US Patent 5,773,443: Voriconazole Claims, Patent Scope, Expiration, and Generic Landscape

US Patent 5,773,443 is the foundational U.S. compound patent for voriconazole, a triazole antifungal marketed by Pfizer as VFEND. Its principal claim covers voriconazole, or a pharmaceutically acceptable salt, defined by a difluorophenyl-substituted triazole antifungal structure. The patent also claims pharmaceutical compositions and treatment of fungal infections, including Aspergillus infections.

The patent expired on June 30, 2015, based on the 17-year term applicable to the pre-URAA patent. It no longer blocks generic voriconazole manufacture or sale in the United States. The patent had substantial historical value because it covered the active pharmaceutical ingredient itself, but its direct exclusionary value is now exhausted.

What drug does US Patent 5,773,443 protect?

US Patent 5,773,443 protects voriconazole, including pharmaceutically acceptable salts of the compound. Voriconazole is a second-generation triazole antifungal structurally related to fluconazole but with a fluoropyrimidine substituent and a substituted triazole-containing alcohol structure.

The active compound is commonly identified as:

Generic name: voriconazole
Brand name: VFEND
Chemical description: (2R,3S)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-2-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol
Therapeutic category: systemic triazole antifungal
Original sponsor: Pfizer Inc.
FDA approval: May 19, 2002

The claim language supplied for claim 1 refers to a formula shown in the patent drawing and defines R as phenyl substituted by two fluoro substituents. In the context of the patent and the approved drug, that substitution pattern identifies the 2,4-difluorophenyl group in voriconazole.

What are the claims of US Patent 5,773,443?

The patent has four relevant claim categories.

Claim	Subject matter	Practical scope
1	Compound of the specified formula, or pharmaceutically acceptable salt, with R as a difluorophenyl group	Active ingredient and covered salts
2	Pharmaceutical composition containing the claim 1 compound and a pharmaceutically acceptable carrier	Drug product compositions
3	Method of treating fungal infection in a mammal by administering the claimed compound or composition	Therapeutic use
4	Method of claim 3 for fungal infection caused by Aspergillus species	Aspergillus-specific use

Claim 1: compound and salts

Claim 1 is the most commercially important claim. It is a product claim directed to the chemical entity rather than to a particular tablet, vial, dosage strength, or manufacturing process.

Its scope reaches:

Voriconazole as the claimed stereochemical compound
Pharmaceutically acceptable salts of the compound
The claimed molecular core with the specified difluorophenyl substitution
Commercial products containing the patented active ingredient, subject to the patent term

The claim does not appear, based on the supplied language, to cover every triazole antifungal. It is limited by the structural formula and the defined R group. Compounds with different substituents, different stereochemistry, or a different heterocyclic arrangement would require a separate infringement analysis.

The structural limitation is important. A generic company cannot avoid claim 1 merely by using a different excipient, tablet coating, or supplier if the finished product contains the claimed voriconazole molecule. A noninfringement position would generally require a meaningful difference in molecular structure, salt status, or claim construction.

Claim 2: pharmaceutical compositions

Claim 2 covers a composition containing an effective amount of the compound and a pharmaceutically acceptable carrier. This language is broad and is not limited to the marketed tablet, injection, or oral suspension unless the claim or specification supplies additional limitations.

Potentially covered dosage forms include:

Immediate-release tablets
Oral suspensions
Intravenous formulations
Solutions or reconstituted products
Other compositions using conventional pharmaceutical carriers

The claim does not, on its face, require a particular excipient, particle size, concentration, release profile, or container system. Those limitations may be relevant to validity or infringement analysis, but they are not stated in the supplied claim.

Claim 2 has less residual significance than claim 1 once the active-ingredient patent expires. A later formulation patent could still create a separate barrier, but claim 2 of Patent 5,773,443 no longer provides enforceable exclusivity after June 30, 2015.

Claim 3: treatment of fungal infection

Claim 3 is a method-of-use claim. It requires administering an effective amount of the claimed compound to a mammal for treatment of a fungal infection.

The claim reaches treatment of fungal infections in mammals without limiting the indication to a named pathogen, body site, dosage, route, or treatment duration. The specification and approved labeling provide important context, but the claim language supplied is broad.

The method claim is directed to conduct by the treating party. In an ANDA case, a generic label that instructs use for a patented indication can create inducement risk even where the generic company does not itself administer the drug. That risk depends on the approved label, the scope of the patent, other noninfringing uses, and the applicable safe-harbor and induced-infringement rules.

Claim 4: Aspergillus infections

Claim 4 narrows claim 3 to fungal infections caused by Aspergillus species. Voriconazole is an important therapy for invasive aspergillosis, and the FDA-approved VFEND label identifies invasive aspergillosis among its indications.

Because claim 4 is narrower than claim 3, it may be easier to distinguish on a claim-scope basis but more directly tied to the drug’s principal clinical use. The claim would not cover treatment of every fungal disease unless the broader method claim is also satisfied.

Does the supplied claim language contain a dependency issue?

Yes. The supplied text states that claim 3 administers “the compound of claim 2,” even though claim 2 is a pharmaceutical composition rather than a compound. That wording is internally inconsistent if reproduced exactly.

A method claim would ordinarily refer to:

The compound of claim 1; or
The composition of claim 2

The legal effect depends on the issued patent text, claim dependency, prosecution history, and any certificate of correction. The issued patent and official prosecution record control over a transcription that omits the formula or misstates the dependency.

This issue does not change the commercial conclusion. Claim 1 is the principal active-ingredient claim, and claim 2 independently addresses compositions.

When did US Patent 5,773,443 expire?

Event	Date
Earliest priority date	December 14, 1993
U.S. patent application	1996
Patent issued	June 30, 1998
FDA approval of VFEND	May 19, 2002
Base patent expiration	June 30, 2015
Current status	Expired

The patent was filed before the effective date of the Uruguay Round Agreements Act patent-term transition rules. Its operative term was therefore generally 17 years from issue, rather than 20 years from the earliest effective nonprovisional filing date. The FDA Orange Book identifies the patent expiration date as June 30, 2015.[2]

A patent term extension based on regulatory review would have appeared in the Orange Book and USPTO records. The principal compound patent is no longer an active U.S. exclusionary right.

What was the FDA and Orange Book status of VFEND?

VFEND received FDA approval for several dosage forms and indications, including:

Tablets
Oral suspension
Intravenous injection
Invasive aspergillosis
Serious infections caused by Scedosporium apiospermum
Serious infections caused by Fusarium species
Certain candidemia and deep-tissue Candida infections
Empirical therapy for febrile neutropenia in specified circumstances

The FDA Orange Book listed US Patent 5,773,443 against VFEND during the period when the patent remained enforceable. The listing was directed principally to the active ingredient and associated approved products rather than to a narrow delivery technology.[2]

Regulatory approval and patent protection were separate. FDA approval authorized marketing based on safety and efficacy. Patent 5,773,443 restricted unauthorized commercial use of the claimed compound and related composition and method claims until expiration.

Which generic companies challenged voriconazole exclusivity?

Voriconazole attracted ANDA activity because the core product patent covered the active ingredient. Publicly reported litigation included Pfizer infringement proceedings involving Apotex and other generic applicants in the mid-2000s.

The central legal issues in an ANDA challenge would have included:

Whether the ANDA product contained the claimed voriconazole structure
Whether the patent claims were valid over prior art
Whether the asserted claims were infringed under the proposed label
Whether a Paragraph IV certification was filed
Whether the applicant could launch before patent expiration

The Federal Circuit decision in Pfizer Inc. v. Apotex, Inc. addressed a patent dispute involving Pfizer’s antifungal product and illustrates the litigation environment surrounding generic entry for this class of medicines.[3]

After expiration of the compound patent, Paragraph IV risk associated specifically with US Patent 5,773,443 ended. A generic applicant could still face separate litigation based on later-listed formulation, manufacturing, or method-of-use patents.

What formulation patents protected voriconazole products?

Patent 5,773,443 is not principally a formulation patent. It claims the compound and broad compositions containing it. Separate patent families may cover particular formulations, manufacturing processes, crystalline forms, particle properties, reconstitution systems, or delivery approaches.

The practical distinction is:

Patent type	Typical protected subject matter	Relevance after compound-patent expiry
Compound patent	Voriconazole molecule and salts	Highest barrier; expired in 2015
Composition patent	Drug plus carrier or dosage-form limitations	May affect specific products if unexpired
Formulation patent	Suspension, injection, stability, excipients, release profile	Product-specific risk
Method-of-use patent	Treatment of a defined infection or patient group	Label and indication-specific risk
Process patent	Synthesis, purification, crystallization, or manufacturing	Manufacturing-route risk
Salt or solid-form patent	Specific crystalline or salt form	Depends on claim coverage and product form

A company assessing a current U.S. generic launch would therefore need to distinguish Patent 5,773,443 from later patent families. The expiration of the base compound patent does not automatically eliminate every possible patent claim concerning a commercial product.

How strong was the patent estate for voriconazole?

Historically, the estate was strong because Patent 5,773,443 contained a product claim to the active ingredient. Product claims generally provide broader enforcement leverage than method-only claims because infringement can be established through commercial manufacture, importation, or sale of the claimed molecule.

The estate’s historical strengths were:

Direct coverage of the approved active ingredient
Coverage of pharmaceutically acceptable salts
Broad composition language
Broad fungal-treatment method language
Specific coverage of Aspergillus treatment
FDA Orange Book listing
A patent term extending more than a decade after FDA approval

Its limitations were:

The claim depended on the precise structural formula
Composition coverage was not necessarily limited to every formulation or product configuration
Method claims could raise label and induced-infringement issues
The patent’s enforceability ended at expiration
Later generic products could rely on the expired compound patent after June 30, 2015

As of 2025, the patent’s strength is historical rather than prospective. It has no remaining blocking value in the United States.

How does voriconazole compare with competing antifungal patent estates?

Drug	Sponsor or originator	Class	Patent-estate profile
Voriconazole	Pfizer	Triazole	Core compound patent US 5,773,443 expired June 30, 2015
Fluconazole	Pfizer	Triazole	Earlier compound estate; generic competition established
Posaconazole	Merck	Triazole	Later compound and formulation patents; delayed-release formulation had separate protection
Isavuconazole	Astellas/Basilea	Triazole	Later-generation compound and prodrug estate
Isavuconazonium sulfate	Astellas/Basilea	Triazole prodrug	Product-specific composition and method claims
Isavuconazole products	Cresemba	Triazole	Later approval and potentially longer remaining patent exposure

Voriconazole had an earlier loss-of-exclusivity profile than posaconazole and isavuconazole because its foundational patent issued in 1998. Its competitive position after 2015 depended on clinical familiarity, hospital protocols, therapeutic drug monitoring, formulation availability, and generic pricing rather than on the expired compound patent.

What generic launch scenarios existed for voriconazole?

The main launch scenarios were:

At-risk launch before patent expiry.
A generic applicant could launch after prevailing in Paragraph IV litigation or securing a settlement permitting early entry. This created damages and injunction risk.
Launch after June 30, 2015.
This was the lowest-risk pathway for the core compound because the principal patent had expired.
Product-specific launch.
A company could enter with tablets, oral suspension, or injection while separately evaluating formulation and method-of-use patents.
Carve-out launch.
A generic could omit a patented indication from its label if the regulatory and patent framework allowed a lawful “skinny label.” This approach would not necessarily eliminate all infringement issues.

The commercial result was broad generic competition in the United States after expiry of the foundational patent. The availability of multiple strengths and dosage forms reduced the practical value of any single remaining product claim unless it targeted a formulation used by the generic.

What geographic coverage did US Patent 5,773,443 provide?

The patent provided rights only in the United States. It did not directly control manufacture, use, importation, or sale in Europe, Japan, Canada, or other jurisdictions.

The corresponding international patent family could contain national counterparts with different:

Claim scope
Filing dates
Patent-term rules
Validity outcomes
Supplementary protection certificates
Regulatory extensions
Litigation histories

The U.S. expiration date cannot be used to calculate foreign expiry dates. Patent rights must be assessed jurisdiction by jurisdiction.

What manufacturing and intellectual-property barriers remain?

After expiration of US Patent 5,773,443, the principal residual barriers are technical and regulatory rather than compound-patent barriers.

Potential barriers include:

Stereochemical control during synthesis
Impurity and degradation control
Reproducible particle characteristics
Oral-suspension stability
Intravenous formulation compatibility
Packaging and reconstitution performance
Bioequivalence for each dosage form
Manufacturing-process patents
Patent claims covering specific solid forms or compositions
Label restrictions tied to remaining method-of-use claims

Voriconazole also has clinically important pharmacokinetic variability and drug-interaction considerations. Those issues can affect product development and labeling, but they do not extend the expired patent term.

Key Takeaways

US Patent 5,773,443 is the foundational U.S. patent for voriconazole.
Claim 1 covers the voriconazole compound and pharmaceutically acceptable salts.
Claim 2 covers pharmaceutical compositions containing the compound.
Claims 3 and 4 cover treatment of fungal infections, with claim 4 focused on Aspergillus infections.
The patent issued June 30, 1998, and expired June 30, 2015.
The patent was listed in the FDA Orange Book for VFEND.
Its historical patent strength came from direct active-ingredient coverage.
Current U.S. generic entry is not blocked by Patent 5,773,443.
Later formulation, manufacturing, solid-form, or method-of-use patents require separate analysis.
The supplied claim text contains a dependency inconsistency in claim 3, which should be checked against the issued patent and prosecution record.

FAQs

Is voriconazole still protected by a U.S. compound patent?

No. The foundational U.S. compound patent, US 5,773,443, expired on June 30, 2015.

Did US Patent 5,773,443 cover voriconazole tablets specifically?

It covered the active compound and broad pharmaceutical compositions. It was not limited to a particular tablet strength, excipient system, or manufacturing process.

Could a generic company sell voriconazole before June 30, 2015?

Only if it defeated the patent, obtained a permitted settlement entry date, or otherwise resolved the patent and regulatory barriers. A Paragraph IV certification could trigger patent litigation.

Does the expired patent cover Aspergillus treatment today?

The claim still describes that method historically, but an expired patent cannot block current U.S. commercial practice.

Are voriconazole injection and oral suspension subject to different patent risks?

Yes. Different dosage forms can implicate separate formulation, stability, process, or composition patents even after the core compound patent expires.

References

U.S. Patent No. 5,773,443. (1998). Triazole antifungal agents. United States Patent and Trademark Office.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.
Pfizer Inc. v. Apotex, Inc., 480 F.3d 1348 (Fed. Cir. 2007).
U.S. Food and Drug Administration. (2021). VFEND (voriconazole) prescribing information. Pfizer Inc.
U.S. Food and Drug Administration. (2002). FDA approves VFEND for serious fungal infections. FDA.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	9002375	Feb 02, 1990

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0440372	⤷ Start Trial	SPC/GB02/031	United Kingdom	⤷ Start Trial
European Patent Office	0440372	⤷ Start Trial	90960	Luxembourg	⤷ Start Trial
European Patent Office	0440372	⤷ Start Trial	02C0030	France	⤷ Start Trial
European Patent Office	0440372	⤷ Start Trial	C300100	Netherlands	⤷ Start Trial
African Regional IP Organization (ARIPO)	223	⤷ Start Trial
African Regional IP Organization (ARIPO)	9000237	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,773,443

Summary for Patent: 5,773,443