United States Drug Patent 5,601,843: Claim Scope, Expiration, and Patent Landscape for Diclofenac-Misoprostol Tablets

U.S. Patent No. 5,601,843 covers oral pharmaceutical products combining an NSAID, principally diclofenac, with misoprostol in a multilayer tablet. The central architecture is an NSAID-containing core surrounded by a misoprostol-containing mantle. Claim 10 is the commercially most important claim because it specifies diclofenac sodium, an enteric coating, and 100-200 micrograms of misoprostol.

The patent issued to G.D. Searle & Co. on February 11, 1997, and its U.S. patent term expired in 2014. It therefore does not presently block generic manufacture or sale in the United States. Current commercial risk depends on other patents, FDA exclusivity, manufacturing know-how, regulatory requirements, and state or foreign rights rather than enforceability of U.S. Patent 5,601,843 itself. [1, 2]

What invention does U.S. Patent 5,601,843 protect?

The patent protects a combined dosage form containing:

An NSAID core containing diclofenac or piroxicam.
A surrounding mantle containing misoprostol.
In one embodiment, an enteric coating between the NSAID core and the misoprostol mantle.
In the narrowest commercial embodiment, 25-75 mg diclofenac sodium, an enteric coating, and 100-200 micrograms of misoprostol.

The patent is directed to a fixed-dose combination rather than to diclofenac, piroxicam, or misoprostol individually. Its technical focus is physical separation and controlled delivery of the two active ingredients in a single oral tablet.

The invention corresponds to the product concept marketed as Arthrotec, a diclofenac sodium and misoprostol delayed-release tablet. Arthrotec was developed to combine anti-inflammatory activity with misoprostol-mediated reduction of NSAID-associated gastric injury risk. The product is regulated as a small-molecule drug, not as a biologic. [2, 3]

How are the claims organized?

Claim group	Subject matter	Principal limitation
Claims 1-5	Pharmaceutical composition	NSAID core and misoprostol mantle
Claims 6-9	Method of treating inflammation	Oral administration of the claimed combination
Claim 10	Specific pharmaceutical tablet	Diclofenac sodium core, enteric coating, and 100-200 mcg misoprostol

Claims 2 and 3 narrow claim 1 by selecting diclofenac or piroxicam. Claim 4 adds an intermediate enteric coating. Claim 5 narrows the diclofenac embodiment to approximately 25-75 mg diclofenac and approximately 200 micrograms misoprostol.

Claims 6-9 mirror the composition claims as treatment claims. They require administration to a patient for treatment of inflammation. Claim 10 is an independent composition claim and does not depend on claim 1.

What does the “core” limitation require?

Claims 1 and 6 require a core “consisting of” a therapeutically effective amount of diclofenac or piroxicam, while the overall composition uses the broader transitional term “comprising.”

The distinction matters:

“Consisting of” generally excludes additional substantive components from the defined core, subject to ordinary interpretation of excipients and incidental materials.
“Comprising” permits additional components in the overall tablet.
The claimed architecture requires the NSAID to be located in the core, not merely dispersed somewhere in the tablet.
A formulation with NSAID and misoprostol blended homogeneously throughout a single matrix may fall outside the literal multilayer structure, depending on the remaining claim limitations.

The claims do not require a particular tablet manufacturing process, compression sequence, polymer, coating apparatus, or dissolution profile. The structural relationship between the NSAID core, optional enteric coating, and misoprostol mantle is the principal infringement issue.

What does the misoprostol “mantle coating” limitation require?

The mantle must surround the core and contain a therapeutically effective amount of misoprostol. The term captures a coating or outer layer rather than a separate tablet administered at the same time.

Important technical variables include:

Whether the misoprostol layer completely surrounds the core.
Whether misoprostol is located in an outer layer or in a non-coating matrix.
Whether the layer contains misoprostol in a therapeutically effective amount.
Whether the product has an intermediate enteric coating.
Whether the formulation releases diclofenac and misoprostol at different locations or times.

The claims do not expressly require the mantle to be enteric-coated. Claim 4 and claim 10 establish that an enteric coating can be located between the NSAID core and the misoprostol mantle.

What is the scope of each claim in U.S. Patent 5,601,843?

Claims 1-3: Broad combination composition claims

Claim 1 covers a tablet containing either diclofenac or piroxicam in the core and misoprostol in the surrounding mantle.

Claim 2 limits claim 1 to diclofenac. Claim 3 limits claim 1 to piroxicam.

These claims do not specify:

A precise dose of the NSAID.
A precise dose of misoprostol.
An enteric coating.
A particular release profile.
Diclofenac sodium rather than another diclofenac form.
A particular excipient system.

The lack of an express enteric-coating limitation gives claims 1-3 potentially broader structural coverage than claim 10. Their practical scope still depends on how “core,” “mantle coating,” and “surrounding” are construed.

Claim 4: Enteric-coated embodiment

Claim 4 adds an intermediate enteric coating surrounding the NSAID core. The sequence is:

NSAID core.
Enteric coating.
Misoprostol-containing mantle.

The enteric layer must be positioned around the core and inside the mantle. A product with an enteric coating only on the outside of the entire tablet may not satisfy this limitation without an equivalent structure.

Claim 5: Diclofenac and approximately 200 micrograms misoprostol

Claim 5 specifies:

Diclofenac at approximately 25-75 mg.
A prostaglandin formulation containing approximately 200 micrograms of misoprostol.

This claim is directed to the dose combination associated with the 50 mg diclofenac/200 microgram misoprostol product configuration. It is narrower than claims 1-4 because it includes both dose ranges and the diclofenac selection.

Claims 6-9: Treatment method claims

Claims 6-9 require oral administration of the claimed dosage form to a patient needing treatment for inflammation.

Potential issues include:

Whether the administered product has the required physical architecture.
Whether the patient is being treated for an inflammatory condition.
Whether the dose and active ingredients satisfy the dependent claim.
Whether direct or induced infringement can be established against a manufacturer based on product labeling.

A product label that directs use for osteoarthritis, rheumatoid arthritis, or another inflammatory indication could be relevant to method-of-use theories. The claims, however, are not limited to one named disease.

Claim 10: Narrow product claim with commercial relevance

Claim 10 requires:

A core containing 25-75 mg diclofenac sodium.
An enteric coating surrounding the core.
A mantle coating surrounding the enteric coating.
100-200 micrograms of misoprostol in the mantle.

The required layer sequence is:

diclofenac sodium core → enteric coating → misoprostol mantle

Claim 10 is narrower than claim 1 but provides a more precise description of the marketed delayed-release architecture. A formulation containing diclofenac potassium, a different diclofenac salt, or misoprostol outside the 100-200 microgram range would require separate analysis under the other claims or an equivalents theory.

What formulations are protected by the patent?

The patent’s strongest formulation coverage is directed to layered diclofenac-misoprostol tablets. The principal covered formulation categories are:

Formulation	Claim relevance
Diclofenac core with misoprostol mantle	Claims 1, 2, 5, 10
Piroxicam core with misoprostol mantle	Claims 1 and 3
Diclofenac core, enteric coating, misoprostol mantle	Claims 4 and 10
25-75 mg diclofenac and about 200 mcg misoprostol	Claim 5
25-75 mg diclofenac sodium and 100-200 mcg misoprostol	Claim 10
Homogeneous single-layer blend	Potentially outside the literal layered structure
Separate diclofenac and misoprostol tablets	Outside the single-tablet composition claims

The patent does not broadly claim every product containing diclofenac and misoprostol. It claims a specific co-formulated dosage form with a defined spatial arrangement.

When did U.S. Patent 5,601,843 lose exclusivity?

U.S. Patent 5,601,843 issued on February 11, 1997. The patent was filed during the transition period governed by the former patent-term rules. Its term expired in 2014, based on the applicable patent-term calculation reflected in public patent and FDA records. [1, 2]

Milestone	Date
U.S. patent application filing	1994
Patent issued	February 11, 1997
U.S. patent term expiration	2014
Present status	Expired; no enforceable patent exclusivity

The expiration eliminated the patent-based barrier to U.S. generic entry. Patent expiration does not itself establish that a generic product satisfies FDA requirements. An applicant still must obtain approval through the abbreviated new drug application pathway and demonstrate pharmaceutical equivalence, bioequivalence, manufacturing quality, and appropriate labeling.

What is the Orange Book status of U.S. Patent 5,601,843?

U.S. Patent 5,601,843 was listed in connection with Arthrotec, the diclofenac sodium/misoprostol product approved under NDA 020607. The relevant FDA product is a delayed-release tablet combination. [2, 3]

The patent’s current commercial significance is limited because an expired patent cannot support a current Paragraph IV litigation barrier. FDA Orange Book listings distinguish patent information from regulatory exclusivity. A listed patent may identify historical protection, but the listing does not extend the patent term.

The patent should therefore be treated as:

Historically relevant to Arthrotec.
Relevant to prior generic-development and litigation analysis.
Not a current U.S. blocking patent.
Not a source of current market exclusivity.

Were Paragraph IV challenges relevant to this patent?

Paragraph IV challenges were commercially relevant before the patent expired. An ANDA applicant could certify that the patent was invalid, unenforceable, or would not be infringed. The patent’s expiration ultimately removed the need to resolve the patent barrier for later generic applicants.

For a current launch analysis, the practical conclusion is direct: a new ANDA applicant cannot be enjoined based solely on U.S. Patent 5,601,843 because the patent has expired.

Historical Paragraph IV analysis should distinguish:

Challenges to U.S. Patent 5,601,843.
Challenges to other Arthrotec-related patents.
FDA approval timing.
Any litigation settlement or launch license.
The actual formulation submitted in the ANDA.

The patent itself does not establish whether a particular generic applicant filed a Paragraph IV certification or entered a settlement. Those facts arise from FDA patent certifications, Abbreviated New Drug Application records, court dockets, and settlement disclosures.

What patent litigation affects Arthrotec and diclofenac-misoprostol products?

The principal historical litigation risk involved the structure of the fixed-dose product and any related patents covering formulation, coating, release, or therapeutic use. Patent 5,601,843 could have supported infringement allegations against a product containing the claimed layered arrangement during its enforceable term.

After expiration:

No new infringement action can obtain prospective exclusion based on the expired patent.
Damages claims for pre-expiration conduct remain legally distinct from post-expiration commercialization.
A generic applicant may still face litigation under other unexpired patents, if any remain listed or enforceable.
FDA approval and patent clearance are separate analyses.

A reliable present-day litigation conclusion must rely on current USPTO and federal-court records. The supplied claim text alone does not establish an active case, settlement, or remaining related patent.

How strong was the patent estate?

During its term, U.S. Patent 5,601,843 had meaningful product-design coverage because it combined composition and method claims. Its strongest features were:

Coverage of both diclofenac and piroxicam embodiments.
Layered dosage-form architecture.
Optional enteric protection.
Specific dose coverage for the commercially important diclofenac/misoprostol product.
Method claims linked to oral treatment of inflammation.

Its weaknesses included:

Dependence on a particular physical arrangement.
Potential design-around opportunities using a homogeneous matrix or separate dosage units.
Limited express coverage of manufacturing processes.
Limited express coverage of alternative diclofenac salts and release technologies.
Lack of current enforceability after expiration.

Patent strength today is therefore zero as a blocking right, although the patent remains relevant as prior art and as evidence of the historical design space.

How does this patent compare with biologic and generic exclusivity?

Arthrotec and its active ingredients are small-molecule products. Biosimilar risk does not apply.

The relevant competitive pathways are:

Issue	Relevance
ANDA approval	Primary pathway for therapeutically equivalent generic tablets
Paragraph IV certification	Historical patent challenge mechanism
30-month stay	Potentially relevant during the patent term
New chemical entity exclusivity	Not a current barrier
Three-year clinical investigation exclusivity	Product-specific and time-limited
Biologics Price Competition and Innovation Act	Not applicable
Patent term extension	Must be confirmed from the Orange Book and USPTO records; it does not appear to preserve current exclusivity for this patent

Generic applicants may develop diclofenac sodium/misoprostol delayed-release tablets using the same general clinical concept while avoiding any still-active formulation or process patents. Because 5,601,843 has expired, it cannot independently prevent an ANDA approval or commercial launch.

Which companies compete in the diclofenac-misoprostol market?

The originator product was Arthrotec, associated with G.D. Searle and later Pfizer following corporate transactions. Generic competition has involved manufacturers developing diclofenac sodium/misoprostol delayed-release tablets for the U.S. market.

The main competitive variables are:

Approval of an ANDA.
Availability of the exact strength, including 50 mg/200 mcg.
Bioequivalence to the reference product.
Manufacturing capacity for multilayer or coated tablets.
Stability of misoprostol, which is sensitive to formulation and storage conditions.
Distribution and reimbursement.
Physician and pharmacy substitution.
Regulatory compliance for delayed-release performance.

The expired patent lowers legal entry barriers but does not eliminate technical barriers. Misoprostol-containing products can require controlled handling, validated coating processes, stability testing, and tight content-uniformity controls.

What manufacturing and intellectual-property barriers remain?

The principal post-expiration barriers are technical and regulatory rather than patent-based.

Manufacturing barriers

A manufacturer may need to control:

Uniform diclofenac loading in the core.
Integrity and dissolution performance of the enteric coating.
Uniform misoprostol distribution in the mantle.
Protection of misoprostol from degradation.
Tablet-layer adhesion and mechanical strength.
Delayed-release specifications.
Packaging and storage conditions.

Intellectual-property barriers

Other potentially relevant rights may include:

Later formulation patents.
Process patents.
Coating-composition patents.
Crystalline or salt-form patents.
Manufacturing equipment or control-system patents.
Trademark rights in Arthrotec and related branding.
Foreign patents with different expiration dates.

Those rights cannot be treated as extensions of U.S. Patent 5,601,843. Each requires separate claim, term, ownership, and jurisdiction analysis.

What is the geographic coverage of U.S. Patent 5,601,843?

The patent provided U.S. rights only. It could support infringement claims involving manufacture, use, sale, offer for sale, or importation connected to the United States during the enforceable term.

Foreign equivalents are separate rights. A U.S. patent expiration date does not establish the status of corresponding patents in:

Canada.
Europe.
Japan.
Australia.
China.
India.
Other national jurisdictions.

A global launch assessment must map each national family member, its legal status, terminal disclaimer, maintenance fees, supplementary protection certificate, and local patent-term rules.

What generic launch scenarios exist now?

The most likely current U.S. launch scenarios are:

Direct generic entry: An applicant markets a therapeutically equivalent diclofenac sodium/misoprostol delayed-release tablet after FDA approval.
Design-around entry: An applicant uses a different layer sequence, matrix system, coating composition, or active-ingredient arrangement.
Multi-source competition: Several ANDA holders compete on price after approval.
Limited commercial entry: A generic is approved but has restricted distribution because demand is modest or manufacturing costs are high.
Regulatory delay without patent blockage: Approval is delayed by bioequivalence, chemistry, manufacturing, or stability issues rather than U.S. Patent 5,601,843.

Key Takeaways

U.S. Patent 5,601,843 covers a single-tablet diclofenac-or-piroxicam and misoprostol dosage form.
The core claim concept is an NSAID-containing core surrounded by a misoprostol mantle.
Claim 10 is the narrow, commercially important embodiment covering diclofenac sodium, an intermediate enteric coating, and 100-200 micrograms of misoprostol.
Claims 6-9 add oral treatment methods for inflammation.
The patent expired in 2014 and is not a current U.S. blocking right.
Biosimilar analysis is irrelevant because the product is a small-molecule drug.
Current entry risk depends on FDA approval, technical formulation capability, later patents, manufacturing rights, and foreign patent status.
A generic product using a homogeneous matrix or different layer arrangement may avoid literal infringement, subject to claim construction and any applicable equivalents theory.
The expired patent remains relevant as historical prior art and as a record of the Arthrotec formulation strategy.

FAQs About U.S. Patent 5,601,843

Can a generic manufacturer still be sued under U.S. Patent 5,601,843?

The expired patent cannot support prospective exclusion of a current generic product. Separate claims concerning pre-expiration conduct or other patents must be analyzed independently.

Does claim 10 cover all diclofenac-misoprostol tablets?

No. Claim 10 requires a specific layered structure: diclofenac sodium core, enteric coating, and misoprostol mantle, with specified dose ranges.

Is piroxicam still covered by the patent?

Claims 1, 3, 6, and 8 expressly include piroxicam, but the patent has expired in the United States.

Is Arthrotec protected by biosimilar law?

No. Arthrotec contains small-molecule active ingredients and is subject to generic-drug, not biosimilar, regulation.

Can a company commercialize a diclofenac-misoprostol product without licensing Pfizer?

Expiration of U.S. Patent 5,601,843 removes that patent as a licensing barrier. Trademark, regulatory, later-patent, contractual, and foreign-rights issues remain separate.

References

United States Patent and Trademark Office. (1997). U.S. Patent No. 5,601,843, pharmaceutical compositions comprising an NSAID and misoprostol.
U.S. Food and Drug Administration. (n.d.). Approved drug products with therapeutic equivalence evaluations: Orange Book.
U.S. Food and Drug Administration. (n.d.). Arthrotec (diclofenac sodium and misoprostol) prescribing information and Drugs@FDA records.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	121625	⤷ Start Trial
Australia	7876491	⤷ Start Trial
Canada	2082944	⤷ Start Trial
Germany	69109286	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,601,843

Summary for Patent: 5,601,843