United States Patent 10,555,993: Scope, Claim Analysis, Expiration, and Fumarate Patent Landscape

U.S. Patent No. 10,555,993 protects a narrow method of treating relapsing multiple sclerosis by administering a fumarate therapy across two consecutive dosing periods while giving a vaccine during the first period. The broadest claim covers dimethyl fumarate, monomethyl fumarate, certain monomethyl fumarate salts, and combinations. The claim does not cover fumarate therapy alone, vaccination alone, or every vaccine-and-fumarate combination.

The principal commercial exposure is dimethyl fumarate, including a regimen corresponding to 480 mg per day after a 240 mg-per-day titration period. The patent is a method-of-use patent. It does not claim the fumarate molecule, a fumarate composition in the abstract, or vaccine manufacture.

What does U.S. Patent 10,555,993 claim?

Claim 1 requires every element below:

Required element	Scope
Disease	Multiple sclerosis
Patient	Human subject in need of treatment
Disease subtype	Relapsing multiple sclerosis
First therapy	Pharmaceutical composition containing monomethyl fumarate, a pharmaceutically acceptable monomethyl fumarate salt, dimethyl fumarate, or a combination
First dosing period	First period during which the fumarate composition is administered
Vaccine	Administered during the first dosing period
Second therapy	Same dose as the first dose
Second dosing period	Begins after the first period and within one day after it ends
Frequency	First and second doses are administered daily
Therapeutic status	First dose must be therapeutically effective
Immune response	Vaccine must induce an anamnestic humoral response, a neoantigen response, or a T-cell-independent response

The claim is therefore a combination and sequencing claim. A potential infringer must practice the fumarate regimen and the vaccination condition in the same patient treatment course.

The claim does not expressly require:

A particular vaccine administration date within the first period;
A specified duration for the first dosing period;
A specified duration for the second dosing period;
A vaccine administered before the fumarate treatment;
A vaccine administered after the fumarate treatment;
A particular mechanism by which fumarate affects vaccine immunogenicity;
A particular multiple sclerosis lesion burden, relapse rate, or disability score.

How broad is claim 1 of Patent 10,555,993?

Claim 1 is chemically broad but operationally narrow.

Its chemical scope includes:

Dimethyl fumarate;
Monomethyl fumarate;
Pharmaceutically acceptable salts of monomethyl fumarate; and
Combinations of the listed fumarate agents.

Its treatment scope is narrower because it is limited to relapsing multiple sclerosis. Claims 17 and 18 further specify relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis.

The most important narrowing feature is the dosing transition. The second dosing period must begin within one day after the first dosing period ends, and the second dose must be the same as the first dose. A regimen with a materially different maintenance dose, a treatment gap exceeding one day, or no identifiable first and second dosing periods may fall outside the literal wording of claim 1.

The vaccine requirement is also material. The vaccine must induce one of the immune responses identified in the claim. Claims 9 through 11 separate those immune-response categories, while claims 12 through 16 identify specific vaccines.

What dosing regimens are protected?

Dimethyl fumarate at 480 mg per day

Claim 3 narrows claim 1 to approximately 480 mg of dimethyl fumarate per day. This corresponds to the standard total daily maintenance amount in the FDA-approved Tecfidera labeling, which generally uses 240 mg twice daily after initial treatment [2].

The patent claim is directed to the daily amount, not necessarily to a single 480 mg administration. A twice-daily 240 mg regimen could potentially satisfy the "about 480 mg" limitation, subject to claim construction and the specific facts of administration.

Dimethyl fumarate titration

Claims 4, 5, 19, and 20 cover a preceding titration dose. The most specific version requires approximately 240 mg of dimethyl fumarate per day before the 480 mg-per-day regimen.

This creates a regimen structure with three practical stages:

Stage	Claimed amount
Titration	About 240 mg dimethyl fumarate daily
First dosing period	Therapeutically effective dose, potentially about 480 mg daily
Second dosing period	Same dose as first period, initiated within one day

The claims do not require titration unless claims 4, 5, 19, or 20 are asserted. A defendant practicing the claim 1 regimen without titration could still face claim 1 exposure if all other limitations are met.

Capsule, tablet, microtablet, and micropellet formulations

Claim 6 covers a capsule or tablet. Claims 7 and 8 are narrower and cover dimethyl fumarate in enterically coated microtablets or micropellets, including those contained in a capsule.

These limitations create separate formulation-based claim positions:

A standard capsule or tablet can implicate claim 6.
An enterically coated microtablet or micropellet formulation can implicate claims 7 and 8.
A formulation outside those physical forms may avoid the narrower claims but can remain exposed to claim 1 if the method limitations are satisfied.

The patent does not appear, from the supplied claims, to require a specific excipient, dissolution profile, particle-size distribution, release site, or manufacturing process.

What vaccines fall within Patent 10,555,993?

The patent claims vaccine categories by immune response and by named vaccine.

Claim	Vaccine or immune-response limitation
1	T-cell-dependent anamnestic humoral, T-cell-dependent neoantigen, or T-cell-independent response
9	T-cell-dependent anamnestic humoral response
10	T-cell-dependent neoantigen response
11	T-cell-independent response
12	Tetanus diphtheria toxoids, keyhole limpet hemocyanin, Pneumovax-23, or combinations
13	Tetanus diphtheria toxoids vaccine
14	Keyhole limpet hemocyanin vaccine
15	Pneumovax-23 vaccine
16	Meningococcal polysaccharide diphtheria conjugate quadrivalent vaccine

The named-vaccine claims are narrower than claim 1. A vaccine not expressly named can still fall within claim 1 or claims 9 through 11 if it produces the required immune response.

The claim language raises an infringement issue concerning proof of immune response. For a marketed vaccine, the relevant evidence could include the vaccine label, clinical pharmacology data, regulatory submissions, immunogenicity studies, or scientific literature. The claim is not limited to a vaccine administered for a particular indication.

When does Patent 10,555,993 lose exclusivity?

U.S. Patent 10,555,993 issued on February 11, 2020. Its ordinary patent term is generally measured from the earliest effective nonprovisional or international filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and any applicable priority-chain facts [1].

A precise expiration date cannot be established from the claims alone. The controlling date must be taken from the USPTO patent record and the patent’s term-adjustment data. The patent should be evaluated separately from the earlier dimethyl fumarate patents, whose expiration dates do not automatically control this patent.

The commercial exclusivity timeline has two distinct components:

Exclusivity type	Relevance
Patent exclusivity	Depends on the 10,555,993 term and enforceability
FDA drug exclusivity	Depends on the approved product and applicable statutory exclusivity
Orange Book listing	Depends on whether the patent is listed against a specific approved drug product
Regulatory approval	A generic applicant can pursue approval even while patent disputes remain pending

The patent’s issue date does not itself establish a 20-year expiration date. Patent-term adjustment and priority data must be included in any transaction, launch, or litigation model.

What is the Orange Book status of Patent 10,555,993?

Patent 10,555,993 should be treated as a method-of-use patent that may be relevant to an approved dimethyl fumarate product, but Orange Book relevance is product-specific.

The Orange Book does not function as a complete registry of every patent that could be asserted against a drug. Listed patents are submitted by the NDA holder or applicant and are associated with a particular approved drug product, strength, dosage form, or method of use [3].

For a generic applicant, the key questions are:

Whether the patent is listed against the relevant dimethyl fumarate NDA;
Whether the listed use corresponds to the generic applicant’s proposed labeling;
Whether the applicant makes a Paragraph IV certification;
Whether a section viii statement can carve out the patented method; and
Whether the FDA determines that the proposed labeling still induces the patented use.

A method-of-use patent creates the strongest Hatch-Waxman risk when the patented use is included in the reference product labeling and cannot be cleanly removed from the generic label. A generic product with a lawful skinny label may reduce exposure, but a label carve-out does not eliminate all induced-infringement risk.

Which companies are challenging dimethyl fumarate exclusivity?

The principal historical challenges to Tecfidera involved generic pharmaceutical companies that filed abbreviated new drug applications and made Paragraph IV certifications against Biogen’s dimethyl fumarate patent estate. Major litigation involving Tecfidera included Biogen’s disputes with Mylan and other generic applicants over earlier fumarate patents, particularly U.S. Patent Nos. 6,509,376 and 7,619,001 [4].

Those earlier cases should not be conflated with Patent 10,555,993. A company that challenged the earlier composition or formulation patents does not necessarily challenge the later vaccine-coadministration method patent.

The relevant competitive groups are:

Generic dimethyl fumarate manufacturers;
Generic monomethyl fumarate manufacturers;
Manufacturers of alternative fumarate products;
Specialty pharmacies and distributors;
Biogen, as the principal Tecfidera commercial sponsor; and
Other multiple sclerosis disease-modifying therapy companies competing for the same patient population.

The supplied claims do not identify a litigation docket, settlement agreement, or party-specific challenge involving Patent 10,555,993. The patent should not be characterized as litigated merely because related Tecfidera patents were litigated.

How does Patent 10,555,993 compare with earlier Tecfidera patents?

Patent 10,555,993 occupies a different position from the foundational Tecfidera patents.

Patent category	Typical protected subject matter	Relevance to 10,555,993
Foundational fumarate patents	Use of fumarates for multiple sclerosis	Earlier and generally broader therapeutic foundation
Composition or formulation patents	Delayed release, enteric coating, dosage forms, or excipients	Potentially overlapping with claims 6 through 8
Dose-regimen patents	Titration, maintenance dose, or dosing frequency	Potentially overlapping with claims 3 through 5 and 19 through 20
Vaccine-combination patent	Fumarate administration during vaccination period	Core subject matter of 10,555,993
Alternative fumarate patents	Monomethyl fumarate or diroximel fumarate products	Separate product and formulation barriers

The patent does not replace the earlier Tecfidera estate. It adds a use-specific layer that may remain relevant after earlier patents expire, particularly if a product label recommends or encourages vaccination during fumarate therapy.

What are the main infringement risks for generic dimethyl fumarate?

Direct method infringement

Direct infringement requires a person or entity to practice every claim limitation. A generic manufacturer ordinarily does not administer the drug to patients. The more likely targets would be healthcare providers, specialty pharmacies, treatment systems, or parties that direct the claimed regimen.

Induced infringement

Induced infringement risk may arise if a generic applicant’s label, promotional material, patient instructions, or clinical-support program encourages:

Dimethyl fumarate treatment for relapsing multiple sclerosis;
Vaccination during the first dosing period;
Continuation into a second dosing period within one day;
A stable daily dose across the two periods; and
The claimed 240 mg-per-day titration followed by 480 mg per day.

A label that merely identifies vaccination as a general medical consideration may present a different risk from instructions that direct vaccination during a specified fumarate dosing period.

Literal and equivalents-based exposure

A regimen that uses monomethyl fumarate rather than dimethyl fumarate remains within claim 1 and claim 21. A pharmaceutically acceptable monomethyl fumarate salt can implicate claim 22.

A product using a different dosage form may avoid claims 6 through 8 while remaining exposed to claim 1. Conversely, a product with the same chemical and clinical regimen but a non-listed vaccine could still implicate claim 1 or claims 9 through 11.

What formulation patents are relevant?

Claims 6 through 8 create formulation relevance but do not claim every enteric fumarate formulation.

The strongest overlap would involve:

Dimethyl fumarate capsules;
Tablets containing dimethyl fumarate;
Enterically coated microtablets;
Enterically coated micropellets; and
Capsules containing those microtablets or micropellets.

A generic developer should separate three questions:

Whether the dosage form satisfies claim 6;
Whether the internal multiparticulate structure satisfies claims 7 and 8; and
Whether the administration regimen and vaccine timing satisfy claim 1 independently of the formulation.

A non-enteric capsule could avoid claims 7 and 8 but would not necessarily avoid claim 6 or claim 1.

Does biosimilar risk apply to Patent 10,555,993?

No conventional biosimilar pathway applies to dimethyl fumarate or monomethyl fumarate because these are chemically synthesized small molecules, not biologic products regulated under the Public Health Service Act.

The relevant U.S. pathway is an abbreviated new drug application under section 505(j) of the Federal Food, Drug, and Cosmetic Act. Patent risk is therefore driven by Orange Book listings, Paragraph IV certifications, section viii statements, labeling, and Hatch-Waxman litigation rather than the Purple Book biosimilar framework [3, 5].

Vumerity, which contains diroximel fumarate, is also a small-molecule product. Its regulatory pathway and patent estate are separate from the claims of Patent 10,555,993 unless a product or regimen independently satisfies the claimed fumarate-agent language. Diroximel fumarate is not expressly listed in the claims supplied.

What manufacturing and geographic barriers exist?

Patent 10,555,993 does not claim a manufacturing process. Its principal barrier is clinical-use behavior, not production technology.

Geographic coverage is limited by the U.S. patent right. Corresponding foreign applications, national-stage patents, or continuations must be reviewed separately. A U.S. patent does not create direct rights in Europe, Canada, Japan, or other markets.

For U.S. commercial planning, the main barriers are:

Patent term and patent-term adjustment;
Orange Book listing status;
Generic labeling strategy;
Physician and pharmacy instructions;
Evidence concerning vaccine timing;
Proof of the claimed immune-response category;
Any continuation or divisional patent; and
Settlement restrictions affecting launch timing.

How strong is the patent estate for the claimed regimen?

The claim estate is strongest against a product or treatment protocol that expressly combines all of the following:

Dimethyl fumarate;
Relapsing multiple sclerosis treatment;
Initial titration at approximately 240 mg per day;
Maintenance at approximately 480 mg per day;
Vaccination during the first dosing period;
A second dosing period beginning within one day; and
The same daily dose in both periods.

The estate is weaker where:

The vaccine is administered outside the first dosing period;
The treatment gap exceeds one day;
The first and second doses differ;
The drug is used for a non-relapsing condition;
The product is labeled without vaccination instructions;
The vaccine is not shown to produce a claimed immune response; or
The proposed label omits the patented use.

The claims are narrower than a basic patent covering dimethyl fumarate for multiple sclerosis. They may, however, provide a later-layer enforcement position against specific clinical-use instructions.

What generic launch scenarios exist?

Scenario	Patent exposure
Generic DMF launches with full Tecfidera-like labeling	Highest risk of induced-use allegations
Generic DMF uses a skinny label omitting the claimed vaccine regimen	Reduced, but not necessarily eliminated, risk
Generic DMF launches after patent expiration	Patent-specific risk largely removed
Generic uses a different dose transition	Potentially avoids dose-specific dependent claims; claim 1 still requires analysis
Generic uses a different formulation	May avoid claims 6 through 8 but not claim 1
Generic monomethyl fumarate launches	Claim 1 and claims 21-22 remain relevant
Alternative fumarate product launches	Requires element-by-element comparison with the defined fumarate agent

What revenue exposure does Patent 10,555,993 create?

The patent does not block all dimethyl fumarate sales. Its revenue exposure depends on the percentage of relapsing multiple sclerosis patients who receive vaccination during the first dosing period and the extent to which manufacturers, physicians, pharmacies, or patient materials direct that sequence.

The economic risk is therefore use-specific rather than product-wide. A successful assertion could affect:

A branded product’s post-expiration label strategy;
Generic launch labeling;
Pharmacy counseling materials;
Vaccination protocols embedded in clinical-support services;
Settlement economics; and
The commercial value of follow-on fumarate products.

The patent is less likely to support a complete exclusion of every generic dimethyl fumarate product than a conventional composition patent. Its value depends on the ability to prove or induce the specific treatment sequence.

Key Takeaways

Patent 10,555,993 is a method-of-use patent covering fumarate treatment combined with vaccination in relapsing multiple sclerosis.
Claim 1 requires a vaccine during the first dosing period and a same-dose second period beginning within one day.
Dimethyl fumarate is the most commercially important embodiment.
Claims 3, 5, 19, and 20 target approximately 480 mg per day after an approximately 240 mg-per-day titration.
Claims 6 through 8 add capsule, tablet, microtablet, micropellet, and enteric-coating limitations.
The patent covers monomethyl fumarate and pharmaceutically acceptable monomethyl fumarate salts, not only dimethyl fumarate.
It is not a biosimilar patent issue. Generic-drug and Hatch-Waxman rules apply.
Earlier Tecfidera litigation over foundational fumarate patents does not establish litigation against Patent 10,555,993.
Generic risk is highest when labeling or commercial instructions encourage vaccination during the claimed dosing sequence.
Exact patent expiration and current Orange Book status require confirmation from the USPTO patent-term record and FDA listing data.

FAQs

Does Patent 10,555,993 cover dimethyl fumarate without vaccination?

No. The independent claim requires administration of a vaccine during the first dosing period. Dimethyl fumarate treatment alone does not satisfy claim 1.

Does the patent cover a vaccine given before dimethyl fumarate starts?

Not necessarily. Claim 1 requires that the subject receive the vaccine during the first dosing period. A vaccine administered before that period may avoid the literal timing requirement.

Can monomethyl fumarate infringe Patent 10,555,993?

Yes. Claim 1 expressly includes monomethyl fumarate, and claims 21 and 22 separately address monomethyl fumarate and its pharmaceutically acceptable salts.

Is a 240 mg twice-daily dimethyl fumarate regimen within the 480 mg claim?

Potentially. A total daily amount of 480 mg can correspond to two 240 mg administrations, although the ultimate analysis depends on claim construction and how the regimen is practiced.

Does an enteric-coated dimethyl fumarate capsule automatically infringe claims 7 and 8?

No. Claims 7 and 8 require enterically coated microtablets or micropellets, with claim 8 requiring that they be contained in a capsule. A conventional enteric-coated capsule without those internal structures may fall outside those dependent claims.

References

United States Patent and Trademark Office. (2020). U.S. Patent No. 10,555,993. https://patents.google.com/patent/US10555993B2/en
U.S. Food and Drug Administration. (2024). Tecfidera (dimethyl fumarate) prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book
United States District Court for the District of Delaware. (2020). Biogen International GmbH v. Mylan Pharmaceuticals Inc., related Tecfidera patent litigation records.
U.S. Food and Drug Administration. (2024). Purple Book: Database of licensed biological products. https://purplebooksearch.fda.gov/

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	10,555,993	⤷ Start Trial				METHOD OF TREATING RELAPSING FORMS OF MULTIPLE SCLEROSIS BEFORE AND AFTER ADMINISTERING AN INACTIVE VACCINE	⤷ Start Trial
Biogen	TECFIDERA	dimethyl fumarate	CAPSULE, DELAYED RELEASE;ORAL	204063-002	Mar 27, 2013	AB	RX	Yes	Yes	10,555,993	⤷ Start Trial				METHOD OF TREATING RELAPSING FORMS OF MULTIPLE SCLEROSIS BEFORE AND AFTER ADMINISTERING AN INACTIVE VACCINE	⤷ 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
Australia	2016244325	⤷ Start Trial
Australia	2018229422	⤷ Start Trial
Australia	2020213345	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 10,555,993

Which drugs does patent 10,555,993 protect, and when does it expire?

Summary for Patent: 10,555,993