient or fumarate patents	Fumaric acid esters and their use in MS	Broad, but many early patents have expired or faced validity challenges
Pharmaceutical composition patents	Dimethyl fumarate formulations and dosage forms	Product-specific
Method-of-treatment patents	Treating MS with dimethyl fumarate	Broad indication exposure
Safety-monitoring patents	Lymphocyte monitoring, PML surveillance and treatment interruption	Narrower, but closely aligned with FDA labeling
Manufacturing patents	Synthesis, purification and solid-state properties	Can create supply-chain barriers
Combination or metabolite patents	Specific fumarate combinations or metabolic approaches	Product-dependent

U.S. 11,129,806 is strongest as a safety-monitoring patent. It does not create a general exclusionary right over all MS treatment with dimethyl fumarate. Its leverage depends on whether the accused product's labeling, prescribing information, or ordinary clinical use causes providers to perform every claimed step.

Which companies face Paragraph IV or generic-entry exposure?

The principal exposure is associated with manufacturers seeking approval for:

• Generic dimethyl fumarate;
• Monomethyl fumarate products;
• Other fumarate products whose labeling includes the claimed lymphocyte-monitoring protocol.

A Paragraph IV certification would assert that the patent is invalid, unenforceable, or not infringed. A section viii statement would seek to omit the patented method from the generic label.

Generic dimethyl fumarate

Generic dimethyl fumarate applicants face the closest overlap because the standard regimen and FDA safety-monitoring language correspond directly to claims 1, 4, 5, 6, 7, 8, and 9.

The principal defenses are:

• The generic label does not include the patented use;
• Physicians will not necessarily perform every claimed step;
• The patient population is not selected before administration;
• The low lymphocyte count is not shown to persist for more than six months;
• Treatment is not actually interrupted;
• The claims are anticipated or obvious based on prior fumarate labeling and clinical practice; or
• The patent is not enforceable against the relevant product or applicant.

Monomethyl fumarate

Bafiertam presents a direct claim 3 issue because that claim isolates monomethyl fumarate. The product-specific analysis turns on whether the approved labeling and actual prescribing practice include the same CBC timing, severe lymphopenia threshold, treatment-interruption rule, and PML-monitoring steps.

Biosimilar risk

There is no biosimilar pathway for Tecfidera, Bafiertam, or Vumerity. These are small-molecule products regulated through the NDA or ANDA pathways. The relevant competitive threat is generic or follow-on small-molecule entry, not biosimilar substitution.

How strong is the patent estate?

Strengths

The patent has several practical strengths:

• Its central protocol closely tracks FDA-approved Tecfidera labeling.
• The numerical threshold is precise.
• The six-month persistence requirement limits ambiguity about the treatment trigger.
• The claims cover both dimethyl fumarate and monomethyl fumarate.
• The dependent claims capture the commercially important Tecfidera dosing regimen.
• The patent may remain in force after earlier fumarate patents expire.

Vulnerabilities

The principal vulnerabilities are:

• Prior-art labeling may disclose the same monitoring schedule.
• Clinical trials may have reported lymphopenia thresholds and treatment interruption practices.
• The claimed method may be viewed as an obvious application of known safety-monitoring requirements.
• Direct infringement requires proof that the treatment, monitoring, persistence determination, and interruption steps were all performed.
• Label-based inducement claims may be limited if a generic applicant successfully carves out the patented use.
• The claims may face divided-infringement issues because physicians, laboratories, patients, and manufacturers may perform different steps.
• The claims do not cover all fumarate products and expressly exclude fumarate salts and additional fumarates.

The patent is commercially meaningful but narrower than a composition-of-matter patent. Its value is highest when the reference product's label requires the same safety-management sequence and when generic labeling cannot realistically omit that information without undermining safe use.

What patent litigation affects the fumarate market?

The Tecfidera market has been shaped by ANDA litigation involving Biogen's earlier fumarate patents. In Biogen Inc. v. Mylan Pharmaceuticals Inc., the Federal Circuit addressed the validity of a Tecfidera patent and affirmed an obviousness determination concerning the claimed dimethyl fumarate dosage regimen. [4]

That litigation does not establish that U.S. Patent 11,129,806 is invalid. It does show that the broader Tecfidera estate has faced substantial obviousness scrutiny, particularly where the claims recite a known dose or regimen supported by clinical-development data.

No conclusion about infringement or validity of U.S. 11,129,806 follows solely from the outcome involving a different patent. Each claim set requires separate analysis.

What licensing and settlement issues matter?

Fumarate licensing and settlement agreements can affect generic launch timing even when a patent remains in force. The relevant terms include:

• Authorized-generic rights;
• Entry dates;
• Product-specific carve-outs;
• Covenants not to sue;
• Geographic restrictions;
• Supply or manufacturing rights; and
• Releases covering later-issued continuation patents.

A settlement covering earlier Tecfidera patents does not automatically resolve U.S. Patent 11,129,806 unless the agreement expressly includes continuation, divisional, reissue, or later-issued family members. Patent-family definitions and release language are decisive.

What generic launch scenarios exist?

Scenario 1: Full-label launch after patent expiry

The generic applicant markets the full MS indication and reproduces the relevant monitoring language after patent expiration. This is the lowest litigation risk after the patent term ends.

Scenario 2: Paragraph IV challenge

The applicant certifies that the patent is invalid, unenforceable, or not infringed. Litigation risk is high, but an adverse judgment could accelerate entry.

Scenario 3: Section viii carve-out

The applicant omits the patented monitoring use from its label. This may reduce formal infringement exposure but can create regulatory and commercial problems if the omitted information is necessary for safe use.

Scenario 4: Limited non-infringing formulation

A manufacturer uses a product outside the expressly claimed fumarate composition, such as a different fumarate prodrug. The composition limitation may reduce literal infringement risk, although doctrine-of-equivalents and inducement theories remain product-specific.

Key Takeaways

• U.S. Patent 11,129,806 is a method-of-treatment and safety-monitoring patent.
• Its core subject is persistent severe lymphopenia during fumarate treatment for MS.
• The key threshold is a lymphocyte count below 0.5 × 10^9/L for more than six months.
• The claimed monitoring schedule is after six months of treatment and every six to 12 months thereafter.
• Claims 3 and 4 separately target monomethyl fumarate and dimethyl fumarate.
• Claims 6 and 7 closely correspond to the approved Tecfidera dosing regimen.
• Tecfidera and generic dimethyl fumarate present the highest direct claim overlap.
• Bafiertam presents direct monomethyl fumarate exposure.
• Vumerity is materially different because it contains diroximel fumarate rather than dimethyl fumarate or monomethyl fumarate.
• The patent does not claim a broad fumarate composition, capsule, coating, or manufacturing process.
• Its strength comes from label overlap; its vulnerabilities include obviousness, prior-art labeling, divided infringement, and label carve-out defenses.
• The patent's term extends beyond the earliest Tecfidera patents and may remain relevant into the early 2030s, subject to the USPTO patent-term record.

FAQs

Does U.S. Patent 11,129,806 cover all patients taking Tecfidera?

No. It covers a defined treatment-management protocol for patients who develop a lymphocyte count below 0.5 × 10^9/L and whose low count persists for more than six months.

Does the patent cover dimethyl fumarate manufacturing?

No. The claims are directed to treating and monitoring patients, not synthesizing, purifying, formulating, or packaging dimethyl fumarate.

Can a generic manufacturer omit the lymphocyte-monitoring language?

Potentially, through a section viii labeling carve-out, but the feasibility depends on the approved indication, FDA labeling requirements, use-code scope, and whether the omitted information is necessary for safe use.

Does the patent cover a fumarate salt?

No. Claim 1 expressly provides that a fumarate salt is not present in the pharmaceutical composition.

Is Vumerity automatically covered because it produces monomethyl fumarate in the body?

No. The claims focus on the fumarate in the administered pharmaceutical composition. Diroximel fumarate is not expressly identified in the claims, so Vumerity requires a separate literal-infringement and equivalents analysis.

References

1. United States Patent and Trademark Office. (2021). U.S. Patent No. 11,129,806, Methods of treating multiple sclerosis.
2. U.S. Food and Drug Administration. (2024). Tecfidera (dimethyl fumarate) prescribing information. Biogen Inc.
3. U.S. Food and Drug Administration. (2020). Bafiertam (monomethyl fumarate) prescribing information. Banner Life Sciences LLC.
4. United States Court of Appeals for the Federal Circuit. (2022). Biogen International GmbH v. Mylan Pharmaceuticals Inc., No. 20-2043.
5. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, 44th ed. Orange Book.

Drugs Protected by US Patent 11,129,806

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	11,129,806					METHOD OF TREATING MULTIPLE SCLEROSIS
Biogen	TECFIDERA	dimethyl fumarate	CAPSULE, DELAYED RELEASE;ORAL	204063-002	Mar 27, 2013	AB	RX	Yes	Yes	11,129,806					METHOD OF TREATING MULTIPLE SCLEROSIS

International Family Members for US Patent 11,129,806

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2015350213
Australia	2020239734
Australia	2021269298
Australia	2024203437
Australia	2026204454
Canada	2967619