United States Patent 4,743,450: Scope, Claim Construction, Expiration, and ACE-Inhibitor Formulation Landscape

United States Patent No. 4,743,450 covers stabilized pharmaceutical compositions and stabilization processes for ACE inhibitors that are vulnerable to cyclization, hydrolysis, and discoloration. The principal combination is an ACE inhibitor, an alkali or alkaline-earth metal carbonate, and a saccharide. The patent issued on May 10, 1988, and its ordinary 17-year patent term expired on May 10, 2005, absent an earlier terminal disclaimer or other exceptional term adjustment.[1][2]

The patent therefore has no current blocking effect in the United States. Its historical claim scope was broad enough to reach certain enalapril, quinapril, quinapril hydrochloride, and indolapril formulations, particularly tablets and candy or lozenge-type dosage forms.

What does United States Patent 4,743,450 protect?

The patent protects two related subject matter categories:

Pharmaceutical compositions containing a degradation-sensitive ACE inhibitor, a carbonate stabilizer, and one or more saccharides.
A process for stabilizing an ACE inhibitor by contacting it with a carbonate and one or more saccharides.

The claims do not cover the ACE inhibitor molecule alone. They do not claim treatment of hypertension or heart failure. They do not claim a general method of administering enalapril or quinapril.

The core composition claim is claim 1:

Claim element	Scope
Drug component	An ACE inhibitor susceptible to cyclization, hydrolysis, and discoloration
Stabilizer 1	An alkali or alkaline-earth metal carbonate
Stabilizer 2	A saccharide
Functional result	The carbonate inhibits cyclization and discoloration; the saccharide inhibits hydrolysis

The claim uses “contains,” which ordinarily operates as an open transitional term. A formulation could therefore include additional excipients, active ingredients, coatings, or processing aids without avoiding claim 1 solely because those additional components are present.

How broad is claim 1 of Patent 4,743,450?

Claim 1 is technically broad but functionally limited. It does not recite a specific ACE inhibitor, carbonate, saccharide, concentration, dosage strength, release profile, particle size, or manufacturing temperature.

Its breadth comes from four features:

The ACE inhibitor is defined by degradation behavior rather than a closed chemical list.
The carbonate category includes alkali-metal and alkaline-earth-metal carbonates.
The saccharide category is not limited to mannitol or lactose in the independent claim.
No quantitative ranges are stated.

The principal limitation is that the components must perform specified stabilizing functions. A composition containing an ACE inhibitor and a carbonate is not necessarily within claim 1 unless the carbonate inhibits cyclization and discoloration and the saccharide inhibits hydrolysis.

This creates several potential claim-construction issues:

Whether “susceptible to cyclization, hydrolysis, and discoloration” requires proof of all three degradation pathways.
Whether the carbonate must be shown experimentally to inhibit both cyclization and discoloration.
Whether the saccharide must be shown experimentally to inhibit hydrolysis.
What constitutes a “suitable amount.”
Whether the functional limitations are inherent properties or express performance requirements.

Those issues would have affected infringement and validity disputes. The absence of numerical ranges made the claim commercially broad, but it also left more room for arguments based on enablement, written description, indefiniteness, and the absence of the claimed stabilizing effect.

Which ACE inhibitors are specifically covered?

Claims 2, 9, 10, and 11 identify specific ACE inhibitors.

Claim	Active ingredient or class	Practical significance
2	Enalapril or a pharmaceutically acceptable acid-addition salt	Directly targets enalapril formulations
9	Quinapril or an acid-addition salt	Covers quinapril formulations generally
10	Quinapril hydrochloride	Narrower species claim
11	Indolapril or an acid-addition salt	Covers indolapril formulations
7-8	Chemical formula class	Covers a broader structural genus, subject to the formula and substituent limitations

Enalapril and quinapril were commercially important small-molecule ACE inhibitors. Indolapril was a more specialized compound and did not create the same commercial exposure as enalapril or quinapril.

Claim 10 is particularly specific. A formulation containing quinapril hydrochloride, a qualifying carbonate, and a qualifying saccharide could have fallen within claim 10, subject to the limitations inherited from claim 1.

What carbonate and saccharide excipients are protected?

Claim 4 identifies magnesium carbonate as a carbonate component. Claim 5 identifies mannitol and lactose as saccharides.

The resulting claim combinations include:

ACE inhibitor + magnesium carbonate + mannitol
ACE inhibitor + magnesium carbonate + lactose
Enalapril or enalapril salt + carbonate + mannitol or lactose
Quinapril hydrochloride + carbonate + mannitol or lactose
Indolapril or an indolapril salt + carbonate + mannitol or lactose

Claims 4 and 5 are dependent claims. They do not stand alone. The formulation must still satisfy all limitations of claim 1, including the functional stabilization requirements.

The patent does not appear, based on the supplied claims, to require that magnesium carbonate be the only carbonate or that mannitol or lactose be the only saccharide. A formulation containing multiple carbonates or multiple saccharides could still satisfy the claims if it meets the other limitations.

What formulations are protected by Patent 4,743,450?

Claims 12 through 15 extend the composition claims to dosage forms.

Claim	Dosage form
12	Tablet containing the claim 1 composition
13	Tablet containing the claim 3 composition, including at least one additional drug
14	Candy formulation containing the claim 1 composition
15	Candy formulation containing the claim 3 composition

Claim 6 further covers conventional formulation materials selected from binders, disintegrants, and lubricants. This claim is formulation-oriented and would have been relevant to compressed tablets containing standard excipient systems.

The candy claims are notable because they extend beyond ordinary tablets. They could potentially reach medicated lozenges, chewable dosage forms, or other confectionery-style products, depending on how “candy formulation” was construed and supported by the specification.

The claims do not expressly require:

Immediate release
Enteric coating
Controlled release
A particular tablet hardness
A particular dissolution profile
A particular dosage strength
A particular route of administration

A later formulation using a different delivery system might avoid claims 12 through 15 but could still implicate claim 1 if it contains the claimed composition.

What does the process claim cover?

Claim 16 covers:

“Contacting” the ACE inhibitor with an alkali or alkaline-earth-metal carbonate and one or more saccharides to stabilize the drug against cyclization.

Claim 17 narrows the drug to quinapril, enalapril, or indolapril, or their pharmaceutically acceptable acid-addition salts.

The process claims are materially narrower in one respect and potentially broader in another:

They are narrower because they focus on stabilization against cyclization.
They may be broader because they do not require a tablet, candy formulation, binder, disintegrant, lubricant, or finished dosage form.

A manufacturing process could have implicated claim 16 before expiration even if the finished product was not a tablet. The word “contacting” could cover dry blending, wet granulation, solution or suspension processing, premixing, or another process in which the drug and stabilizing excipients are brought into contact, subject to the specification and ordinary claim-construction principles.

The process claim does not expressly require that the carbonate inhibit discoloration or that the saccharide inhibit hydrolysis. Those functional limitations appear in claim 1 but not in the same form in claim 16.

How do the dependent claims change infringement exposure?

The dependent claims create narrower but commercially recognizable fall-back positions.

A formulation containing enalapril, magnesium carbonate, lactose, and tablet excipients could potentially satisfy:

Claim 1
Claim 2
Claim 4
Claim 5
Claim 6
Claim 12

If the product also contains another active drug, claims 3 and 13 could become relevant.

A quinapril hydrochloride tablet containing magnesium carbonate and mannitol could potentially satisfy:

Claim 1
Claim 4
Claim 5
Claim 10
Claim 12

The claims are cumulative. Avoiding one dependent claim does not avoid the independent claim. For example, replacing magnesium carbonate with another qualifying carbonate could avoid claim 4 while leaving claim 1 potentially relevant.

When did Patent 4,743,450 lose exclusivity?

The patent’s ordinary term expired on May 10, 2005.

Event	Date
Patent issued	May 10, 1988
Ordinary term for pre-1995 grant	17 years from issue
Expected expiration	May 10, 2005
Current enforceability	Expired

Patent term rules for patents issued before June 8, 1995 generally provided a 17-year term from the grant date, subject to terminal disclaimers and other statutory adjustments.[2] Patent-term restoration under Hatch-Waxman would not ordinarily create a meaningful extension for a formulation patent of this age without a qualifying regulatory-delay record.

Because the patent expired in 2005, it cannot support a current infringement action or block an abbreviated new drug application, commercial launch, licensing transaction, or formulation redesign in the United States.

What is the Orange Book status of Patent 4,743,450?

The patent is not a current Orange Book barrier because its patent term has expired. FDA Orange Book listings are relevant to approved drug products and regulatory certification, but an expired patent does not create a continuing Paragraph IV obstacle.[3]

The patent also does not appear from the supplied claims to be a drug-substance patent or a method-of-use patent. It is a formulation and manufacturing-stabilization patent. Its historical Orange Book relevance, if any, would have depended on its association with a specific approved NDA and qualifying listed drug product.

The claims do not identify:

An NDA number
A brand-name product
A listed strength
A specific approved dosage form
A patent-use code
A pediatric-exclusivity period
A regulatory exclusivity period

Accordingly, the patent should be treated primarily as a historical formulation patent rather than as an active Orange Book asset.

Were Paragraph IV challenges or generic launch risks material?

Before expiration, an ANDA applicant seeking approval for a product that potentially practiced the claims could have considered:

A Paragraph IV certification that the patent was invalid.
A certification that the product did not infringe.
A Paragraph III certification with launch after expiration.
A formulation design-around using a different stabilizer system.

The most plausible design-around strategies would have included:

Replacing the carbonate with a non-carbonate alkalizing agent.
Replacing mannitol or lactose with a non-saccharide hydrolysis-control excipient.
Separating the ACE inhibitor from the stabilizer during processing.
Using a coating or packaging system that controls moisture without the claimed carbonate-saccharide combination.
Selecting a dosage form that avoided the tablet or candy limitations while still evaluating claim 1.

A generic product using enalapril or quinapril without the claimed carbonate-saccharide combination would have had a stronger noninfringement position. A product using magnesium carbonate and lactose would have faced greater historical exposure, especially if stability data demonstrated the claimed functions.

There is no current generic-entry risk attributable to Patent 4,743,450 because the patent expired nearly two decades ago.

Which companies were commercially exposed?

The claims were directed to formulation technology rather than a single company’s active ingredient. Historical exposure could have included manufacturers of:

Enalapril products, including products associated with Merck’s Vasotec franchise.
Quinapril products, including products associated with Warner-Lambert’s Accupril franchise.
Products containing indolapril or related ACE inhibitors.

A formulation patent does not establish ownership of the active ingredient patent estate. The active ingredient, polymorph, salt, method-of-use, process, and formulation patents must be analyzed separately.

The patent therefore would not have prevented competitors from making enalapril or quinapril generally. It could have affected only products practicing the claimed stabilization architecture during the patent term.

How strong was the patent estate?

The patent had broad initial formulation coverage but limited long-term strategic value.

Factor	Assessment
Independent composition claim	Broad, because no specific amounts or dosage strengths are recited
Chemical coverage	Broad through ACE-inhibitor and formula language
Excipient coverage	Moderate to broad through carbonate and saccharide classes
Specific formulation coverage	Stronger for magnesium carbonate, mannitol, lactose, tablets, and candy forms
Process coverage	Potentially broad because “contacting” is not tied to a finished dosage form
Validity pressure	Functional terms and “suitable amount” could invite interpretation disputes
Current value	None as an enforceable U.S. exclusionary right
Biosimilar relevance	None; the claims concern small-molecule ACE-inhibitor formulations
Geographic value	U.S.-only; corresponding foreign rights would require separate review

The strongest historical claims were likely the narrower combinations tied to commercially recognizable products, particularly quinapril hydrochloride and tablets containing specified stabilizing excipients. The broadest claim, claim 1, was more valuable for portfolio coverage but more exposed to prior-art and claim-construction challenges.

What patent litigation and settlements affect this patent?

The supplied claim record does not establish any litigation, Paragraph IV settlement, license, covenant not to sue, or terminal disclaimer associated with Patent 4,743,450. Because the patent expired in 2005, any historical settlement would have no current blocking effect unless it contained independent contractual restrictions, and such restrictions cannot be inferred from the patent claims.

No current biosimilar litigation is relevant. Enalapril, quinapril, and indolapril are small molecules regulated through the ANDA pathway, not biologics regulated through the biosimilar pathway.

What manufacturing and intellectual-property barriers remain?

Patent 4,743,450 no longer creates a manufacturing barrier. Current barriers would arise from other rights or regulatory requirements, including:

Active-ingredient patents
Salt, polymorph, or crystalline-form patents
Process patents
Combination-product patents
Device or delivery-system patents
Trade secrets covering excipient selection or stability processing
Current FDA labeling and quality requirements
Regulatory exclusivity tied to a different approved product

The expired patent may still have technical value as prior art and as a formulation-development reference. Its disclosure can inform stability screening for ACE inhibitors, particularly where cyclization, hydrolysis, moisture, and discoloration are formulation risks.

Key Takeaways

Patent 4,743,450 covers ACE-inhibitor compositions using a carbonate and a saccharide for stabilization.
Enalapril, quinapril, quinapril hydrochloride, and indolapril are expressly identified.
Magnesium carbonate, mannitol, and lactose are specifically claimed dependent species.
Tablets and candy formulations are separately claimed.
The process claims cover contacting the ACE inhibitor with a carbonate and saccharide.
The patent does not claim enalapril, quinapril, or indolapril as active ingredients by themselves.
The patent issued May 10, 1988, and ordinarily expired May 10, 2005.
It presents no current United States Orange Book or Paragraph IV barrier.
It has no biosimilar relevance because the covered products are small-molecule drugs.
Current freedom-to-operate analysis must focus on later active-ingredient, polymorph, process, formulation, and regulatory rights.

FAQs About United States Patent 4,743,450

Does Patent 4,743,450 cover enalapril maleate itself?

No. It covers compositions containing an ACE inhibitor, a qualifying carbonate, and a qualifying saccharide. Enalapril or an acid-addition salt is covered only when used within the claimed composition.

Could a formulation with sodium carbonate avoid the patent?

It could avoid the magnesium carbonate dependent claim, but not necessarily claim 1. Sodium carbonate is within the broader alkali-metal carbonate category if the formulation satisfies the remaining limitations.

Does the patent cover lisinopril?

The supplied claims do not expressly identify lisinopril. Claim 1 could theoretically reach another ACE inhibitor if it satisfies the stated degradation and stabilization limitations, but the specific formula and factual requirements would control.

Could packaging alone satisfy the stabilization claims?

Packaging alone would not ordinarily satisfy the composition claims unless the claimed drug, carbonate, and saccharide are present in the pharmaceutical composition. Packaging might be relevant to stability but is not itself the claimed combination.

Is a license needed to use the disclosed carbonate-saccharide formulation today?

No license is required solely because of Patent 4,743,450 after its expiration. A separate analysis of later patents, trade secrets, regulatory restrictions, and contractual obligations would remain necessary for a commercial product.

References

United States Patent No. 4,743,450, “Stabilized pharmaceutical compositions containing an angiotensin converting enzyme inhibitor,” issued May 10, 1988.
35 U.S.C. § 154(c)(1). Patent term transition provisions for patents issued before June 8, 1995.
U.S. Food and Drug Administration. (2025). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	84210	⤷ Start Trial
Australia	1130588	⤷ Start Trial
Australia	597471	⤷ Start Trial
Canada	1300510	⤷ Start Trial
Germany	3877226	⤷ Start Trial
Denmark	169593	⤷ Start Trial
Denmark	94088	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,743,450

Summary for Patent: 4,743,450