Details for Patent: 10,149,829

Which drugs does patent 10,149,829 protect, and when does it expire?

Patent 10,149,829 protects HETLIOZ and HETLIOZ LQ and is included in two NDAs.

This patent has one hundred and fifty-three patent family members in twenty-three countries.

Summary for Patent: 10,149,829

Title:	Treatment of circadian rhythm disorders
Abstract:	Embodiments of the invention relate to the use of a melatonin agonist in the treatment of free running circadian rhythms in patients, including light perception impaired patients, e.g., blind patients, and to methods of measuring circadian rhythm.
Inventor(s):	Marlene Michelle Dressman, John Joseph Feeney, Louis William Licamele, Mihael H. Polymeropoulos
Assignee:	Vanda Pharmaceuticals Inc
Application Number:	US15/382,526
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,149,829
Patent Claim Types: see list of patent claims	Use;

US Drug Patent 10,149,829: Claims, Scope, Expiration, Orange Book Status, and Tasimelteon Patent Landscape

US Patent No. 10,149,829 protects a treatment sequence for administering tasimelteon to patients receiving strong CYP1A2 inhibitors. The claims focus on reducing or discontinuing fluvoxamine, ciprofloxacin, or verapamil before administering tasimelteon, particularly 20 mg once daily for Non-24-Hour Sleep-Wake Disorder. The patent is a method-of-treatment patent, not a composition, formulation, or manufacturing patent.

The commercial significance is concentrated in Hetlioz, Vanda Pharmaceuticals’ tasimelteon product. A generic applicant seeking approval for tasimelteon could face infringement risk if its proposed labeling recommends use in patients who discontinue or reduce one of the named CYP1A2 inhibitors before receiving tasimelteon.

What does US Patent 10,149,829 protect?

US 10,149,829 protects a clinical management protocol involving two sequential steps:

1. Reduce or discontinue treatment with a strong CYP1A2 inhibitor.
2. Treat the patient with tasimelteon for a circadian rhythm or sleep disorder.

The independent claims cover two related pathways:

Claim	Core protected subject matter
Claim 1	Reduce the dose of fluvoxamine, ciprofloxacin, or verapamil, then administer tasimelteon
Claim 13	Discontinue fluvoxamine, ciprofloxacin, or verapamil, then administer 20 mg tasimelteon once daily

The claims are narrower than a general patent on tasimelteon-drug interactions. They require the specific inhibitors identified in the claims and require a treatment sequence involving dose reduction or discontinuation before tasimelteon administration.

The patent does not broadly claim:

• Tasimelteon as a chemical compound
• All CYP1A2 inhibitors
• All drug-drug interactions involving tasimelteon
• A tasimelteon formulation
• A tablet, capsule, or controlled-release dosage form
• Manufacturing tasimelteon
• Treatment of every circadian rhythm disorder without the inhibitor-management step

How do the independent claims differ?

Claim 1: Dose reduction followed by tasimelteon

Claim 1 requires a patient who is being treated with a strong CYP1A2 inhibitor selected from:

• Fluvoxamine
• Ciprofloxacin
• Verapamil

The claimed method requires reducing the inhibitor dose and then treating the patient with tasimelteon. It also recites that tasimelteon exposure is reduced.

The claim is directed to an interaction-management strategy. The apparent clinical rationale is that strong CYP1A2 inhibition can increase tasimelteon exposure. Reducing the inhibitor treatment before administering tasimelteon is intended to reduce that interaction.

Claim 13: Discontinuation followed by 20 mg tasimelteon

Claim 13 is more specific in dosage but structurally simpler. It requires:

• Discontinuing treatment with one of the three listed inhibitors; and
• Treating the patient with 20 mg tasimelteon once daily.

Unlike claim 1, claim 13 does not expressly recite reduced tasimelteon exposure. It also does not require the patient to have light-perception impairment or Non-24-Hour Sleep-Wake Disorder, although claim 14 adds the Non-24 limitation.

What dependent claims add to the patent scope?

The dependent claims divide the patent into inhibitor-specific and disease-specific embodiments.

Claims	Added limitation
2, 8	Fluvoxamine
3, 14	Non-24-Hour Sleep-Wake Disorder
4	Patient is light perception impaired
5	20 mg tasimelteon once daily before target bedtime
6	Entrainment to a 24-hour cycle with 7 to 9 hours of sleep
7	Discontinuation of the strong CYP1A2 inhibitor
9, 10	Ciprofloxacin, with discontinuation in claim 10
11, 12	Verapamil, with discontinuation in claim 12

The narrowest commercially important embodiment is the combination of claims 2, 3, 4, and 5:

• Fluvoxamine treatment is reduced or discontinued.
• The patient has Non-24-Hour Sleep-Wake Disorder.
• The patient is light-perception impaired.
• Tasimelteon is administered orally at 20 mg once daily before target bedtime.

Claims 13 and 14 create a separate route to protection for 20 mg once-daily tasimelteon following discontinuation of one of the named inhibitors, with claim 14 limiting the disorder to Non-24.

What is the likely claim construction for US 10,149,829?

The principal claim-construction issues concern sequencing, patient treatment status, inhibitor strength, and the meaning of reduced tasimelteon exposure.

“Being treated with” a strong CYP1A2 inhibitor

The patient must be receiving treatment with fluvoxamine, ciprofloxacin, or verapamil before the claimed reduction or discontinuation. A patient who has never received one of these agents would not ordinarily satisfy this limitation.

The claim language may also support disputes over whether a patient who stopped the inhibitor before the relevant treatment decision remains a patient “being treated with” the inhibitor. The answer would depend on the timing of the treatment steps and the evidence of continued pharmacologic or clinical treatment.

“Reducing the dose”

Claim 1 requires dose reduction, not necessarily complete cessation. A prescribing change from a higher dose to a lower dose could satisfy this limitation if the change is made as part of the claimed treatment method.

Claims 7, 8, 10, and 12 separately address discontinuation. This distinction is important. A generic label that recommends stopping the inhibitor may implicate the discontinuation claims even if it does not recommend a partial dose reduction.

“Then treating”

The claims require an order of operations. The inhibitor dose must be reduced or treatment must be discontinued before tasimelteon is administered.

A label that merely warns against concomitant use may not, by itself, practice the claimed method. Infringement risk increases if the label instructs prescribers to stop or reduce the named inhibitor and subsequently administer tasimelteon.

“Strong CYP1A2 inhibitor”

The claims identify the compounds by name. The list is closed because it uses “selected from a group consisting of.” Other CYP1A2 inhibitors, including an inhibitor not listed in the claims, would not ordinarily satisfy the express Markush limitation.

The inclusion of verapamil is potentially important because classification of verapamil as a strong CYP1A2 inhibitor may be contested based on regulatory labeling, pharmacology references, or the patent’s intrinsic record. The claim does not leave the selection open to every drug that a later source might classify as a CYP1A2 inhibitor.

“Exposure to tasimelteon ... is reduced”

This limitation appears in claim 1 and may create a separate proof requirement. A plaintiff would need to establish that the claimed intervention produces reduced tasimelteon exposure in the relevant patient or treatment context.

Claims 7 through 12 and claim 13 do not repeat this exposure limitation in the same form. Those claims may therefore provide broader enforcement positions for discontinuation followed by tasimelteon administration.

What disorders and patient populations are covered?

The claims cover treatment of a “circadian rhythm disorder or ... sleep disorder.” The dependent claims narrow the principal disease population to Non-24-Hour Sleep-Wake Disorder.

Claim 4 further limits the patient to a person who is light perception impaired. This aligns with the principal FDA-approved use of Hetlioz in totally blind adults with Non-24, although the patent claims are not limited entirely to the FDA-approved population.

The patient population can be mapped as follows:

Population	Covered by
Any patient with a circadian rhythm disorder or sleep disorder meeting the inhibitor and sequencing limitations	Claims 1 and 13
Patient with Non-24	Claims 3 and 14
Light perception-impaired patient with Non-24	Claim 4
Patient receiving 20 mg once daily	Claims 5 and 13
Patient achieving a 24-hour sleep-wake cycle	Claim 6

Claim 6 is an outcome-based limitation. It requires entrainment to a 24-hour cycle and awakening near a target wake time after approximately 7 to 9 hours of sleep. That limitation may be difficult to prove in litigation because it requires patient-specific clinical evidence rather than only proof of prescribing instructions.

What FDA regulatory status does the patent relate to?

Tasimelteon is marketed in the United States as Hetlioz. The FDA approved Hetlioz for:

• Non-24-Hour Sleep-Wake Disorder in totally blind individuals; and
• Certain nighttime sleep disturbances associated with Smith-Magenis syndrome, following a later supplemental approval.

The FDA prescribing information warns against use with strong CYP1A2 inhibitors because those agents can increase tasimelteon exposure. The label identifies fluvoxamine as a strong CYP1A2 inhibitor and advises avoidance of coadministration. The interaction information is directly relevant to the method claims in US 10,149,829.[1]

The patent claims extend beyond the literal approved-label indication in several respects. Claims 1 and 13 refer generally to a circadian rhythm disorder or sleep disorder, while claims 3 and 14 narrow the method to Non-24. The broader disease language could support enforcement against uses outside the narrowest FDA indication if the remaining claim elements are practiced.

What patents protect Hetlioz and tasimelteon?

Tasimelteon has a layered patent estate involving compound, formulation, therapeutic-use, and drug-interaction subject matter. US 10,149,829 is primarily an interaction-management patent.

The relevant categories are:

Patent category	Typical protected subject matter	Relevance to US 10,149,829
Compound patents	Tasimelteon molecule and related chemical entities	Separate from the asserted method
Use patents	Treatment of Non-24 and circadian rhythm disorders	Adjacent protection
Formulation patents	Oral dosage forms and product characteristics	Not claimed in the provided claims
Interaction patents	Managing CYP1A2 inhibition before tasimelteon	Core subject of US 10,149,829
Manufacturing patents	Synthesis, intermediates, purification, and processes	Separate technical barrier

The Orange Book must be reviewed by product and patent number because FDA listing status can change through delisting, patent-term adjustments, pediatric extensions, court decisions, or new ANDA certifications. A patent’s issuance alone does not establish that it is listed for a particular NDA.

What is the patent expiration date?

US 10,149,829 is a post-1995 U.S. patent and is generally subject to a term of 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and other statutory adjustments.[2]

The public patent record identifies US 10,149,829 as a Vanda Pharmaceuticals patent directed to methods of treating circadian rhythm and sleep disorders. The exact enforceable expiration date should be taken from the USPTO Patent Center record and the applicable Orange Book listing because the term depends on the patent’s continuity data and any term adjustment.

For commercial planning, the patent should be treated as a long-dated method-of-use barrier extending into the 2030s unless a court invalidates or limits the claims. The patent’s practical value is therefore tied less to the basic availability of tasimelteon and more to whether an ANDA label directs the specific inhibitor-discontinuation sequence.

Is US 10,149,829 an Orange Book patent?

The patent is associated with the Hetlioz patent estate and is relevant to Orange Book analysis. Orange Book listing must be assessed against the specific NDA and the patent’s claim scope. FDA listing generally concerns patents claiming the drug substance, drug product, or an approved method of use under the Hatch-Waxman framework.[3]

For this patent, the method-of-use question is central. The claims recite treatment of circadian rhythm or sleep disorders using tasimelteon after management of named CYP1A2 inhibitors. If listed for Hetlioz, an ANDA applicant could address the patent through:

• Paragraph IV certification;
• A section viii statement carving out the patented method, if the FDA-approved labeling permits a lawful carve-out; or
• A paragraph III certification if the applicant accepts delayed approval until patent expiration.

A section viii strategy would be difficult if the proposed label necessarily includes the inhibitor-management instructions. It would be more viable if the generic applicant could obtain approval without instructing use in the patented patient population or without recommending dose reduction or discontinuation followed by tasimelteon.

Which companies are likely to challenge the patent?

The most relevant challengers are generic pharmaceutical companies seeking approval for tasimelteon. A biosimilar pathway is not applicable because tasimelteon is a chemically synthesized small molecule, not a biologic subject to the abbreviated biosimilar pathway.

Potential challengers would typically be:

• ANDA applicants seeking to market generic tasimelteon;
• Companies developing 505(b)(2) products containing tasimelteon;
• Licensees or commercial partners with rights to distribute tasimelteon products.

The public record should be checked for individual ANDA filers, Paragraph IV notices, and district-court complaints. A Paragraph IV notice is not itself a final invalidity determination. It creates a potential 30-month stay if the NDA holder files a timely patent-infringement action under the Hatch-Waxman framework.[4]

What Paragraph IV risks arise from a generic tasimelteon label?

A generic applicant faces several possible infringement theories.

Label-induced infringement

The highest-risk scenario is a label that tells physicians to:

• Stop fluvoxamine, ciprofloxacin, or verapamil;
• Reduce the dose of one of those agents; and
• Begin tasimelteon at 20 mg once daily.

That label could directly encourage performance of claims 1, 7 through 13, or 14, depending on the indication and dosing language.

Direct infringement by prescribing

A physician or healthcare provider could directly practice the method by changing the inhibitor regimen and administering tasimelteon. The generic manufacturer’s exposure would generally depend on whether its labeling actively encourages that conduct.

Section viii carve-out

A generic applicant may attempt to omit the patented method from its labeling. The viability of this approach depends on whether the remaining label can accurately describe approved uses without including the protected interaction-management instructions.

A carve-out is less effective when the FDA-approved labeling itself contains the same instructions needed to use tasimelteon safely with patients receiving CYP1A2 inhibitors.

Product sale without method instructions

Selling tasimelteon tablets without an express instruction to discontinue or reduce a named CYP1A2 inhibitor may reduce induced-infringement risk. It would not eliminate all litigation risk if marketing materials, physician communications, patient support programs, or other conduct promote the patented method.

How strong is the patent estate for US 10,149,829?

The patent has meaningful commercial leverage but a narrower technical scope than a compound or formulation patent.

Strengths

• It covers a clinically specific safety-management sequence.
• It names three inhibitors directly.
• Claim 13 captures discontinuation followed by 20 mg tasimelteon once daily.
• Claims 3, 4, and 14 align with an important commercial patient population.
• The FDA labeling provides regulatory context supporting the interaction rationale.

Vulnerabilities

• The claims are method claims and require proof of patient treatment conduct.
• The “strong CYP1A2 inhibitor” classification may create evidentiary disputes, especially for verapamil.
• Claim 1’s reduced-exposure limitation may require pharmacokinetic proof.
• Prior-art references concerning CYP1A2-mediated tasimelteon interactions could support obviousness challenges.
• A generic label may avoid infringement through a carefully drafted section viii carve-out.
• The broad phrase “circadian rhythm disorder or sleep disorder” may face written-description, enablement, or construction challenges if the specification does not support the full breadth.

The strongest claims for enforcement are likely claims 8, 10, 12, and 13 because they focus on discontinuation and do not depend as heavily on proving a measured reduction in tasimelteon exposure. The narrowest claims, especially claims 4 and 6, may be easier to design around but can provide fallback positions in litigation.

What manufacturing and formulation barriers remain?

US 10,149,829 does not create a manufacturing barrier. It does not claim:

• A synthesis route;
• A particular intermediate;
• A purification process;
• A crystalline form;
• A salt or polymorph;
• An excipient system;
• A tablet coating; or
• A controlled-release profile.

A generic manufacturer could potentially reproduce tasimelteon using a noninfringing process and formulate an equivalent immediate-release product. The principal barrier created by this patent is regulatory and labeling-related rather than manufacturing-related.

How does US 10,149,829 compare with competing sleep drugs?

Product	Active ingredient	Primary mechanism or use	Relationship to US 10,149,829
Hetlioz	Tasimelteon	Melatonin MT1/MT2 receptor agonist; Non-24	Directly implicated
Rozerem	Ramelteon	Melatonin receptor agonist for insomnia	Not covered by the claims
Melatonin products	Melatonin	Circadian and sleep regulation	Not covered
Belsomra	Suvorexant	Orexin receptor antagonist	Not covered
Quviviq	Daridorexant	Orexin receptor antagonist	Not covered
Dayvigo	Lemborexant	Orexin receptor antagonist	Not covered

The patent does not prevent competition from non-tasimelteon sleep products. Its commercial impact is concentrated on generic or alternative tasimelteon products.

Key Takeaways

• US 10,149,829 is a method-of-treatment patent covering tasimelteon administration after reducing or discontinuing fluvoxamine, ciprofloxacin, or verapamil.
• Claim 13 is commercially important because it covers discontinuation followed by 20 mg tasimelteon once daily.
• Claims 3, 4, and 14 target Non-24, including light-perception-impaired patients.
• The patent does not claim tasimelteon itself, a formulation, or a manufacturing process.
• Generic tasimelteon applicants face Paragraph IV and induced-infringement risk if their labeling recommends the claimed inhibitor-management sequence.
• A section viii carve-out may be possible only if the generic label can omit the patented method while preserving an approvable FDA use.
• No biosimilar pathway applies because tasimelteon is a small-molecule drug.
• The estate’s main weakness is its dependence on proof of a patient-specific treatment sequence and, for claim 1, reduced tasimelteon exposure.
• The patent should be analyzed together with the broader Hetlioz compound, use, formulation, and Orange Book-listed patent estate.

FAQs About US Patent 10,149,829

Does US 10,149,829 cover all tasimelteon use?

No. It covers specified treatment methods involving fluvoxamine, ciprofloxacin, or verapamil and a required dose-reduction or discontinuation sequence.

Can a generic company sell tasimelteon before this patent expires?

Potentially. The outcome depends on the generic label, Orange Book status, Paragraph IV certification, litigation, and whether the proposed use can be carved out without inducing infringement.

Does the patent cover coadministration of tasimelteon with fluvoxamine?

The claims are directed primarily to reducing or discontinuing the inhibitor before tasimelteon treatment. They do not broadly authorize or claim ordinary concomitant administration.

Is verapamil treated as a CYP1A2 inhibitor under the patent?

Verapamil is expressly listed in claims 1, 9, 11, and 13. Its classification and the evidentiary basis for calling it a strong CYP1A2 inhibitor could be disputed in claim construction or validity litigation.

Does the patent cover tasimelteon tablets manufactured outside the United States?

Not by manufacture alone. The patent claims treatment methods. Liability would depend on conduct involving the patented method, including U.S. marketing, labeling, promotion, or performance of the treatment steps.

References

1. U.S. Food and Drug Administration. (2024). Hetlioz (tasimelteon) prescribing information. FDA.

2. U.S. Patent and Trademark Office. (n.d.). Patent term adjustment and patent term calculation resources. USPTO.

3. U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.

4. U.S. Code. (2024). 21 U.S.C. § 355(j): Abbreviated applications for new drugs.

5. U.S. Patent No. 10,149,829. (2018). Methods of treating circadian rhythm disorders. United States Patent and Trademark Office.

Drugs Protected by US Patent 10,149,829

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Vanda Pharms Inc	HETLIOZ	tasimelteon	CAPSULE;ORAL	205677-001	Jan 31, 2014	AB	RX	Yes	Yes	10,149,829					TREATMENT OF NON-24 HOUR SLEEP-WAKE DISORDER BY AVOIDING THE USE OF TASIMELTEON IN COMBINATION WITH CYP1A2 STRONG INHIBITORS
Vanda Pharms Inc	HETLIOZ	tasimelteon	CAPSULE;ORAL	205677-001	Jan 31, 2014	AB	RX	Yes	Yes	10,149,829					TREATMENT OF NIGHTTIME SLEEP DISTURBANCES IN SMITH-MAGENIS SYNDROME NON-24 HOUR SLEEP-WAKE DISORDER BY AVOIDING THE USE OF TASIMELTEON IN COMBINATION WITH CYP1A2 STRONG INHIBITORS
Vanda Pharms Inc	HETLIOZ LQ	tasimelteon	SUSPENSION;ORAL	214517-001	Dec 1, 2020		RX	Yes	Yes	10,149,829					TREATMENT OF NIGHTTIME SLEEP DISTURBANCES IN SMITH-MAGENIS SYNDROME NON-24 HOUR SLEEP-WAKE DISORDER BY AVOIDING THE USE OF TASIMELTEON IN COMBINATION WITH CYP1A2 STRONG INHIBITORS

International Family Members for US Patent 10,149,829

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2013211878
Australia	2013211880
Australia	2013361459
Australia	2015206797
Australia	2016204178
Australia	2016204217