United States Patent 4,416,682: Claim Scope, Expiration, and Antifungal Patent Landscape

U.S. Patent No. 4,416,682 covers a broad class of substituted 1,3-bis-triazolyl tertiary alcohols, related salts, metal complexes, ethers and esters, plus pharmaceutical, veterinary, agricultural and therapeutic uses. Claim 3 narrows the patent to 1,3-bis-(1,2,4-triazolyl)-2-(2,4-dichlorophenyl)propan-2-ol. The patent issued on November 22, 1983, and, under the pre-Uruguay Round patent term applicable to the patent, expired no later than November 22, 2000, absent an unusual term adjustment or enforceable extension. The claims therefore present historical, not current, exclusionary risk in the United States.

What does U.S. Patent 4,416,682 cover?

The patent has four principal protection categories:

Claim category	Claims	Protected subject matter
Chemical compounds	1-3	Substituted bis-triazolyl tertiary alcohols and specified derivatives
Pharmaceutical and veterinary compositions	4	Compositions containing a covered compound
Agricultural compositions and uses	5-6	Fungicidal and plant-growth-regulating compositions and application methods
Human and animal treatment	7	Treatment of candidiasis and dermatophyte infections

The central structural concept is a tertiary alcohol bearing:

A substituted phenyl or benzyl group;
Two heteroaryl substituents attached through the adjacent carbon framework; and
Two ring systems in which each Y substituent is either =CH- or =N-.

The =CH- option corresponds to a carbon-containing heteroaryl ring such as an imidazole-type system, while the =N- option broadens the claim to nitrogen-richer heteroaryl systems, including 1,2,4-triazole-type structures.

How broad is independent claim 1?

Claim 1 is a large Markush compound claim. Its breadth comes from several independent variables.

R1 substitution scope

R1 may be phenyl or benzyl substituted with one or more of:

Halogen;
C1-C5 alkyl;
C1-C5 haloalkyl;
C1-C4 alkoxy;
C1-C4 haloalkoxy;
Nitro;
Cyano;
Hydroxy;
C1-C40 alkylthio;
Vinyl;
Phenyl; or
Phenoxy.

For benzyl substituents, the alkyl portion may be unsubstituted or substituted with C1-C4 alkyl, phenyl or chlorophenyl.

The C1-C40 alkylthio limitation is particularly expansive. It permits long-chain thioether substituents that are structurally remote from the core antifungal pharmacophore. Claim 2 narrows this field by limiting the substituent pattern to one, two or three selected groups, including halogen, methyl, methoxy, trifluoromethyl, trifluoromethoxy, phenyl, halophenyl, phenoxy and vinyl.

Heteroaryl alternatives

Each of Y1 and Y2 may independently be =CH- or =N-. On its face, that creates four combinations:

Y1	Y2	Structural consequence
CH	CH	Two carbon-containing heteroaryl rings
CH	N	One carbon-containing and one nitrogen-containing ring
N	CH	The reverse mixed arrangement
N	N	Two nitrogen-containing heteroaryl rings

The actual scope depends on the chemical formula incorporated by the issued patent. The claim language supplied identifies the permitted atom alternatives but does not reproduce the structural drawing needed to assign every combination to a specific ring nomenclature.

Derivatives included in claim 1

Claim 1 expressly covers:

Salts;
Metal complexes;
Methyl, ethyl, propyl and butyl ethers;
Phenyl, benzyl, p-chlorobenzyl, allyl and propargyl ethers;
Acetate esters;
Pivaloate esters;
Benzoate esters;
Tosylate esters; and
Mesylate esters.

This derivative language expands protection beyond the free tertiary alcohol. A compound that avoids the free alcohol by forming one of the specified ethers or esters may remain within claim 1.

What compound is specifically protected by claim 3?

Claim 3 covers:

1,3-Bis-(1,2,4-triazolyl)-2-(2,4-dichlorophenyl)propan-2-ol

This is a species claim. It is narrower than claim 1 but generally more straightforward to evaluate because infringement turns primarily on whether the accused molecule has the specified molecular structure.

The compound has:

A 2,4-dichlorophenyl substituent;
A tertiary alcohol at the central carbon;
Two 1,2,4-triazolyl substituents;
A three-carbon propan-2-ol framework.

A product containing the exact free alcohol would fall within claim 3 if the claim remained enforceable. Specified derivatives could still fall within claim 1 even if they did not literally satisfy claim 3.

What pharmaceutical and veterinary products are covered?

Claim 4 covers a pharmaceutical or veterinary fungicidal composition containing an effective amount of a claim 1 compound with an acceptable diluent or carrier.

This is a composition claim, not a claim to every use of the molecule. It requires:

A covered compound;
A fungicidal pharmaceutical or veterinary purpose; and
A pharmaceutically or veterinary-acceptable carrier or diluent.

The claim could reach oral, topical, injectable or other dosage forms if the formulation contains a covered compound and satisfies the fungicidal-purpose limitation. The claim does not expressly limit the composition to a particular concentration, dosage form, excipient, route or disease.

What agricultural formulations and uses are protected?

Claims 5 and 6 address plant protection.

Claim 5 covers a composition for:

Combating fungi; or
Regulating plant growth,

where the active ingredient is a claim 1 compound.

Claim 6 covers applying an effective amount:

To a plant;
To seed; or
To the locus of a plant or seed.

The agricultural claims are materially broader in use than claim 4 because they are not confined to pharmaceutical or veterinary formulations. They can reach agricultural preparations, seed treatments, soil or locus applications, and foliar applications, subject to the requirement that the active compound fall within claim 1.

The claims do not expressly require a particular crop, fungal species, formulation type, application rate or timing.

What human therapeutic uses are protected?

Claim 7 covers treatment of:

Candidiasis; or
Human dermatophyte infections.

The method requires administering an effective amount of a claim 1 compound to a human or animal.

The claim is narrower than a general antifungal-treatment claim. It does not expressly cover all fungal infections, systemic mycoses, aspergillosis, cryptococcosis or nonfungal indications. It also does not specify a route, dosage regimen, treatment duration or pharmaceutical form.

Because claim 7 covers a method of treatment, it would not ordinarily appear as an Orange Book product patent unless tied to an approved drug and listed under FDA listing rules. The patent number itself is not a substitute for an FDA-approved product listing.

When did U.S. Patent 4,416,682 lose exclusivity?

U.S. Patent 4,416,682 issued on November 22, 1983. Patents governed by the pre-June 8, 1995 term rules generally ran for 17 years from grant rather than 20 years from the earliest effective filing date. On that basis, the ordinary expiration date was November 22, 2000.[1][2]

Event	Date or status
U.S. patent issued	November 22, 1983
Ordinary pre-1995 patent term	17 years from grant
Expected expiration	November 22, 2000
Current enforceability	Expired
Current U.S. generic-blocking value	None from this patent alone

Patent term adjustment was not generally available in the modern form for a patent issued in 1983. Patent term extension under 35 U.S.C. § 156 also would require a qualifying approved product and statutory eligibility. No current enforceable term should be attributed to U.S. Patent 4,416,682 based solely on the patent record.

What is the Orange Book status of U.S. Patent 4,416,682?

U.S. Patent 4,416,682 should not be treated as a current Orange Book patent.

The Orange Book lists patents submitted by sponsors for approved drug products, subject to FDA regulations and listing requirements. An old compound patent can have pharmaceutical claims without ever becoming an Orange Book-listed patent. The patent’s claim 7 treatment language does not establish that the claimed compound was approved by FDA, marketed as a prescription drug or listed against an approved reference product.[3]

The practical result is:

No current Orange Book exclusivity should be assigned to the patent;
No Paragraph IV notice obligation arises merely from the existence of this expired patent;
A generic sponsor would not need to defeat this patent to obtain approval of an unrelated product; and
Any historical Orange Book relevance would depend on a specific approved product and historical listing record.

Were Paragraph IV challenges possible?

A Paragraph IV certification could have been relevant only while the patent was listed against an approved reference drug and remained within its enforceable term. The patent’s expiration removes the principal litigation incentive associated with a current Paragraph IV challenge.

For an ANDA applicant, the relevant questions would have been:

Whether the reference product sponsor listed U.S. Patent 4,416,682;
Whether the patent claimed the approved product, an approved formulation or an approved method of use;
Whether the applicant sought a carve-out from a listed method-of-use claim; and
Whether the patent remained enforceable on the proposed launch date.

Because the patent expired in 2000, a present-day ANDA applicant would ordinarily rely on patent expiration rather than a Paragraph IV challenge to this patent.

What formulation patents are protected?

The patent does not contain a detailed formulation platform. Claim 4 protects a composition containing a covered compound and an acceptable carrier or diluent, but it does not recite:

A particular excipient;
A particle-size distribution;
A polymorph;
A salt-selection process;
A controlled-release matrix;
A liposomal or nanoparticle system;
A specific cream, gel, suspension or tablet composition; or
A defined dissolution or bioavailability profile.

The formulation coverage is therefore ingredient-centered. It may capture conventional formulations containing a claimed compound, but it is weaker than a later patent directed to a narrowly defined dosage form or manufacturing process.

Does the patent cover manufacturing methods?

The supplied claims do not include a chemical process claim. They cover compounds, compositions and therapeutic or agricultural uses.

There is no express claim to:

A synthetic intermediate;
A particular reaction sequence;
A catalyst;
A solvent system;
A crystallization method;
A purification process;
A polymorphic form; or
A method for producing the specific bis-triazolyl alcohol.

A competing manufacturer could therefore face no process-claim barrier from U.S. Patent 4,416,682, although a product made by an alternative process could historically have infringed the compound claim if the resulting molecule fell within claim 1 or claim 3.

How strong was the patent estate?

Strengths

The patent had several features associated with a strong historical compound patent:

A broad Markush claim;
A specific species claim;
Express coverage of salts, complexes, ethers and esters;
Pharmaceutical and veterinary composition claims;
Agricultural composition claims;
Plant-treatment process claims; and
Human and animal treatment claims.

The species claim in claim 3 would have been particularly useful against manufacture or sale of the exact named compound. Claim 1 could have created additional risk for structurally related analogues.

Weaknesses

The principal limitations were:

The patent is expired;
The supplied claims do not include a synthesis claim;
The therapeutic method claim is limited to candidiasis and dermatophyte infections;
The formulation claim lacks detailed formulation limitations;
The patent does not itself establish FDA approval or Orange Book listing;
The claim scope depends heavily on the missing structural drawing and claim construction of the heteroaryl framework; and
Later patents could have covered particular formulations, polymorphs, combinations or manufacturing processes independently.

Which companies or products could challenge the patent?

No current company has a live Paragraph IV exposure to U.S. Patent 4,416,682 solely because the patent expired. Historical challengers would have included generic pharmaceutical companies, agricultural chemical manufacturers and other firms seeking to commercialize compounds structurally within the claim 1 Markush group.

The relevant competitive landscape would have separated into four groups:

Competitor type	Historical risk
Exact-compound manufacturer	High if the compound satisfied claim 3
Close triazole analogue manufacturer	Dependent on claim 1 construction
Generic formulation company	Dependent on compound identity and any listed product patent
Agricultural fungicide manufacturer	Dependent on whether the active ingredient fell within claim 1

Modern antifungal competition is dominated by products such as fluconazole, itraconazole, voriconazole, posaconazole and isavuconazole. Those products have distinct molecular structures and separate patent histories. The existence of a broad historical triazole Markush claim does not establish that each later antifungal falls within U.S. Patent 4,416,682.

How does this patent compare with later antifungal patent estates?

Issue	U.S. Patent 4,416,682	Later antifungal estates
Primary protection	Broad chemical genus and specific species	Often compound, formulation and method combinations
Term	Expired around 2000	Many later patents run into the 2020s or beyond
FDA relevance	Not established by the patent	Often linked to approved reference products
Orange Book relevance	Not established	Common for approved drug products
Manufacturing claims	None apparent in supplied claims	Frequently included in later continuation families
Formulation detail	General carrier language	Often specific to dosage form and delivery system
Litigation value today	None as an enforceable U.S. patent	Depends on remaining patent and regulatory exclusivity

The older patent is best understood as an originating compound-and-use patent, not as a modern product lifecycle estate.

What is the geographic coverage?

U.S. Patent 4,416,682 provides rights only in the United States. Corresponding foreign applications may have existed in jurisdictions sharing the same priority family, but U.S. expiration does not determine foreign status.

For freedom-to-operate analysis, each jurisdiction requires separate review of:

The national patent;
Continuations and divisionals;
Patent term rules;
Supplementary protection certificates;
National prosecution history;
Maintenance fee status;
Reexamination or opposition records; and
Local product and regulatory exclusivity.

The U.S. patent’s expiration does not eliminate a foreign patent that had a different term or supplemental protection.

What generic launch risks remain?

For the United States, the direct launch risk from U.S. Patent 4,416,682 is effectively zero because the patent expired more than two decades ago.

Residual commercial risks could arise only from separate rights, such as:

A later patent on a specific salt or polymorph;
A later formulation patent;
A process patent;
A combination patent;
A patent on a different therapeutic indication;
Regulatory exclusivity associated with a separately approved product; or
State or federal regulatory requirements unrelated to patent scope.

Those risks cannot be attributed to U.S. Patent 4,416,682 itself.

Key Takeaways

U.S. Patent 4,416,682 claims a broad class of substituted bis-triazolyl tertiary alcohols.
Claim 3 specifically covers 1,3-bis-(1,2,4-triazolyl)-2-(2,4-dichlorophenyl)propan-2-ol.
Claim 1 extends to specified salts, metal complexes, ethers and esters.
Claims 4-7 cover pharmaceutical, veterinary, agricultural and therapeutic uses.
The patent issued November 22, 1983, and ordinarily expired November 22, 2000.
It is not a current source of U.S. patent exclusivity.
The supplied claims do not include a manufacturing-process claim.
The patent does not establish FDA approval or current Orange Book listing.
Present-day generic launch analysis should focus on later patents, regulatory exclusivity and any separate foreign rights.

FAQs

Does U.S. Patent 4,416,682 cover fluconazole?

Not based on the claims provided. Fluconazole has a different molecular structure and must be compared against the complete structural formula and prosecution history before any infringement conclusion.

Is claim 3 stronger than claim 1?

Claim 3 is narrower but easier to evaluate because it identifies one specific compound. Claim 1 is broader but more dependent on interpretation of the Markush formula, heteroaryl alternatives and derivative language.

Can an expired compound patent block a generic launch?

No. An expired U.S. patent cannot block commercialization, although separate unexpired patents or regulatory exclusivities may remain relevant.

Does claim 7 cover every candidiasis treatment?

No. Claim 7 is limited to treatment using a claim 1 compound and is directed to candidiasis or human dermatophyte infections. It does not expressly cover every antifungal compound or every fungal disease.

Are the ethers and esters automatically covered as prodrugs?

They are expressly included in claim 1 when they match the listed ether or ester categories. Their historical coverage does not depend on whether they were characterized as prodrugs, although chemical identity and claim construction would control.

References

United States Patent and Trademark Office. (1983). U.S. Patent No. 4,416,682.
United States Code. (1982). 35 U.S.C. § 154 (pre-1995 patent term provisions).
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, 44th ed. [Orange Book]. FDA.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	8017959	Jun 02, 1980
United Kingdom	8109923	Mar 30, 1981

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	229803	⤷ Start Trial
Austria	17944	⤷ Start Trial
Austria	24476	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,416,682

Summary for Patent: 4,416,682