United States Drug Patent 5,116,844: Claim Scope, Voriconazole Coverage, Expiration, and Patent Landscape

U.S. Patent No. 5,116,844 is an antifungal compound patent assigned to Pfizer. Its claims cover a broad genus of substituted aryl, heteroaryl, and triazole-containing tertiary alcohols, together with pharmaceutical compositions and human antifungal treatment methods. The claims narrow through specific aryl substitution patterns, heteroaryl groups, methyl substitution, selected compounds, and Aspergillus infections.

The patent is historically important to the U.S. patent estate for voriconazole, marketed as Vfend. Its composition and method claims are no longer an effective U.S. exclusivity barrier. The patent was granted on May 26, 1992, and its relevant commercial protection ended in the 2011 period after statutory patent-term adjustments and pediatric exclusivity considerations reflected in the FDA product record. Current generic competition is governed primarily by later formulation, process, and regulatory requirements rather than by the expired claims of U.S. Patent 5,116,844.

What does U.S. Patent 5,116,844 protect?

The patent protects antifungal compounds built around a substituted tertiary alcohol framework containing:

A substituted phenyl group, designated R0.
An alkyl group, designated R1.
Hydrogen or a lower alkyl group, designated R2.
A nitrogen-containing heteroaryl group, designated Het'.
A triazole-containing side chain in the illustrated core structure.
Pharmaceutically acceptable acid-addition salts.
Pharmaceutical compositions containing the compounds.
Human treatment methods using the compounds.

The claims are drafted as a descending scope hierarchy. Claim 1 covers a pharmaceutical composition. Claim 2 covers the corresponding method of treating a fungal infection. Claims 3 through 9 progressively narrow the chemical structure and the disease indication.

The claim language uses “comprises,” which generally makes the composition and method claims open-ended. A product or treatment can therefore contain additional excipients, active ingredients, or treatment steps without avoiding the claim solely because of those additions.

How broad is the chemical genus in claim 1?

Claim 1 is the broadest enforceable claim presented in the set. It covers a pharmaceutical composition containing an antifungal-effective amount of any compound within the specified structural genus, or a pharmaceutically acceptable acid-addition salt.

R0: substituted phenyl

R0 is mono- or disubstituted phenyl. The permitted substituents are:

Chloro
Fluoro
Bromo
Trifluoromethyl

This limitation excludes unsubstituted phenyl and phenyl groups carrying substituents outside the listed halogen and trifluoromethyl classes. The claim does not restrict the substitution positions at this level, so positional isomers can fall within the genus if the remaining structural requirements are met.

R1 and R2: lower alkyl substitution

R1 is alkyl containing one to four carbon atoms. R2 is hydrogen or alkyl containing one to four carbon atoms.

The practical scope includes methyl, ethyl, propyl, and butyl groups, together with branched lower-alkyl variants where the term “alkyl” is interpreted in its ordinary patent-law sense. Claim 4 narrows R1 to methyl and R2 to hydrogen.

Het': nitrogen-containing heteroaryl groups

Het' may be:

Pyridinyl
Pyridazinyl
Pyrimidinyl
Pyrazinyl
Triazinyl

The heteroaryl group may also contain one or more listed substituents, including lower alkyl, lower alkoxy, halogen, trifluoromethyl, cyano, nitro, amino, alkanoylamino, or alkoxycarbonylamino groups.

This creates a broad heteroaryl genus. The claim is not limited to one ring system or one positional isomer. A substituted pyrimidine or pyridine can fall within the claim even when its substitution pattern differs from the compounds identified in the narrower claims.

What do claims 2 through 9 add?

Claim	Claim type	Main limitation
1	Composition	Broad antifungal composition containing the defined compound genus
2	Method	Human treatment method using the same broad genus
3	Method	R0 narrowed to fluoro-, difluoro-, chloro-, or dichlorophenyl; Het' narrowed to listed heteroaryl groups, optionally cyano-substituted
4	Method	R1 is methyl and R2 is hydrogen
5	Method	R0 is 2-chlorophenyl, 2-fluorophenyl, 2,4-dichlorophenyl, or 2,4-difluorophenyl; Het' is 2-pyridinyl, 4-pyridinyl, or 4-pyrimidinyl
6	Method	Three specifically identified compounds
7	Method	One compound from claim 6
8	Method	Treatment of an Aspergillus infection
9	Method	Treatment of Aspergillus fumigatus infection

Claims 3 through 7 are structurally narrower than claims 1 and 2. Claims 8 and 9 add a microbiological limitation rather than another structural limitation. A treatment must satisfy both the compound limitation and the specified Aspergillus limitation to fall within those claims.

Does U.S. Patent 5,116,844 cover voriconazole?

The patent is closely associated with the voriconazole chemical family and was part of the historical U.S. patent estate relied on by Pfizer for Vfend. Voriconazole is a triazole antifungal used against invasive fungal infections, including infections caused by Aspergillus species.

The specific compound identified in claim 7 should not be equated automatically with the approved active ingredient without comparing the complete structural formula, including heteroaryl substitution and stereochemistry. The claim set supplied in the question identifies a pyrimidin-4-yl compound, while voriconazole is generally identified as a substituted fluoropyrimidinyl triazole alcohol. The broad genus in claim 2 is more important for coverage analysis than the isolated wording of claim 7.

A proper infringement analysis would require:

The complete chemical structure represented by the missing “STR” formula.
The exact substitution position and identity on the heteroaryl ring.
The stereochemical configuration.
Whether the commercial active ingredient is present as a claimed salt or free base.
The applicable claim construction for “compound of the formula.”

On the claim text provided, the strongest historical relevance to voriconazole is the broad genus in claims 1 and 2 and the narrower Aspergillus treatment claims in claims 8 and 9.

What is the patent expiration status of U.S. Patent 5,116,844?

U.S. Patent 5,116,844 was granted on May 26, 1992. Because it is a pre-Uruguay Round patent, the ordinary term framework was generally 17 years from grant, subject to statutory patent-term adjustment and any patent-term extension under 35 U.S.C. § 156.

Event	Date or period
U.S. patent grant	May 26, 1992
Nominal 17-year term from grant	May 26, 2009
Commercial protection after applicable adjustments	2011 period
Current U.S. enforceability	Expired

The FDA Orange Book and Pfizer’s historical Vfend litigation record treated the patent as an Orange Book-listed barrier during the pre-generic period. Generic voriconazole approvals and launches occurred after the relevant patent and regulatory exclusivity barriers ended.

The patent cannot currently block a U.S. generic launch. It also cannot support a new Paragraph IV litigation campaign because an expired patent no longer creates prospective infringement liability for ordinary commercial manufacture, use, or sale.

What was the Orange Book status of the patent?

U.S. Patent 5,116,844 was listed in connection with Pfizer’s Vfend products. Orange Book listings can cover patents claiming the active ingredient, a formulation, or an approved method of use. The patent at issue is principally a compound and method-of-treatment patent.

The listing had commercial significance because an ANDA applicant seeking approval for voriconazole could have faced:

A Paragraph IV certification asserting that the patent was invalid, unenforceable, or not infringed.
A 30-month stay of FDA approval if the NDA holder or patent owner filed timely infringement litigation.
Litigation over whether the generic active ingredient fell within the listed genus.
Disputes concerning claim scope, stereochemistry, and the relationship between the patented genus and the approved voriconazole structure.

That regulatory framework is historical for this patent. The patent’s expiration removes the statutory basis for a current Orange Book stay.

Which companies challenged the Vfend patent estate?

Pfizer faced generic challenges to the Vfend franchise from companies seeking U.S. approval of voriconazole products. Publicly reported generic entrants included Teva and other ANDA sponsors. The litigation strategy generally involved Paragraph IV challenges to listed patents and disputes over the timing of generic approval.

The commercial outcome was generic entry after expiration of the principal patent barriers. The relevant competitive issue was not biosimilar substitution. Voriconazole is a chemically synthesized small molecule, so the applicable pathway is an ANDA under section 505(j) of the Federal Food, Drug, and Cosmetic Act, not a biosimilar application under the Public Health Service Act.

What formulation patents protected Vfend?

Vfend was commercialized in multiple dosage forms, including:

Oral tablets
Oral suspension
Intravenous formulation

The compound patent did not by itself protect every formulation-specific technical feature. Separate patent claims may address:

Solubility enhancement.
Stabilized aqueous suspensions.
Injectable compositions.
Excipients and pH control.
Manufacturing processes.
Solid-state or crystalline forms.
Dosage regimens and treatment methods.

For current freedom-to-operate analysis, an expired compound patent must be separated from later formulation and process patents. A generic product can avoid an expired compound patent while still requiring review of surviving patents directed to a particular formulation, manufacturing process, dosage regimen, or use.

The principal generic products generally rely on alternative formulation designs or non-infringing manufacturing processes. A generic tablet need not copy Pfizer’s excipient system if it meets the FDA’s bioequivalence requirements.

What method-of-use scope remains in claims 8 and 9?

Claim 8 covers treating an Aspergillus infection with a qualifying compound. Claim 9 narrows the infection to Aspergillus fumigatus.

These claims have two distinct limitations:

The administered compound must fall within the chemical scope incorporated from claim 6.
The infection must satisfy the Aspergillus limitation in claim 8 or the A. fumigatus limitation in claim 9.

The claims do not cover every use of every triazole antifungal against Aspergillus. They are limited to the claimed structural class and the claimed treatment context. They also do not necessarily cover prophylaxis, nonhuman treatment, environmental antifungal use, or treatment of fungal species outside the claim language.

Because the patent has expired, these distinctions now matter mainly for historical validity analysis, patent-landscape reconstruction, and freedom-to-operate records.

How strong was the patent estate?

Historically, the patent was commercially strong because it combined:

A broad chemical genus.
Pharmaceutical composition coverage.
Human treatment claims.
Narrower fallback claims directed to specific aryl and heteroaryl combinations.
Aspergillus-specific method claims.
A relationship to a clinically important systemic antifungal product.

Its main weakness was term exhaustion. The patent was filed and granted under an older patent-term regime, so the commercial life of the patent was substantially shorter than the modern 20-year-from-effective-filing framework used for later applications.

The estate also depended on claim construction. Broad genus claims can face validity and enablement challenges when they cover many combinations of substituents and heteroaryl groups. Narrow claims provide stronger structural precision but cover fewer commercial alternatives.

What generic entry risks existed?

Before expiration, the main generic-entry risks were:

Risk	Relevance
Paragraph IV litigation	High for listed compound and method claims
30-month FDA stay	Possible after timely patent litigation
Claim construction disputes	Significant because of broad genus language
Stereochemistry disputes	Relevant to the active ingredient and intermediates
Formulation patent exposure	Dependent on the generic dosage form
Method-of-use carve-out	Relevant where the generic label omitted protected indications
Manufacturing-process patents	Dependent on process identity and claim scope
Regulatory exclusivity	Separate from patent expiration

After expiration, the risk profile changed. The main barriers became FDA approval, bioequivalence, supply-chain reliability, manufacturing compliance, and any unexpired formulation or process patents.

How does this patent compare with a modern pharmaceutical patent?

U.S. Patent 5,116,844 reflects an older small-molecule drafting strategy:

Broad genus claims at the front.
Lower-alkyl and halogen substitution definitions.
Composition and method claims in parallel.
Species claims as fallback positions.
Disease-specific claims for clinically important pathogens.

Modern drug estates commonly divide protection among separate patents covering:

The active ingredient.
Specific stereoisomers.
Polymorphs and salts.
Formulations.
Dosing regimens.
Combination therapy.
Manufacturing intermediates.
Crystalline forms.
Biomarker-defined patient populations.

The 5,116,844 patent concentrated much of the basic chemical and therapeutic coverage in one patent family. That structure supported early product exclusivity but left less opportunity to extend protection through later formulation and use patents than is common in current pharmaceutical portfolios.

What is the current commercial and regulatory significance?

Voriconazole remains an FDA-approved systemic antifungal for specified invasive fungal infections. The product is available through generic competition, and U.S. market access is based on ANDA approval rather than biosimilar interchangeability.

The expired patent has no current blocking effect on:

Generic voriconazole tablets.
Generic oral suspension products.
Generic injectable products, subject to formulation and manufacturing compliance.
New antifungal products that do not practice a live patent claim.
Research involving the claimed compounds, subject to other applicable legal restrictions.

No biosimilar risk analysis is appropriate for voriconazole because it is not a biologic. The competitive landscape is a small-molecule generic market with potential differentiation through dosage form, supply reliability, hospital contracting, and formulation performance.

Key Takeaways

U.S. Patent 5,116,844 covers a broad class of substituted triazole antifungal compounds, pharmaceutical compositions, and human treatment methods.
Claims 1 and 2 are the principal genus claims.
Claims 3 through 7 narrow the chemical structure to selected aryl, heteroaryl, alkyl, and specific compound embodiments.
Claims 8 and 9 target Aspergillus and Aspergillus fumigatus treatment.
The patent is historically linked to Pfizer’s voriconazole/Vfend franchise.
The missing structural formula prevents a final compound-by-compound infringement conclusion from the text alone.
The patent was granted on May 26, 1992, and its commercial protection ended in the 2011 period.
It is expired and cannot support a current Paragraph IV litigation barrier.
Voriconazole is a small molecule subject to ANDA competition, not biosimilar regulation.
Current freedom-to-operate analysis should focus on later formulation, process, solid-state, and dosing patents rather than U.S. Patent 5,116,844.

FAQs About U.S. Patent 5,116,844

Is U.S. Patent 5,116,844 still enforceable?

No. The patent’s relevant U.S. protection expired in the 2011 period.

Is voriconazole protected by a biologic patent?

No. Voriconazole is a chemically synthesized small molecule. Generic versions use the ANDA pathway.

Can a generic company still receive a Paragraph IV challenge based on this patent?

No. An expired patent does not create a current Paragraph IV litigation barrier.

Do claims 8 and 9 cover all Aspergillus treatments?

No. They require both the claimed compound structure and the specified Aspergillus treatment limitation.

Does the patent cover every formulation of voriconazole?

No. The patent’s composition claims cover compositions containing qualifying compounds, but later formulation-specific patents may raise separate questions. The patent does not automatically capture every formulation design or manufacturing process.

References

U.S. Patent and Trademark Office. (1992). U.S. Patent No. 5,116,844: Antifungal compounds. Washington, DC: U.S. Department of Commerce.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book. Silver Spring, MD: U.S. Department of Health and Human Services.
U.S. Food and Drug Administration. (2002). Vfend (voriconazole) prescribing information. Silver Spring, MD: U.S. Department of Health and Human Services.
U.S. Food and Drug Administration. (n.d.). Abbreviated new drug application pathway. Silver Spring, MD: U.S. Department of Health and Human Services.
Pfizer Inc. (2002). Vfend product labeling and regulatory information. New York, NY: Pfizer Inc.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	8819308	Aug 13, 1988

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
African Regional IP Organization (ARIPO)	104	⤷ Start Trial
African Regional IP Organization (ARIPO)	8900135	⤷ Start Trial
Argentina	246963	⤷ Start Trial
Austria	101600	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,116,844

Summary for Patent: 5,116,844