US Patent 4,252,721: Claim Scope, Patent Expiration, Orange Book Relevance and Competitive Landscape

US Patent 4,252,721 covers a broad chemical genus of substituted tetrahydro-s-triazolopyridine and tetrahydro-s-triazoloazepine compounds bearing an N-aryl piperazine side chain. Claims 3 through 9 identify specific compounds within that genus. The patent issued on February 24, 1981, and its pre-URAA term would have expired on February 24, 1998. It therefore has no current blocking effect against generic or competing products.

The claims describe small-molecule chemical entities, not a biologic, formulation platform, manufacturing process, or therapeutic method. The supplied claim text does not identify an FDA-approved active ingredient, an Orange Book-listed product, or a currently marketed drug.

What does US Patent 4,252,721 cover?

The patent covers substituted triazolopyridine and triazoloazepine compounds linked to aryl-substituted piperazine groups.

The core structural elements are:

Structural element	Claimed scope
Heterocyclic core	Fused s-triazolopyridine or s-triazoloazepine system
Saturated ring	Tetrahydro pyridine or azepine ring
Side chain	Divalent chain connecting the triazole portion to piperazine
Chain length	“alk” from 1 to 10 carbon atoms; “alk'” from 1 to 5 carbon atoms
Piperazine substituent	Aryl-substituted piperazine
Permitted aryl substituents	Hydrogen, C1-C5 alkyl, halogen, C1-C3 alkoxy, hydroxy, trifluoromethyl, or methylthio
Salt coverage	Pharmaceutically acceptable, nontoxic acid-addition salts
Claim type	Composition-of-matter claims

The claim text uses “divalent alkene chains.” That wording is chemically inconsistent with the specifically named ethyl and propyl compounds in claims 3 through 9. The intended term was likely “alkylene,” or the issued patent may contain a transcription or OCR error. The original patent document controls claim interpretation.

What is the likely chemical architecture?

The claimed molecules have four principal regions:

A fused triazole-containing bicyclic ring.
An alkyl or alkylene linker.
A piperazine ring.
An optionally substituted phenyl group attached to the piperazine nitrogen.

The genus is broad because it permits multiple linker lengths, ring sizes, and aryl substitution patterns. The genus also encompasses both tetrahydro-s-triazolo[4,3-a]pyridine and tetrahydro-s-triazolo[4,3-a]azepine systems.

The claims do not cover every piperazine-containing triazole compound. A candidate molecule would need to satisfy the claimed ring system, linker arrangement, piperazine substitution, and permitted substituent limitations.

How broad is claim 1 of US 4,252,721?

Claim 1 is the principal genus claim. It covers compounds of the patent’s formula I in which:

The triazole-fused bicyclic core falls within the disclosed pyridine or azepine structures.
The relevant divalent chains fall within the stated carbon ranges.
The piperazine nitrogen is substituted by an aryl group.
The aryl ring contains only the listed substituent classes and carbon ranges.
The molecule otherwise conforms to the structural formula shown in the patent.

The claim is composition-specific rather than use-specific. It does not require treatment of depression, anxiety, psychosis, insomnia, or any other disease. It also does not require a particular pharmaceutical composition, dosage, route of administration, or patient population.

What limitations constrain claim 1?

The principal limitations are structural:

The fused triazole system must have the claimed ring fusion and saturation pattern.
The side chain must connect the designated positions in the claimed configuration.
The piperazine must occupy the claimed position in the molecule.
The aryl substituent must come from the closed list in the claim.
Linker lengths must remain within the specified ranges.
Substituents outside the listed groups would fall outside the literal scope of the genus.

A compound with a carbonyl group in the core, a different heterocyclic fusion, a non-piperazine nitrogen ring, or an unlisted aryl substituent would require a separate infringement analysis. Such a compound might still raise an equivalents issue, but it would not fall within the literal wording of claim 1 based solely on the supplied text.

What compounds are specifically protected by claims 3 through 9?

Claims 3 through 9 narrow the genus to named chemical species.

Claim	Specifically identified compound
3	3-[3-[4-(2-tolyl)-1-piperazinyl]propyl]-5,6,7,8-tetrahydro-s-triazol[4,3-a]pyridine
4	3-[2-[4-(2-tolyl)-1-piperazinyl]ethyl]-6,7,8,9-tetrahydro-5H-s-triazol[4,3-a]azepine
5	3-[2-[4-(2-tolyl)-1-piperazinyl]ethyl]-5,6,7,8-tetrahydro-s-triazol[4,3-a]pyridine
6	3-[2-[4-(3-chlorophenyl)-1-piperazinyl]ethyl]-5,6,7,8-tetrahydro-s-triazol[4,3-a]pyridine
7	A propyl-linked 2-tolyl-piperazine triazoloazepine compound
8	3-[2-[4-(2,5-dichlorophenyl)-1-piperazinyl]ethyl]-6,7,8,9-tetrahydro-5H-s-triazol[4,3-a]azepine
9	3-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-6,7,8,9-tetrahydro-5H-s-triazol[4,3-a]azepine

Claim 7 contains an apparent typographical error in the supplied text: “propyl/-6,7,8,9...” The intended syntax is likely a propyl-linked compound followed by the triazoloazepine ring designation.

Claim 9 also appears to omit a closing parenthesis in “2-methoxyphenyl-1-piperazinyl.” These defects do not change the need to consult the issued patent and prosecution history for authoritative interpretation.

How do the dependent claims affect infringement analysis?

Claims 3 through 9 are narrower than claim 1 because each identifies a particular compound. A product that falls within claim 3, for example, would also need to satisfy claim 1 because the claim depends on claim 1. A product outside the specific species but inside the broader genus could still implicate claim 1.

The species claims can be important in validity analysis. A specific compound may be easier to distinguish from prior art than the broader genus. Conversely, a species claim may be vulnerable if the exact compound was disclosed, exemplified, or rendered obvious by earlier chemical literature or patent references.

When did US Patent 4,252,721 expire?

US Patent 4,252,721 issued on February 24, 1981. For a U.S. utility patent governed by the pre-1995 patent-term regime, the ordinary term was 17 years from issuance. On that basis, the patent expired on February 24, 1998.

Event	Date or status
U.S. patent issued	February 24, 1981
Applicable term regime	Pre-URAA, generally 17 years from issue
Expected expiration	February 24, 1998
Current status	Expired
Current exclusionary force	None for future conduct

The expiration analysis should be confirmed against the USPTO patent record for any terminal disclaimer, disclaimer, reexamination adjustment, or other unusual term event. Nothing in the supplied claims indicates a term extension or patent-term adjustment.

Because the patent expired decades ago, it cannot support a current injunction against manufacture, sale, or use of a covered compound. Historical infringement questions may be fact-specific, but they do not create current product exclusivity.

What is the Orange Book status of US Patent 4,252,721?

The patent does not have an apparent Orange Book role based on the supplied claims.

The Orange Book lists patents submitted by sponsors for approved drug products under FDA regulatory procedures. A patent is not an Orange Book patent merely because it claims a pharmacologically active chemical compound. The sponsor must identify the patent in connection with an approved reference listed drug, and the patent must satisfy FDA listing requirements.[2]

The claim text provides no:

Established drug name.
New Drug Application number.
Reference listed drug.
FDA approval date.
Patent-use code.
Listed dosage form.
Approved therapeutic indication.

The patent therefore cannot be treated as an Orange Book barrier without a demonstrated connection to an approved product. Its 1998 expiration would also prevent it from creating current Hatch-Waxman exclusivity.

Does US Patent 4,252,721 create Paragraph IV risk?

No current Paragraph IV risk is apparent from the patent itself.

A Paragraph IV certification addresses a patent listed in the Orange Book for a reference listed drug. It does not apply merely because an old composition-of-matter patent once covered a chemical class. Since US 4,252,721 expired in 1998, it cannot provide a current patent basis for delaying an ANDA approval.

If a covered compound had been approved and the patent had been listed historically, an ANDA filer could have confronted the patent before expiration. The litigation and regulatory consequences would have depended on the filing date, listing status, patent-use code, and any settlement. The supplied material does not identify such an ANDA, a Paragraph IV notice, or related litigation.

What patent litigation affects US 4,252,721?

The supplied information does not identify litigation involving US 4,252,721. The patent’s expiration materially limits the commercial importance of any present-day litigation.

Potential historical litigation issues would include:

Whether an accused compound satisfied the structural formula.
Whether the asserted claim was enabled across the full genus.
Whether prior art anticipated the claimed species.
Whether the patent was obvious in view of known triazole, azepine, pyridine, and aryl-piperazine chemistry.
Whether any accused activity occurred before February 24, 1998.
Whether damages were limited by patent marking, notice, and the applicable statute of limitations.

Any current claim based solely on this patent would face the threshold problem that the exclusionary term has ended.

What formulation patents are protected by US 4,252,721?

None are apparent from the supplied claims.

The claims cover compounds and acid-addition salts. They do not claim:

Tablets.
Capsules.
Injectable formulations.
Controlled-release systems.
Transdermal systems.
Solid dispersions.
Specific excipients.
Particle-size distributions.
Crystalline polymorphs.
Hydrates or solvates as separate formulations.
Pharmaceutical manufacturing processes.

Claim 2 covers pharmaceutically acceptable, nontoxic acid-addition salts of the claimed compounds. That is salt-form composition coverage, not a finished dosage-form claim. The claim does not identify particular acids, salt stoichiometries, crystal forms, dissolution profiles, or stability characteristics.

Are manufacturing methods or process barriers covered?

No process claim appears in the claims supplied by the user.

The patent could still contain process disclosures or examples in its specification, but the listed claims do not establish enforceable protection for a synthetic route. A competitor using a different process to make the same claimed compound would not avoid composition-of-matter liability during the patent term. Conversely, after expiration, the composition claim no longer creates a current barrier, and any unclaimed process protection would need to be assessed separately.

The covered compounds are conventional small molecules from a chemical manufacturing perspective. They do not present biologic manufacturing barriers such as cell-line ownership, living-cell expression, viral clearance, or comparability requirements.

How strong is the patent estate for commercial purposes?

The current estate is commercially weak because US 4,252,721 has expired.

Estate factor	Assessment
Core compound protection	Expired
Species claims	Expired
Salt claim	Expired
Formulation claims identified	None
Method-of-use claims identified	None
Manufacturing claims identified	None
Orange Book barrier	Not established
Current generic launch blocker	None from this patent
Biosimilar relevance	None
Royalty leverage	No current statutory leverage from the expired U.S. patent

Historically, the composition claims would have been valuable if a claimed compound had reached the market. Composition-of-matter claims generally provide stronger protection than method-of-use claims because they can cover making, selling, and using the compound regardless of indication. Their value depends on whether the claimed molecule is an approved or commercially important active ingredient.

The supplied claims do not establish that any of the named compounds became a marketed drug. Patent coverage alone does not prove clinical efficacy, FDA approval, commercial success, or licensing value.

How does this patent compare with modern drug patent estates?

US 4,252,721 is materially narrower in patent-estate architecture than a modern branded-drug portfolio.

Protection category	US 4,252,721	Typical modern small-molecule estate
Core molecule	Yes	Yes
Salt and solid form	Limited salt claim	Often separate patents
Formulation	Not shown	Frequently claimed
Method of use	Not shown	Frequently claimed
Dosing regimen	Not shown	Often claimed
Combination therapy	Not shown	Sometimes claimed
Manufacturing process	Not shown in supplied claims	Often claimed
Pediatric or regulatory exclusivity	Not shown	May apply separately
Patent term	Expired in 1998	Often extends into the 2030s
Orange Book relevance	Not established	Common for approved drugs

This older patent appears to rely primarily on chemical genus and species protection. It lacks the layered formulation, dosing, crystalline-form, use, and process protections that often extend the commercial life of contemporary products.

Which companies are challenging US 4,252,721?

No current challenger is relevant because the patent expired in 1998. A company does not need to file a Paragraph IV challenge against an expired patent to launch a product that would have been covered during the patent term.

The supplied record does not identify:

An ANDA filer.
A Paragraph IV notice letter.
A declaratory judgment action.
A patent settlement.
A license agreement.
A post-grant validity challenge.

No licensing deal or settlement can be attributed to this patent from the claim text alone.

What generic launch scenarios exist?

The patent creates no current generic launch delay.

For a hypothetical product corresponding to one of the claimed compounds, the relevant current barriers would instead be:

FDA approval requirements for the active ingredient and dosage form.
Any later, unexpired U.S. patents owned by other parties.
Regulatory exclusivity attached to a reference product.
Controlled-substance, safety, or clinical-development requirements, if applicable.
Manufacturing, supply, and formulation know-how.

A product could not be blocked today solely because its active ingredient falls within US 4,252,721. The patent’s historical status is different from its present enforceability.

What is the geographic coverage of the patent?

US 4,252,721 provided protection only in the United States. Any foreign protection would have required separate national or regional patent rights.

A U.S. patent does not automatically cover:

Canada.
Europe.
Japan.
China.
India.
Australia.
Other jurisdictions.

Foreign family members may have had different filing dates, claim scope, prosecution outcomes, and expiration dates. The supplied information does not establish the existence or status of corresponding foreign patents. The U.S. patent’s expiration does not determine foreign legal status.

Key Takeaways

US 4,252,721 claims a genus of substituted tetrahydro-s-triazolopyridine and triazoloazepine compounds with aryl-substituted piperazine side chains.
Claims 3 through 9 cover specific 2-tolyl, 3-chlorophenyl, 2,5-dichlorophenyl, and 2-methoxyphenyl derivatives.
Claim 2 covers pharmaceutically acceptable acid-addition salts.
The patent issued on February 24, 1981, and expired on February 24, 1998, under the pre-URAA term regime.
No formulation, method-of-use, dosage, combination, or manufacturing claims appear in the supplied claims.
No current Orange Book, Paragraph IV, biosimilar, or generic-entry barrier is established.
The patent is relevant as historical chemical IP, not as a current exclusionary right.
Any present commercial risk must come from later patents, FDA exclusivity, regulatory requirements, or manufacturing know-how.

FAQs

Does US Patent 4,252,721 cover trazodone?

The supplied claims do not establish coverage of trazodone. Trazodone has a different triazolopyridinone structure and substitution pattern. A definitive comparison requires the exact chemical structure and the patent’s formula drawing.

Can an expired chemical patent still block FDA approval?

No. An expired patent cannot create a current patent-based approval stay or injunction. FDA approval may still require safety, efficacy, quality, and other regulatory showings.

Does claim 2 cover every salt of the claimed compounds?

No. Claim 2 is limited to pharmaceutically acceptable, nontoxic acid-addition salts of compounds falling within claim 1. It does not automatically cover every salt, solvate, polymorph, or formulation.

Could a later patent extend protection for one of these compounds?

Yes. A later patent could potentially claim a new crystalline form, formulation, therapeutic use, dosing regimen, or manufacturing process if statutory patentability requirements were satisfied. Such a later patent would be separate from US 4,252,721.

Are the named compounds still commercially relevant?

The claims alone do not show that any named compound became an approved or marketed drug. Their current relevance depends on later development history, regulatory approval, commercial adoption, and surviving patents.

References

United States Patent and Trademark Office. (1981). Substituted triazolopyridines and triazoloazepines, U.S. Patent No. 4,252,721.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: The Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book
United States Code, 35 U.S.C. § 154. (2024). Contents and term of patent; provisional rights.
United States Code, 21 U.S.C. § 355. (2024). New drugs.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Italy	22421 A/78	Apr 18, 1978

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	374477	⤷ Start Trial
Austria	380251	⤷ Start Trial
Austria	A292479	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,252,721

Summary for Patent: 4,252,721