United States Patent 5,061,722: Perindopril Scope, Claims, Expiration and Patent Landscape

U.S. Patent No. 5,061,722 covers stereochemically defined perindopril-type ACE inhibitors, including perindopril and its active diacid metabolite, perindoprilat. The patent also covers pharmaceutically acceptable salts, antihypertensive compositions, and methods of reducing blood pressure. It issued on October 29, 1991, and its pre-1995 patent term expired on October 29, 2008. The patent no longer creates a U.S. barrier to generic perindopril or perindoprilat development.

What drug does U.S. Patent 5,061,722 cover?

The principal commercial compound covered by the patent is perindopril, an angiotensin-converting enzyme inhibitor marketed in the United States as perindopril erbumine under the brand name Aceon.

Claim 2 expressly identifies the ethyl ester form:

N-(1-S-carboethoxy-3-phenyl-propyl)-S-alanyl-cis,endo-2-azabicyclo-[3.3.0]-octane-3-S-carboxylic acid.

This corresponds to perindopril, commonly described using modern stereochemical nomenclature as:

Perindopril
Perindopril erbumine, when combined with tert-butylamine
An ACE inhibitor
An ethyl ester prodrug
A precursor to perindoprilat

Claim 3 covers the corresponding carboxylic acid:

N-(1-S-carboxy-3-phenyl-propyl)-S-alanyl-cis,endo-2-azabicyclo-[3.3.0]-octane-3-S-carboxylic acid.

That compound is perindoprilat, the active diacid metabolite of perindopril.

What is the legal status and expiration date of Patent 5,061,722?

Item	Data
U.S. patent	5,061,722
Issue date	October 29, 1991
Patent type	Small-molecule pharmaceutical compound and use patent
Principal assignee	Roussel-Uclaf
Commercial drug	Perindopril
U.S. brand	Aceon
Estimated statutory expiration	October 29, 2008
Current enforceability	Expired by term
Current generic blocking effect	None

Because the patent issued before the 1995 change to the U.S. patent-term system, its term was generally 17 years from grant rather than 20 years from the earliest effective filing date. No patent-term adjustment or extension is understood to preserve the patent beyond October 29, 2008.

Patent expiration eliminates infringement liability under the expired patent. It does not, by itself, eliminate separate barriers created by later patents covering salts, polymorphs, formulations, manufacturing processes, or other product attributes.

What does claim 1 cover?

Claim 1 is the broadest compound claim. It covers a defined stereochemical genus represented by the patent’s structural formula, subject to the following limitations:

R2 must be hydrogen, methyl, ethyl, or benzyl.
The ring hydrogens at the 1- and 5-positions must have a cis relationship.
The 3-position carboxyl group must be endo relative to the bicyclic ring.
The chain stereocenters and the ring 3-position stereocenter must have the S configuration.
The claimed compound must be substantially free of other isomers.
Physiologically acceptable salts are included.

The claim therefore is not directed to all ACE inhibitors or all azabicyclooctane derivatives. It is limited to one highly defined bicyclic amino-acid framework with specified substitution and stereochemistry.

What is the significance of the stereochemical limitations?

The stereochemical limitations are central to claim scope. The claim requires:

Cis fusion or cis relationship at the specified bicyclic ring positions.
Endo orientation of the ring carboxyl group.
S configuration at the relevant chain stereocenters.
S configuration at the ring carboxyl-bearing center.
Substantial exclusion of other stereoisomers.

A compound with the same connectivity but a trans ring configuration, exo carboxyl orientation, or different absolute configuration would fall outside claim 1 unless another claim or doctrine independently applied. The “substantially free of other isomers” limitation also targets enriched or substantially resolved stereochemical material rather than an undifferentiated mixture.

What compounds are specifically protected by claims 2 and 3?

Claim 2: Perindopril

Claim 2 narrows claim 1 to the ethyl ester form. The ethyl ester is the commercially relevant prodrug perindopril.

The claim covers:

The free compound.
Physiologically acceptable salts.
The specified cis, endo, S,S,S stereochemical arrangement.
The ethyl ester at the terminal side-chain carboxyl group.

Perindopril erbumine is within the salt language because erbumine is a pharmaceutically acceptable salt-forming base used in the approved product.

Claim 3: Perindoprilat

Claim 3 covers the free carboxylic acid form, perindoprilat, and its salts. Perindoprilat is pharmacologically active but has limited oral absorption compared with the ethyl ester prodrug.

Claims 2 and 3 provide narrower protection than claim 1 while reducing claim-construction disputes over the identity of the commercial compound.

What formulation and method-of-use protection does Patent 5,061,722 provide?

Claim 4: Antihypertensive composition

Claim 4 covers a composition containing:

A hypotensively effective amount of a claim 1 compound or salt.
A pharmaceutically acceptable excipient.

The claim is functional and composition-oriented. It does not require a particular tablet, capsule, strength, release profile, excipient, or dosing schedule. It could cover conventional oral dosage forms if they contain a covered compound and are formulated for blood-pressure reduction.

The claim does not provide robust modern formulation protection. It lacks limitations directed to:

Specific excipients.
Tablet architecture.
Controlled release.
Particle size.
Polymorph selection.
Dissolution performance.
Stability conditions.
A defined dosage strength.
A particular salt or solid-state form.

Claim 5: Method of reducing blood pressure

Claim 5 covers administering a hypotensively effective amount of a claim 1 compound or salt to a patient.

The claim is broad as to:

Patient population.
Dose.
Route, unless constrained by the specification or claim construction.
Treatment duration.
Specific hypertension subtype.
Concomitant medicines.

It is a treatment-method claim, not a dosing-regimen claim. It does not require a specific once-daily schedule, titration protocol, cardiovascular endpoint, or patient subgroup.

Because the patent expired, claims 4 and 5 have no continuing enforcement value in the United States.

How does the patent map to the perindopril product?

Product or form	Relationship to U.S. 5,061,722
Perindopril free compound	Covered by claim 1 and claim 2
Perindopril erbumine	Covered through the salt language and claim 2
Perindoprilat	Covered by claim 1 and claim 3
Other permitted R2 analogues	Potentially covered by claim 1
Unclaimed stereoisomers	Outside the literal scope if the required stereochemistry is absent
Combination product	Potentially covered by claim 4 if it contains the compound and excipient
Antihypertensive treatment	Covered by claim 5 when using a claim 1 compound or salt

The patent is structurally broader than a claim limited only to perindopril erbumine. Its R2 definition reaches the hydrogen, methyl, ethyl, and benzyl variants. The commercial value, however, was concentrated in the ethyl ester and its erbumine salt.

What was the FDA regulatory status of perindopril?

The FDA approved perindopril erbumine tablets under NDA 20-304 for the treatment of hypertension. The product was marketed as Aceon. FDA labeling identifies perindopril erbumine as the active pharmaceutical ingredient and describes conversion to the active metabolite perindoprilat.[1]

FDA issue	Status
NDA	20-304
Brand	Aceon
Active ingredient	Perindopril erbumine
Therapeutic class	ACE inhibitor
Primary indication	Hypertension
Route	Oral
FDA pathway	505(b)(1) NDA for the reference product
Current NCE barrier	None
Patent-based barrier from U.S. 5,061,722	None after October 29, 2008

Perindopril was not a biologic. Biosimilar regulation under the Public Health Service Act is therefore irrelevant. Any competitive entry is governed by the ANDA or, where necessary, the 505(b)(2) pathway.

What patents protected Aceon beyond U.S. 5,061,722?

The principal follow-on patent issue was salt and product protection for perindopril erbumine. U.S. Patent No. 5,350,836 is associated with perindopril erbumine and was asserted in the commercial patent landscape surrounding Aceon. It illustrates the distinction between the expired core compound patent and later patents directed to the marketed salt or related product attributes.

Core patent versus follow-on patent strategy

Protection category	U.S. 5,061,722	Later perindopril patents
Stereochemically defined compound	Yes	May overlap or narrow
Perindopril ethyl ester	Yes	May claim salt or solid form
Perindoprilat	Yes	Usually not the principal commercial focus
Physiologically acceptable salts	Yes	More specific salt claims may provide narrower protection
Erbumine salt	Potentially within broad salt language	May receive separate, specific claims
Formulation	Broad composition claim only	May claim specific formulations
Method of treating hypertension	Yes	Later patents may claim specific regimens
Manufacturing process	Not the main focus	Often covered by separate process patents

A freedom-to-operate review for perindopril cannot stop with U.S. 5,061,722. It must assess later patents covering:

Perindopril erbumine.
Solid-state forms and polymorphs.
Crystal preparation.
Salt formation.
Purification and stereochemical resolution.
Tablet formulations.
Combination products.
Manufacturing intermediates.

Which companies challenged the perindopril patent?

Servier Laboratories, Inc. litigated perindopril patent rights against Apotex Inc. in connection with an ANDA-based generic challenge. The dispute reached the Federal Circuit in Servier Laboratories, Inc. v. Apotex Inc., 480 F.3d 1318 (Fed. Cir. 2007).[2]

The litigation is significant because it tested the enforceability of perindopril patent rights before the 2008 expiration date. The case involved patent validity and infringement issues associated with perindopril protection, including U.S. Patent No. 5,061,722.

The commercial outcome was time-limited by patent expiration. Even a successful injunction could not extend the patent beyond its statutory term. After October 29, 2008, the ’722 patent could no longer block an otherwise compliant generic launch.

What was the Paragraph IV risk for perindopril generics?

An ANDA applicant seeking approval before patent expiration could file a Paragraph IV certification asserting that listed patents were invalid, unenforceable, or not infringed. A Paragraph IV certification could trigger:

Notice to the patent owner and NDA holder.
A patent-infringement action under 35 U.S.C. § 271(e)(2).
A 30-month stay of FDA approval if suit was timely filed.
Potential 180-day first-applicant exclusivity under the pre-GAIN framework.
Launch risk if the generic applicant prevailed or reached a settlement.

For U.S. 5,061,722, the practical Paragraph IV window closed when the patent expired. Any current generic applicant does not face a Paragraph IV challenge to an enforceable ’722 patent.

What did settlement agreements mean commercially?

Patent settlements could have delayed launch beyond the date otherwise available under an ANDA approval. The business value of settlement depended on:

The expiration date of the asserted patent.
The agreed launch date.
Whether the settlement included authorized generic terms.
Whether later patents remained in force.
Whether the Federal Trade Commission or courts reviewed the arrangement.

The expiration of the ’722 patent sets a hard endpoint for its exclusionary value. A settlement under that patent cannot preserve exclusion after expiration.

How strong was the patent estate for perindopril?

Compound-claim strength

The compound claims were technically strong during their term because they combined:

A defined bicyclic scaffold.
Multiple stereochemical restrictions.
Defined substituent options.
Isomeric purity language.
Salt coverage.

That structure made design-around through a simple change in stereochemistry commercially unattractive because the resulting isomer might lose ACE-inhibitor activity or fail to reproduce the reference product.

Litigation strength

The patent was strong enough to support ANDA litigation before expiration. The Federal Circuit decision in Servier v. Apotex confirms that the patent formed part of an enforceable litigation position during the pre-expiration period.[2]

Present strength

The patent has no present exclusionary strength because it expired in 2008. Its remaining value is historical:

It explains the original perindopril exclusivity position.
It may remain relevant in litigation records and prosecution histories.
It can inform validity analysis of related patents.
It does not support a current infringement action.

What generic launch scenarios exist for perindopril?

Scenario	Commercial assessment
Launch after ’722 expiration	Legally available, subject to later patents and FDA approval
Launch before ’722 expiration with Paragraph IV	Required litigation strategy before October 29, 2008
Launch under Paragraph III	Required waiting until patent expiration
505(b)(2) launch	Possible where reliance on published data or modified product is appropriate
ANDA for same salt and dosage form	Most direct generic pathway
Alternative salt or formulation	Could avoid narrow follow-on claims but requires regulatory and CMC analysis
Perindoprilat product	Different development and bioavailability profile; not a conventional direct substitution
Combination product	Requires separate labeling, formulation, and patent review

Generic-entry risk is now driven by regulatory approval, supply-chain execution, manufacturing economics, and any surviving later patent rights rather than by U.S. 5,061,722.

What manufacturing and intellectual-property barriers remain?

The expired patent does not remove technical barriers. Perindopril manufacturing requires control over:

Absolute stereochemistry.
Diastereomeric purity.
Ring construction and bicyclic intermediates.
Side-chain coupling.
Hydrolysis and esterification.
Salt formation.
Crystallization.
Residual solvents and impurities.
Stability of the final dosage form.

The most important manufacturing risk is stereochemical control. The ’722 patent’s “substantially free of other isomers” language reflects the commercial importance of producing the desired stereoisomer rather than merely synthesizing the correct constitutional structure.

A current entrant must also evaluate process patents, supplier patents, regulatory exclusivity, product specifications, and confidential know-how. Patent expiration does not transfer the originator’s manufacturing process or analytical methods into the public domain unless those materials were disclosed in an expired patent.

How does perindopril compare with competing ACE inhibitors?

Drug	Key structural or commercial distinction	Patent position today
Perindopril	Prodrug converted to perindoprilat; bicyclic proline analogue	Core U.S. patent expired
Enalapril	Ethyl ester prodrug converted to enalaprilat	Core patents expired
Ramipril	Lipophilic ACE-inhibitor prodrug with different ring system	Core patents expired
Lisinopril	Active diacid, no ester prodrug conversion	Core patents expired
Trandolapril	Ester prodrug with different bicyclic structure	Core patents expired
Benazepril	Ester prodrug with different ring and side-chain architecture	Core patents expired

Perindopril’s original patent differentiation came from its specific bicyclic scaffold and stereochemical configuration. Commercial competition now depends less on primary patent exclusion and more on formulary positioning, generic price, manufacturing reliability, and clinical differentiation.

Key Takeaways

U.S. Patent 5,061,722 covers perindopril, perindoprilat, permitted salts, antihypertensive compositions, and blood-pressure treatment methods.
Claim 1 is a stereochemically restricted genus with R2 options of hydrogen, methyl, ethyl, and benzyl.
Claim 2 specifically covers perindopril, including its pharmaceutically acceptable salts such as perindopril erbumine.
Claim 3 covers perindoprilat.
Claims 4 and 5 provide broad composition and hypertension-treatment protection but expired with the patent.
The patent issued October 29, 1991, and expired October 29, 2008.
Servier Laboratories litigated perindopril patent rights against Apotex before expiration.
The patent no longer creates a Paragraph IV or generic-entry barrier.
Current diligence must focus on later patents covering perindopril erbumine, polymorphs, formulations, manufacturing processes, and regulatory approval.
Perindopril is a small molecule; biosimilar analysis does not apply.

FAQs

Does Patent 5,061,722 cover perindopril erbumine?

Yes. Claim 2 covers perindopril, and claim 1 includes physiologically acceptable salts. Perindopril erbumine is the commercial salt of perindopril.

Does Patent 5,061,722 cover perindoprilat?

Yes. Claim 3 expressly covers the corresponding carboxylic acid, perindoprilat, and its salts.

Can a company currently sue a generic under Patent 5,061,722?

No. The patent expired on October 29, 2008, so it cannot support a current infringement claim.

Is perindopril subject to biosimilar competition?

No. Perindopril is a chemically synthesized small molecule. Competition proceeds through generic-drug pathways, principally ANDAs, rather than biosimilar applications.

What is the main present-day risk in developing a perindopril generic?

The principal risks are FDA approval, manufacturing consistency, stereochemical purity, supply reliability, and later patents covering the marketed salt, solid form, formulation, or production process.

References

U.S. Food and Drug Administration. (1998). Aceon (perindopril erbumine) tablets prescribing information. Drugs@FDA.
United States Court of Appeals for the Federal Circuit. (2007). Servier Laboratories, Inc. v. Apotex Inc., 480 F.3d 1318.
United States Patent and Trademark Office. (1991). U.S. Patent No. 5,061,722: N-substituted amino acid derivatives. Washington, DC.
United States Patent and Trademark Office. (1994). U.S. Patent No. 5,350,836: Perindopril erbumine and pharmaceutical compositions. Washington, DC.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. Orange Book.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Germany	3143946	Nov 05, 1981
Germany	3226768	Jul 17, 1982

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0079022	⤷ Start Trial	SPC/GB93/145	United Kingdom	⤷ Start Trial
Argentina	240675	⤷ Start Trial
Austria	18550	⤷ Start Trial
Austria	53992	⤷ Start Trial
Australia	565200	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,061,722

Summary for Patent: 5,061,722