US Patent 5,583,152: Scope, Claims, Expiration, and Zafirlukast Patent Landscape

US Patent 5,583,152 covered methods of using substituted indole compounds as leukotriene antagonists, including zafirlukast, the active ingredient in Accolate. The patent issued to Zeneca Limited on December 10, 1996, and its reported patent term expired on April 12, 2012. Its claims are no longer enforceable in the United States. The patent had historical importance because several dependent claims specifically recited zafirlukast and related indole sulfonamide compounds.

What drug does US Patent 5,583,152 protect?

The patent specifically covers zafirlukast and seven structurally related compounds.

Claim 10 recites:

N-[4-[5-(cyclopentyloxycarbonyl)amino-1-methylindol-3-ylmethyl]-3-methoxybenzoyl]-2-methylbenzenesulphonamide.

This is zafirlukast, marketed by AstraZeneca under the Accolate brand.

Zafirlukast is a cysteinyl leukotriene receptor antagonist used for the prophylaxis and chronic treatment of asthma. The FDA approved Accolate in 1996 for patients aged 5 years and older. It is not indicated for the relief of acute bronchospasm or as a rescue treatment for acute asthma attacks (FDA, 2024a).

Key product identification

Item	Data
Active ingredient	Zafirlukast
Brand	Accolate
Original sponsor	Zeneca, later AstraZeneca
Therapeutic class	Leukotriene receptor antagonist
Primary target	CysLT1 leukotriene receptor
FDA approval	1996
Patent specifically claiming zafirlukast	US 5,583,152, claim 10
Patent status	Expired
Reported expiration	April 12, 2012
Current US exclusivity	None based on this patent

What is the claim structure of US Patent 5,583,152?

The patent uses a layered claim strategy. The broadest claims cover a large chemical genus and methods of treatment. Later claims narrow the genus to indole compounds, named substituent combinations, specific compounds, compositions, and therapeutic uses.

Claim hierarchy

Claim group	Subject matter	Scope
Claim 1	Treatment of vasospastic cardiovascular disease with Formula Ia compounds	Broad genus and method claim
Claims 2-6	Narrower substituent selections and positional limitations	Intermediate chemical and structural scope
Claim 7	Indole derivatives of Formula IIa	Indole-specific genus
Claim 8	Selected Formula IIa compounds	Narrower subgroup
Claim 9	Eight named compounds	Compound-specific method claim
Claims 10-11	Zafirlukast and one related compound	Highly narrow compound claims
Claims 12-13	Pharmaceutical compositions and aerosol forms	Formulation and delivery limitations
Claim 14	Use of eight named compounds to antagonize leukotrienes	Standalone pharmacological method
Claims 15-16	Zafirlukast and a related compound under claim 14	Narrow compound-specific claims
Claims 17-18	Treatment of allergic, inflammatory, endotoxic, traumatic shock conditions, and asthma	Indication-specific claims

How broad is claim 1?

Claim 1 is a broad method-of-treatment claim covering a genus of compounds defined by Formula Ia. It requires:

A warm-blooded mammal.
A vasospastic cardiovascular disease.
Administration of an effective amount.
A compound satisfying the specified substituent definitions.
A pharmaceutically acceptable salt where applicable.

The claim covers variation at several positions:

Ra: hydrogen or C1-C4 alkyl.
Rb and Rc: hydrogen or a bond forming an unsaturated linkage.
Rd: hydrogen, alkyl, substituted alkyl, cycloalkyl, acyl, or substituted benzyl.
R1.L: an amide or thioamide-derived substituent.
R2: hydrogen, halogen, alkyl, or alkoxy.
Q: substituted phenylene.
A1 and A2: alkylene, vinylene, or direct linkages.
M: carboxy, tetrazole, or acylsulfonamide.

The functional limitation is treatment of vasospastic cardiovascular disease. A compound that falls within the chemical genus but is used for a different indication may not satisfy claim 1, although other claims could apply.

Chemical breadth of claim 1

Claim 1 is materially broader than zafirlukast. Zafirlukast is only one specific species within the claimed genus. The genus includes:

Carboxylic acid derivatives.
Tetrazole derivatives.
Acylsulfonamide derivatives.
Various N-substituted indoles.
Carbamate, urea, amide, and related side chains.
Multiple aromatic and aliphatic substituents.
Free acids and pharmaceutically acceptable salts.

The breadth is reduced by the requirement that every structural feature conform to the defined formula. A compound outside any required element, including the attachment position or acidic group, would not literally infringe.

Which claims specifically cover zafirlukast?

Claims 9, 10, 14, and 15 are the most important claims for zafirlukast.

Claim 9

Claim 9 lists eight compounds, including zafirlukast. It covers the use of those compounds for treating vasospastic cardiovascular disease under claim 1.

Claim 10

Claim 10 narrows claim 9 to zafirlukast alone. This is the strongest historical claim for direct literal coverage of zafirlukast because it identifies the compound by its complete chemical name.

Claim 14

Claim 14 independently recites the same eight compounds for antagonizing one or more actions of leukotrienes. It does not depend on the broad Formula Ia limitations of claim 1.

Claim 15

Claim 15 narrows claim 14 to zafirlukast.

This dual claim path was commercially significant. Claims 10 and 15 reach zafirlukast through different therapeutic formulations:

Claim 10: treatment of vasospastic cardiovascular disease.
Claim 15: leukotriene antagonism.

Claims 17 and 18 further identify allergic disease, inflammatory disease, endotoxic conditions, traumatic shock, and allergic asthma as covered uses under claims 14-16.

What formulations are protected by US Patent 5,583,152?

Claims 12 and 13 extend the patent beyond administration of the active compound alone.

Claim 12 covers a composition containing:

A claimed active compound; and
A non-toxic pharmaceutically acceptable diluent or carrier.

Claim 13 narrows the composition to a liquid or powdered aerosol.

The patent therefore contains formulation coverage, but the formulation claims are limited. They do not broadly cover every zafirlukast tablet, capsule, suspension, or other dosage form. A product must satisfy the composition and aerosol limitations to fall within the literal scope of claim 13.

The commercial Accolate dosage forms were oral tablets rather than the aerosol form singled out in claim 13. The core commercial relevance of the patent therefore came from the compound and method claims, particularly claims 10 and 15, rather than from the aerosol limitation.

What are the key technical limitations?

The patent's technical center is a substituted indole pharmacophore linked to a substituted benzoyl group and an acidic or acid-mimetic moiety.

Zafirlukast structural elements

Zafirlukast contains:

An N-methyl indole core.
A 5-position cyclopentyloxycarbonylamino substituent.
A 3-position benzyl linkage.
A 3-methoxybenzoyl group.
An ortho-tolylsulfonamide-derived acidic group.

These structural elements correspond closely to the restrictions in claims 5, 6, 8, and 10.

Claim 6 requires the R1.L group to be para to the -NRd- group on the benzene ring. This positional limitation is relevant to the specific architecture of zafirlukast and helps distinguish covered compounds from positional isomers.

When did US Patent 5,583,152 lose exclusivity?

The reported patent term ended on April 12, 2012. The patent is expired and cannot currently block US manufacture, sale, or use of zafirlukast on the basis of its expired claims.

Exclusivity timeline

Date	Event
April 12, 1991	Reported priority date for the patent family
December 10, 1996	US patent issued
1996	Accolate approved by FDA
2010	Earlier zafirlukast-related patent term reported to have ended
April 12, 2012	US 5,583,152 patent term expired
After 2012	Generic zafirlukast entry became legally possible, subject to regulatory approval and other applicable rights

The patent did not provide current market exclusivity after its expiration. Any present commercial protection must come from other sources, such as regulatory requirements, trademarks, manufacturing know-how, supply arrangements, or separate patents, not US 5,583,152.

What was the Orange Book status of US Patent 5,583,152?

US 5,583,152 was associated with the Accolate regulatory patent estate and was relevant to the FDA's Orange Book listing history for zafirlukast. Orange Book listings identify patents that a sponsor asserts cover an approved drug substance, formulation, or method of use. They do not determine ultimate infringement or validity.

The patent's practical Orange Book significance was greatest before April 2012. After expiration, it no longer created a patent barrier to an approved generic product.

Orange Book relevance

Issue	Assessment
Drug linked to patent	Zafirlukast
Brand product	Accolate
Patent category	Method and compound-use coverage
Formulation coverage	Limited aerosol composition claim
Current listing value	Historical only
Current blocking effect	None because the patent is expired

Were there Paragraph IV challenges to this patent?

A Paragraph IV certification is an ANDA applicant's assertion that a listed patent is invalid, unenforceable, or will not be infringed. A generic applicant may submit a Paragraph IV certification before patent expiration, potentially triggering litigation under the Hatch-Waxman Act.

The public commercial history of zafirlukast included generic-entry activity after the expiration of the principal patent barriers. Because US 5,583,152 expired in 2012, later generic applicants could rely on expiration rather than win a present-day Paragraph IV dispute against this patent.

No current Paragraph IV risk exists for US 5,583,152. Any historical challenge would be relevant to the pre-expiration litigation record, not to current enforceability.

Which companies challenged or commercialized generic zafirlukast?

Generic zafirlukast products entered the US market after expiration of the principal Accolate patent barriers. Public FDA product records identify generic zafirlukast products from multiple manufacturers over time, including Apotex and other generic suppliers.

The commercial issue was therefore resolved through patent expiration and subsequent abbreviated approval activity rather than through an active dispute over US 5,583,152. Current manufacturer-level conclusions require matching each marketed National Drug Code to the applicable FDA approval record and product status.

What patent litigation affected zafirlukast?

The relevant litigation window was the period before the 2012 expiration date, when generic applicants had an economic incentive to challenge the Accolate patent estate. The principal legal questions would have included:

Whether the ANDA product contained zafirlukast or a pharmaceutically acceptable salt within the claims.
Whether the proposed generic labeling induced use for a patented indication.
Whether the listed claims were valid and enforceable.
Whether the patent term had expired before commercial launch.
Whether other zafirlukast patents created a separate blocking right.

After April 12, 2012, litigation based solely on US 5,583,152 could not support prospective injunctive relief against continued commercial activity. Any historical infringement claims would remain distinct from present enforceability.

How strong was the patent estate?

The patent estate was historically strong against products containing zafirlukast because claims 10 and 15 named the compound directly. A generic product using the same active ingredient would have faced a substantial literal-infringement risk before expiration, subject to claim validity and statutory defenses.

Historical strength assessment

Factor	Assessment
Direct compound claim	Strong
Broad genus claim	Broad but more vulnerable to prior-art and written-description attacks
Method-of-use claim	Strong where labeling matched the claimed use
Leukotriene-antagonist claim	Strong for the eight named compounds
Aerosol formulation claim	Narrow
Design-around potential	Meaningful for different chemical species
Current enforceability	None

The strongest claims were claims 10 and 15. They did not depend on proving that every structural element of the broad genus was satisfied through an involved Markush analysis. The compound was expressly named.

The broad genus claims had more potential validity exposure because they covered many combinations of substituents. Such claims are more dependent on the patent's written description, enablement, novelty, and obviousness record than a claim directed to a single named compound.

What generic launch risks existed?

Before expiration, generic launch risk depended on three main factors:

The applicant's certification strategy.
The scope of its proposed labeling.
The survival of the listed patents.

A product containing zafirlukast would have had limited ability to avoid claims 10 and 15 through chemical design-around because those claims were directed to the named active ingredient. A generic applicant could instead have relied on:

A Paragraph IV challenge.
A section viii statement carving out a patented method, where legally available.
Launch after patent expiration.
A dispute over whether the listed patent properly covered the approved product or proposed use.

After expiration, those risks fell sharply. The remaining barriers were regulatory approval, manufacturing scale, bioequivalence, supply reliability, and commercial competition.

How does US 5,583,152 compare with other zafirlukast protections?

US 5,583,152 should be analyzed as one component of the Accolate patent estate rather than as the only relevant patent.

Protection type	Relevance to zafirlukast
Compound-specific method claim	High historical relevance
Broad chemical genus	Supports wider research coverage
Leukotriene-antagonist method claim	High historical relevance
Disease-specific claims	Relevant to asthma and allergic disease
Aerosol composition claim	Narrower commercial relevance
Regulatory exclusivity	Ended long before current generic competition
Trademark protection	Separate from patent rights
Manufacturing know-how	May persist independently of patent expiration

US 5,583,152 was distinct from other zafirlukast-related patents, including earlier patents cited in connection with Accolate. A complete freedom-to-operate review for a historical launch would require checking all Orange Book entries, continuations, divisionals, terminal disclaimers, patent-term adjustments, and litigation outcomes.

What manufacturing and geographic barriers remain?

The patent's geographic scope was limited to the United States. It did not directly establish rights in Europe, Japan, Canada, or other jurisdictions. Foreign family members required separate analysis of:

National phase status.
Local claim amendments.
Patent-term adjustments or supplementary protection certificates.
Local opposition and revocation proceedings.
Country-specific regulatory exclusivity.
Local generic approval rules.

After US expiration, manufacturing barriers could still include:

Process control for the active pharmaceutical ingredient.
Control of polymorphs or solid-state forms, if separately protected.
Purity and impurity specifications.
Scale-up of the multi-step indole synthesis.
Bioequivalence and dissolution performance.
Supply-chain qualification.

Those barriers are commercial or technical. They do not revive the expired claims of US 5,583,152.

What is the current commercial significance of US 5,583,152?

The patent has no current blocking value in the United States. Its commercial significance is historical and analytical:

It identifies zafirlukast as a directly claimed compound.
It explains the original Accolate patent position.
It provides a reference point for historical generic litigation risk.
It illustrates the use of compound-specific method claims alongside broad Markush claims.
It helps distinguish expired patent rights from continuing regulatory, trademark, and manufacturing rights.

For current US diligence, the patent should be classified as expired background IP rather than an enforceable barrier.

Key Takeaways

US Patent 5,583,152 covered leukotriene-antagonist indole compounds, including zafirlukast.
Claim 10 specifically recited zafirlukast by chemical name.
Claim 15 separately covered zafirlukast for leukotriene antagonism.
Claims 17 and 18 extended the therapeutic framework to allergic disease and allergic asthma.
Claims 12 and 13 covered pharmaceutical compositions, with claim 13 limited to liquid or powdered aerosols.
The reported US patent expiration date was April 12, 2012.
The patent is expired and does not currently block generic zafirlukast in the United States.
Its strongest historical protection came from the compound-specific claims, not the broad genus claims.
Current commercial barriers, if any, must be analyzed separately from this expired patent.

FAQs About US Patent 5,583,152 and Zafirlukast

Is US Patent 5,583,152 still active?

No. The patent's reported term expired on April 12, 2012.

Does US Patent 5,583,152 cover Accolate tablets?

Historically, the patent was relevant to Accolate because claims 10 and 15 covered zafirlukast methods of use. Claim 13 separately addressed aerosol compositions and did not broadly cover every oral tablet formulation.

Can a generic company still challenge US Patent 5,583,152?

No current challenge is necessary because the patent has expired. A generic company can rely on expiration rather than establish invalidity or noninfringement against an enforceable patent.

Does the patent cover montelukast?

No. The claims are directed to defined indole derivatives, including zafirlukast. Montelukast is a chemically distinct leukotriene receptor antagonist and is covered by a separate patent and regulatory history.

Does patent expiration eliminate all barriers to generic zafirlukast?

No. Patent expiration removes this patent barrier. Generic applicants must still satisfy FDA approval, bioequivalence, manufacturing, quality, labeling, and supply requirements.

References

AstraZeneca Pharmaceuticals LP. (2024). Accolate (zafirlukast) prescribing information. U.S. Food and Drug Administration.
U.S. Food and Drug Administration. (2024a). Drugs@FDA: Accolate (zafirlukast) drug approval and labeling information. https://www.accessdata.fda.gov/scripts/cder/daf/
U.S. Food and Drug Administration. (2024b). Approved drug products with therapeutic equivalence evaluations, Orange Book. https://www.accessdata.fda.gov/scripts/cder/ob/
United States Patent and Trademark Office. (1996). U.S. Patent No. 5,583,152: Indole derivatives. Issued December 10, 1996.
U.S. Congress. (1984). Drug Price Competition and Patent Term Restoration Act of 1984, Pub. L. No. 98-417, 98 Stat. 1585.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	85/09882	Apr 17, 1985
United Kingdom	85/25658	Oct 17, 1985

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0199543	⤷ Start Trial	SPC/GB98/033	United Kingdom	⤷ Start Trial
European Patent Office	0199543	⤷ Start Trial	97C0031	Belgium	⤷ Start Trial
Argentina	242569	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 5,583,152