US Patent 4,217,347: Scope, Claim Construction, Expiration, and Generic Drug Patent Landscape

US Patent 4,217,347 protected oral antihypertensive combinations containing captopril or related mercaptoacyl-proline compounds with specified diuretics. Its strongest commercial claims covered captopril combined with hydrochlorothiazide or furosemide, including lower-dose formulations. The patent issued August 12, 1980, and its enforceable US term expired in 1997. It presents no current US patent barrier to generic captopril-hydrochlorothiazide or captopril-furosemide products.

What drug and combination does US Patent 4,217,347 protect?

The patent covers two related product concepts:

A method of reducing blood pressure by orally administering a claimed compound and a diuretic.
An oral antihypertensive composition containing both components and a physiologically acceptable carrier.

The principal commercial compound is:

(D-3-mercapto-2-methylpropanoyl)-L-proline
Common name: captopril
ATC classification: C09AA01
Therapeutic class: angiotensin-converting enzyme inhibitor, or ACE inhibitor

The patent combines captopril with diuretics that reduce fluid volume and blood pressure. The claims identify hydrochlorothiazide and furosemide as preferred combinations, while also listing chlorothiazide, ticrynafen, triamterene, spironolactone, ethacrynic acid, chlorthalidone, bumetanide and other diuretics.

The patent is therefore a combination-therapy patent rather than a patent directed solely to captopril.

What is the claimed chemical genus?

Claims 1, 12 and 25 use a Markush formula covering a broad family of mercaptoacyl-proline and related compounds. The variables permit changes to:

The terminal functional group, including hydroxy, lower alkoxy or amino
Alkyl and phenylalkyl substituents
Acyl substitution
Hydroxy or alkyl substitution
Ring or chain length represented by n, which may be 0, 1 or 2

The dependent claims progressively narrow that genus. Claims 4, 9, 10, 11, 19, 20, 21, 22 and 23 identify captopril specifically or place it in a preferred combination.

The practical commercial center of gravity is not the entire chemical genus. It is the captopril combination with hydrochlorothiazide or furosemide.

How many independent claims does US 4,217,347 contain?

The patent has three principal independent claim groups.

Claim	Claim type	Core subject matter
1	Method	Oral administration of the compound genus plus a listed diuretic at 30-600 mg and 15-300 mg daily
12	Composition	Oral composition containing the compound genus, a listed diuretic and a physiologically acceptable carrier
25	Composition	Lower-dose composition containing the compound genus and a listed diuretic

Claims 2-11 narrow the method claim. Claims 13-24 narrow the composition claims or identify specific compounds and dose ranges. Claim 25 is particularly important because it covers lower-dose combinations, including the later captopril-hydrochlorothiazide and captopril-furosemide formulations addressed by claims 22 and 23.

What are the strongest claims?

The most commercially specific claims are:

Claim 9: captopril with hydrochlorothiazide or furosemide
Claim 10: captopril, 30-300 mg, with hydrochlorothiazide, 15-200 mg
Claim 11: captopril, 30-300 mg, with furosemide, 15-200 mg
Claim 19: captopril composition with hydrochlorothiazide or furosemide
Claim 20: captopril, 30-300 mg, with hydrochlorothiazide, 15-200 mg
Claim 21: captopril, 30-300 mg, with furosemide, 15-200 mg
Claims 22 and 23: lower-dose captopril compositions with hydrochlorothiazide or furosemide
Claim 24: lower-dose captopril with triamterene

These claims provide narrower chemical and therapeutic coverage than claims 1, 12 and 25, but they are easier to map to a commercial product.

What formulations are protected by US 4,217,347?

The composition claims require an oral antihypertensive composition containing:

The claimed ACE-inhibitor compound
A listed diuretic
A physiologically acceptable carrier

The claims do not require a particular tablet, capsule, coating, release profile or manufacturing process. They therefore reach ordinary immediate-release oral dosage forms if the active ingredients and claimed quantities are present.

Covered formulation categories

Potentially covered formulations include:

Captopril-hydrochlorothiazide tablets
Captopril-furosemide tablets or capsules
Captopril-triamterene tablets
Captopril-chlorothiazide tablets
Fixed-dose oral compositions containing the claimed active ingredients within the specified ranges

The claims do not expressly require a fixed-dose combination manufactured as one tablet. A product sold as a kit or administered as separate oral dosage units could raise different infringement questions, particularly under the composition claims. The method claims are broader in the sense that they focus on administering the combination as a daily dosage, rather than requiring a single dosage form.

Dose-range limitations

The principal dose bands are:

Claim group	ACE-inhibitor amount	Diuretic amount
Claims 1 and 12	About 30-600 mg	About 15-300 mg
Claims 2, 13 and 20-21	About 30-300 mg	About 15-200 mg
Claims 22-23 and 25	About 5-125 mg	About 2.5-50 mg
Claim 24	About 5-125 mg captopril	About 5-75 mg triamterene

The use of “about” creates ordinary claim-construction issues concerning measurement precision and commercial formulation tolerances. It does not eliminate the requirement that the accused product fall within, or be equivalent to, the claimed ranges.

When did US Patent 4,217,347 expire?

US Patent 4,217,347 issued on August 12, 1980. Because it was an older US patent subject to the pre-Uruguay Round patent-term regime, its ordinary term ran 17 years from issuance. The patent therefore expired on August 12, 1997, absent a special adjustment or extension.

Event	Date
US patent issued	August 12, 1980
Ordinary 17-year expiration	August 12, 1997
Current enforceable US term	Expired
Current US exclusivity value	None

The patent predates modern patent term adjustment and patent term extension practice. A Hatch-Waxman patent-term extension is not material to the current status of this patent.

What is the Orange Book status?

An expired patent cannot presently block FDA approval or commercial launch of a generic product. Any historical Orange Book listing associated with a captopril/diuretic product would have ceased to create a live patent barrier when the patent expired.

The FDA Orange Book distinguishes between listed patents, regulatory exclusivity and current enforceability. Patent 4,217,347 has no remaining enforceable term and cannot support a present-day Paragraph IV challenge with commercial launch consequences.[1]

Which companies challenged or bypassed this patent?

The relevant competition involved generic manufacturers seeking approval for captopril and captopril-hydrochlorothiazide products after the underlying exclusivity period. Companies active in the broader captopril and antihypertensive-generic markets have included:

Mylan
Teva
Par Pharmaceutical
Watson, later Actavis
Sandoz
Roxane
Heritage Pharmaceuticals
Other abbreviated new drug application sponsors

The patent’s 1997 expiration removed the principal patent barrier. Current generic entry does not depend on defeating the patent through a new Paragraph IV litigation campaign.

What was the Paragraph IV risk?

During the patent’s active life, a generic applicant seeking approval for a product that could fall within the claims could have used a Paragraph IV certification, asserting that the patent was invalid, unenforceable or not infringed. A Paragraph IV notice could have triggered patent litigation and a potential 30-month FDA approval stay under Hatch-Waxman.[2]

After expiration:

A Paragraph IV certification no longer provides a meaningful path to launch before the patent expires.
A generic applicant can rely on patent expiration rather than litigating validity.
Any historical litigation would have no continuing blocking effect unless another unexpired patent independently covered the product.

No active Paragraph IV risk remains under US 4,217,347.

What patent litigation affects US 4,217,347?

The patent’s meaningful litigation window ended with expiration in 1997. There is no current infringement remedy for conduct occurring after expiration, and no prospective injunction can issue based solely on an expired patent.

Historical litigation must be separated from current freedom to operate:

Issue	Current effect
Infringement before August 12, 1997	Potentially actionable subject to limitation periods and case-specific facts
Manufacture after expiration	Not blocked by this patent
FDA approval today	Not blocked by this patent
Generic captopril-hydrochlorothiazide launch	Not blocked by this patent
Patent settlement	Cannot extend the statutory patent term
Patent reissue or reexamination	Cannot revive an expired patent

No current settlement agreement can preserve exclusivity beyond the statutory expiration date. A historical settlement could have controlled launch timing before 1997, but it has no present blocking effect from this patent alone.

How strong was the patent estate for captopril combinations?

The patent was commercially important when active because it combined a potent ACE inhibitor with established diuretics and claimed both treatment methods and compositions. Its strength varied by claim category.

Dimension	Assessment
Chemical breadth	Broad Markush genus
Captopril-specific coverage	Stronger and easier to enforce
Combination coverage	Focused on listed diuretics
Formulation coverage	Moderate; no detailed release or manufacturing limitation
Method-of-use coverage	Direct treatment of elevated blood pressure
Dose limitation	Potentially narrowing
Manufacturing protection	Minimal or absent
Current enforceability	None

The broad genus claims could have faced validity pressure based on written description, enablement, obviousness or claim-construction arguments. The specific captopril combination claims were more commercially practical because they mapped to identifiable products and therapeutic regimens.

The absence of manufacturing claims is significant. A manufacturer using the same active ingredients but changing compression conditions, excipients or production equipment would not avoid infringement if the resulting composition satisfied an active composition claim during the patent term. Conversely, process changes would not have created a separate infringement risk under this patent because the patent does not claim a manufacturing method.

How does US 4,217,347 compare with the foundational captopril patent?

The foundational captopril patent was US Patent 4,046,889, which covered captopril and related ACE-inhibitor compounds. US 4,217,347 is a later combination patent.

Patent	Primary subject	Commercial role
US 4,046,889	Captopril and related ACE inhibitors	Foundational compound protection
US 4,217,347	Captopril or related compounds plus diuretics	Combination and treatment protection
Later product patents	Specific formulations, dosage forms or combinations	Potential secondary protection

US 4,217,347 could have remained relevant after a compound patent if the combination claims had a later expiration date. In practice, its 1997 expiration also places it in the historical captopril exclusivity period. Current products must be assessed against later patents, regulatory requirements and labeling restrictions rather than this expired patent.

What biosimilar risk exists for this patent?

There is no biosimilar issue. Captopril and hydrochlorothiazide are chemically synthesized small molecules, not biologics. The relevant competitive pathway is the abbreviated new drug application, or ANDA, rather than a biosimilar application under the Public Health Service Act.

The commercial risks are therefore:

Generic price competition
ANDA approval
Labeling and therapeutic-equivalence requirements
Manufacturing capacity
Supply reliability
Product discontinuation or limited-market status

No biologic exclusivity or biosimilar interchangeability analysis applies.

What is the geographic coverage of this patent?

US Patent 4,217,347 had territorial effect only in the United States. It did not create rights in Canada, Europe, Japan or other jurisdictions.

Foreign counterpart patents would require separate review of:

Priority claims
National-phase or Paris Convention filings
Local patent-term rules
Supplementary protection certificates
Local combination-product claims
National litigation and settlement records

The US expiration date cannot be transferred automatically to foreign counterparts, although many related patents from the same development program would have expired decades ago.

What generic launch risks remain?

The expired patent creates no current generic launch risk. A present-day sponsor should instead evaluate the broader product estate and regulatory record.

Risk category	Risk from US 4,217,347
Compound patent	None from this patent
Combination patent	None from this patent
Formulation patent	None from this patent
Method-of-use patent	None from this patent
Paragraph IV litigation	None currently
Biosimilar litigation	Not applicable
FDA approval barrier	None from this patent
Manufacturing barrier	None from this patent
Commercial barrier	Generic competition and market economics only

Captopril-hydrochlorothiazide products may still face practical barriers unrelated to patent exclusivity, including limited demand, manufacturing economics, product discontinuations, drug-shortage exposure and the need to match the approved reference labeling.

Key Takeaways

US 4,217,347 covers oral antihypertensive methods and compositions combining captopril or related compounds with specified diuretics.
Claims 9-11 and 19-24 are the most commercially specific captopril combination claims.
Hydrochlorothiazide and furosemide are the principal diuretics identified in the narrow claims.
The patent issued August 12, 1980, and expired August 12, 1997.
It has no current Orange Book blocking effect and cannot support a present-day generic injunction.
No biosimilar pathway applies because the products are small-molecule drugs.
The patent contains no meaningful manufacturing-process protection.
Current freedom-to-operate analysis should focus on later patents, FDA labeling, product-specific regulatory records and non-patent commercial constraints.

FAQs About US Patent 4,217,347

Does US 4,217,347 cover Capoten?

Historically, yes. Capoten is a brand name for captopril, and the patent’s narrow claims expressly identify captopril in combination with hydrochlorothiazide or furosemide. The patent is expired.

Can a generic manufacturer launch captopril-hydrochlorothiazide without a license?

Yes, US 4,217,347 does not require a license because its US patent term expired in 1997. Other unexpired rights and FDA requirements would need separate review.

Did US 4,217,347 protect Capozide?

The patent covered the captopril-diuretic combination underlying Capozide-type products, particularly captopril with hydrochlorothiazide. It did not create current exclusivity because the patent expired.

Is captopril-furosemide still patent protected?

Not by US 4,217,347. Claims 11, 21 and 23 covered the combination historically, but those claims expired with the patent in 1997.

Is the patent’s broad chemical formula still relevant to new ACE inhibitors?

No enforceable US rights remain under this patent. The formula is relevant for historical claim-scope analysis, but it cannot presently block development or commercialization.

References

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
U.S. Food and Drug Administration. (2024). Abbreviated new drug application process and Paragraph IV certifications. https://www.fda.gov/drugs/abbreviated-new-drug-application-anda
U.S. Patent No. 4,217,347. (1980). Antihypertensive compositions. U.S. Patent and Trademark Office. https://patents.google.com/patent/US4217347A
U.S. Patent No. 4,046,889. (1977). Proline derivatives. U.S. Patent and Trademark Office. https://patents.google.com/patent/US4046889A
U.S. Patent and Trademark Office. (2024). Patent term adjustment and patent term calculation. https://www.uspto.gov/patents/laws/patent-term-calculator

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	230378	⤷ Start Trial
Australia	4204178	⤷ Start Trial
Australia	526239	⤷ Start Trial
Belgium	873092	⤷ Start Trial
Canada	1120400	⤷ Start Trial
Switzerland	642542	⤷ Start Trial
Germany	2854316	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,217,347

Summary for Patent: 4,217,347