US Patent 5,856,529: Scope, Claims, Expiration, and Tasimelteon Patent Landscape

US Patent 5,856,529 is the foundational compound patent covering a broad class of benzofuran-derived cyclopropyl amides, including tasimelteon. Its claims cover chemical compounds, stereoisomers, solvates, pharmaceutical compositions, and methods for treating sleep and circadian-rhythm disorders. The patent issued on January 5, 1999, and its 20-year US patent term expired in April 2017, subject to any applicable patent-term adjustment or extension. It no longer provides an enforceable US exclusion right.

The patent remains commercially important because its claim 8 appears to cover the active tasimelteon enantiomer, while claim 12 covers treatment of sleep disorders using compounds within the claim 1 genus. FDA approval of Hetlioz occurred after this patent issued, but the product’s current US protection depends on later patents, regulatory exclusivity, orphan-drug protections, and litigation positions rather than US 5,856,529.

What compounds does US Patent 5,856,529 claim?

The patent claims a genus of substituted benzofuran and dihydrobenzofuran compounds connected through a cyclopropylmethyl amide structure.

The principal structural elements are:

Claim element	Scope
Core heterocycle	Benzofuran or dihydrobenzofuran-type ring system
Ring substituents Q1 and Q2	Hydrogen or halogen in claim 1; hydrogen or iodine in claim 2
Cyclopropyl linker	A substituted cyclopropyl group attached to the heterocyclic ring
Amide substituent R1	Alkyl, cycloalkyl, haloalkyl, alkenyl, alkoxyalkyl, alkylthioalkyl, or trifluoromethylalkyl
Amide nitrogen substituent R2	Hydrogen or C1-C4 alkyl
Ring substitution	Hydrogen or lower alkyl, including methyl
Stereochemistry	Racemic and optically active compounds, with trans configurations expressly recited in the dependent claims
Pharmaceutical form	Pharmaceutically acceptable solvates
Therapeutic use	Sleep disorders and circadian-rhythm-related disorders

Claim 1 is the broadest compound claim. It covers two principal ring arrangements:

A dihydrobenzofuran-type system in which X is CH2 and Z is oxygen.
An alternative heterocyclic arrangement in which X is oxygen and Z is CH2 or CH.

The claim language supplied contains formatting and chemical-structure ambiguities, including the expression “Y is CR3, CR3R4 or (CH2)n, with n=1.” The claim must be read together with the issued patent drawings and specification to resolve the exact ring topology. The substantive scope, however, is clear: it is directed to cyclopropyl-linked benzofuran derivatives carrying an amide side chain.

Which claims cover tasimelteon?

Tasimelteon is the principal commercial compound associated with US 5,856,529. Its chemical name is generally expressed as N-[[(1R,2R)-2-(2,3-dihydrobenzofuran-4-yl)cyclopropyl]methyl]propanamide, with the precise stereochemical nomenclature depending on the naming convention used.

The relevant claim path is:

Claim	Scope relevant to tasimelteon
Claim 1	Broad genus of compounds and pharmaceutically acceptable solvates
Claim 2	Narrows Q1 and Q2 to hydrogen or iodine and m to 1
Claim 3	Narrows R1 and requires R2 to be hydrogen
Claim 4	Requires X to be CH2 and Z to be oxygen
Claim 5	Lists specific dihydrobenzofuran compounds
Claim 6	Further selects compounds from claim 5
Claim 7	Claims the trans propanamide compound without the negative optical rotation designation
Claim 8	Specifically claims the (-)-(trans) propanamide compound associated with tasimelteon
Claim 12	Treating sleep disorders with a compound of claim 1
Claim 13	Pharmaceutical composition for sleep disorders
Claim 14	Treating circadian-rhythm-related disorders
Claim 15	Pharmaceutical composition for circadian-rhythm-related disorders

Claim 8 is the most commercially significant compound claim because it expressly identifies the (-)-(trans) form of the unsubstituted dihydrobenzofuran propanamide. Claim 7 is broader as to optical rotation because it recites the trans compound without the “(-)” designation.

The claim set therefore contains three layers of protection:

A broad chemical genus in claim 1.
Narrower species and stereochemical selections in claims 5 through 11.
Therapeutic-use and composition claims in claims 12 through 15.

How broad is claim 1?

Claim 1 is substantially broader than tasimelteon. It covers a large Markush genus defined by independently variable substituents.

The R1 substituent alone permits multiple commercial and noncommercial analogues:

C1-C6 alkyl
C3-C6 cycloalkyl
C1-C3 haloalkyl
C1-C6 alkylamino
C2-C6 alkenyl
C1-C4 alkoxy-C1-C4 alkyl
C1-C4 alkylthio-C1-C4 alkyl
C1-C4 trifluoromethylalkyl

The genus also allows:

Hydrogen or halogen substitution on the aromatic ring.
Iodine substitution at one or both positions.
Methyl or other lower-alkyl substitution in the heterocyclic ring.
Hydrogen or lower-alkyl substitution at the amide nitrogen.
Alternative oxidation states and ring configurations represented by the X, Y, and Z variables.
Solvated forms of the claimed compounds.

A molecule falls within claim 1 only if all structural limitations are met. The claim is not a functional claim covering every melatonin-receptor agonist. It requires the specified benzofuran/cyclopropane/amide architecture and the defined substituent ranges.

What specific compounds are protected by claims 5 through 11?

Claims 5 through 11 divide the commercial and research compounds into dihydrobenzofuran and benzofuran series.

Dihydrobenzofuran series

Claims 5 through 8 cover compounds containing a saturated dihydrobenzofuran ring. The listed amide groups include:

Acetamide
Propanamide
Butanamide
Methoxyacetamide
Cyclopropanecarboxamide
Trifluoroacetamide
Chloroacetamide
2-Methylpropanamide

The heterocycle may be:

Unsubstituted 2,3-dihydrobenzofuran
2-Methyl-2,3-dihydrobenzofuran
2,2-Dimethyl-2,3-dihydrobenzofuran
5-Iodo or 5,7-diiodo derivatives

Claim 8 is directed to the negative trans enantiomer of the unsubstituted dihydrobenzofuran propanamide. This is the narrow claim most closely associated with tasimelteon.

Benzofuran series

Claims 9 through 11 cover the unsaturated benzofuran series. Claim 9 requires:

X = CH
Y = CR3
Z = oxygen

Claim 10 lists benzofuran and 2-methylbenzofuran derivatives with several amide substituents. Claim 11 selects a smaller group containing acetamide, propanamide, and butanamide analogues.

These claims are chemically distinct from the dihydrobenzofuran compounds in claims 5 through 8. A product with an unsaturated benzofuran ring would need to be analyzed against claims 9 through 11 rather than only against the tasimelteon-specific claim 8.

What therapeutic uses are protected?

Claims 12 through 15 are method and composition claims.

Claim	Protected subject matter
12	Administering a claim 1 compound to treat a sleep disorder
13	A pharmaceutical composition containing a claim 1 compound for sleep disorders
14	Administering a claim 1 compound to treat a circadian-rhythm-related disorder
15	A pharmaceutical composition containing a claim 1 compound for circadian-rhythm-related disorders

These claims are not limited to Non-24-hour sleep-wake disorder. The express language covers sleep disorders generally and circadian-rhythm-related disorders generally, although enforceability would depend on the claim construction, specification support, prosecution history, and the specific product labeling or conduct at issue.

A method claim would require proof of the claimed administration and therapeutic purpose. A composition claim would require the presence of a covered compound and a suitable pharmaceutical carrier. Neither claim automatically covers every formulation containing tasimelteon if the formulation does not satisfy the relevant composition limitations.

When did US Patent 5,856,529 expire?

US Patent 5,856,529 issued January 5, 1999. Its US patent term was governed by the 20-year term applicable to applications filed after June 8, 1995. The patent’s term ran from its US nonprovisional filing date and expired in April 2017, based on the published filing and term data. The patent is therefore expired and cannot presently support an infringement action for US conduct.

Event	Date
US application filing	April 1997
Patent issuance	January 5, 1999
Approximate 20-year term end	April 2017
Current status	Expired

Patent expiration eliminates the exclusionary right, but it does not erase the historical relevance of the patent. The patent remains relevant for:

Prior-art analysis.
Freedom-to-operate reviews outside the United States.
Obviousness and written-description analysis of later patents.
Determining whether later patents claim genuine improvements or merely repackaged subject matter.
Assessing the historical origin of tasimelteon’s compound protection.

What is the Orange Book status of US Patent 5,856,529?

US Patent 5,856,529 is not a current source of Orange Book exclusivity for Hetlioz because its patent term expired before the current commercial period.

The FDA approved Hetlioz capsules on January 31, 2014, for Non-24-hour sleep-wake disorder in totally blind individuals. The product contains tasimelteon, the active compound corresponding to the patent’s claim 8 species. FDA-approved labeling later included Hetlioz for nighttime sleep disturbances in Smith-Magenis syndrome. [2,3]

The Orange Book evaluates listed patents in connection with approved drug products. Patent listing does not extend an expired patent term. Any current Orange Book relevance for Hetlioz must therefore be assessed through later formulation, method-of-use, or other patents listed for the product, not through US 5,856,529 itself. [4]

Did US 5,856,529 create a Paragraph IV barrier?

No current Paragraph IV barrier arises from US 5,856,529 because the patent has expired.

Before expiration, an ANDA applicant could have challenged the patent through a Paragraph IV certification if it had been listed for the reference product. A Paragraph IV certification would assert that the patent was invalid, unenforceable, or not infringed. The patent’s expiration removes the need to maintain a Paragraph IV challenge against this patent.

Later ANDA risk may remain if other unexpired patents are listed for Hetlioz. Those patents could involve:

Treatment of Non-24-hour sleep-wake disorder.
Patient-selection criteria.
Dosing schedules.
Formulations.
Specific pharmaceutical compositions.
Other methods of using tasimelteon.

A generic applicant could receive approval for an indication not covered by an unexpired method-of-use patent through a section viii “skinny label,” although the commercial feasibility of that strategy depends on the remaining approved indications and the patent claims.

What later patents may affect generic entry for tasimelteon?

The key distinction is between the expired foundational compound patent and later patents directed to clinical use or product implementation.

Protection category	US 5,856,529	Later tasimelteon patents
Active compound	Yes	Usually no, unless a new form or derivative is claimed
Broad chemical genus	Yes	Usually no
Tasimelteon enantiomer	Yes, claim 8	Potentially narrower forms or formulations
Sleep-disorder treatment	Yes, claims 12 and 13	May include more specific disease or patient limitations
Circadian-rhythm treatment	Yes, claims 14 and 15	May include specific dosing or patient populations
Formulation	Only generic composition language	Potentially specific dosage forms or excipients
Current enforceability	No	Depends on expiration and claim validity

The main generic-entry risk is therefore not the original compound patent. It is the possibility that later method-of-use patents remain enforceable and are listed for the FDA-approved reference product.

What formulations are protected by the patent?

Claims 13 and 15 cover compositions containing a therapeutic amount of a claim 1 compound and a pharmaceutically acceptable carrier. These are broad composition claims, but they do not expressly claim:

A particular tablet coating.
A specific capsule shell.
A defined dissolution profile.
A controlled-release matrix.
A particular excipient combination.
A specific particle-size distribution.
A particular polymorph.
A defined bioavailability profile.

The patent’s composition claims can cover conventional dosage forms if the formulation contains a covered compound and is useful for the stated disorder. They are less likely to block a later formulation patent that requires narrowly defined excipients, release characteristics, or solid-state properties, although the later formulation could still contain a compound within claim 1.

Because US 5,856,529 is expired, its composition claims do not create a current manufacturing barrier in the United States.

Does the patent cover biosimilar risk?

No. Tasimelteon is a small-molecule drug, not a biologic. Biosimilar provisions under the Public Health Service Act do not apply. The relevant competitive pathway is an abbreviated new drug application, or ANDA, under section 505(j) of the Federal Food, Drug, and Cosmetic Act.

The competitive risks are therefore:

Generic tasimelteon capsules.
Authorized-generic strategies.
Formulation workarounds.
Label carve-outs for patented indications.
Patent litigation over later method-of-use patents.
Regulatory exclusivity or orphan-drug restrictions.

Which companies are challenging tasimelteon exclusivity?

The supplied information does not establish a specific current ANDA filer, Paragraph IV case, or settlement agreement involving US 5,856,529. No company can be identified as a current challenger to this expired patent based solely on the claim text.

Publicly reported litigation involving later Vanda patents and tasimelteon-related indications must be separated from the original patent. A later patent litigation outcome does not revive US 5,856,529 or extend its term.

What licensing deals affect the patent estate?

US 5,856,529 is a patent document, not a license agreement. Its face does not establish the commercial allocation of rights, royalty obligations, or sublicensing arrangements.

Commercial control of Hetlioz has been associated with Vanda Pharmaceuticals, which developed and commercialized tasimelteon in the United States. Ownership, licensing, and enforcement rights must be determined from assignment records, SEC filings, and executed agreements rather than inferred from the patent claims. [5]

The practical licensing issue is whether a party seeking to commercialize tasimelteon needs rights under later patents, trademarks, know-how, regulatory data, or supply agreements. It does not need a license under US 5,856,529 after the patent’s expiration.

How strong is the patent estate for tasimelteon?

The original patent estate was strong during its term because it combined:

A broad genus claim.
Narrow species claims.
A stereochemically specific tasimelteon claim.
Sleep-disorder method claims.
Circadian-rhythm method claims.
Composition claims.

Its current strength is limited to historical and analytical value. The patent has no remaining US exclusionary power.

Factor	Assessment
Original compound coverage	Broad
Tasimelteon-specific coverage	Strong, particularly claim 8
Stereochemical coverage	Expressly included
Therapeutic-use coverage	Broadly drafted
Formulation specificity	Limited
Current US enforceability	None
Generic-entry impact today	None from this patent
Prior-art significance	High
Need to review later patents	High

What geographic coverage does US 5,856,529 provide?

The patent provides rights only in the United States. It does not establish protection in Europe, Japan, Canada, or other jurisdictions.

The corresponding international landscape would require review of:

The PCT application and national-phase filings.
European Patent Office family members.
Japanese and Canadian counterpart patents.
Patent-term calculations in each jurisdiction.
National validation and lapse records.
Any supplementary protection certificate or equivalent extension.

The US expiration date cannot be transferred mechanically to foreign family members. Foreign patents may have different filing dates, prosecution histories, term adjustments, maintenance status, or supplementary protection rights.

What manufacturing and intellectual-property barriers remain?

US 5,856,529 no longer creates a manufacturing barrier for tasimelteon in the United States. A manufacturer may still face other barriers:

Active-pharmaceutical-ingredient process patents.
Solid-state or polymorph patents.
Formulation patents.
Method-of-use patents.
Regulatory exclusivity.
Trade secrets covering synthesis, purification, or scale-up.
Drug-master-file controls.
FDA requirements for bioequivalence and product quality.
Trademark and labeling restrictions.

The patent itself claims compounds, uses, and general compositions. It does not claim a detailed manufacturing process in the claims provided. Process freedom to operate must therefore be reviewed separately against the patent family and later process patents.

Key Takeaways

US Patent 5,856,529 is the foundational tasimelteon compound patent.
Claim 1 covers a broad genus of benzofuran and dihydrobenzofuran cyclopropyl amides.
Claims 5 through 11 narrow the genus to identified species, stereoisomers, and benzofuran analogues.
Claim 8 most directly covers the (-)-(trans) tasimelteon compound.
Claims 12 through 15 cover sleep-disorder and circadian-rhythm treatment methods and compositions.
The US patent term expired in April 2017.
The patent currently creates no US patent barrier to generic tasimelteon entry.
Tasimelteon is a small molecule, so biosimilar analysis is inapplicable.
Current market-exclusivity analysis must focus on later patents, FDA exclusivity, orphan-drug protections, formulation rights, and any pending ANDA litigation.
The patent’s international family must be analyzed separately by jurisdiction.

FAQs About US Patent 5,856,529 and Tasimelteon

Is tasimelteon still protected by US Patent 5,856,529?

No. The patent’s US term expired in April 2017. Later patents or regulatory protections may still affect commercialization.

Does claim 8 cover the active ingredient in Hetlioz?

Yes. Claim 8 expressly identifies the negative trans propanamide compound corresponding to tasimelteon.

Can a generic company manufacture tasimelteon after the patent expired?

The expired patent does not prevent manufacture. The company must still satisfy FDA approval requirements and clear any later unexpired patents, regulatory exclusivity, formulation rights, and trade-secret issues.

Does US 5,856,529 cover ramelteon?

No conclusion follows from the claim text that it covers ramelteon. The claims are directed to a specific benzofuran/cyclopropylmethyl amide architecture associated with tasimelteon.

Are the sleep-disorder claims limited to Non-24-hour sleep-wake disorder?

No. Claims 12 and 13 refer broadly to sleep disorders. Claims 14 and 15 refer broadly to circadian-rhythm-related disorders. Their current enforceability is nevertheless eliminated by the patent’s expiration.

References

United States Patent and Trademark Office. (1999). U.S. Patent No. 5,856,529, Benzofuran derivatives, processes for their preparation and pharmaceutical compositions containing them.
U.S. Food and Drug Administration. (2014). Hetlioz (tasimelteon) prescribing information.
U.S. Food and Drug Administration. (2020). FDA approves Hetlioz for nighttime sleep disturbances in Smith-Magenis syndrome.
U.S. Food and Drug Administration. (2025). Approved drug products with therapeutic equivalence evaluations, Orange Book.
Vanda Pharmaceuticals Inc. (2024). Annual report on Form 10-K.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	010346	⤷ Start Trial
Austria	281833	⤷ Start Trial
Australia	5598598	⤷ Start Trial
Australia	719994	⤷ Start Trial
Brazil	9713690	⤷ Start Trial
Canada	2274183	⤷ Start Trial
China	1152679	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,856,529

Summary for Patent: 5,856,529