US Drug Patent 5,387,598: Claim Scope, Expiration, Orange Book Status, and Patent Landscape

US Patent 5,387,598 protected pharmaceutical, veterinary, bactericidal, and food-preservative compositions combining nifuroxazide, the active agent represented by formula I, with a wetting agent. The patent did not claim nifuroxazide as a compound. Its protection was directed to selected combinations, dosage forms, and uses.

The patent issued on February 7, 1995. Because it was filed before the 1995 change to the US patent-term statute, its ordinary term was 17 years from issuance. The patent therefore expired on February 7, 2012, absent an unusual term adjustment or later correction. It no longer creates an enforceable US exclusion right.

What drug does US Patent 5,387,598 cover?

Formula I is nifuroxazide, also known as nifuroxazide or nifuroxazid. Nifuroxazide is a nitrofuran antibacterial historically used for intestinal infections and diarrhea, particularly in markets outside the United States.

The compound is generally identified as:

Attribute	Description
Active ingredient	Nifuroxazide
Drug class	Nitrofuran antibacterial
Principal historical use	Intestinal infections and diarrhea
Molecular formula	C12H9N3O5
US regulatory position	No established FDA-approved Orange Book product associated with this patent
Patent type	Formulation, composition, process, veterinary, and food-preservation claims

The patent’s inventive focus was the use of a wetting agent to improve the performance of nifuroxazide-containing compositions. The claims also address starch derivatives, low-moisture formulations, ointments, antibacterial treatment, animal diarrhea, and food preservation. (US Patent No. 5,387,598, 1995)

What are the independent claims in US Patent 5,387,598?

The patent has several claim groups rather than a single pharmaceutical composition claim.

Claim	Claim category	Core limitation
1	Oral composition	Nifuroxazide plus a wetting agent for lower-abdominal conditions
7	Galenic oral formulation	Core containing nifuroxazide, wetting agent, starch derivative, and less than 25% water
9	Ointment	Nifuroxazide plus a wetting agent
13	Bactericidal composition	Nifuroxazide mixed with a wetting agent
15	Antibacterial process	Treating aerobic and anaerobic bacteria with the claimed composition
16	Preservation process	Treating a medium to prevent bacterial growth
17	Veterinary method	Orally administering nifuroxazide, wetting agent, and starch derivative to animals with diarrhea
18	Food composition	Nifuroxazide, wetting agent, and starch derivative as a preservative

The patent therefore covers multiple statutory categories:

Composition of matter in the limited sense of a combination formulation.
Pharmaceutical composition.
Galenic dosage form.
Ointment.
Method of treating bacteria.
Method of preventing bacterial growth.
Veterinary treatment method.
Food-preservative composition.

It does not claim the nifuroxazide molecule itself.

How broad is claim 1?

Claim 1 covers an oral composition containing:

An effective amount of nifuroxazide; and
A wetting agent.

The claim does not specify:

A particular nifuroxazide dose.
A particular tablet, capsule, suspension, or powder.
A minimum or maximum amount of wetting agent.
A specific disease organism.
A specific wetting-agent identity.
A required starch derivative.
A dissolution or bioavailability threshold.

The phrase “for combatting affections of the lower abdomen” supplies a therapeutic-use context, but the principal structural limitations are nifuroxazide and a wetting agent.

The breadth of claim 1 is limited by the wetting-agent requirement. A nifuroxazide product without a wetting agent would not fall within the literal wording of claim 1. A composition containing a wetting agent for manufacturing or processing reasons could create a closer infringement question if the ingredient remains in the finished oral product and satisfies the claim’s functional and compositional interpretation.

Because claim 1 does not impose a quantitative wetting-agent threshold, the claim could theoretically reach formulations containing very small quantities. Claim 6 narrows the invention by adding numerical limits.

What wetting agents are protected?

Claim 2 narrows the composition to anionic surfactants.

Claim 3 contains an extensive Markush group covering numerous classes of wetting agents and excipients, including:

Sugar esters.
Polyoxyethylene compounds.
Polyoxypropylene compounds.
Anhydrohexitol derivatives.
Fatty alkanolamides.
Fatty amine oxides.
Sucrose.
Mannitol.
Sorbitol.
Lecithins.
Polyvinylpyrrolidones.
Fatty-acid esters.
Sucrose glycerides.
Xylose esters.
Polyoxyethylene glycerides.
Polyoxyethylene ethers of fatty alcohols.
Polyoxyethylene fatty-acid esters.
Sorbitan derivatives.
Polyglycide and glyceride esters.
Mixtures of the listed materials.

The drafting is chemically and linguistically broad. Some listed materials, such as sucrose, mannitol, sorbitol, and polyvinylpyrrolidone, are commonly used as excipients but are not universally classified as surfactants in the same way as anionic or nonionic surfactants. Claim construction would likely turn on the patent specification’s definition of “wetting agent,” technical usage at the filing date, and prosecution history.

What protection does claim 6 add?

Claim 6 limits the formulation to:

Up to 20% by weight of surfactant relative to the weight of nifuroxazide; and
Up to 20% by weight of starch derivative relative to the weight of nifuroxazide.

This is a relative-weight limitation, not a percentage of total formulation weight.

For example, if a formulation contains 100 mg of nifuroxazide, claim 6 permits no more than 20 mg of surfactant and no more than 20 mg of starch derivative, assuming the claim’s “up to 20%” language is applied directly to the active-agent weight.

Claim 6 is narrower than claim 1 because it requires both a surfactant and a starch derivative within specified relative amounts. It may have been intended to capture a balance between wetting performance and dosage-form processability.

What formulations are protected by claims 7 and 8?

Claims 7 and 8 address a galenic formulation with a core containing:

Nifuroxazide.
A wetting agent.
A starch derivative.
Less than 25% water by weight in the composition.

Claim 8 specifies carboxymethyl starch or a salt of carboxymethyl starch.

This claim group is narrower than claim 1 in four respects:

It requires a core.
It requires a starch derivative.
It imposes a water-content limitation.
Claim 8 specifically identifies carboxymethyl starch or a salt.

The water limitation is important. A formulation with 25% or more water would not literally satisfy claim 7. The patent does not establish from the supplied claim text whether water is measured at manufacture, after drying, at release, or under another analytical condition. That issue could matter in any historical infringement dispute.

Carboxymethyl starch is commonly used as a disintegrant. Its inclusion suggests that the patent addressed the combined effects of wetting and disintegration in a solid oral dosage form.

What does the ointment claim cover?

Claim 9 covers an ointment containing:

An effective amount of nifuroxazide; and
A wetting agent.

Claims 10 and 12 add starch derivatives and carboxymethyl starch, respectively.

The ointment claims are unusual in the context of an active ingredient primarily associated with intestinal antibacterial use. They extend the patent’s formulation concept beyond oral dosage forms. The supplied text contains an apparent dependency inconsistency: claim 11 refers to claim 8 while describing an ointment-related wetting-agent limitation. That drafting issue could affect the scope of claim 11, but it does not eliminate the independent protection in claim 9 or the properly dependent limitations in claims 10 and 12.

What do claims 13 through 16 protect?

Bactericidal composition

Claim 13 covers a bactericidal composition containing a mixture of nifuroxazide and a wetting agent.

This language is potentially broader in purpose than claim 1 because it is not expressly limited to oral administration or lower-abdominal treatment. The composition could be directed to antibacterial use generally, subject to the claim’s interpretation of “bactericidal composition.”

Claim 14 repeats a wetting-agent group but contains another apparent dependency problem in the supplied text. It refers to claim 2 while using the broader wetting-agent list associated with claim 3.

Bacterial-treatment process

Claim 15 covers treating aerobic and anaerobic bacteria with the nifuroxazide and wetting-agent composition.

Claim 16 covers treating a medium to prevent bacterial growth. This could reach applications involving a non-pharmaceutical medium, depending on the patent specification and claim construction. The claim is materially different from a patient-treatment claim because it focuses on bacterial growth in a medium rather than administration to a human or animal.

These claims would be relevant to industrial, laboratory, food, or environmental uses if the required composition and bactericidal function were present.

What veterinary and food uses are protected?

Claim 17 covers orally administering a composition containing nifuroxazide, wetting agent, and starch derivative to animals for diarrhea.

Claim 18 covers a food composition containing the same core components, with nifuroxazide used as a preservative.

The veterinary claim requires all three components. A veterinary nifuroxazide formulation containing only the active ingredient and a wetting agent would fall outside the literal wording of claim 17 unless another claim or doctrine applied.

The food-preservation claim is commercially distinct from the pharmaceutical claims. It raises separate regulatory issues because the use of nifuroxazide in food would require authorization under applicable food-additive, ingredient, or contaminant rules. The patent itself does not establish regulatory approval for that use.

When did US Patent 5,387,598 lose exclusivity?

Event	Date or status
Patent issued	February 7, 1995
Ordinary pre-1995 patent term	17 years from issuance
Expected expiration	February 7, 2012
Current status	Expired
Enforceable patent rights	None, subject to any extraordinary correction not indicated in the supplied record

The patent was filed before the US shifted most utility patents to a 20-year term measured from the earliest effective nonprovisional filing date. For a patent issued in 1995 from a pre-June 8, 1995 application, the 17-year-from-issue rule generally applies. (35 U.S.C. § 154, historical version)

Any patent-term adjustment under the modern framework would not ordinarily alter the analysis for a pre-1995 application. Patent expiration removes infringement risk from the US patent itself, although separate patents, regulatory restrictions, trademarks, or foreign rights could have affected commercial entry.

What is the Orange Book status of nifuroxazide?

Nifuroxazide is not associated with a conventional FDA-approved US drug product listed in the Orange Book based on the patent and drug identity identified here.

The practical consequences are significant:

No Orange Book-listed patent is expected for a US-approved nifuroxazide reference product.
No conventional Hatch-Waxman Paragraph IV challenge is linked to Patent 5,387,598 today.
An ANDA applicant would not normally use this expired patent as a basis for a Paragraph IV certification.
The absence of an Orange Book listing does not itself authorize marketing.
A US sponsor would still need an FDA-approved pathway, such as an NDA or another legally available route.

The patent’s expiration eliminates its patent barrier, but it does not convert nifuroxazide into an FDA-approved product.

Are there Paragraph IV challenges or patent litigation?

No current Paragraph IV litigation risk is attributable to US Patent 5,387,598 because the patent expired in 2012.

The patent’s age also makes modern Hatch-Waxman litigation unlikely. Any historical infringement dispute would have been subject to the patent’s expiration date, statutory damages limitations, prosecution history, and the specific formulation accused.

The patent number alone does not establish:

A Paragraph IV notice.
A district-court infringement action.
A settlement agreement.
A license.
A covenant not to sue.
A commercial launch restriction.

No licensing deal or settlement agreement is apparent from the claim text or the patent record cited here. Patent ownership or assignment history would need to be distinguished from any commercial license.

How strong was the patent estate?

The patent was technically broad in concept but narrow in legal structure.

Strength factor	Assessment
Compound protection	None; nifuroxazide itself was not claimed
Formulation breadth	Moderate for compositions containing a wetting agent
Quantitative limitations	Limited except in claim 6
Dosage-form coverage	Oral forms and ointments
Use coverage	Human, veterinary, bactericidal, and food-preservation uses
Enablement exposure	Potentially relevant because the wetting-agent list is extensive
Claim-dependency quality	Apparent inconsistencies in claims 11 and 14
Current enforceability	None because the patent expired
Biosimilar relevance	None; nifuroxazide is a small molecule
Generic-entry impact today	No patent-based US delay from this patent

The strongest historical claims were likely claims 1, 7, 9, and 13 because they established independent formulation categories. Claims 15 through 18 broadened the commercial field but depended on proving the claimed composition and the specified use.

The main weakness was the absence of compound protection. A competitor could avoid the patent by using another antibacterial, by omitting the wetting agent, or potentially by adopting a formulation that did not satisfy the relevant starch or water limitation.

How does this patent compare with competing drug patents?

Nifuroxazide’s patent position differs materially from the estates for commercially important US gastrointestinal drugs.

Drug or class	US patent position	Regulatory profile
Nifuroxazide	Historical formulation patent, now expired	No established FDA-approved Orange Book product
Rifaximin	Multiple product, formulation, and method-of-use patents have historically supported US products	FDA-approved products, including gastrointestinal indications
Loperamide	Older compound and product history; core rights expired	FDA-approved antidiarrheal
Nitazoxanide	Compound and formulation rights developed separately	FDA-approved for specified antiparasitic use
Fidaxomicin	Product and formulation patent estate	FDA-approved antibacterial for C. difficile infection

Rifaximin is the closest commercial comparator in terms of intestinal antibacterial positioning, but its US patent estate and FDA status are materially stronger because it is linked to approved products and indication-specific exclusivity. Nifuroxazide’s expired formulation patent does not provide a comparable US commercial moat.

What generic launch risks exist?

For the expired patent itself, the patent-related launch risk is zero in the United States.

The remaining risks would be regulatory and commercial:

Whether FDA accepts a proposed nifuroxazide product.
Whether the sponsor can establish safety and efficacy.
Whether the proposed indication is legally supportable.
Whether manufacturing complies with current good manufacturing practice.
Whether the formulation uses a different, still-protected excipient technology.
Whether foreign countries retain unexpired family patents.
Whether trademark or unfair-competition rights restrict branding.
Whether food or veterinary use requires separate authorization.

The patent does not prevent a modern sponsor from developing a nifuroxazide product, but it also does not create an abbreviated regulatory pathway.

What manufacturing and formulation barriers remain?

The patent describes a formulation strategy based on wetting and starch-derived excipients. Those technical concepts are generally reproducible using conventional pharmaceutical manufacturing equipment.

Potential development issues include:

Uniform distribution of a low-dose active ingredient.
Control of particle size and wetting performance.
Compatibility between nifuroxazide and surfactants.
Moisture control for the less-than-25%-water formulation.
Tablet disintegration when carboxymethyl starch is used.
Stability under accelerated and long-term storage.
Microbiological quality for oral and food-related products.
Control of nitrofuran impurities and degradation products.

These are development barriers, not continuing rights under Patent 5,387,598.

What is the geographic coverage?

The US patent protected only conduct within the United States or conduct with a sufficient US nexus under US patent law. Foreign counterparts, if any, had separate expiration dates and separate claim scopes.

The supplied record does not establish a complete international family, current foreign status, or ownership chain. The US expiration does not imply that every corresponding foreign patent expired on the same date.

Key Takeaways

US Patent 5,387,598 covers nifuroxazide compositions containing a wetting agent.
It also covers selected starch-containing formulations, ointments, antibacterial methods, veterinary diarrhea treatment, and food-preservation compositions.
It does not claim nifuroxazide as a standalone compound.
Claims 1, 7, 9, and 13 are the principal independent formulation and composition claims.
Claims 15 through 18 extend the patent into bacterial treatment, preservation, veterinary, and food uses.
The patent issued on February 7, 1995, and ordinarily expired on February 7, 2012.
The patent has no current US enforcement value.
Nifuroxazide is not associated with a conventional FDA Orange Book product based on the identified record.
No current Paragraph IV risk, biosimilar risk, or patent-based generic delay arises from this patent.
Any current commercial barrier would arise from FDA approval, manufacturing, foreign rights, later patents, or market-access issues rather than Patent 5,387,598.

Frequently Asked Questions

Is nifuroxazide patented in the United States today?

US Patent 5,387,598 is expired. A later patent could theoretically cover a different nifuroxazide formulation, process, or use, but this patent does not provide current US exclusivity.

Does Patent 5,387,598 claim nifuroxazide tablets?

It claims oral compositions and a galenic formulation with a core, wetting agent, and starch derivative. It does not expressly require the dosage form to be a tablet, so a tablet could fall within the claims if it satisfies the listed composition and structural limitations.

Could a nifuroxazide formulation without starch infringe claim 1?

Potentially, yes. Claim 1 requires nifuroxazide and a wetting agent but does not require starch. Claims 4 through 8 add starch-related limitations and are narrower dependent claims.

Is nifuroxazide eligible for an abbreviated new drug application?

The expired patent does not determine eligibility. Because nifuroxazide lacks an established FDA-approved reference product in the conventional Orange Book framework, a sponsor may need an NDA or another FDA-recognized regulatory pathway rather than a standard ANDA pathway.

Do the patent claims cover food preservatives containing nifuroxazide?

Claim 18 expressly addresses a food composition containing nifuroxazide, a wetting agent, and a starch derivative as a preservative. Patent coverage, however, is separate from authorization to use nifuroxazide in food.

References

United States Patent No. 5,387,598. (1995). United States Patent and Trademark Office. https://patents.google.com/patent/US5387598A
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/orange-book
United States Code, 35 U.S.C. § 154. Patent term. https://uscode.house.gov/view.xhtml?req=granuleid:USC-prelim-title35-section154
World Health Organization. (n.d.). WHO ATC/DDD index: Nifuroxazide. https://www.whocc.no/atc_ddd_index/

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
African Regional IP Organization (ARIPO)	1103	⤷ Start Trial
African Regional IP Organization (ARIPO)	645	⤷ Start Trial
African Regional IP Organization (ARIPO)	9600866	⤷ Start Trial
African Regional IP Organization (ARIPO)	9901675	⤷ Start Trial
Argentina	008355	⤷ Start Trial
Argentina	057242	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,387,598

Summary for Patent: 5,387,598