United States Drug Patent 4,254,129: Claim Scope, Fexofenadine Coverage, Expiration and Patent Landscape

US Patent 4,254,129 is a foundational Merrell patent covering substituted piperidine antihistamines, including fexofenadine and related compounds. Its broad genus claim reaches carboxylic acids, lower alkyl esters, selected hydroxylated analogs, optical isomers and pharmaceutically acceptable salts. Claims 7 and 8 specifically identify fexofenadine's ethyl ester precursor and fexofenadine itself. The patent issued March 3, 1981, and its ordinary U.S. patent term expired in 1998. Any historical regulatory extension did not create a live patent right today. Current generic competition is governed by later fexofenadine patents and regulatory exclusivity, not by US 4,254,129.

What drug does US Patent 4,254,129 protect?

The patent protects a chemical genus that includes fexofenadine, the active ingredient in Allegra and related antihistamine products.

Fexofenadine is:

4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-alpha,alpha-dimethylbenzeneacetic acid

It is the carboxylic-acid metabolite of terfenadine. Unlike terfenadine, fexofenadine does not have the same clinically important cardiac liability associated with QT-interval prolongation. Fexofenadine hydrochloride was later developed as a second-generation, nonsedating H1 antihistamine.

The patent's chemical structure covers a broader family than fexofenadine. The relevant variables include:

Variable	Scope in claim 1
R1	Hydrogen or hydroxy
R2	Hydrogen, or forms a double bond with R1
n	Integer from 1 to 5
R3	Carboxylic acid or C1-C6 straight or branched alkyl ester
A and B	Hydrogen or hydroxy
A/B limitation	At least one of A or B must be hydrogen
Salt form	Pharmaceutically acceptable salts
Stereochemistry	Individual optical isomers

The claim therefore reaches saturated and unsaturated side-chain variants, acid and ester forms, mono-hydroxylated diphenylmethyl analogs, and individual stereoisomers.

How broad is claim 1 of US 4,254,129?

Claim 1 is a Markush genus claim. Its breadth comes from the combination of several independently variable structural elements.

Piperidine core and side-chain length

The central scaffold is a substituted 1-piperidine structure attached through a carbon chain to a substituted alpha,alpha-dimethylbenzeneacetic acid or ester group. The variable n permits a chain length from one to five carbon units.

The dependent claims narrow the chain length:

Claim 3 limits n to 3 or 4.
Claim 6 limits n to 3.
Claims 7 through 9 identify compounds with a four-carbon hydroxybutyl chain as written in the chemical names.

This distinction matters because the claim set includes both a broad chemical genus and commercially relevant embodiments within that genus.

R1 and R2: hydroxy and unsaturation

Claim 1 permits either:

R1 as hydrogen and R2 as hydrogen; or
R1 and R2 together forming a second bond; or
R1 as hydroxy with R2 as hydrogen.

Claim 2 removes the R1-hydroxy embodiment. It covers the saturated and unsaturated alternatives only. Claims 3 through 5 depend from claim 2 and narrow the chain length or terminal acid/ester group.

Diphenylmethyl substituent

Each of A and B may be hydrogen or hydroxy, but at least one must be hydrogen. The claim therefore permits:

An unsubstituted diphenylmethyl group, where A and B are both hydrogen.
A mono-hydroxylated diphenylmethyl group, where one of A or B is hydroxy.
No structure in which both A and B are hydroxy.

This limitation distinguishes the claimed compounds from a diphenylmethyl group hydroxylated at both designated positions.

Acid and ester forms

R3 may be:

-COOH; or
-COOalkyl, where the alkyl group contains one to six carbon atoms and may be straight or branched.

The scope includes methyl, ethyl, propyl, isopropyl, butyl and other C1-C6 ester forms, subject to the claim's structural requirements. Claim 7 specifically covers the ethyl ester corresponding to fexofenadine, while claim 8 covers the free acid.

Which claims specifically cover fexofenadine?

Claim 8 is the principal fexofenadine claim.

Claim	Subject matter	Relevance
1	Broad substituted piperidine genus	Encompasses fexofenadine
2	Saturated or unsaturated subset	Encompasses fexofenadine
3	n = 3 or 4	Encompasses fexofenadine's n = 3 embodiment under the patent's numbering
4	Ester compounds	Encompasses fexofenadine ester forms
5	Carboxylic acids	Encompasses fexofenadine
6	Narrow acid or salt formula, n = 3	Directly relevant to fexofenadine-type structures
7	Ethyl ester named compound	Fexofenadine ethyl ester precursor
8	Named carboxylic acid	Fexofenadine
9	3-hydroxybenzene analog	Hydroxylated fexofenadine analog
10	Unit-dose pharmaceutical composition	Composition containing a claim 1 compound
11	Treatment of allergic reactions	Method-of-use claim using a claim 1 compound

The nomenclature in claim 8 corresponds to fexofenadine, while claim 7 corresponds to ethyl fexofenadine, an ester form used in the patent's chemical disclosure and development work.

What formulations are protected by US 4,254,129?

Claim 10 covers a pharmaceutical composition in unit dosage form containing:

An effective antiallergic amount of a claim 1 compound; and
A significant amount of a pharmaceutically acceptable carrier.

The claim is functional and formulation-light. It does not require a particular tablet excipient, coating, dissolution profile, dosage strength, release mechanism or manufacturing process.

Formulation limitations

Claim 10 does not expressly limit:

Immediate-release versus modified-release dosage forms.
Tablet, capsule, liquid or other oral forms.
A particular salt, although claim 1 includes pharmaceutically acceptable salts.
A particular excipient system.
A specific amount of fexofenadine.
A specific pharmacokinetic profile.

A formulation that contains a compound outside the scope of claim 1 would not infringe claim 10 merely because it is an antiallergic composition. Conversely, a composition containing fexofenadine during the patent term could have raised both compound and composition infringement issues.

The claim does not provide a modern formulation barrier comparable to later patents directed to crystalline forms, particle size, dissolution, dosage strength or controlled release.

What method-of-use rights does US 4,254,129 contain?

Claim 11 covers treating allergic reactions by administering an effective amount of a claim 1 compound to a patient in need.

The method claim is broad in therapeutic language. It is not limited to:

Allergic rhinitis.
Chronic idiopathic urticaria.
A specific H1-receptor-mediated condition.
A particular patient subgroup.
A particular dosage.
A specific route of administration.

The method claim is dependent on the chemical scope of claim 1. It does not independently cover every antihistamine treatment or every use of fexofenadine. The administered compound must fall within the claimed substituted piperidine genus.

For current market analysis, claim 11 has no meaningful exclusionary value because the patent term has expired. Historically, it could have supported infringement allegations involving administration of a covered compound for allergic reactions.

When did US Patent 4,254,129 expire?

US 4,254,129 issued on March 3, 1981. It arose from a pre-June 8, 1995 application, so the ordinary term was generally 17 years from issuance under the pre-URAA patent-term regime. On that basis, the patent's ordinary expiration date was March 3, 1998, absent a valid term adjustment, terminal disclaimer or patent-term extension.

Event	Date
Patent issued	March 3, 1981
Ordinary 17-year term	March 3, 1998
Present status	Expired
Current Paragraph IV significance	None for a new ANDA challenge

The patent cannot currently block generic manufacture, sale or use of fexofenadine in the United States. The patent's historical importance is its early disclosure and claim coverage of the fexofenadine chemical class.

Did FDA exclusivity outlast the patent?

Fexofenadine was approved by the FDA in 1996. FDA regulatory exclusivity and patent rights are separate. A drug can retain regulatory exclusivity after a patent expires, and a later patent can remain enforceable after the foundational compound patent expires.

For fexofenadine, later patents and FDA-listed rights were more important to the timing of generic entry than US 4,254,129. The original patent did not provide a current barrier after 1998.

What is the Orange Book status of US 4,254,129?

US 4,254,129 should be treated as expired and commercially inactive for Orange Book purposes. The Orange Book is a regulatory listing of patents submitted by the NDA holder and accepted for listing in connection with approved drug products. It is not a complete historical register of every patent that once covered a molecule.

The principal Orange Book implications are:

An expired patent cannot support a current Paragraph IV litigation campaign.
An expired patent may remain relevant as prior art against later patent applications.
A generic applicant does not need to defeat an expired patent to obtain approval.
Current listed patents, if any, must be analyzed by product, dosage form and NDA rather than by molecule alone.

The FDA's Approved Drug Products with Therapeutic Equivalence Evaluations, commonly called the Orange Book, should be used to determine the live patent listing for the specific fexofenadine product and dosage form at the relevant filing date (FDA, 2024).

What later patents covered fexofenadine?

The commercial fexofenadine patent estate extended beyond US 4,254,129. Later U.S. patents associated with fexofenadine included patents directed to the active ingredient, pharmaceutical products and methods of treatment.

Patent	General commercial relevance	Approximate statutory period
US 4,254,129	Foundational substituted piperidine compounds; includes fexofenadine	Expired in 1998 under ordinary term
US 5,578,610	Later fexofenadine-related patent; product or use coverage	Mid-2010s
US 5,589,492	Fexofenadine hydrochloride-related protection	Mid-2010s
US 5,631,287	Additional fexofenadine product or formulation coverage	Mid-2010s
US 5,750,703	Later product or formulation-related protection reported in the fexofenadine estate	Mid-2010s

The exact enforceability of each later patent depended on claim construction, prosecution history, terminal disclaimers, patent-term adjustments, regulatory listing and any settlement or license arrangement. Patent numbers should be matched to the relevant Orange Book product record and the issued claims, rather than evaluated solely from their titles.

Active ingredient versus formulation protection

The strategic difference between US 4,254,129 and later patents is material:

US 4,254,129 is principally a foundational chemical genus patent.
Later patents were capable of targeting fexofenadine hydrochloride, pharmaceutical compositions, dosage forms, manufacturing processes or approved uses.
A generic company could avoid a formulation claim while still practicing a broad compound claim, but that strategy had little value once the compound patent expired.
After compound expiry, formulation and method patents became the primary potential litigation points.

Which companies challenged fexofenadine patents?

Fexofenadine became subject to the standard generic-entry process under section 505(j) of the Federal Food, Drug, and Cosmetic Act. Generic applicants could file ANDAs with certifications addressing listed patents, including Paragraph IV certifications alleging that a listed patent was invalid, unenforceable or not infringed.

Companies associated with U.S. generic antihistamine competition included:

Teva Pharmaceuticals.
Barr Laboratories.
Mylan.
Ranbaxy.
Watson Pharmaceuticals.
Sandoz and other major ANDA sponsors.

The precise defendant group varied by patent, dosage form and litigation period. The relevant legal issue was not whether these companies challenged US 4,254,129. That patent was already expired by the time modern fexofenadine ANDA litigation became commercially important. The disputes focused on later fexofenadine patents and their Orange Book listings.

Paragraph IV risk

A Paragraph IV certification against US 4,254,129 would have no current commercial value because the patent is expired. A Paragraph IV certification against a later listed fexofenadine patent could trigger:

A 45-day period for the NDA holder or patent owner to file suit.
A potential 30-month FDA approval stay under the Hatch-Waxman framework.
Launch-at-risk exposure.
Invalidity, noninfringement and enforceability litigation.
Possible settlement or license arrangements.

The scope of a later patent's claims, rather than the broad language of the 1981 patent, determined the commercial risk during the generic-entry period.

What patent litigation affected fexofenadine generic entry?

Fexofenadine litigation centered on later patents covering the commercial product and related formulations. The litigation pattern was consistent with other major small-molecule products:

The NDA holder listed later patents in the Orange Book.
ANDA applicants filed certifications addressing those patents.
Paragraph IV filings created potential statutory litigation.
The parties negotiated launch dates, licenses or other settlement terms.
Generic approval followed patent expiry, settlement, delisting or successful invalidity/noninfringement arguments.

Public litigation databases and FDA records should be used to distinguish:

Cases involving Allegra tablets.
Cases involving oral suspensions or other dosage forms.
Cases involving fexofenadine alone.
Cases involving fexofenadine-pseudoephedrine combination products such as Allegra-D.
Cases involving product patents versus method-of-use patents.

The combination products had separate patent and regulatory considerations because pseudoephedrine added another active ingredient and could create distinct product claims.

Are there biosimilar risks for fexofenadine?

No. Fexofenadine is a chemically synthesized small molecule, not a biologic. It is regulated through the ANDA pathway, not the abbreviated biologics license application pathway.

The relevant competitive risks are:

Generic fexofenadine hydrochloride.
Authorized generic products.
Private-label store brands.
Combination products with pseudoephedrine.
OTC switching and retailer substitution.
International suppliers of active pharmaceutical ingredient.

Biosimilar competition is not a relevant category for fexofenadine.

How strong is the patent estate for fexofenadine?

The patent estate was strong during the period when later product and formulation patents remained enforceable, but US 4,254,129 alone is no longer a barrier.

Factor	Assessment
Foundational chemical coverage	Historically strong; now expired
Claim breadth	Broad genus with direct fexofenadine claims
Compound-specific protection	Historically significant through claim 8
Formulation coverage	Limited in US 4,254,129; later patents mattered more
Method-of-use coverage	Broad allergic-reaction treatment claim, now expired
Current U.S. blocking power	None from US 4,254,129
Biosimilar protection	Not applicable
Generic vulnerability	High after later patent expiry and regulatory clearance
Manufacturing barrier	Low at the expired-patent level; process patents require separate review

The principal surviving commercial value is historical prior-art position. The patent may be cited against later attempts to patent the same compounds, salts or uses, but it cannot be asserted as an exclusionary right.

What manufacturing and geographic barriers remain?

US 4,254,129 does not create a current manufacturing barrier in the United States. A company may manufacture fexofenadine or its hydrochloride salt without infringing this expired patent.

Remaining barriers may arise from:

Later process patents.
Crystalline-form or polymorph patents.
Salt-selection patents.
Particle-size or formulation patents.
Manufacturing know-how.
Regulatory requirements for impurity control.
Drug-master-file access.
API qualification and supply-chain validation.
Foreign patents with different expiration dates.

Patent rights are territorial. Expiration in the United States does not establish freedom to operate in Europe, Japan, China, India or other jurisdictions. A global launch requires a country-by-country review of national family members, supplementary protection certificates, pediatric extensions, term adjustments and local litigation.

What generic launch scenarios exist for fexofenadine?

Scenario 1: Immediate generic substitution

This is the standard post-expiry outcome for a product with no live blocking patent. An ANDA applicant obtains approval, and pharmacies substitute an AB-rated generic where applicable.

Scenario 2: Formulation-specific delay

A generic compound may be approvable while a particular dosage form remains exposed to a later formulation patent. The applicant can launch a noninfringing formulation or wait for expiry.

Scenario 3: Combination-product separation

Generic fexofenadine can enter independently from fexofenadine-pseudoephedrine products. The combination product may have separate patents, labeling and regulatory requirements.

Scenario 4: Authorized-generic competition

The brand owner or a partner may supply an authorized generic. This can reduce price erosion for the brand owner while increasing competitive pressure on independent ANDA entrants.

What is the revenue exposure from US 4,254,129?

There is no current revenue protected by US 4,254,129. Its economic value ended when the patent term expired.

The historical revenue exposure was associated with:

Allegra-branded fexofenadine products.
Fexofenadine hydrochloride tablets and capsules.
Pediatric liquid formulations.
Allegra-D combination products.
International products relying on related patent families.

By the time generic fexofenadine reached the U.S. market, the relevant revenue defense depended primarily on later patents, brand equity, OTC distribution and formulation differentiation. The expired 1981 patent could not support a royalty claim or injunction against post-expiry sales.

Key Takeaways

US 4,254,129 is a foundational Merrell patent for substituted piperidine antihistamines.
Its claim 1 Markush structure covers acids, C1-C6 esters, selected hydroxylated analogs, salts and optical isomers.
Claim 8 specifically covers fexofenadine, while claim 7 covers its ethyl ester.
Claims 10 and 11 cover pharmaceutical compositions and allergic-reaction treatment methods using the claimed compounds.
The patent issued March 3, 1981 and expired under its ordinary term in 1998.
It creates no current U.S. blocking right and cannot support a present Paragraph IV lawsuit.
Later fexofenadine patents, not US 4,254,129, controlled the timing and litigation risk of generic entry.
Fexofenadine is a small molecule, so biosimilar analysis does not apply.
Current freedom to operate requires review of later U.S. patents, process rights, combination products and foreign family members.

FAQs About US 4,254,129 and Fexofenadine

Does US 4,254,129 claim Allegra?

Yes. Claim 8 covers the fexofenadine compound used in Allegra, subject to the precise chemical interpretation of the issued claim.

Can a company sue a generic manufacturer under US 4,254,129 today?

No. The patent is expired and cannot provide a current injunction or damages claim for post-expiry conduct.

Is fexofenadine hydrochloride the same compound named in claim 8?

Fexofenadine is the free carboxylic acid, and fexofenadine hydrochloride is a pharmaceutically acceptable salt form. Claim 1 expressly includes pharmaceutically acceptable salts, so the hydrochloride form falls within the claim's salt coverage.

Does the patent cover cetirizine or loratadine?

No. Cetirizine and loratadine have different chemical structures and are not compounds within the substituted piperidine genus described by this patent.

What is the primary patent risk for a new fexofenadine product?

The primary risk is not US 4,254,129. It is any unexpired patent covering a specific salt, polymorph, formulation, dosage form, manufacturing process, combination product or method of treatment in the target jurisdiction.

References

Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. U.S. Department of Health and Human Services. https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book-data-files
United States Patent and Trademark Office. (1981). U.S. Patent No. 4,254,129, Piperidine derivatives. U.S. Department of Commerce. https://patents.google.com/patent/US4254129
United States Patent and Trademark Office. (1996). U.S. Patent No. 5,578,610. U.S. Department of Commerce. https://patents.google.com
United States Patent and Trademark Office. (1996). U.S. Patent No. 5,589,492. U.S. Department of Commerce. https://patents.google.com
United States Patent and Trademark Office. (1997). U.S. Patent No. 5,631,287. U.S. Department of Commerce. https://patents.google.com
United States Patent and Trademark Office. (1998). U.S. Patent No. 5,750,703. U.S. Department of Commerce. https://patents.google.com
U.S. Food and Drug Administration. (1996). Allegra NDA approval materials. Center for Drug Evaluation and Research, U.S. Department of Health and Human Services.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	376207	⤷ Start Trial
Austria	376208	⤷ Start Trial
Austria	A126080	⤷ Start Trial
Austria	A144880	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 4,254,129