U.S. Patent 6,037,353: Claim Scope, Fexofenadine Coverage, Expiration, and Patent Landscape

U.S. Patent No. 6,037,353 protects a patient-selection and treatment method using fexofenadine-related compounds in patients with impaired liver function, where terfenadine treatment could create cardiac risk. The patent does not claim fexofenadine as a composition of matter. Its claims are directed to a narrow method of treatment defined by the patient’s hepatic status, the avoidance of terfenadine-associated cardiac events, and administration of specified antihistaminic compounds.

The most commercially important subject matter is racemic fexofenadine in claim 5 and the individual R and S enantiomers in claims 6 and 7. The patent was granted on March 14, 2000, and its ordinary 20-year patent term ran from the applicable nonprovisional filing date, placing expiration in 2017. The patent is therefore expired and does not currently create an enforceable U.S. patent barrier to generic fexofenadine products. [1]

What does U.S. Patent 6,037,353 cover?

The patent covers a method of treating a histamine-mediated condition in a patient with impaired liver function while avoiding cardiac events associated with terfenadine.

The independent claim requires all of the following:

A patient has a histamine-mediated condition.
The patient has impaired liver function caused by disease or by a concomitant drug that inhibits normal liver metabolism.
The treatment is conducted while avoiding cardiac events associated with terfenadine.
The patient receives an effective antihistaminic amount of a compound within the claimed chemical genus.
The compound is administered as the free acid, an ester, a pharmaceutically acceptable salt, or an individual isomer.

The claim is therefore both chemically and clinically limited. It is not a broad claim to every use of fexofenadine, every antihistamine treatment, or every patient with liver disease.

Claim structure of U.S. 6,037,353

Claim	Scope	Commercial relevance
1	Genus method claim covering specified piperidine antihistamine derivatives, salts, and individual isomers	Broadest claim; limited by hepatic impairment and terfenadine-cardiac-event avoidance
2	Claim 1, with R1 as hydroxy	Narrows the side-chain structure
3	Claim 2, with n = 3	Defines the four-carbon linker associated with fexofenadine
4	Claim 3, with A and B both hydrogen	Removes hydroxyl substitution on the diphenylmethyl group
5	Treatment using fexofenadine, identified by its full chemical name	Principal racemic fexofenadine claim
6	Treatment using the R enantiomer of fexofenadine	Enantiomer-specific method claim
7	Treatment using the S enantiomer of fexofenadine	Enantiomer-specific method claim

[1]

What compound is claimed by U.S. Patent 6,037,353?

The principal compound is fexofenadine, also known as 4-[1-hydroxy-4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]butyl]-alpha,alpha-dimethylbenzeneacetic acid.

Fexofenadine is the active carboxylic-acid metabolite of terfenadine. Terfenadine was associated with QT-interval prolongation and serious ventricular arrhythmias when administered at excessive exposure levels or with drugs that inhibited CYP3A4 metabolism. Fexofenadine was developed as a nonsedating antihistamine with substantially lower cardiac liability than terfenadine. [2]

The chemical limitations in the claims operate as follows:

R1 may be hydrogen or hydroxy.
R2 is hydrogen, or R1 and R2 together form a double bond.
n may range from 1 to 5.
R3 may be a carboxylic acid or a C1-C6 alkyl ester.
A and B may independently be hydrogen or hydroxy, but at least one must be hydrogen.
Pharmaceutically acceptable salts and individual isomers are included.

Claim 5 identifies the fexofenadine structure directly. Claims 6 and 7 separately cover its R and S stereoisomers. The claims do not expressly require the hydrochloride salt, although the pharmaceutically acceptable salt language encompasses fexofenadine hydrochloride.

How broad is claim 1 compared with claims 5, 6, and 7?

Claim 1 is a genus claim. Claims 5 through 7 are species claims directed to fexofenadine and its enantiomers.

Claim 1 reaches compounds with structural variation at several positions. It potentially covers:

Unsaturated or hydroxy-substituted side chains;
Linker lengths from one to five carbon units;
Carboxylic acids and lower alkyl esters;
Hydroxy substitution on the diphenylmethyl portion;
Salts and individual stereoisomers.

The breadth of claim 1 is constrained by the treatment context. A compound falling within the chemical formula does not infringe merely because it is manufactured, sold, or administered. The claimed use must involve the specified hepatic-impairment population and the stated objective of avoiding terfenadine-associated cardiac events.

Claims 5, 6, and 7 are narrower chemically but easier to analyze against a product-specific treatment protocol. A treatment using fexofenadine in the claimed patient population is the clearest target of the patent. The enantiomer claims could become relevant only if an R- or S-fexofenadine product were developed and marketed for the claimed use.

What formulations are protected by U.S. 6,037,353?

The patent does not claim a tablet, capsule, liquid, orally disintegrating tablet, suspension, dosage regimen, excipient system, particle-size distribution, polymorph, or manufacturing process.

Its salt language covers pharmaceutically acceptable salts, including fexofenadine hydrochloride, but that coverage is part of a method claim. The patent does not independently protect the salt as a composition.

A formulation would fall within the patent only when the formulation is used in the claimed method and the administered active ingredient satisfies the structural limitations. A conventional fexofenadine hydrochloride tablet used for ordinary seasonal allergic rhinitis in a patient without the specified hepatic impairment would not satisfy the full claim 1 limitation.

When did U.S. Patent 6,037,353 expire?

The patent was granted on March 14, 2000. Its ordinary U.S. patent term expired in 2017 based on the applicable filing and priority records. Public patent records identify a 1997 priority date and a 1998 U.S. filing history. The patent is now expired. [1]

Event	Date or status
Earliest reported priority	1997
U.S. application filing	1998
Patent grant	March 14, 2000
Ordinary patent-term endpoint	2017
Current status	Expired
Current enforceability	No live exclusionary right based on the expired patent

Patent expiration removes the ability to obtain damages or injunctive relief for post-expiration conduct. It does not eliminate the historical relevance of the patent in earlier generic-entry disputes or patent-term calculations.

What was the FDA Orange Book status of this patent?

The Orange Book identifies patents submitted by NDA sponsors for approved drug products. Allegra, the original branded fexofenadine product, was approved by the FDA as an antihistamine. [3]

Patent 6,037,353 was directed to a method of use rather than a composition or formulation. If listed for an Allegra or fexofenadine NDA, its practical role would have been as a method-of-use patent. An ANDA applicant could address such a listing through a Paragraph IV certification or, where the applicant did not seek the patented indication, a section viii statement carving out the use.

The commercial impact of a method-of-use listing depends on three factors:

Whether the patented use appears in the reference-labeling indication;
Whether the generic applicant seeks that indication;
Whether the applicant can omit the patented use through a permissible skinny label.

Because the patent has expired, it no longer blocks FDA approval or commercial launch on its own. Current Orange Book status should be evaluated against the relevant NDA and product listing rather than the patent’s historical existence. [3]

What Paragraph IV challenges affected fexofenadine?

Fexofenadine faced generic competition through the ANDA pathway after the relevant composition, formulation, and method patents expired or became vulnerable to challenge. Paragraph IV certifications are used when an ANDA applicant asserts that a listed patent is invalid, unenforceable, or not infringed. The certification can trigger a 45-day period for the NDA holder to file patent litigation and can create a statutory approval stay of up to 30 months. [4]

For Patent 6,037,353, the key issue would have been the distinction between:

A generic fexofenadine product intended for ordinary antihistamine indications; and
A generic product whose labeling expressly included treatment of patients with impaired liver function while avoiding terfenadine-associated cardiac events.

A generic applicant could argue noninfringement if its proposed labeling omitted the patented patient population or use. The patent holder, in turn, would need to establish that the proposed product and labeling induce performance of every material claim limitation.

The patent’s method format created a narrower enforcement pathway than a composition-of-matter patent. A compound patent can reach manufacture, sale, and use of the active ingredient. Patent 6,037,353 required proof tied to a specific clinical use.

What patent litigation affects U.S. Patent 6,037,353?

The patent document establishes the claims and prosecution history but does not itself provide a complete litigation record. The relevant legal exposure historically would have centered on infringement, validity, written description, enablement, and claim-construction issues.

Likely infringement issues

A claimant would need to prove that the accused treatment protocol includes:

A histamine-mediated condition;
Hepatic impairment caused by disease or an interacting drug;
Administration of an effective amount of a claimed compound; and
The claimed avoidance of terfenadine-associated cardiac events.

The phrase “while avoiding cardiac events associated with the administration of terfenadine” could generate claim-construction disputes. It may be read as a treatment objective or as a substantive method limitation. The narrower the interpretation, the more difficult infringement becomes where a generic label does not expressly identify the avoidance objective.

Likely validity issues

Potential validity challenges would include:

Anticipation by earlier disclosures of fexofenadine or related metabolites;
Obviousness based on terfenadine metabolism and antihistamine research;
Written-description support for the full chemical genus;
Enablement across the range of linker lengths, ester groups, substitutions, salts, and stereoisomers;
Indefiniteness involving the “avoiding cardiac events” language.

The patent’s inclusion of the specific fexofenadine species in claims 5 through 7 reduces dependence on the validity of the broad genus claim.

How strong is the patent estate for fexofenadine?

The estate was commercially significant during the protected period but is no longer a current barrier because the principal patents have expired.

Patent-strength assessment

Factor	Assessment
Composition-of-matter protection	Historically stronger than the method claim, but expired
Method-of-use protection	Narrower; limited to hepatic impairment and terfenadine cardiac-risk avoidance
Formulation protection	Not the principal subject of Patent 6,037,353
Enantiomer protection	Claims 6 and 7 provide specific stereochemical coverage
Generic vulnerability	High after expiration; previously dependent on labeling and claim construction
Current blocking power	None from Patent 6,037,353
Manufacturing barrier	None created by this patent
Geographic reach	United States only

The patent estate should be separated into three layers:

Core fexofenadine chemical patents.
Formulation, salt, polymorph, or dosage-form patents.
Method-of-use patents such as U.S. 6,037,353.

Patent 6,037,353 was the third category. It could supplement core exclusivity but could not replace a composition patent as a barrier to manufacture or sale.

How does fexofenadine compare with competing antihistamines?

Fexofenadine competed primarily with loratadine, desloratadine, cetirizine, and levocetirizine in the second-generation antihistamine market.

Drug	Active ingredient	Principal commercial distinction	Generic pathway
Allegra	Fexofenadine	Active metabolite of terfenadine; low sedating profile	ANDA
Claritin	Loratadine	Nonsedating oral antihistamine	ANDA
Clarinex	Desloratadine	Active metabolite of loratadine	ANDA
Zyrtec	Cetirizine	Potent antihistamine; sedation can occur in some users	ANDA
Xyzal	Levocetirizine	Enantiomer of cetirizine	ANDA

Fexofenadine’s regulatory and commercial positioning depended on the safety distinction from terfenadine. That distinction is central to Patent 6,037,353 because the claims expressly connect treatment in impaired hepatic patients with avoidance of terfenadine-associated cardiac events.

What licensing deals and commercial rights are relevant?

The patent was associated with the Hoechst Marion Roussel research and commercial lineage that later became part of Aventis and Sanofi. Allegra was commercialized through the original innovator organization and related commercial partners. The patent record does not establish a separate license specifically limited to U.S. Patent 6,037,353.

Relevant commercial transitions include:

Hoechst Marion Roussel as the historical innovator organization;
Aventis following the Hoechst and Rhône-Poulenc combination;
Sanofi following the Aventis acquisition;
Later generic manufacturers entering through FDA-approved ANDAs.

A corporate transaction or product commercialization agreement does not extend the patent term. Any license would have contractual significance, but the patent’s statutory expiration controls enforceability against third parties.

What generic launch risks existed, and what risks remain?

Before expiration, generic launch risk depended on the product’s labeling and the remaining fexofenadine patent portfolio.

Pre-expiration risks

A generic applicant faced:

Paragraph IV litigation risk;
A possible 30-month FDA approval stay;
Induced-infringement allegations based on labeling;
Risk that a proposed indication would read directly on the patented hepatic-impairment method;
Separate challenges involving formulation or composition patents;
Potential launch-at-risk exposure before final judgment.

Post-expiration risks

Patent 6,037,353 no longer creates a current launch barrier. Remaining risks are commercial and regulatory:

ANDA approval timing;
Bioequivalence failure;
Product-specific FDA requirements;
Controlled launch strategy and price erosion;
Competing generic suppliers;
Trademark and trade-dress restrictions involving Allegra branding.

Fexofenadine is a small molecule. Biosimilar law does not apply. Competition proceeds through the ANDA pathway under section 505(j) of the Federal Food, Drug, and Cosmetic Act, not through the biosimilar pathway under section 351(k) of the Public Health Service Act. [4,5]

Does the patent create manufacturing or geographic barriers?

No. Patent 6,037,353 is a U.S. method-of-treatment patent. It does not claim:

A manufacturing process;
A synthetic intermediate;
A crystallization process;
A particular polymorph;
A dosage-form technology;
A device or delivery system;
Foreign rights outside the United States.

A manufacturer could have faced U.S. infringement risk if it supplied a product with knowledge that it would be used in the claimed method and the required inducement elements were established. The patent did not independently prevent manufacture or sale of fexofenadine for noninfringing uses.

Foreign market access required separate analysis of corresponding national patents. A U.S. patent cannot block manufacture, sale, or use in Europe, Canada, Japan, or other jurisdictions.

Key Takeaways

U.S. Patent 6,037,353 is a method-of-treatment patent, not a composition-of-matter patent.
Its central use is fexofenadine treatment in patients with impaired liver function where terfenadine-associated cardiac events are to be avoided.
Claim 1 covers a chemical genus; claims 5, 6, and 7 focus on racemic, R-, and S-fexofenadine.
The patent does not independently protect tablets, capsules, liquids, excipients, polymorphs, dosage regimens, or manufacturing methods.
Method-of-use infringement would require the claimed patient population, compound, treatment, and cardiac-risk limitation.
The patent expired in 2017 under the ordinary U.S. patent term.
It is not a current barrier to generic fexofenadine entry.
Fexofenadine is a small molecule, so biosimilar rules are irrelevant.
Historical generic challenges would have focused on Paragraph IV certification, skinny labeling, claim construction, obviousness, enablement, and induced infringement.
Current commercial exposure is driven by generic price competition and FDA requirements rather than this expired patent.

FAQs About U.S. Patent 6,037,353

Is U.S. Patent 6,037,353 still enforceable?

No. The patent’s ordinary U.S. term expired in 2017, eliminating current infringement remedies based on the patent.

Does U.S. Patent 6,037,353 cover Allegra tablets?

It does not claim Allegra tablets as a formulation. It covers a method of using covered antihistamine compounds, including fexofenadine, in a defined impaired-liver-function treatment setting.

Does the patent cover all fexofenadine uses?

No. The claims require the specified hepatic impairment and the treatment context involving avoidance of terfenadine-associated cardiac events.

Could a generic manufacturer have used a skinny label to avoid this patent?

Potentially. A label omitting the patented patient population or method could reduce induced-infringement risk, subject to the exact Orange Book listing, FDA labeling rules, and the product’s remaining patent estate.

Are R-fexofenadine and S-fexofenadine separately claimed?

Yes. Claims 6 and 7 separately identify the R and S enantiomers of fexofenadine for the claimed treatment method.

References

United States Patent and Trademark Office. (2000). U.S. Patent No. 6,037,353, Methods of treating patients with impaired liver function. U.S. Department of Commerce.
U.S. Food and Drug Administration. (1996). Allegra approval materials and prescribing information for fexofenadine hydrochloride. U.S. Department of Health and Human Services.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, Orange Book. U.S. Department of Health and Human Services.
U.S. Food and Drug Administration. (2024). Abbreviated new drug application process and patent certifications. U.S. Department of Health and Human Services.
U.S. Food and Drug Administration. (2024). Biosimilar and interchangeable products. U.S. Department of Health and Human Services.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	194913	⤷ Start Trial
Australia	3973493	⤷ Start Trial
Australia	679910	⤷ Start Trial
Canada	2134211	⤷ Start Trial
Chile	2004000304	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,037,353

Summary for Patent: 6,037,353