United States Patent 5,162,362: Claim Scope, Expiration, and Patent Landscape for Octahydroindole ACE Inhibitors

United States Patent 5,162,362 covers a genus of substituted octahydroindole-2-carboxylic acid compounds, including indolapril-type compounds, their physiologically tolerated salts, pharmaceutical compositions, and therapeutic use in hypertension. The patent issued on November 10, 1992, and its ordinary pre-Uruguay Round patent term would have ended on November 10, 2009, absent an unusual adjustment, disclaimer, or extension. The patent is therefore expired and does not present a current U.S. blocking right.

The claims are directed to small-molecule angiotensin-converting enzyme, or ACE, inhibitors. They do not cover biologics, biosimilars, or a currently marketed U.S. reference product.

What does U.S. Patent 5,162,362 cover?

The patent covers compounds built around an octahydroindole-2-carboxylic acid scaffold linked through an alanine-derived amide to a substituted amino-acid side chain. Claim 1 defines the principal chemical genus. Claims 2 through 6 identify specific compounds within that genus. Claims 7 and 8 cover pharmaceutical and therapeutic use.

The claim architecture is:

Claim	Subject matter	Legal category
1	Broad genus of substituted octahydroindole compounds and physiologically tolerated salts	Composition of matter
2	Phenoxyethyl-substituted compound	Specific chemical species
3	3-indolylpropyl-substituted compound	Specific chemical species
4	3-indolylethyl-substituted compound	Specific chemical species
5	2-thienylpropyl-substituted compound	Specific chemical species
6	Phenylthioethyl-substituted compound	Specific chemical species
7	Pharmaceutical preparation for hypertension	Composition/use
8	Oral, intravenous, or subcutaneous treatment of hypertension	Method of treatment

The patent is attributed to Hoechst AG and belongs to the first-generation patent family surrounding substituted octahydroindole ACE inhibitors. The patent document itself is the primary source for the claim language and disclosed chemical classes (U.S. Patent No. 5,162,362, 1992).

How broad is claim 1?

Claim 1 is a Markush composition-of-matter claim. It covers a broad set of compounds defined by variable substituents R1, R2, and R3.

The claim includes:

R1 as C1-C6 alkyl;
R1 as C1-C6 alkyl substituted with cycloalkyl, amino, alkoxycarbonylamino, alkanoylamino, or alkoxyphenyl groups;
R2 as C1-C6 alkyl;
R2 as substituted C1-C6 alkyl bearing numerous aromatic, heteroaromatic, amino, urea, thioether, sulfoxide, or sulfone groups;
R3 as hydrogen, C1-C6 alkyl, or benzyl; and
physiologically tolerated salts of the claimed compounds.

The R2 list is the main source of breadth. It reaches aliphatic, aromatic, heteroaromatic, amino, urea, sulfide, sulfoxide, sulfone, and benzylthio substituent classes. The heterocyclic options include indole, imidazole, pyrrole, pyrazole, thiophene, and thiazole, as well as selected substituted versions of those rings.

Because the chemical formula image is not reproduced in the supplied text, the exact attachment points and stereochemical relationships must be read from the issued patent drawing and claim formatting. The textual limitations nevertheless establish that claim 1 is intended to cover a peptide-like ACE-inhibitor scaffold with a substituted side chain and an octahydroindole carboxylate moiety.

What structural features define the invention?

The claims identify five commercially and technically relevant structural features:

An octahydroindole-2-carboxylic acid core.
An alanine-derived amide linkage.
An ester or carboalkoxy side-chain arrangement, illustrated by the “S-carboethoxy” language in claims 2 through 6.
A variable hydrophobic or heteroaromatic side chain.
Defined stereochemistry, reflected by the repeated use of “S” descriptors.

The stereochemical limitations are material. A compound with the same connectivity but the wrong configuration could fall outside the literal claim, although racemic mixtures, stereoisomer mixtures, salt forms, and equivalents would require separate analysis under the patent’s claim construction and applicable infringement law.

Which compounds are specifically claimed?

Claims 2 through 6 narrow the genus to five named chemical structures.

Claim	Substituent profile	Development significance
2	2-Phenoxyethyl side chain	Hydrophobic aryl-ether ACE-inhibitor analogue
3	3-(3-Indolyl)propyl side chain	Indolapril-type compound
4	3-(3-Indolyl)ethyl side chain	Shorter indolyl analogue
5	3-(2-Thienyl)propyl side chain	Thiophene-containing analogue
6	2-Phenylthioethyl side chain	Thioether-containing analogue

Claim 3 corresponds to the compound commonly identified as indolapril in the ACE-inhibitor literature. Indolapril was investigated as an ACE inhibitor but did not become an approved U.S. mass-market product comparable to enalapril, lisinopril, ramipril, perindopril, or benazepril.

The patent therefore has greater historical relevance to ACE-inhibitor discovery than to current U.S. pharmaceutical exclusivity.

What pharmaceutical formulations are protected?

Claim 7 covers a pharmaceutical preparation containing:

a hypotensively effective amount of a claim 1 compound or salt; and
a pharmaceutically acceptable carrier.

The claim is not limited to a particular tablet, capsule, injectable formulation, excipient, release profile, particle size, or dosage strength. It is a broad product claim to a preparation containing a covered active compound.

Claim 7 could theoretically reach oral, injectable, or other dosage forms if the active compound and carrier satisfy the claim. It does not create a separate formulation patent in the modern sense because it does not recite a specific excipient combination, dissolution profile, controlled-release matrix, coating system, or manufacturing process.

The claim does not expressly protect:

a specific polymorph;
a specific crystalline form;
a particular salt beyond the broad “physiologically tolerated salt” language;
a fixed dose;
a once-daily regimen;
an enteric coating;
a sustained-release system; or
a combination product with another antihypertensive.

Those subject matters would normally require separate claims.

What method-of-use rights does claim 8 provide?

Claim 8 covers treating hypertension by administering a claim 1 compound orally, intravenously, or subcutaneously.

The method claim has four principal limitations:

The patient must suffer from hypertension.
The administered compound must fall within claim 1.
The administered amount must be hypotensively effective.
Administration must occur by the listed route.

The claim does not specify:

a particular blood-pressure threshold;
treatment duration;
dosing frequency;
patient age;
combination therapy;
a renal or cardiovascular subpopulation; or
a particular disease stage.

The inclusion of oral, intravenous, and subcutaneous administration gives claim 8 broader route coverage than an oral-only claim. It also creates potential enforcement issues because direct infringement would generally require evidence that the claimed compound was administered to a qualifying patient for hypertension.

When did U.S. Patent 5,162,362 lose exclusivity?

The patent issued on November 10, 1992. For a U.S. patent subject to the pre-June 8, 1995 term regime, the ordinary term was 17 years from issuance rather than 20 years from the earliest effective U.S. nonprovisional filing date. On that basis, the ordinary expiration date was November 10, 2009.

Event	Date
U.S. patent issued	November 10, 1992
Ordinary statutory term	17 years from issue
Ordinary expiration	November 10, 2009
Current status	Expired

Patent term adjustment did not generally apply to patents issued under the older term regime in the same manner as to post-1995 patents. There is no identified FDA patent-term extension associated with this patent. The claimed compounds were not approved as a U.S. drug product supported by an NDA that would ordinarily generate an Orange Book patent-term-extension analysis.

What is the Orange Book status of Patent 5,162,362?

Patent 5,162,362 is not a current Orange Book barrier for an approved U.S. reference drug.

The Orange Book lists patents associated with approved drug products and approved uses, generally based on NDA-holder submissions. Because the claimed indolapril-type compounds did not become an approved U.S. reference product with a marketed NDA, the patent does not function as an Orange Book-listed product patent for a current U.S. generic applicant (FDA, 2024).

The practical consequences are:

no current Orange Book-listed patent expiration date controlling an ANDA;
no current 30-month stay based on this patent;
no present Paragraph IV certification directed to this patent for a marketed U.S. reference drug;
no current NDA-specific method-of-use listing; and
no branded product exposure tied directly to this patent.

Are there Paragraph IV challenges or generic litigation?

No meaningful current Paragraph IV litigation is associated with Patent 5,162,362.

A Paragraph IV certification is relevant when an ANDA applicant seeks approval for a generic drug referencing an approved NDA and alleges that an Orange Book-listed patent is invalid, unenforceable, or not infringed. That framework does not create a current dispute for an expired patent covering an unmarketed or non-reference compound.

Any historical challenge would have had limited commercial value unless a U.S. applicant was seeking approval for the same active ingredient under an approved reference product. The absence of an approved indolapril reference product substantially reduces the likelihood of a conventional ANDA-based patent fight.

How strong is the patent estate?

The estate was technically broad at the time of filing but is commercially weak today because the central U.S. patent is expired.

Historical strength

The principal strengths were:

broad Markush coverage in claim 1;
composition-of-matter protection rather than only a method claim;
explicit coverage of salts;
numerous aromatic and heteroaromatic substituent classes;
species claims directed to selected lead compounds;
formulation and method-of-treatment claims; and
coverage of several administration routes.

Composition claims generally provide stronger protection than claims limited to therapeutic use because they can reach manufacture, importation, sale, and possession of the compound itself.

Current strength

The current position is materially different:

claim 1 is expired;
claims 2 through 6 are expired;
claims 7 and 8 are expired;
no current U.S. exclusivity remains under this patent;
no biosimilar issue exists;
no Orange Book litigation value remains; and
a new entrant would not need a license to practice the expired U.S. claims.

The expired patent may still matter as prior art against later patent applications. Its disclosures could affect novelty or obviousness for later claims directed to the same scaffold, analogues, salts, formulations, or uses.

What manufacturing and intellectual-property barriers remain?

The expired patent does not eliminate all barriers to commercialization. It removes one patent barrier.

Potential remaining barriers include:

process patents covering improved synthesis;
later patents on crystalline forms or salts;
formulation patents;
combination-therapy patents;
polymorph and particle-engineering claims;
regulatory exclusivity attached to a different product;
trade secrets involving stereoselective synthesis;
freedom-to-operate issues in non-U.S. jurisdictions; and
clinical and regulatory requirements for an unapproved active ingredient.

The patent’s stereochemical requirements may also create manufacturing complexity. Commercial production would require control of the relevant enantiomeric composition and confirmation that the final product matches the claimed configuration.

The disclosed analogues contain indole, thiophene, phenoxy, and phenylthio substituents. These groups can create process-control, impurity, oxidation-state, and analytical challenges. Those issues are technical and commercial barriers, not surviving rights under Patent 5,162,362.

How does this patent compare with patents for marketed ACE inhibitors?

Patent 5,162,362 is narrower commercially than the major patent estates for approved ACE inhibitors because its compounds did not establish a major U.S. branded product.

Drug or class	Commercial status	Patent relevance
Enalapril	Approved and widely marketed	Large historical composition, formulation, and use estate
Lisinopril	Approved and widely marketed	Separate active ingredient and patent family
Ramipril	Approved and marketed	Separate composition and formulation estate
Perindopril	Approved in multiple markets	Separate octahydroindole ACE-inhibitor family
Indolapril	Investigational/non-major U.S. product	Patent 5,162,362 is historically relevant
Trandolapril	Approved in certain markets	Separate later ACE-inhibitor patent estate

Patent 5,162,362 should not be treated as the principal U.S. patent for perindopril, trandolapril, enalapril, or lisinopril. Similar pharmacology and related peptide-mimetic design do not establish common patent ownership or common claim scope.

What licensing deals affect Patent 5,162,362?

No current commercial license is needed to practice the expired U.S. claims.

The patent’s original ownership by Hoechst AG reflects the historical origin of the research program. Hoechst’s pharmaceutical assets were later associated with the corporate lineage that included Aventis and Sanofi, but corporate succession does not revive expired patent rights.

No publicly material current license, co-development agreement, or royalty stream tied specifically to U.S. Patent 5,162,362 is identified in the patent record or in the commercial status of indolapril. Any historic internal or regional licensing arrangement would not change the expired U.S. term.

What generic entry risks exist?

For a new U.S. entrant, the direct patent risk from Patent 5,162,362 is zero because the claims have expired.

The relevant entry scenarios are:

Entry scenario	Risk from Patent 5,162,362	Principal remaining issue
Manufacture of a claim 3 indolapril-type compound in the U.S.	None from this patent	Regulatory approval and later patents
Importation of a claimed compound	None from this patent	Process and jurisdiction-specific patents
Development of a new formulation	None from this patent	Later formulation or polymorph patents
Development of an analogue	None from this patent	Patentability over the disclosed genus
ANDA filing for a marketed reference product	None from this patent	Relevant Orange Book patents for that product
Sale of an unapproved indolapril product	None from this patent	FDA approval, safety, efficacy, and manufacturing compliance

The primary regulatory obstacle is that the patent does not provide a pathway to approval. A sponsor would still need an NDA or another applicable FDA pathway for an active ingredient without an approved U.S. reference product.

Key Takeaways

U.S. Patent 5,162,362 covers a broad genus of substituted octahydroindole ACE inhibitors and physiologically tolerated salts.
Claims 2 through 6 cover specific phenoxy, indolyl, thienyl, and phenylthio compounds.
Claim 3 covers an indolapril-type compound.
Claims 7 and 8 cover pharmaceutical preparations and hypertension treatment methods.
The patent issued November 10, 1992, and its ordinary term ended November 10, 2009.
The patent is expired and is not a current U.S. exclusivity barrier.
It is not a current Orange Book patent for a marketed U.S. reference product.
No current Paragraph IV or biosimilar litigation is associated with the patent.
The patent remains relevant as prior art against later patents directed to related octahydroindole compounds, formulations, salts, and manufacturing processes.
Commercial entry risk now depends on later patents, regulatory approval, manufacturing capability, and non-U.S. rights rather than Patent 5,162,362.

FAQs

Is indolapril protected by an active U.S. patent?

No. The relevant claims in U.S. Patent 5,162,362 expired in 2009.

Does Patent 5,162,362 cover perindopril?

The patent covers a related octahydroindole ACE-inhibitor design space, but the supplied claims should not be treated as the principal patent protection for perindopril. Perindopril has its own historical patent family.

Can an applicant file a Paragraph IV certification against this patent?

Not in the ordinary current sense. Paragraph IV certifications apply to patents listed for an approved reference drug. Patent 5,162,362 is expired and is not a current Orange Book barrier for an approved indolapril product.

Does the patent cover salts of the claimed compounds?

Yes. Claim 1 expressly includes physiologically tolerated salts. That protection expired with the underlying patent term.

Does the patent create biosimilar risk?

No. The patent covers small-molecule chemical compounds, not biologics. Biosimilar approval and litigation frameworks do not apply.

References

Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. U.S. Department of Health and Human Services.

United States Patent and Trademark Office. (1992). U.S. Patent No. 5,162,362: N-substituted octahydroindole derivatives, process for their preparation, agents containing them and their use. U.S. Department of Commerce.

World Intellectual Property Organization. (n.d.). Patent term and patent-related legal status resources. WIPO.

35 U.S.C. § 154. (2024). Contents and term of patent; provisional rights. United States Code.

21 C.F.R. pt. 314. (2024). Applications for FDA approval to market a new drug. Code of Federal Regulations.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Germany	3032709	Aug 30, 1980
Germany	3118191	May 08, 1981

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	240702	⤷ Start Trial
Argentina	240949	⤷ Start Trial
Argentina	244241	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,162,362

Summary for Patent: 5,162,362