United States Patent 5,738,872: Fexofenadine Formulation Claims, Scope, Expiration and Generic Risk

U.S. Patent No. 5,738,872 protected solid oral formulations of fexofenadine-related piperidinoalkanol compounds, with the commercially relevant embodiment being fexofenadine hydrochloride. The patent was granted on April 14, 1998, and its ordinary patent term expired in January 2016. Its claims focused on wet granulation, tablet excipients, ingredient ranges, fexofenadine hydrochloride dose levels, and a dissolution requirement rather than on the underlying active pharmaceutical ingredient.

The patent no longer creates a U.S. patent barrier to generic fexofenadine products. It remains relevant as a historical formulation patent and as a reference point for assessing earlier ANDA litigation, Orange Book listings, and formulation design-around strategies.

What drug does U.S. Patent 5,738,872 protect?

The compound identified in claim 16 is fexofenadine hydrochloride:

4-[4-[4-(hydroxydiphenylmethyl)-1-piperidinyl]-1-hydroxybutyl]-α,α-dimethylbenzeneacetic acid hydrochloride.

Fexofenadine is the active metabolite of terfenadine and is marketed primarily as an oral, non-sedating antihistamine under the Allegra brand. The relevant dosage forms include immediate-release tablets, orally disintegrating products, oral suspension and other solid oral formulations.

The patent claims use a Markush-style chemical formula in which “X is a number ranging from about zero to 5.” The supplied claim text does not reproduce the chemical structures represented by the original patent drawings. Claim 16, however, identifies fexofenadine hydrochloride expressly. Claims 1 through 15 and 18 can therefore cover fexofenadine hydrochloride when the claimed formulation and process limitations are satisfied.

When did U.S. Patent 5,738,872 expire?

Event	Date or status
U.S. application filing	January 19, 1996
Patent grant	April 14, 1998
Patent number	5,738,872
Listed subject matter	Pharmaceutical compositions containing piperidinoalkanol compounds
Ordinary 20-year term	January 19, 2016
Current status	Expired
Current generic blocking effect	None

The patent term is measured from the earliest effective nonprovisional filing date, subject to any applicable patent-term adjustment or terminal disclaimer. Public patent databases report U.S. Patent 5,738,872 as expired after the January 2016 term date. Any pediatric exclusivity associated with the fexofenadine regulatory program would have been a regulatory exclusivity issue, not a permanent extension of the patent term.

Because the patent expired, a current generic manufacturer does not need to design around the claims to launch a fexofenadine product. The historic patent still matters when evaluating earlier launch dates, damages periods or old ANDA litigation.

What are the main claim categories in Patent 5,738,872?

The 18 claims divide into five functional groups.

Claims	Primary subject matter	Relative breadth
1-2	Wet-granulated pharmaceutical composition and process	Broad process-defined claims
3-8	Specific tablet manufacturing sequences and excipient systems	Narrower process and formulation claims
9-15	Solid unit dosage compositions with excipient classes and ranges	Intermediate composition claims
16-17	Fexofenadine hydrochloride in the claimed formulation, including 5-180 mg	Narrow, commercially focused claims
18	Specific excipient composition plus dissolution performance	Narrow performance-limited claim

The claims combine composition and manufacturing limitations. This structure was intended to protect both the finished tablet and the production method used to obtain it.

How broad are claims 1 and 2?

Claims 1 and 2 cover a pharmaceutical composition prepared by wet granulation. The process requires:

Mixing the active compound, a diluent and a disintegrant with a solution of a binding agent.
Screening the wet granulation.
Drying the granulation.
Screening the dry granulation.
Adding a lubricant in claim 2.

The key distinction is that claim 1 does not expressly require the lubricant step, while claim 2 requires the dry granulation to be combined with a lubricant.

These claims are broad relative to claims 3 through 18 because they do not identify particular excipients or fixed concentration ranges. Their scope depends on how the terms “diluent,” “disintegrant,” “binding agent,” “wet granulation,” “screened” and “dried” are construed.

A product made by direct compression, dry granulation or a non-granulated process would have a stronger noninfringement position against claims 1 and 2. A product made by wet granulation could fall within the claims even if it used excipients different from those described in the examples, provided the required functional categories and process steps were present.

What formulations are protected by claims 3 through 8?

Claims 3 through 8 identify a specific tablet platform based on:

Microcrystalline cellulose
Calcium carbonate
Pregelatinized starch
Gelatin or water
Sodium starch glycolate
Magnesium stearate

Claim 3 requires the active compound to be blended with microcrystalline cellulose, calcium carbonate and pregelatinized starch. A gelatin-in-water solution is then added, followed by drying. Additional microcrystalline cellulose and sodium starch glycolate are blended into the dried granulation, followed by magnesium stearate.

Claim 4 limits the product to a pressed tablet.

Claim 5 specifies approximate total excipient amounts:

Ingredient	Approximate amount
Microcrystalline cellulose	34.9%
Calcium carbonate	15.6%
Pregelatinized starch	29.4%
Gelatin	3.3%
Sodium starch glycolate	5.6%
Magnesium stearate	0.5%

Claim 6 substitutes water for the gelatin solution. Claims 7 and 8 add the tablet limitation and corresponding excipient composition.

The supplied text states “336.5%” for microcrystalline cellulose in claim 8. That value cannot represent a weight percentage in a conventional tablet composition. It is almost certainly a transcription or OCR error, likely intended to be approximately 36.5%. The issued patent should control any legal analysis of claim 8.

What do claims 9 through 15 cover?

Claims 9 through 15 are composition claims rather than pure manufacturing-process claims. They require a therapeutically effective amount of a piperidinoalkanol compound and specified inert ingredients.

Claim 9 requires:

Microcrystalline cellulose
Pregelatinized starch
Gelatin
Magnesium stearate
Calcium carbonate
Sodium starch glycolate

Claim 10 establishes broad ingredient ranges:

Ingredient	Claimed range
Microcrystalline cellulose	20% to 85%
Pregelatinized starch	5% to 50%
Gelatin	1% to 15%
Magnesium stearate	0.05% to 3%
Calcium carbonate	5% to 50%
Sodium starch glycolate	1% to 15%

Claim 11 narrows the formulation to the approximate composition listed above.

Claims 12 through 15 remove gelatin from the required ingredient set. Claim 13 provides broad ranges, while claims 14 and 15 identify two more specific formulations.

The composition claims create potential coverage even where a manufacturer does not follow the exact process described in claims 3 or 6. A tablet could therefore present separate infringement questions under the process claims and the composition claims.

What is the significance of claims 16 and 17?

Claims 16 and 17 connect the formulation technology to fexofenadine hydrochloride.

Claim 16 limits the compound in claims 11, 14 or 15 to fexofenadine hydrochloride. Claim 17 further limits the amount to approximately 5 mg to 180 mg.

The 5 mg to 180 mg range is commercially significant because it encompasses common fexofenadine strengths, including 60 mg, 120 mg and 180 mg tablets. The claim does not require every strength within the range to be marketed. It covers a solid dosage form containing fexofenadine hydrochloride within the stated amount if the other incorporated formulation limitations are met.

The claim is narrower than a claim to fexofenadine hydrochloride alone. A competitor would have needed to satisfy the referenced excipient and formulation requirements, not merely sell fexofenadine.

What does claim 18 add?

Claim 18 requires a solid formulation containing approximately:

Ingredient	Approximate amount
Microcrystalline cellulose	21.1%
Pregelatinized starch	30.0%
Magnesium stearate	0.75%
Calcium carbonate	15.6%
Sodium starch glycolate	10.0%

The final mixture must be pressed into a tablet. The claim also requires that at least 75% of the compound dissolve within 45 minutes in 0.001N aqueous hydrochloric acid at approximately 37°C and 50 rpm using USP Apparatus 2.

This is a formulation-plus-performance claim. A competing product could avoid literal infringement by using a different excipient profile, a different manufacturing route, or a dissolution result outside the claimed limitation. The dissolution requirement also creates evidentiary issues because testing conditions, sampling, apparatus qualification and product variability can affect the result.

Was Patent 5,738,872 listed in the Orange Book?

Patent 5,738,872 was associated with the Allegra fexofenadine product family and was listed in the FDA Orange Book during the period in which the patent had remaining term. The listing concerned a formulation patent rather than the basic chemical identity of fexofenadine.

The Orange Book distinguishes between:

Drug-substance patents
Drug-product or formulation patents
Method-of-use patents

Patent 5,738,872 is principally a drug-product and formulation patent. Its claims do not primarily cover the therapeutic use of fexofenadine. They cover the composition and manufacturing characteristics of solid dosage forms.

Since the patent expired in 2016, it is no longer an active Orange Book barrier to approval or launch. Current regulatory review of generic fexofenadine is governed by the applicable FDA abbreviated new drug application requirements, including pharmaceutical equivalence, bioequivalence, quality controls and labeling.

What Paragraph IV challenges affected fexofenadine?

A Paragraph IV certification is used when an ANDA applicant asserts that a listed patent is invalid, unenforceable or will not be infringed. For fexofenadine, generic applicants historically challenged the remaining Allegra patents through ANDA certifications and related patent litigation.

The commercial consequences depended on:

The specific Allegra dosage form.
The patent listed against that dosage form.
Whether the generic applicant filed a Paragraph IV certification.
Whether the innovator filed suit within 45 days.
Whether a 30-month stay applied.
Whether the parties settled.
Whether other patents or regulatory exclusivities remained.

A Paragraph IV dispute involving an expired formulation patent has no current launch-blocking effect. The historical litigation record may still matter for damages, settlement analysis and the chronology of generic entry. Patent 5,738,872 cannot presently support a new 30-month stay or an injunction against a new fexofenadine ANDA product.

Which companies challenged Allegra exclusivity?

Generic fexofenadine competition developed through multiple ANDA applicants, including major generic manufacturers such as Barr, Teva, Mylan and Ranbaxy-related entities. The precise patent claims challenged varied by product and dosage form.

The principal competitive issue was the transition from branded Allegra to generic fexofenadine hydrochloride. Once the relevant patents and regulatory exclusivities expired, generic manufacturers could enter without obtaining a license from the brand owner, subject to FDA approval and ordinary market requirements.

A company’s historic participation in an ANDA challenge does not establish that every product it marketed infringed or challenged every claim of Patent 5,738,872. Paragraph IV notices are product- and patent-specific.

How strong was the patent estate?

The estate was commercially useful but technically narrow.

Strengths

It covered a widely used immediate-release tablet architecture.
Claims 9 through 15 captured ingredient combinations and concentration ranges.
Claims 16 and 17 targeted fexofenadine hydrochloride and commercially relevant dose levels.
Claim 18 added an objective dissolution limitation that could support product-specific enforcement.
The formulation claims could apply even where the active pharmaceutical ingredient itself was no longer protected.

Weaknesses

The patent did not broadly claim fexofenadine as a molecule.
Process claims required proof of the accused manufacturing process or legally equivalent process.
Composition claims depended on the presence and amounts of particular excipients.
Fixed percentages provided design-around opportunities.
The patent term expired before the current generic market matured.
Claims 5, 8, 11, 14, 15 and 18 used approximate percentages, creating potential construction and measurement disputes.
The supplied claim text contains an apparent numerical error in claim 8.

The patent therefore had meaningful pre-expiration leverage against closely matching tablets but was less effective against products using different excipients, non-wet-granulation manufacturing or materially different dissolution profiles.

How could a generic manufacturer design around the claims?

Before expiration, the most direct design-around options included:

Using direct compression rather than wet granulation.
Using dry granulation or roller compaction.
Replacing calcium carbonate with another diluent.
Removing gelatin where claims 9 through 11 were implicated.
Changing the relative amounts of microcrystalline cellulose, pregelatinized starch or sodium starch glycolate.
Using a different lubricant or lubricant concentration.
Developing a dosage form with a different dissolution profile.
Marketing a formulation that did not include the complete claimed excipient combination.
Using an oral suspension or another non-tablet dosage form, where commercially and regulatorily appropriate.

The effectiveness of a design-around would depend on the issued claim language, prosecution history, product composition, manufacturing records and doctrine-of-equivalents analysis. Because the patent is expired, these strategies are now relevant mainly to historical litigation and technical freedom-to-operate assessments.

Are biosimilars relevant to fexofenadine?

No. Fexofenadine is a chemically synthesized small-molecule drug, not a biologic. The relevant competitive pathway is the ANDA process for generic drugs under section 505(j) of the Federal Food, Drug, and Cosmetic Act.

Biosimilar applications under section 351(k) do not apply to fexofenadine. The key regulatory issues are pharmaceutical equivalence, bioequivalence, dosage-form requirements, manufacturing quality and labeling.

What manufacturing and intellectual-property barriers remain?

Patent 5,738,872 presents no current U.S. manufacturing barrier because it expired. Residual barriers may arise from:

Manufacturing validation and process reproducibility.
Control of polymorphic or salt forms, if separately protected or technically relevant.
Trade secrets concerning granulation parameters.
Supplier qualification for excipients.
Dissolution and stability performance.
FDA inspection and quality-system requirements.
Trademarks and brand presentation.
Foreign patents with different expiration dates.

A U.S. patent expiration does not eliminate patent risk in Canada, Europe, Japan, China or other markets. Geographic freedom to operate must be assessed jurisdiction by jurisdiction. The expiration of the U.S. patent cannot be used to infer the status of corresponding foreign family members.

What is the commercial impact of the patent expiration?

The expiration removed a potential formulation barrier to generic fexofenadine tablets. Its commercial effect was amplified by the size of the Allegra franchise and the availability of multiple strengths.

The largest exposure was associated with the 60 mg, 120 mg and 180 mg immediate-release tablet market. The patent’s expiry did not by itself guarantee generic substitution. Actual erosion also depended on FDA approvals, pharmacy substitution, payer contracting, OTC commercialization and the status of other Allegra-related intellectual property.

After patent expiry, the brand’s ability to maintain exclusivity depended primarily on brand loyalty, OTC positioning, product differentiation, supply-chain execution and non-patent commercial factors.

Key Takeaways

U.S. Patent 5,738,872 is a formulation patent associated with fexofenadine hydrochloride solid dosage forms.
Its principal protection covers wet granulation, specified excipients, concentration ranges, tablet manufacture and dissolution performance.
Claims 16 and 17 specifically identify fexofenadine hydrochloride in amounts of approximately 5 mg to 180 mg.
Claim 18 requires a defined excipient composition and at least 75% dissolution within 45 minutes under specified USP conditions.
The patent’s ordinary U.S. term expired in January 2016.
It is not a current barrier to generic fexofenadine approval or launch.
Fexofenadine is a small molecule, so biosimilar law is irrelevant; ANDA law governs generic competition.
The claim set was vulnerable to formulation and process design-arounds even before expiry.
Claim 8 in the supplied text contains an apparent “336.5%” transcription error that should be checked against the issued patent.
Current freedom-to-operate analysis must examine later patents, foreign family members, regulatory exclusivities, trademarks and manufacturing trade secrets separately.

FAQs

Does Patent 5,738,872 cover fexofenadine itself?

No. It covers pharmaceutical compositions and manufacturing processes containing a class of piperidinoalkanol compounds. Fexofenadine hydrochloride is expressly identified only in the narrower claims.

Did the patent cover Allegra 180 mg tablets?

Claims 16 and 17 could cover a fexofenadine hydrochloride solid dosage form containing approximately 5 mg to 180 mg, if the incorporated excipient and formulation limitations were also satisfied.

Can a company launch a generic fexofenadine tablet without licensing this patent?

Yes, in the United States, because the patent expired in January 2016. FDA approval and compliance with other active patent, regulatory and commercial requirements remain necessary.

Is Patent 5,738,872 a method-of-use patent?

No. Its claims are directed principally to pharmaceutical compositions, tablet formulations, wet granulation and dissolution performance. They do not claim the therapeutic use of fexofenadine as the primary subject matter.

Does expiration in the United States eliminate foreign fexofenadine patent risk?

No. Patent terms and claim scope are jurisdiction-specific. U.S. expiration does not determine the status of corresponding patents in Europe, Canada, Japan, China or other markets.

References

U.S. Patent and Trademark Office. (1998). U.S. Patent No. 5,738,872: Pharmaceutical compositions containing piperidinoalkanol 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. (n.d.). Drugs@FDA: FDA-approved drugs. Silver Spring, MD: U.S. Department of Health and Human Services.
U.S. Food and Drug Administration. (n.d.). Abbreviated new drug application process for generic drugs. Silver Spring, MD: U.S. Department of Health and Human Services.
World Intellectual Property Organization. (n.d.). Patent term and patent family information. Geneva, Switzerland: WIPO.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Argentina	003929	⤷ Start Trial
Austria	226819	⤷ Start Trial
Australia	4909896	⤷ Start Trial
Australia	701042	⤷ Start Trial
Canada	2213700	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,738,872

Summary for Patent: 5,738,872