United States Patent 4,382,093: Claim Scope, Expiration, and Pirmenol Patent Landscape

U.S. Patent No. 4,382,093 covers pharmaceutical formulations containing certain 9-aminoalkylfluorene antiarrhythmic agents, including 9-(3-isopropylaminopropyl)-9-aminocarbonylfluorene and its hydrochloride salt. The patent issued May 3, 1983, and, under the pre-URAA patent-term rule, expired May 3, 2000, absent an unusual term adjustment or effective extension. The patent therefore does not create a current U.S. blocking right.

The claims are formulation claims rather than composition-of-matter claims directed solely to the active molecule. Their commercial importance centered on formulations containing pirmenol-type compounds, particularly 9-(3-isopropylaminopropyl)-9-aminocarbonylfluorene hydrochloride.

What does U.S. Patent 4,382,093 cover?

The patent claims a pharmaceutical formulation comprising:

A carrier or diluent; and
An antiarrhythmic amount of a defined 9-aminoalkylfluorene compound or pharmaceutically acceptable salt.

Claim 1 is the controlling genus claim. It covers compounds having:

A fluorene core;
A 9-aminoalkyl substituent;
A second 9-position substituent designated Ro;
An aminoalkyl chain containing three, four, or five methylene units;
Broad substitution on the terminal amino group;
Optional alkyl or halogen substitution on the fluorene ring;
Pharmaceutically acceptable salts.

The claim does not require a particular tablet, capsule, injectable, liquid, or release profile. “Carrier or diluent” is broad enough to encompass conventional pharmaceutical excipients, subject to ordinary claim-construction limits.

What is the chemical genus in claim 1?

The principal chemical variables are:

Claim variable	Permitted scope
Ro	Hydroxy, cyano, CONR4R5, or COOR9
R4 and R5	Independently hydrogen or C1-C6 alkyl
R9	Hydrogen or C1-C4 alkyl
R2 and R3	Hydrogen, C1-C6 alkyl, CH2C2-C5 alkenyl, or phenyl-C1-C3 alkyl
R2 and R3 together	Cyclic amino substituent containing A and y as specified
A	CH2, O, or NH
y	Zero or one
n	Three, four, or five
R6 and R7	Independently hydrogen, C1-C4 alkyl, or halogen
Counterion	Any pharmaceutically acceptable salt

The formula reproduced in the claim contains a likely drafting inconsistency: the proviso refers to “R1” even though the principal variable is identified as “Ro.” The intended limitation appears to be that R2 must be hydrogen when the 9-position substituent is hydroxy. The inconsistency would require review of the issued patent drawings, prosecution history, and applicable claim-construction principles before being used in litigation.

Which claims cover pirmenol or pirmenol hydrochloride?

The key product-specific claims are claims 8 through 11.

Claim 8

Claim 8 narrows the terminal amino substituent to isopropyl:

n = 3;
R2 = hydrogen;
R3 = isopropyl;
R6 and R7 = hydrogen;
Ro is limited through the preceding dependency structure.

Claim 9

Claim 9 identifies the active ingredient as:

9-(3-isopropylaminopropyl)-9-aminocarbonylfluorene.

This is the free-base form of the compound.

Claim 10

Claim 10 covers a pharmaceutically acceptable salt of the compound defined in claim 9.

Claim 11

Claim 11 specifically identifies:

9-(3-isopropylaminopropyl)-9-aminocarbonylfluorene hydrochloride.

This is the most commercially focused claim in the set because it addresses the hydrochloride salt used for pharmaceutical development and commercialization.

How narrow are the dependent claims?

The dependent claims progressively move from a broad chemical-formulation genus to a specific antiarrhythmic formulation.

Claim	Limitation
1	Broad formulation genus covering 9-aminoalkylfluorene agents
2	Ro limited to hydroxy, cyano, or CONR4R5
3	n = 3
4	R2 = hydrogen
5	R3 = C1-C6 alkyl
6	R6 and R7 = hydrogen
7	R3 = C1-C3 alkyl
8	R3 = isopropyl
9	Specific free-base active ingredient
10	Pharmaceutically acceptable salt
11	Specific hydrochloride salt
12	Ro = COOR9
13	R9 = C1-C4 alkyl
14	n = 4
15	n = 5

Claims 9 and 11 are substantially narrower than claim 1 but are easier to evaluate against a marketed product. A formulation containing the exact hydrochloride active ingredient would fall within the literal subject matter of claim 11 if the formulation also contains a carrier or diluent and uses the active ingredient in an antiarrhythmic amount.

Is U.S. Patent 4,382,093 a compound patent or a formulation patent?

It is a formulation patent.

The claims require a pharmaceutical formulation. They do not independently claim:

The isolated active compound;
A method of synthesizing the active compound;
A specific tablet coating;
A controlled-release system;
A particular dosage strength;
A method of treating arrhythmia;
A manufacturing process for the drug product.

This distinction limits the patent’s infringement theory. A party that makes the pure compound without formulating it would not necessarily infringe these claims. By contrast, a tablet, capsule, solution, suspension, or other pharmaceutical preparation containing the claimed active ingredient and a carrier or diluent could satisfy the formulation requirement.

What formulations are protected by the patent?

The claims are not limited to a particular dosage form. Potentially covered products include:

Immediate-release tablets;
Capsules;
Oral powders;
Oral solutions or suspensions;
Parenteral preparations containing a suitable carrier;
Salt-based formulations;
Formulations containing conventional diluents or excipients.

The patent does not expressly require:

A particular excipient;
A specific dissolution profile;
A controlled-release matrix;
A particular particle size;
A specific concentration;
A defined pharmacokinetic profile.

The practical scope therefore depends primarily on the identity and substitution pattern of the active ingredient, not on sophisticated formulation technology.

What is the scope of claim 1?

Claim 1 has four principal scope dimensions.

1. Broad Ro substitution

Ro may be hydroxy, cyano, an amide group, or an ester group. This allows multiple 9-substituted fluorene classes to enter the claim.

2. Broad terminal amine substitution

R2 and R3 may independently be hydrogen, alkyl, alkenyl, or phenylalkyl. The claim also covers certain cyclic amines formed by joining R2 and R3 through a heterocyclic structure.

3. Variable linker length

The aminoalkyl chain may contain three, four, or five methylene units. Claims 3, 14, and 15 divide this scope into three-atom, four-atom, and five-atom linker embodiments.

4. Ring substitution

R6 and R7 may be hydrogen, C1-C4 alkyl, or halogen. The preferred dependent claims remove this variability by requiring both positions to be hydrogen.

The broad genus could have faced validity pressure based on written description, enablement, obviousness, or anticipation if a challenger identified earlier antiarrhythmic fluorene compounds or inadequate support for the full Markush scope. The narrower claims directed to the named compound and hydrochloride salt would generally present a more focused validity analysis.

When did U.S. Patent 4,382,093 lose exclusivity?

The patent issued on May 3, 1983. For a U.S. application governed by the pre-June 8, 1995 patent-term regime, the ordinary term was 17 years from issuance. On that basis, the expiration date was May 3, 2000.

Event	Date
Patent issuance	May 3, 1983
Ordinary 17-year expiration	May 3, 2000
Current enforceability	Expired
Current blocking effect	None, subject to any unrelated later patent rights

Patent-term extension under 35 U.S.C. § 156 applies only where statutory regulatory criteria are met and is distinct from patent-term adjustment. A historical regulatory extension would need to appear in the patent and FDA regulatory records. The patent’s original term alone does not support current enforcement.

What is the Orange Book status of the patent?

An expired 1983 patent cannot support current Orange Book exclusivity. FDA Orange Book listings may include historical patents associated with an approved drug, but a patent’s presence in an Orange Book record does not revive an expired patent or create a current right to exclude generic entry.

For a drug product containing the specifically claimed hydrochloride compound, the relevant regulatory questions are separate from the patent’s historical scope:

Whether an approved NDA existed;
Whether the drug remained an active listed product;
Whether any patent was timely submitted for listing;
Whether a patent was expired when an ANDA was filed;
Whether any later formulation, method-of-use, or manufacturing patents existed.

U.S. Patent 4,382,093 itself cannot generate a current 30-month stay under the Hatch-Waxman framework because the patent expired in 2000. A Paragraph IV certification directed solely to this patent would not create a present litigation barrier based on enforceable patent rights.

Does the patent contain method-of-use claims?

No. The claims are directed to formulations “useful in the treatment of cardiac arrhythmias.” That language identifies the intended utility of the formulation, but it does not create a conventional method-of-treatment claim requiring steps such as administering the formulation to a patient.

The patent therefore does not directly claim:

Treating atrial fibrillation;
Treating ventricular tachycardia;
Suppressing premature ventricular contractions;
Administering a defined dose;
Treating a specified patient population.

A later patent could theoretically claim a particular dosing regimen, patient population, combination therapy, or clinical use. Such a later right would need to be analyzed separately from the expired formulation patent.

What manufacturing and intellectual-property barriers remain?

The patent does not claim a manufacturing process. It therefore does not directly block:

Synthesis of the free base;
Formation of the hydrochloride salt;
Crystallization;
Milling;
Granulation;
Tablet compression;
Packaging;
Conventional pharmaceutical processing.

Potential barriers could still arise from separate rights covering:

A proprietary synthetic intermediate;
A salt or polymorph;
A specific crystalline form;
A controlled-release formulation;
A process impurity profile;
A manufacturing route;
A combination product;
A regulatory exclusivity period.

Those rights are not established by the claims supplied for U.S. Patent 4,382,093.

How strong is the patent estate for the claimed antiarrhythmic?

The enforceable strength of this specific patent estate is zero today because the patent has expired. Its historical claim strength was mixed:

Issue	Assessment
Product specificity	Strong for the compound in claims 9 and 11
Formulation breadth	Broad because no dosage form or excipient is specified
Compound-only protection	Absent
Method-of-use protection	Absent
Manufacturing protection	Absent
Current enforceability	None after expiration
Design-around potential during term	Material, particularly through nonclaimed compounds or noninfringing formulations
Generic-entry relevance today	Historical only

During the patent term, a generic or competing manufacturer could have challenged the patent by arguing that its product did not contain the claimed compound, did not contain a carrier or diluent, used a non-claimed salt or chemical species, or did not meet the antiarrhythmic-amount limitation. Validity challenges could have focused on prior art and the breadth of the Markush genus.

Which companies are challenging the patent?

The supplied claim text does not establish a Paragraph IV challenger, ANDA filing, district-court case, Federal Circuit appeal, or settlement agreement. Because the patent expired in 2000, any historical challenge would have no current effect on market entry.

No current biosimilar issue exists. The claimed products are small-molecule chemical drugs, not biological products. The relevant competitive pathway would have been an ANDA under section 505(j) of the Federal Food, Drug, and Cosmetic Act, not a biosimilar application under the Public Health Service Act.

How does this patent compare with typical antiarrhythmic patent estates?

U.S. Patent 4,382,093 is narrower than a conventional modern pharmaceutical estate because it appears to provide only formulation protection for a chemical genus and selected species.

Estate component	U.S. Patent 4,382,093
Composition-of-matter patent	No
Formulation patent	Yes
Method-of-use patent	No
Dose or regimen patent	No
Polymorph patent	Not shown
Manufacturing patent	No
Combination patent	No
Patent-term extension	Not established
Current patent life	None

A stronger commercial estate would normally include the active compound, salts, solid forms, formulations, manufacturing processes, therapeutic indications, dosing regimens, and supplementary patents. The supplied claims cover only one part of that structure.

What generic launch risks existed?

Before expiration, a generic applicant would have faced three principal risks:

Literal infringement risk. A product containing the named hydrochloride active ingredient in a pharmaceutical formulation could have met claim 11.
Equivalents risk. A materially different salt or closely related formulation could have generated a doctrine-of-equivalents dispute, depending on prosecution history and claim amendments.
Regulatory timing risk. A listed patent could have triggered a Paragraph IV notice and litigation-driven stay during the patent term.

After May 3, 2000, those risks no longer arise from this patent. A generic manufacturer’s current exposure would depend on later unexpired patents, regulatory exclusivity, product-specific manufacturing rights, or other non-patent barriers.

Key Takeaways

U.S. Patent 4,382,093 is a formulation patent covering 9-aminoalkylfluorene antiarrhythmic agents.
Claims 9 and 11 focus on 9-(3-isopropylaminopropyl)-9-aminocarbonylfluorene and its hydrochloride salt.
The patent does not claim the active compound alone, a treatment method, a dosage regimen, or a manufacturing process.
The patent issued May 3, 1983, and ordinarily expired May 3, 2000.
It cannot support current Orange Book exclusivity, a current Paragraph IV stay, or a present generic-entry block.
The claims are broad in formulation format but limited by the specified chemical genus.
The product is a small-molecule drug, so biosimilar regulation is not relevant.
Any current freedom-to-operate analysis must focus on later patents, regulatory exclusivity, solid forms, formulations, manufacturing processes, and other rights outside U.S. Patent 4,382,093.

FAQs

Is claim 11 limited to pirmenol hydrochloride tablets?

No. Claim 11 requires the specified hydrochloride active ingredient in a formulation with a carrier or diluent. It is not expressly limited to tablets, a particular dose, or a particular excipient.

Could a formulation containing the free base avoid claim 11?

It could avoid claim 11 if the product does not contain the hydrochloride salt, but claim 9 separately addresses the corresponding free-base active ingredient. Claim 1 may also apply if the formulation satisfies the broader genus limitations.

Does the expired patent prevent a company from selling pirmenol?

No. An expired patent cannot prevent commercial sale. Other unexpired patents, regulatory requirements, or product-specific rights could create separate issues.

Is pirmenol hydrochloride eligible for a biosimilar application?

No. Pirmenol hydrochloride is a small-molecule chemical drug. A generic applicant would use the ANDA pathway rather than the biosimilar pathway.

Can a later patent extend the exclusivity created by U.S. Patent 4,382,093?

No. A later patent cannot extend the term of the 1983 patent. It may protect a distinct invention, such as a polymorph, formulation, manufacturing process, or dosing regimen, if the later claims satisfy patentability requirements.

References

United States Patent and Trademark Office. (1983). U.S. Patent No. 4,382,093.
United States Code, 35 U.S.C. § 154. Patent term.
U.S. Food and Drug Administration. (2025). Approved drug products with therapeutic equivalence evaluations: The Orange Book.
U.S. Food and Drug Administration. (2024). Abbreviated new drug application regulatory review and patent certification requirements.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	225526	⤷ Start Trial
Argentina	227318	⤷ Start Trial
Argentina	228059	⤷ Start Trial
Argentina	228851	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,382,093

Summary for Patent: 4,382,093