United States Drug Patent 4,642,384: Claim Scope, Expiration, and Flecainide Patent Landscape

U.S. Patent No. 4,642,384 covers three narrowly defined chlorinated acetophenone compounds containing two 2,2,2-trifluoroethoxy substituents at the 2- and 5-positions of the aromatic ring. The patent does not claim flecainide, flecainide acetate, a pharmaceutical formulation, a therapeutic method, or a manufacturing process. It issued on February 10, 1987, and its ordinary 17-year patent term expired on February 10, 2004.[1]

The patent therefore has no current U.S. blocking effect. Its historical relevance is as an intermediate-compound patent associated with the chemical architecture used to manufacture flecainide.

What compounds does U.S. Patent 4,642,384 claim?

The patent contains three independent compound claims:

Claim	Claimed compound	Functional group
1	2,5-Bis(2,2,2-trifluoroethoxy)acetophenone	Methyl ketone, Ar-COCH3
2	2,5-Bis(2,2,2-trifluoroethoxy)-alpha,alpha-dichloroacetophenone	Dichloromethyl ketone, Ar-COCHCl2
3	2,5-Bis(2,2,2-trifluoroethoxy)-alpha,alpha,alpha-trichloroacetophenone	Trichloromethyl ketone, Ar-COCCl3

The common aromatic core is:

A benzene ring;
A carbonyl-containing acetophenone side chain;
2,2,2-trifluoroethoxy substituents at the 2- and 5-positions.

The claims are species claims rather than broad genus claims. They do not cover all trifluoroethoxy-substituted acetophenones, all substituted benzoyl compounds, or all intermediates containing a 2,5-disubstituted benzene ring.

How broad is the claim scope?

The claim scope is narrow and structurally exact.

Claim 1 scope

Claim 1 covers the specific methyl ketone:

2,5-bis(2,2,2-trifluoroethoxy)acetophenone.

A compound would need to retain:

The 2,5-substitution pattern;
Two 2,2,2-trifluoroethoxy groups;
An acetophenone methyl ketone;
The claimed connectivity between the aromatic ring and carbonyl group.

Changing the trifluoroethoxy substituent, moving either substituent to another ring position, replacing the methyl group, or converting the ketone into an acid, ester, amide, or other derivative would take the resulting compound outside the literal wording of claim 1.

Claim 2 scope

Claim 2 covers the alpha,alpha-dichloro derivative, in which the methyl group of the acetophenone is chlorinated to CHCl2.

The claim does not expressly cover:

The corresponding monochloro compound;
The trichloro compound of claim 3;
Other halogenated derivatives;
A process for producing the dichloro compound;
A pharmaceutical composition containing the compound.

Claim 3 scope

Claim 3 covers the alpha,alpha,alpha-trichloro derivative, structurally corresponding to a trichloromethyl ketone.

This type of compound can function as a precursor to conversion of the ketone side chain into a carboxylic-acid derivative through haloform-type chemistry. That synthetic relationship does not expand claim 3 into a claim covering the resulting acid or any downstream amide.

Are the claims compound claims or process claims?

They are compound claims.

None of the three claims recites:

Reactants;
Solvents;
Catalysts;
Temperature or pressure;
Reaction sequence;
Isolation steps;
Yield;
Pharmaceutical use;
Dosage form;
Administration route.

A party that practiced a claimed synthesis during the patent term could have faced process-related liability under other patent provisions if a separate process claim existed elsewhere in the patent. The three claims supplied, however, principally establish rights in the chemical compounds themselves.

The claims also do not use broad functional language such as "a compound of Formula I." There is no Markush group covering alternatives. The patent’s enforceable chemical scope was consequently limited to the three named molecules and legally equivalent variants, subject to ordinary claim-construction principles.

What drug is associated with these intermediates?

The structural motif is associated with flecainide.

Flecainide is N-(2-piperidylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide. Flecainide acetate is a Class Ic antiarrhythmic approved for the treatment of selected supraventricular and ventricular arrhythmias. The FDA-approved labeling identifies flecainide acetate as the active pharmaceutical ingredient in products such as Tambocor and generic flecainide acetate tablets.[2]

The claimed acetophenones are chemically upstream of the 2,5-bis(2,2,2-trifluoroethoxy)benzoyl portion of flecainide. A simplified relationship is:

Substituted acetophenone;
Alpha-halogenated acetophenone;
Trichloromethyl ketone or related oxidation intermediate;
2,5-bis(2,2,2-trifluoroethoxy)benzoic-acid derivative;
Flecainide or flecainide acetate.

This pathway explains the patent’s commercial relevance. It does not mean that U.S. Patent 4,642,384 claims flecainide. A downstream drug molecule must be claimed separately to receive composition-of-matter protection.

Does U.S. Patent 4,642,384 claim flecainide?

No.

The patent claims do not include:

Flecainide;
Flecainide acetate;
The piperidylmethyl benzamide structure;
A salt of flecainide;
A pharmaceutical composition;
A method of treating arrhythmia.

The distinction is material. A manufacturer could not be accused of infringing these claims merely because it marketed flecainide acetate after the patent expired. During the patent term, infringement would have depended on making, using, selling, offering to sell, or importing one of the claimed intermediate compounds, or on another applicable claim not included in the three claims provided.

When did U.S. Patent 4,642,384 lose exclusivity?

The patent issued on February 10, 1987. For a pre-June 8, 1995 patent, the standard term was generally 17 years from grant under the pre-URAA patent-term regime.[3]

Event	Date
Patent issued	February 10, 1987
Standard 17-year term	February 10, 2004
Current status	Expired
Current U.S. exclusivity	None

The patent was not eligible for the modern 20-year-from-earliest-effective-filing-date term in the manner applicable to later-filed patents. Its age also places it outside the practical scope of current patent-term-extension strategies for flecainide products.

What is the Orange Book status of U.S. Patent 4,642,384?

U.S. Patent 4,642,384 is not the type of patent ordinarily listed in the Orange Book for flecainide acetate.

FDA Orange Book patent listings generally concern patents that claim:

The approved drug substance;
The approved drug product or formulation;
A method of using the approved drug.

A patent directed only to chemical intermediates normally does not qualify as a patent claim covering the approved drug product or its approved use.[4]

The practical consequences are:

It does not create an Orange Book-listed barrier to an ANDA for flecainide acetate;
It cannot support a current Paragraph IV certification strategy because the patent has expired;
It does not create a 30-month stay against an ANDA;
It does not establish exclusivity for a flecainide formulation or dosage strength.

Are there Paragraph IV challenges or generic-entry risks?

There is no current Paragraph IV risk associated with this patent because its term expired in 2004.

Paragraph IV litigation is relevant when an ANDA applicant certifies that a listed patent is invalid, unenforceable, or not infringed before expiration. An expired intermediate patent cannot delay FDA approval of a current flecainide acetate ANDA.

Generic entry for flecainide acetate is instead governed by:

The status of any unexpired Orange Book-listed drug-product or method-of-use patents;
Regulatory exclusivity, if any;
Formulation-specific rights;
FDA requirements for bioequivalence and labeling;
Commercial manufacturing economics.

For a conventional immediate-release flecainide acetate tablet, the main barriers are regulatory and commercial rather than rights under U.S. Patent 4,642,384.

What formulation patents protect flecainide products?

U.S. Patent 4,642,384 does not claim a formulation.

It contains no limitations directed to:

Tablets;
Capsules;
Excipients;
Particle size;
Dissolution;
Modified release;
Enteric coating;
Liquid dosage forms;
Injectable products;
Stability packaging.

Any formulation protection for flecainide acetate would need to arise from separate patents. Those rights would be assessed independently by dosage form, formulation composition, release profile, and expiration date. The existence of this intermediate patent does not imply formulation protection.

What method-of-use patents are covered?

None of the three supplied claims is a method-of-use claim.

The claims do not cover treatment of:

Atrial fibrillation;
Atrial flutter;
Paroxysmal supraventricular tachycardia;
Ventricular arrhythmias;
Other cardiac rhythm disorders.

A method patent would need to recite administration of the active compound, a patient population, a disease or condition, a dosage regimen, or another therapeutic limitation. No such limitation appears in these claims.

How strong is the patent estate?

The estate is narrow in claim breadth and has no current U.S. enforcement value.

Factor	Assessment
Claim type	Three specific chemical compounds
Genus coverage	None apparent from the supplied claims
Drug substance coverage	No
Formulation coverage	No
Method-of-use coverage	No
Process coverage in supplied claims	No
Orange Book relevance	None apparent
Current U.S. enforceability	None because expired
Generic-entry impact	None
Manufacturing relevance	Historical intermediate protection only

During its active term, the patent could have created a manufacturing constraint if a commercial route required one of the claimed compounds. The constraint would have been avoidable through a non-infringing route that did not make, use, sell, or import the claimed intermediates. The claims do not establish that every route to flecainide must pass through one of these molecules.

What licensing or settlement value remains?

The patent has no ordinary present-day U.S. licensing value for exclusivity because it expired more than two decades ago.

Historical licensing may have been relevant to:

Flecainide development;
Supply of protected intermediates;
Cross-border manufacturing;
Technology transfer;
Related patent families covering flecainide or its synthesis.

A current license under this U.S. patent would not provide a live U.S. exclusionary right. Rights in foreign counterparts would require separate country-by-country review because expiration dates, prosecution histories, maintenance payments, and national-phase status may differ.

No settlement involving this expired U.S. patent can now delay a U.S. generic launch through an Orange Book mechanism.

What geographic coverage remains?

The U.S. patent’s territorial scope ended with U.S. expiration. It never directly controlled:

European manufacture;
Canadian manufacture;
Asian manufacture;
Importation into countries outside the United States.

Foreign patent counterparts, if any, would be separate legal rights. Their analysis would require review of the relevant national patents, grant dates, terminal disclaimers, maintenance status, supplementary protection rights, and local claim scope.

The U.S. expiration does not establish that every foreign counterpart expired on the same date.

What patent litigation affects this patent?

The supplied claims do not indicate an active litigation issue. Because the patent expired on February 10, 2004, it cannot support a current U.S. injunction against manufacture or sale of the claimed compounds.

Any historical litigation would require review of court dockets and patent-family records. Such historical disputes would not restore exclusivity or create a current FDA approval barrier.

Key Takeaways

U.S. Patent 4,642,384 claims three specific 2,5-bis(2,2,2-trifluoroethoxy) acetophenone derivatives.
The claims are narrow compound claims, not broad pharmaceutical or process claims.
The compounds are chemically associated with the synthesis of flecainide, but flecainide and flecainide acetate are not claimed.
No supplied claim covers a formulation, therapeutic use, dosage regimen, or finished drug product.
The patent issued February 10, 1987, and expired February 10, 2004.
It has no current U.S. Orange Book, Paragraph IV, generic-entry, or injunction significance.
Any remaining commercial analysis should focus on separate flecainide composition, formulation, method-of-use, process, and foreign patent families.

FAQs

Can a generic manufacturer make flecainide acetate without licensing U.S. Patent 4,642,384?

Yes. The patent expired in 2004 and does not claim flecainide acetate in any event.

Does the patent cover the 2,5-bis(2,2,2-trifluoroethoxy)benzoyl group?

No broad group claim is provided. The supplied claims cover three acetophenone derivatives, not every compound containing that aromatic substituent pattern.

Could a new flecainide formulation infringe this patent?

No. The patent does not claim a formulation, and it is expired.

Are the claimed compounds active pharmaceutical ingredients?

They are best understood as chemical intermediates associated with flecainide synthesis, not as the approved active ingredient flecainide acetate.

Can the expired patent create biosimilar risk?

No. Flecainide acetate is a small-molecule drug, so biosimilar regulation is not the applicable pathway. The expired patent also creates no current regulatory or commercial barrier.

References

U.S. Patent No. 4,642,384. (1987). United States Patent and Trademark Office. https://patents.google.com/patent/US4642384
U.S. Food and Drug Administration. (2023). Flecainide acetate prescribing information. https://www.accessdata.fda.gov
35 U.S.C. § 154. Patent term. https://www.law.cornell.edu/uscode/text/35/154
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Belgium	882318	⤷ Start Trial
Canada	1137486	⤷ Start Trial
Switzerland	643829	⤷ Start Trial
Germany	3010195	⤷ Start Trial
Denmark	112180	⤷ Start Trial
Denmark	122290	⤷ Start Trial
Denmark	164857	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,642,384

Summary for Patent: 4,642,384