United States Patent 6,034,239: Ramelteon Claims, Scope, Expiration and Patent Landscape

U.S. Patent No. 6,034,239 is the foundational composition patent for ramelteon, marketed by Takeda as Rozerem. Its broad claims cover melatonin-receptor-binding fused oxygen-containing heterocycles, while claim 25 specifically covers the ramelteon molecule. The patent also includes process, intermediate, pharmaceutical-composition and therapeutic-use claims. The patent issued on March 7, 2000, and its listed U.S. patent term expired on September 8, 2017, including reported patent-term adjustment. It is no longer an enforceable barrier to generic ramelteon entry. [1]-[4]

What drug and active ingredient does U.S. Patent 6,034,239 protect?

The patent protects ramelteon, chemically identified as:

(S)-N-[2-(1,6,7,8-tetrahydro-2H-indeno[5,4-b]furan-8-yl)ethyl]propionamide

Ramelteon is a melatonin MT1 and MT2 receptor agonist approved by the FDA for the treatment of insomnia characterized by difficulty with sleep onset. Takeda developed and commercialized the drug as Rozerem. The FDA approved Rozerem on July 22, 2005, under NDA 21-782. [3]

Claim 25 expressly recites ramelteon. This is the most commercially significant claim in the patent because it covers the active pharmaceutical ingredient itself rather than only a formulation, manufacturing route or method of use.

Item	Information
Patent	U.S. 6,034,239
Title	Indane derivatives
Patent holder at commercialization	Takeda
Inventive subject	Melatonin receptor ligands
Commercial product	Rozerem
Active ingredient	Ramelteon
FDA approval	July 22, 2005
NDA	21-782
Issue date	March 7, 2000
Reported expiration	September 8, 2017
Principal commercial claim	Claim 25
Current enforceability	Expired

What is the scope of independent claim 1?

Claim 1 is a broad Markush composition claim. It covers a large genus of compounds having a fused ring system that includes:

An optionally substituted oxygen-containing 5- to 7-membered heterocyclic ring, designated ring A;
An optionally substituted benzene ring, designated ring B;
A linker of variable length, with m equal to 1 through 4;
Multiple possible heteroatoms or carbon units in the core, including CHR4, NR4, O and S;
Variable substituents R1, R2, R3 and R4;
Single- or double-bond alternatives; and
Pharmaceutically acceptable salts.

The claim is directed to compounds capable of encompassing ramelteon and related melatonin-receptor ligands. Its breadth comes primarily from the definitions of R1, R2, R3, R4, ring A and ring B.

Claim 1 does not require the compound to be ramelteon, to bind a particular melatonin receptor subtype, or to be administered for insomnia. It is principally a chemical-composition claim.

How broad are the Markush substituent definitions?

Claim 2 substantially expands the genus by defining the permitted substituents in detail. R1, R2 and R3 may include:

Alkyl, alkenyl, alkynyl, cycloalkyl and aryl groups;
Substituted amino groups;
Nitrogen-, oxygen- or sulfur-containing heterocycles;
Halogen, hydroxy, nitro, cyano and alkoxy substituents;
Carbonyl, carbamoyl, carboxyl and ester groups;
Sulfonyl, sulfinyl, sulfamoyl and phosphono groups; and
Additional aryl, aralkyl and heterocyclic substituents.

These definitions create a potentially very large chemical space. The practical scope is narrower than the text alone suggests because an accused compound must satisfy the complete structural arrangement, ring fusion pattern, substitution limits and bond configurations required by claim 1.

Which claims specifically cover ramelteon?

Claim 25 recites ramelteon by its structural chemical name. The claim is a direct compound claim and historically provided the strongest basis for blocking unauthorized manufacture, sale or importation of ramelteon in the United States.

Claims 1, 4, 5-14, 18-21 and 23 may also encompass ramelteon through broader or narrower structural definitions. These claims operate as overlapping layers:

Claim group	Subject matter	Relationship to ramelteon
1	Broad compound genus	Encompasses ramelteon
2	Detailed substituent definitions	Narrows claim 1
3-4	Alternative ring and core structures	May encompass related compounds
5-21	Substituent and ring limitations	Creates narrower subgenuses
23-24	More defined indane/furan-type structures	More closely approaches ramelteon
25	Named ramelteon species	Direct protection
26-29	Specific analogs	Covers related compounds
30-31	Manufacturing processes	Protects selected synthetic routes
32-33	Intermediates and related compounds	Supports manufacturing and chemical development
34-35	Pharmaceutical compositions	Covers compositions containing claimed compounds
36-41	Therapeutic use and formulation processes	Covers selected medical and manufacturing activities

Claims 26 through 29 cover related amide compounds, including indole and phenyl-substituted analogs. They do not automatically cover ramelteon unless the accused compound falls within the claim language as construed.

What formulations are protected by U.S. Patent 6,034,239?

The patent does not appear to contain a detailed formulation platform comparable to a modern extended-release, multiparticulate or controlled-release patent. Claim 34 covers a pharmaceutical composition containing a compound of claim 1 or a pharmaceutically acceptable salt and a pharmaceutically acceptable carrier.

That language is broad but functional only at a basic composition level. It can cover a conventional dosage form containing ramelteon, such as a tablet or capsule, if the formulation includes the claimed compound and a pharmaceutically acceptable carrier.

The patent does not, based on the claims provided, require:

A particular tablet coating;
A specific dissolution profile;
A defined particle-size distribution;
A controlled-release mechanism;
A particular excipient combination;
A specified dosage strength; or
A proprietary manufacturing parameter.

A generic manufacturer could therefore avoid any still-active formulation patent by using a noninfringing formulation. Because the patent itself expired, its formulation claims no longer create a current U.S. infringement risk.

What manufacturing methods and intermediates are claimed?

Claims 30 and 31 cover process routes.

Claim 30 covers acylation of an amino-containing intermediate with R1COOH or a reactive derivative, followed where necessary by reduction or alkylation. This claim is directed to producing compounds within claim 1.

Claim 31 covers cyclization of a precursor bearing a leaving group to produce compounds within claim 4, with optional reduction.

Claims 32 and 33 cover chemical intermediates or related core structures. These claims could have supported a manufacturing infringement theory if a third party used a claimed intermediate or route, even where the final product claim presented a more difficult enforcement issue.

The process claims are narrower than claim 25 in one important respect. A manufacturer could infringe a product claim by making ramelteon through any process. A process claim generally requires proof that the accused manufacturer used the claimed steps or an equivalent process. Process claims therefore provide less universal coverage than a direct active-ingredient claim.

What method-of-use claims cover melatonin-related treatment?

Claims 36 through 40 cover administering the claimed composition to treat or prevent diseases related to melatonin activity. The stated uses include:

Regulation of circadian rhythm;
Regulation of sleep-wake rhythm;
Treatment of time-zone change syndrome; and
Treatment or prevention of sleep disorders.

Claim 35 requires that the compound or salt have binding affinity for a melatonin receptor. Claim 41 covers manufacturing a pharmaceutical composition by selecting the compound or salt and mixing it with a pharmaceutically acceptable carrier.

These claims are narrower than the compound claims because they require a therapeutic method or manufacturing step. Their commercial significance was secondary to claim 25 because a generic product containing ramelteon could be blocked by the active-ingredient claim without proving a method-of-use case.

When did U.S. Patent 6,034,239 expire?

The patent issued on March 7, 2000. Its reported expiration date was September 8, 2017, reflecting patent-term adjustment. The base term was tied to the relevant U.S. filing framework rather than the Japanese priority date. Foreign priority generally does not independently shorten or extend the 20-year U.S. patent term. [1], [2]

Milestone	Date
Earliest reported priority	March 8, 1996
U.S./PCT filing period	March 7, 1997
Patent issued	March 7, 2000
FDA approval of Rozerem	July 22, 2005
Reported patent expiration	September 8, 2017

Patent term extension under 35 U.S.C. § 156 is distinct from patent-term adjustment under 35 U.S.C. § 154. The commercially reported September 8, 2017 date is the relevant expiration date for this patent. [1], [2]

What was the Orange Book status of ramelteon?

The FDA Orange Book historically listed U.S. Patent 6,034,239 for Rozerem. The listing identified a composition-of-matter patent associated with ramelteon. The patent has expired, so it no longer supports an active Orange Book exclusivity position or a current statutory stay against an ANDA applicant. [3], [4]

FDA exclusivity and patent protection are separate:

Patent protection arises from the enforceable patent claims.
New chemical entity exclusivity arose from the NDA approval and lasted for five years, subject to applicable statutory rules.
Orange Book listing provided notice to generic applicants.
Expiration removed the patent-based barrier even though the product could remain commercially marketed.

The patent’s expiration also eliminates the practical significance of a Paragraph IV certification directed solely to U.S. 6,034,239.

Were there Paragraph IV challenges or generic-entry litigation?

A Paragraph IV certification is relevant when an ANDA applicant asserts that a listed patent is invalid, unenforceable or will not be infringed. Once U.S. 6,034,239 expired, a generic applicant no longer needed to rely on Paragraph IV litigation to obtain market entry against that patent.

The supplied record does not establish a particular ANDA filer, complaint number, settlement agreement or litigation outcome involving this patent. A definitive litigation chronology cannot be stated from the patent text alone.

The commercial result is clear: any historical litigation or settlement concerning U.S. 6,034,239 has no continuing blocking effect from the expired patent. Current generic risk depends on other active patents, regulatory requirements, trade-secret manufacturing issues and product-specific FDA filings.

How strong was the patent estate for ramelteon?

Historically, the estate was strong because it included a direct composition claim to ramelteon. A valid composition-of-matter claim generally provides broader enforcement leverage than a method-of-use or formulation claim.

Estate component	Historical strength	Current status
Claim 25, ramelteon molecule	High if valid and infringed	Expired
Claim 1 Markush genus	Broad but validity-sensitive	Expired
Process claims 30-31	Route-dependent	Expired
Intermediate claims 32-33	Manufacturing-dependent	Expired
Composition claim 34	Broad conventional formulation coverage	Expired
Sleep and circadian-use claims 36-40	Narrower, use-dependent	Expired

Potential historical validity issues would have included written description, enablement, anticipation, obviousness, indefiniteness and double patenting. The breadth of claim 1 could have created greater validity exposure than claim 25, particularly if the specification did not adequately support or enable the full Markush genus. Claim 25 had a more defined chemical identity and therefore a more direct infringement analysis.

Expiration now makes those validity questions commercially immaterial for prospective U.S. enforcement.

How does U.S. 6,034,239 compare with typical follow-on patents?

The patent is a first-generation active-ingredient patent. Follow-on patents for drugs such as ramelteon commonly target narrower subject matter:

Patent type	Typical protected subject matter	Relative commercial effect
Composition of matter	Active molecule or chemical genus	Highest
Salt or polymorph	Solid-state form or salt	Potentially high
Formulation	Tablet, capsule, release profile or excipients	Product-specific
Method of use	Insomnia, circadian disorders or dosing regimen	Narrower
Manufacturing	Synthetic route or purification	Route-specific
Intermediate	Key precursor	Manufacturing-specific

The provided patent is strongest as a composition patent and less important as a formulation patent. Any current freedom-to-operate review for ramelteon would need to separately assess later U.S. patents, Orange Book records and nonpatent regulatory exclusivities. U.S. 6,034,239 alone does not establish current exclusivity.

What generic launch risks remain after expiration?

After expiration, generic entry risks shift away from the expired composition patent. The principal issues are:

FDA ANDA approval and bioequivalence.
Any later-listed formulation, polymorph or method-of-use patent.
Regulatory exclusivity associated with a later-approved product or indication.
Ability to reproduce the reference product’s quality attributes.
Manufacturing capacity, supply and API sourcing.
Trademark and labeling compliance.
Any separate patent rights in non-U.S. jurisdictions.

Because claim 25 covers the active molecule and has expired, a generic manufacturer does not face a continuing U.S. infringement threat from that claim. The same conclusion applies to the expired process, composition and method claims in this patent.

What is the geographic coverage of U.S. Patent 6,034,239?

The patent provides rights only in the United States. Related applications or foreign counterparts may have existed in Japan, Europe and other jurisdictions, but U.S. expiration does not determine foreign expiration.

A multinational launch assessment must review each country separately for:

National patent family members;
Patent-term adjustments or supplementary protection certificates;
Local formulation and process patents;
Patent litigation and settlement history;
Regulatory data exclusivity; and
Local generic approval rules.

The U.S. patent cannot be used to block manufacture, sale or importation outside the United States.

Key Takeaways

U.S. Patent 6,034,239 is the foundational ramelteon patent.
Claim 25 specifically covers ramelteon.
Claim 1 covers a broad genus of melatonin-receptor ligand compounds.
Claims 30 and 31 cover selected manufacturing processes.
Claims 34 through 41 cover pharmaceutical compositions, melatonin-receptor activity and therapeutic use.
The patent issued on March 7, 2000.
Its reported U.S. expiration date was September 8, 2017.
The patent is expired and does not create current U.S. exclusivity.
Historical patent strength came primarily from the direct composition claim to ramelteon.
Current generic-entry analysis must focus on later patents, FDA requirements and nonpatent commercial barriers.

FAQs About U.S. Patent 6,034,239 and Ramelteon

Is ramelteon still patented in the United States?

U.S. Patent 6,034,239, including its ramelteon composition claim, expired on September 8, 2017. Any current protection would have to arise from a different unexpired patent or regulatory exclusivity.

Does claim 25 cover Rozerem?

Yes. Claim 25 recites the chemical structure of ramelteon, the active ingredient in Rozerem.

Can a generic manufacturer use a different synthesis to avoid claim 30?

A different synthesis could avoid a process claim if it does not practice the claimed steps or their legally relevant equivalents. It would not avoid an applicable active-ingredient claim, although claim 25 is now expired.

Did the patent protect a specific Rozerem tablet formulation?

Claim 34 broadly covers a pharmaceutical composition containing a claimed compound and a pharmaceutically acceptable carrier. It does not, based on the supplied claims, require a specific Rozerem formulation, dissolution profile or excipient system.

Does expiration of U.S. 6,034,239 eliminate all ramelteon patent risk?

No. It eliminates the risk from this patent. Later patents covering formulations, solid forms, dosing methods, manufacturing processes or other product attributes would require separate review.

References

United States Patent and Trademark Office. (2000). U.S. Patent No. 6,034,239, Indane derivatives.
United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term information.
U.S. Food and Drug Administration. (2005). Rozerem (ramelteon) prescribing information and approval history.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Japan	8-051491	Mar 08, 1996
Japan	8-183667	Jul 12, 1996
Japan	9-029185	Feb 13, 1997

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	219071	⤷ Start Trial
Australia	2231897	⤷ Start Trial
Australia	706610	⤷ Start Trial
Canada	2241666	⤷ Start Trial
China	100441574	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,034,239

Summary for Patent: 6,034,239