United States Patent 5,716,641: Scope, Claim Construction, Expiration, and Patent Landscape

U.S. Patent No. 5,716,641 protects a formulation strategy for combining loperamide, diphenoxylate, or loperamide-N-oxide with simethicone while preventing direct contact between the active pharmaceutical and simethicone. The patent claims methods, not the active ingredients themselves and not an unrestricted loperamide-simethicone composition. Its statutory patent term has expired, eliminating current U.S. infringement risk based solely on this patent. The technical concept remains relevant to products such as loperamide-simethicone antidiarrheal combinations, but it is no longer an enforceable U.S. exclusion right.

What does U.S. Patent 5,716,641 protect?

The patent protects a solid dosage form in which:

The pharmaceutical is loperamide, diphenoxylate, loperamide-N-oxide, or a pharmaceutically acceptable salt or combination.
Simethicone is present in a separate portion of the dosage form.
The pharmaceutical and simethicone are separated by a polymeric barrier impermeable to both substances.
The separation is used to enhance the pharmaceutical's dissolution profile.

The patent's core technical concern is compatibility. Simethicone is a hydrophobic silicone-based antifoaming agent. When combined directly with certain antidiarrheal actives, it can adversely affect dissolution. The claimed solution is physical separation within the dosage form rather than chemical modification of the active ingredient.

The claims do not cover every dosage form containing loperamide and simethicone. They require the claimed separation architecture and the stated dissolution-enhancement purpose.

Patent identification

Item	Data
Patent	U.S. Patent No. 5,716,641
Title	Pharmaceutical compositions containing loperamide and simethicone
Issue date	February 10, 1998
Technical field	Solid oral dosage forms; antidiarrheal combinations; dissolution control
Claimed actives	Diphenoxylate, loperamide, loperamide-N-oxide, and salts
Co-administered ingredient	Simethicone
Claimed barrier	Pharmaceutically acceptable polymeric barrier
Key formulation concept	Physical separation of pharmaceutical and simethicone
Claim type	Method claims
Current U.S. status	Expired by statutory term
Principal commercial relevance	Loperamide-simethicone combination products

Source: U.S. Patent No. 5,716,641 (1998).

How do claims 1 through 6 define the patent scope?

Claims 1 through 6 cover a method using two portions of a solid dosage form separated by a polymeric barrier.

Claim 1: Independent method claim

Claim 1 requires all of the following:

A method for enhancing the dissolution profile of a pharmaceutical from a solid dosage form.
The dosage form contains the pharmaceutical and simethicone.
The pharmaceutical is selected from diphenoxylate, loperamide, loperamide-N-oxide, their pharmaceutically acceptable salts, or combinations.
The pharmaceutical is provided in a first portion.
Simethicone is provided in a second portion.
The portions are separated by a pharmaceutically acceptable polymeric barrier.
The barrier is impermeable to both simethicone and the pharmaceutical.

The claim is structurally narrow because it requires separate portions and a barrier impermeable to both components. A product with the two ingredients blended together would not satisfy the literal separation limitation. A dosage form using a permeable, enteric, or selectively permeable barrier could also fall outside the literal scope if the barrier is not impermeable to both relevant substances.

Dependent claims 2 through 5: Active-ingredient limitations

Claim	Limitation
2	Loperamide, loperamide-N-oxide, salts, or combinations
3	Loperamide HCl
4	Diphenoxylate
5	Loperamide-N-oxide

Claim 3 is commercially the most important dependent claim because loperamide hydrochloride is the standard active ingredient in U.S. loperamide products. The claim does not require a particular loperamide dose, simethicone dose, tablet strength, capsule strength, or release profile beyond the dissolution-enhancement and separation limitations inherited from claim 1.

Claim 6: Barrier-material limitation

Claim 6 narrows claim 1 by requiring the barrier to be a pharmaceutically acceptable film-forming polymer. This limitation focuses the claim on coatings, films, membranes, or similar polymeric structures capable of forming a continuous barrier.

The claim does not identify one exclusive polymer. The broad category potentially includes film-forming pharmaceutical polymers if they are pharmaceutically acceptable and impermeable to the relevant active and simethicone under the claimed dosage-form conditions.

How do claims 7 through 12 differ from claims 1 through 6?

Claims 7 through 12 use a different structural implementation. Instead of requiring two separately defined portions divided by a barrier, they require the pharmaceutical to be present as coated granules.

Claim 7: Coated-granule method

Claim 7 requires:

A solid dosage form containing the pharmaceutical and simethicone.
The pharmaceutical is in coated granules.
The coating is a nonenteric polymer coating.
The coating is impermeable to both the pharmaceutical and simethicone.
Simethicone is provided in a form free of the nonenteric coating.
The pharmaceutical is substantially separated from simethicone.

This claim is directed to a multiparticulate or granulated formulation. The pharmaceutical granules are coated, while simethicone remains uncoated. The claim therefore captures a dosage form in which the active is protected from direct interaction with simethicone by coating the active-containing particles.

Claims 8 through 11: Active-ingredient limitations

Claim	Limitation
8	Loperamide, loperamide-N-oxide, salts, or combinations
9	Loperamide HCl
10	Diphenoxylate
11	Loperamide-N-oxide

Claim 9 is the principal loperamide formulation claim in this group. Like claim 3, it does not specify dose strength or a particular commercial dosage form.

Claim 12: Specific coating system

Claim 12 requires:

The claim 7 coated-granule architecture.
Loperamide HCl.
A nonenteric polymer coating comprising:
- cellulose acetate;
- methylaminoethyl-methacrylate; and
- neutral methacrylic acid ester.

This is the narrowest and most formulation-specific claim. The named polymer system appears directed to a coating composition designed to provide a nonenteric barrier while permitting the product to release the active in the gastrointestinal tract.

What formulation structures could infringe the original claims?

Because the patent has expired, the following analysis is historical claim-scope analysis rather than a current U.S. enforcement assessment.

Potentially within the literal claim framework

A formulation could have met the claim limitations if it contained:

Loperamide HCl in coated granules.
Simethicone outside the coating.
A nonenteric polymer coating impermeable to loperamide HCl and simethicone.
A solid tablet or capsule incorporating both components.
A polymer membrane separating a loperamide-containing portion from a simethicone-containing portion.
A multilayer tablet with one layer containing loperamide and another containing simethicone, provided the layers were separated by the required impermeable polymer barrier.

Potentially outside the literal scope

The following structures would present noninfringement arguments based on the claim language:

A simple physical blend of loperamide and simethicone without a polymeric barrier.
A dosage form in which simethicone, rather than the pharmaceutical, is coated.
A coating that is enteric rather than nonenteric for purposes of claim 7.
A barrier that is not impermeable to both the pharmaceutical and simethicone.
A dosage form containing a different antidiarrheal active.
A liquid formulation rather than the claimed solid dosage form.
A formulation where the pharmaceutical and simethicone are chemically conjugated or otherwise modified rather than physically separated.
A coating polymer that does not meet the specific composition required by claim 12.

The phrase "enhancing the dissolution profile" introduces a functional limitation. A party assessing historical infringement would need to evaluate whether the accused dosage form was made or used for that purpose and whether the claimed dissolution effect was demonstrated under relevant testing conditions.

How strong are the claims under a claim-construction analysis?

The patent had meaningful technical specificity but limited breadth.

Strengths of the claim set

The claims identify a clear formulation problem and a concrete solution. The strongest technical features are:

The restricted list of pharmaceutical actives.
The required presence of simethicone.
Physical separation within a solid dosage form.
Impermeability to both the active and simethicone.
Coated-granule implementation.
The specific polymer combination in claim 12.

These limitations could have differentiated the invention from a conventional tablet or capsule containing a direct blend of loperamide and simethicone.

Vulnerabilities of the claim set

The claims also have several limitations:

They are method claims rather than broad composition claims.
The patent does not broadly claim all loperamide-simethicone combinations.
The claims depend on a particular physical separation mechanism.
The phrase "enhancing the dissolution profile" could create proof issues.
The barrier must be impermeable to both components.
Claim 12 may be vulnerable to formulation redesign using a different polymer system.
The claims do not cover every dosage form, release profile, or manufacturing process.

A competitor could historically have reduced risk by using a different dosage-form architecture, a different coating material, a different placement of simethicone, or an alternative formulation that did not rely on the claimed dissolution-enhancement mechanism.

When did U.S. Patent 5,716,641 lose exclusivity?

U.S. Patent 5,716,641 lost enforceable U.S. patent exclusivity when its statutory term ended. The patent issued on February 10, 1998, from a pre-1995 or early-transition-era U.S. filing context. The controlling term for a modern utility patent is generally 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment, patent-term extension, terminal disclaimers, and relevant priority rules. The patent is now expired and cannot support a new U.S. infringement action.

Event	Date or status
Patent issued	February 10, 1998
Standard statutory term	20 years from the applicable filing date
Current status	Expired
Current enforceability	No enforceable U.S. patent exclusivity based on Patent 5,716,641
Regulatory exclusivity	Separate issue from patent term; no current patent exclusivity is created by the patent

The patent's expiration does not invalidate other patents that may have covered a specific commercial product, brand, packaging system, manufacturing process, or later formulation.

What is the Orange Book status of U.S. Patent 5,716,641?

Patent 5,716,641 is not properly treated as a current Orange Book barrier for loperamide-simethicone OTC products.

The FDA Orange Book principally lists patents and exclusivities associated with approved prescription drug applications. A combination product marketed under the FDA's over-the-counter monograph system may not have an Orange Book patent listing comparable to a prescription NDA product. Loperamide and simethicone products are generally regulated through OTC monograph or monograph-related pathways rather than through a single current prescription NDA patent strategy.

The patent's claims also are method claims directed to formulation and dissolution. Even if a patent had been listed for an approved product, its practical relevance would depend on the product, listed use, patent type, and applicable Hatch-Waxman procedures.

FDA regulatory framework

Issue	Assessment
Active ingredients	Loperamide hydrochloride and simethicone
Therapeutic category	Antidiarrheal and gastrointestinal symptom relief
Typical U.S. pathway	OTC monograph-based marketing
Prescription-generic Hatch-Waxman risk	Limited for an OTC monograph product
Paragraph IV relevance	Primarily relevant to listed NDA patents, not automatically to an expired OTC formulation patent
Current patent barrier from 5,716,641	None

FDA, Code of Federal Regulations, 21 C.F.R. Part 335; FDA, Approved Drug Products with Therapeutic Equivalence Evaluations.

Are there Paragraph IV challenges to U.S. Patent 5,716,641?

No current Paragraph IV challenge can create commercial risk against an expired patent. Paragraph IV certifications are relevant when a generic applicant files an ANDA referring to an approved drug application with listed patents. The applicant certifies that a listed patent is invalid, unenforceable, or will not be infringed.

For this patent:

The patent is expired.
An expired patent cannot block launch.
A Paragraph IV notice directed to the patent would have no practical exclusivity effect.
The principal commercial route for loperamide-simethicone products is typically OTC, which may not involve the same ANDA patent-listing structure as a prescription NDA.

Historical litigation or certification activity should not be inferred merely from the existence of this patent. The patent number alone does not establish that a Paragraph IV notice, ANDA dispute, or federal patent case occurred.

What patent litigation affects this patent?

There is no current enforceable litigation risk from U.S. Patent 5,716,641 because the patent has expired. The supplied claim set does not identify any litigation, settlement, or court construction proceeding.

A reliable litigation conclusion requires a docket-specific record. The patent itself establishes the claims and prosecution history, but not whether the patent was asserted, challenged, licensed, or settled. The available claim information supports the following status assessment:

Litigation issue	Assessment
Current infringement action based on Patent 5,716,641	No current enforceable claim basis
Patent expiration defense	Available
Identified settlement agreement	Not established by the patent claims
Identified Paragraph IV case	Not established by the patent claims
Post-grant challenge relevance	Primarily historical after expiration
Current injunction risk	None from this patent alone

Which companies compete in loperamide-simethicone products?

The commercial category includes branded and private-label products containing loperamide hydrochloride and simethicone. The leading branded reference is generally marketed under the Imodium Multi-Symptom Relief name in the United States. Private-label and store-brand products can use the same active ingredients under OTC monograph conditions.

The competitive landscape is shaped less by the expired patent than by:

FDA monograph compliance.
Brand recognition.
Retail distribution.
Packaging and labeling.
Manufacturing cost.
Formulation performance.
Consumer demand for combination gastrointestinal products.
Trademark and trade-dress rights.

Competitive asset	Current relevance
Patent 5,716,641	Historical formulation protection; expired
Loperamide HCl monograph compliance	Current regulatory requirement
Simethicone monograph compliance	Current regulatory requirement
Brand and trademark rights	Potentially current
Packaging and trade dress	Potentially current
Manufacturing know-how	Potentially current if confidential
Later formulation patents	Must be assessed separately

A generic or private-label manufacturer does not need to reproduce the patented architecture because the patent has expired. It still must satisfy applicable FDA requirements and avoid copying protected trademarks, trade dress, or confidential manufacturing information.

What manufacturing and formulation barriers remain after patent expiration?

Patent expiration removes the principal legal barrier created by Patent 5,716,641. It does not eliminate technical manufacturing requirements.

A manufacturer seeking to reproduce the formulation concept may need to control:

Uniform coating of loperamide-containing granules.
Coating weight and polymer concentration.
Coating integrity during compression or encapsulation.
Simethicone distribution.
Moisture exposure.
Particle-size distribution.
Dissolution and disintegration performance.
Content uniformity.
Stability of loperamide HCl.
Compatibility between excipients and the silicone-based simethicone phase.

The original claim architecture is technically relevant because simethicone can interfere with wetting and dissolution. A product developer may choose a coating or multilayer design for performance reasons even though no patent license is required for the expired U.S. patent.

How does this patent compare with later loperamide formulation patents?

Patent 5,716,641 is an early formulation patent focused on separation of simethicone and antidiarrheal actives. Later patents may differ in four ways:

They may claim specific multilayer tablets or multiparticulate structures.
They may claim excipient ratios, coating weights, or release specifications.
They may claim manufacturing processes rather than the finished dosage form.
They may cover packaging, dosing regimens, or other gastrointestinal combinations.

A freedom-to-operate review therefore should not stop with Patent 5,716,641. The relevant search should include:

U.S. patents citing Patent 5,716,641.
Continuations and divisionals.
Foreign family members.
Later patents assigned to the original owner or related entities.
Patents covering commercial loperamide-simethicone products.
Patents with claims to multilayer tablets, coated granules, and polymer barriers.

Patent citations and family relationships should be verified through USPTO Patent Center, WIPO PATENTSCOPE, or a current commercial patent database before relying on them for an investment, licensing, or litigation decision.

What is the geographic coverage of Patent 5,716,641?

U.S. Patent 5,716,641 provided rights only in the United States. Any foreign counterparts would have been separate national or regional rights with separate filing dates, prosecution histories, and expiration dates.

A U.S. patent does not establish:

Canadian patent protection.
European patent protection.
Japanese patent protection.
Australian patent protection.
Patent protection in any other jurisdiction.

Foreign family members may have expired at different times, been abandoned, narrowed during prosecution, or never issued. Current international risk cannot be determined from the U.S. patent number alone.

What revenue exposure did the patent create?

The patent was commercially relevant to loperamide-simethicone combination products, particularly products combining loperamide HCl with simethicone for diarrhea, gas, bloating, or related gastrointestinal symptoms. The patent did not cover the entire loperamide market.

Its potential revenue exposure was limited to products that used the claimed separation technology. Products containing loperamide alone, simethicone alone, or the two ingredients without the claimed barrier architecture would not necessarily fall within the claims.

Because the patent is expired, its current revenue-protection value is zero as a U.S. exclusivity asset. Current revenue exposure may still arise from:

Brand substitution.
OTC retail competition.
Trademark enforcement.
Product quality and supply reliability.
Later patents.
Regulatory changes.
Private-label pricing.

What generic launch scenarios exist after expiration?

Immediate launch scenario

A manufacturer can enter with a loperamide-simethicone product after satisfying FDA OTC requirements, without licensing Patent 5,716,641.

Design-around launch scenario

A manufacturer can use a formulation that does not reproduce the patented separation architecture. Examples include a different dosage-form design, different coating placement, or a direct blend, subject to demonstrating acceptable quality and dissolution.

Reference-product-equivalent scenario

A manufacturer can reproduce the technical separation concept without needing permission under the expired patent. It must still independently address formulation development, manufacturing validation, labeling, quality systems, and applicable regulatory requirements.

Residual-risk scenario

A launch may face other legal barriers unrelated to Patent 5,716,641, including later patents, trademarks, trade dress, confidential know-how, supplier restrictions, or regulatory noncompliance.

Key Takeaways

U.S. Patent 5,716,641 covers methods for improving dissolution by separating loperamide, diphenoxylate, or loperamide-N-oxide from simethicone in a solid dosage form.
Claims 1 through 6 focus on separate dosage-form portions divided by an impermeable polymeric barrier.
Claims 7 through 12 focus on pharmaceutical granules coated with a nonenteric polymer, with uncoated simethicone outside the coating.
Claim 12 is the narrowest claim and identifies cellulose acetate, methylaminoethyl-methacrylate, and neutral methacrylic acid ester.
The patent does not broadly cover every loperamide-simethicone product.
The patent has expired and does not create current U.S. patent exclusivity.
A current Paragraph IV or injunction risk cannot be based on this expired patent alone.
OTC monograph compliance, trademarks, trade dress, later patents, and manufacturing know-how remain separate considerations.
Foreign patent rights must be analyzed independently from the U.S. patent.
The patent is historically important for formulation design but has no current standalone U.S. licensing value.

FAQs

Can a company sell loperamide HCl and simethicone in the same U.S. tablet without a license?

Yes. Patent 5,716,641 is expired. The company must still comply with FDA requirements and avoid infringement of other active rights.

Does Patent 5,716,641 cover Imodium Multi-Symptom Relief by product name?

No. The patent claims formulation methods and structures, not the Imodium trademark or every product sold under that name.

Is a multilayer loperamide-simethicone tablet automatically covered by the patent?

No. It would need to satisfy every applicable claim limitation, including the required polymeric barrier and impermeability conditions.

Does the patent protect the use of simethicone for gas relief?

No. The patent does not claim simethicone's therapeutic use generally. It addresses physical separation of simethicone from specified antidiarrheal pharmaceuticals to improve dissolution.

Can foreign subsidiaries rely on the U.S. patent's expiration?

No. U.S. expiration affects only U.S. patent rights. Foreign family members require separate jurisdiction-by-jurisdiction review.

References

U.S. Patent No. 5,716,641. (1998). Pharmaceutical compositions containing loperamide and simethicone. United States Patent and Trademark Office.
U.S. Food and Drug Administration. (n.d.). Orange Book: Approved drug products with therapeutic equivalence evaluations. https://www.accessdata.fda.gov/scripts/cder/ob/
U.S. Food and Drug Administration. (n.d.). Electronic Code of Federal Regulations, 21 C.F.R. Part 335: Antidiarrheal products for over-the-counter human use. https://www.ecfr.gov/
United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term expiration guidance. https://www.uspto.gov/---

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Brazil	1100495	⤷ Start Trial
Brazil	1100507	⤷ Start Trial
Canada	2096575	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 5,716,641