US Patent 5,482,963: Scope, Claims, Expiration, and Zafirlukast Patent Landscape

US Patent 5,482,963 protects a specific amorphous physical form of zafirlukast, the active ingredient in Accolate, formulated with polyvinylpyrrolidone. Its scope is narrower than a basic compound patent or a broad zafirlukast composition patent because infringement requires the claimed amorphous form, the specified infrared characteristics, and the formulation relationship with polyvinylpyrrolidone.

The patent issued January 9, 1996, and, under the pre-URAA patent-term regime applicable to the underlying application, its ordinary 17-year term from grant would have ended January 9, 2013, subject to any applicable adjustment or terminal-disclaimer issue. The patent is therefore expired and does not presently block generic zafirlukast commercialization in the United States.[1]

What drug and physical form does US Patent 5,482,963 protect?

The claimed compound is zafirlukast, a leukotriene receptor antagonist formerly marketed by AstraZeneca as Accolate tablets.

The patent does not claim every form of zafirlukast. It claims an amorphous physical form that is:

Substantially free of other physical forms;
Identified by specified sharp infrared absorption peaks; and
Formulated with polyvinylpyrrolidone, commonly known as povidone or PVP.

The relevant chemical entity is identified in the claims as:

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

This is the chemical structure associated with zafirlukast. The FDA-approved product was Accolate tablets in 10-mg and 20-mg strengths.[2]

What is the commercial product associated with the patent?

Item	Data
Active ingredient	Zafirlukast
Drug class	Leukotriene receptor antagonist
Reference product	Accolate
Original sponsor	AstraZeneca
Dosage form	Oral tablet
FDA approval	NDA 020547
Approved strengths	10 mg and 20 mg
Patent at issue	US 5,482,963
Patent subject	Amorphous zafirlukast composition with PVP
Patent status	Expired
Patent expiration	January 9, 2013, based on ordinary 17-year post-grant term

Accolate was approved for prophylaxis and chronic treatment of asthma. It was not approved as an acute rescue treatment for bronchospasm.[2]

What does claim 1 of US Patent 5,482,963 cover?

Claim 1 is the central composition claim. It requires all of the following elements:

A pharmaceutical composition;
Zafirlukast as the active ingredient;
Zafirlukast in an amorphous physical form;
The amorphous form to be substantially free of other physical forms;
An infrared spectrum, measured at 0.5% in KBr, with sharp peaks at:
- 1690 cm⁻¹;
- 1530 cm⁻¹;
- 1490 cm⁻¹;
- 1420 cm⁻¹;
- 1155 cm⁻¹;
- 1060 cm⁻¹;
- 862 cm⁻¹; and
- 550 cm⁻¹; and
Polyvinylpyrrolidone in the composition.

A product containing zafirlukast alone would not fall within claim 1. A product containing crystalline zafirlukast would not fall within claim 1. A product containing an amorphous form but lacking PVP would also be outside the literal language of claim 1.

Why is the infrared limitation important?

The infrared spectrum functions as a structural and identity limitation for the claimed solid-state form. The claim does not merely require amorphous zafirlukast in a general sense. It requires a form exhibiting the listed spectral peaks under the specified testing condition.

That limitation narrows the claim in two ways:

It provides a testable characteristic for distinguishing the claimed form from crystalline zafirlukast and potentially from other amorphous forms.
It creates a potential non-infringement position for a manufacturer using a different polymorph, a different amorphous form, or a formulation in which the claimed spectral profile is absent.

The phrase “substantially free of other physical forms” adds a purity limitation. A mixed amorphous-crystalline product could present a dispute over whether the amount of crystalline material is sufficiently low to remain “substantially free.” The patent text supplied does not establish a numerical threshold for that phrase.

How narrow are claims 2 through 7?

Claims 2 through 7 depend on claim 1 and add formulation limitations. They do not independently broaden claim 1.

Claim	Additional limitation	Practical effect
1	Amorphous zafirlukast, specified IR peaks, substantially free of other forms, and PVP	Core composition claim
2	Pharmaceutically acceptable carrier	Requires a carrier in addition to the claim 1 elements
3	Zafirlukast at 1% to 90% by weight	Adds a broad concentration range
4	PVP at 1% to 20% by weight	Adds a PVP concentration range
5	Carrier selected from specified excipients	Narrows the carrier to listed materials
6	Processing adjuvant selected from specified materials	Requires one listed processing aid
7	Tablet dosage form	Requires tablet presentation

What formulations are protected?

Claim 5 identifies the following pharmaceutically acceptable carriers:

Mannitol;
Lactose;
Sorbitol;
Glucose;
Sucrose;
Dextrose;
Fructose;
Xylitol;
Microcrystalline cellulose;
Powdered cellulose; and
Hydroxypropylmethylcellulose.

Claim 6 identifies the following processing adjuvants:

Croscarmellose sodium;
Sodium starch glycolate;
Starch;
Magnesium stearate;
Stearic acid;
Talc; and
Powdered vegetable stearine.

A tablet containing the claimed amorphous zafirlukast and PVP does not necessarily infringe claim 7 unless it also meets the relevant incorporated limitations. Claims 5 and 6 are narrower because they require specified excipient categories.

What concentration ranges matter?

Claim 3 covers zafirlukast at 1% to 90% by weight of the total composition. Claim 4 covers PVP at 1% to 20% by weight.

These ranges are broad enough to capture conventional solid oral formulations, but they do not remove the central solid-state and spectral requirements in claim 1. A formulation outside either range may still implicate claim 1 or claim 2 if the remaining limitations are met.

What does claim 8 protect?

Claim 8 is a method-of-use claim directed to antagonizing one or more leukotriene actions in a living mammal. It requires administration of an effective amount of the pharmaceutical composition of claim 1.

The claim therefore includes two distinct requirements:

The administered product must satisfy claim 1; and
The administration must antagonize leukotriene activity.

The method claim does not broadly cover every use of zafirlukast. It is tied to the claimed amorphous zafirlukast/PVP composition.

A manufacturer could face a method-of-use theory if its product used the claimed formulation and promotional materials encouraged a leukotriene-antagonist indication. After patent expiration, claim 8 no longer creates a live US exclusivity barrier.

When did US Patent 5,482,963 lose exclusivity?

US Patent 5,482,963 issued on January 9, 1996. For patents governed by the pre-URAA term rule, the standard term was 17 years from issue. On that basis, the ordinary expiration date was January 9, 2013.[1]

Milestone	Date
Patent issued	January 9, 1996
Ordinary 17-year expiration	January 9, 2013
Current status	Expired
Current blocking value	None for US patent enforcement

The exact term analysis should distinguish this patent from later-filed continuation or improvement patents. Expiration of US 5,482,963 does not automatically establish expiration of every zafirlukast patent held by the same sponsor.

What was the broader zafirlukast patent estate?

The zafirlukast estate historically included multiple patent categories:

Basic compound patents covering zafirlukast and related leukotriene antagonists;
Pharmaceutical composition patents;
Solid-state or amorphous-form patents;
Tablet and excipient formulations;
Manufacturing and processing disclosures; and
FDA regulatory exclusivity associated with the original NDA.

The distinction between the basic compound patent and US 5,482,963 is commercially important. A compound patent can block use of the molecule regardless of polymorph or excipient. US 5,482,963 instead targets a particular solid-state formulation.

How does US 5,482,963 compare with a basic compound patent?

Issue	Basic zafirlukast patent	US 5,482,963
Primary subject	Chemical compound	Amorphous physical form and formulation
Requires PVP	No, unless expressly claimed	Yes in claim 1
Requires IR peaks	No	Yes
Covers crystalline zafirlukast	Potentially, depending on claim	No, based on claim 1
Covers amorphous zafirlukast	Potentially	Only the specified form
Formulation-specific	Usually limited	Yes
Design-around potential	Lower	Higher
Current status	Historical estate issue	Expired

The patent at issue was therefore best understood as a product-quality and formulation patent, rather than the principal molecule patent.

What was the FDA Orange Book status?

Accolate was approved under NDA 020547. The FDA Orange Book historically listed patents associated with the reference product and included patent information relevant to generic applicants.[3]

For a generic applicant, an Orange Book-listed patent can require one of four certifications under section 505(j):

Paragraph I: no patent information is listed;
Paragraph II: the patent has expired;
Paragraph III: the applicant will wait until patent expiration; or
Paragraph IV: the patent is invalid, unenforceable, or will not be infringed.

Because US 5,482,963 expired in 2013, a current applicant would generally rely on an expired-patent certification for this patent rather than maintain a Paragraph IV challenge against a live right.

Did the patent create a Paragraph IV risk?

During its active term, the patent could have created Paragraph IV exposure for a generic zafirlukast applicant if the patent was listed for the reference product and the applicant certified that the patent was invalid or not infringed.

The most credible technical non-infringement positions would have focused on:

Use of crystalline rather than amorphous zafirlukast;
Use of an amorphous form lacking the claimed IR peaks;
Inclusion of a material other than PVP;
A composition not substantially free of other physical forms;
PVP outside the claimed dependent range; or
A dosage form outside narrower tablet or excipient limitations.

A Paragraph IV challenge would not need to defeat every zafirlukast patent. It would need to address the specific Orange Book-listed patent and any other listed patents relevant to approval timing.

Which companies challenged or competed with Accolate?

The US generic market developed after the principal exclusivity period and patent barriers had ended or become commercially manageable. Generic zafirlukast products were pursued by abbreviated new drug application sponsors, including companies operating through the conventional ANDA pathway.

The principal competitive factors were:

Expiration of the core zafirlukast compound protection;
Expiration of US 5,482,963;
Availability of the FDA-approved reference product for bioequivalence comparison;
Limited commercial differentiation between 10-mg and 20-mg tablets;
Competition from montelukast and other asthma therapies; and
Declining strategic importance of Accolate relative to inhaled corticosteroids and other controller medicines.

Publicly available patent records do not establish, from the claim text alone, a complete list of every Paragraph IV filer, litigation defendant, or settlement party. US 5,482,963 itself is expired, so historical ANDA disputes no longer create a current market-entry restriction.[1,3]

What litigation and settlement issues affected generic entry?

The main litigation risk during the patent term would have involved three questions:

Whether the generic product used the claimed amorphous zafirlukast form;
Whether the generic formulation contained PVP in the claimed relationship; and
Whether the IR spectrum and “substantially free” limitations were satisfied.

A generic company could seek to avoid infringement by selecting a different physical form or excipient system. That strategy would have required attention to bioequivalence, dissolution, stability, manufacturability, and regulatory comparability.

No current litigation effect remains from US 5,482,963 because the patent has expired. A historical settlement, if any, would have had value only for the period before January 9, 2013, unless it contained separate contractual restrictions surviving patent expiration.

How strong was the patent estate?

Strengths

The patent had meaningful technical specificity:

The amorphous form was defined by an analytical fingerprint;
PVP was required in the independent composition claim;
The claims reached tablets and common excipients;
The method claim linked the formulation to leukotriene antagonism; and
The patent could support a formulation-based infringement theory even after broader chemical claims became vulnerable or expired.

Weaknesses

The estate also had material limitations:

It did not cover all zafirlukast forms;
It required a particular solid-state profile;
The claim used qualitative language such as “substantially free” without a stated numerical cutoff in the supplied text;
A competitor could investigate alternative excipients and physical forms;
The patent term ended in 2013; and
The commercial value of a zafirlukast formulation patent was constrained by competition from montelukast and other asthma therapies.

Overall, US 5,482,963 was a moderate-strength formulation patent during its remaining term, but it was not a durable substitute for basic compound protection.

What generic launch scenarios existed?

Scenario 1: Launch after expiration

This was the lowest-risk pathway. A generic applicant could wait until January 9, 2013, and certify expiration for the patent, subject to any other unexpired listed patents or regulatory exclusivities.

Scenario 2: Paragraph IV launch

A pre-expiration applicant could argue that its product did not contain the claimed amorphous form, lacked PVP, or used a non-infringing physical form. This pathway created litigation risk and a possible 30-month stay if the statutory conditions were met.

Scenario 3: Formulation design-around

A company could use:

Crystalline zafirlukast;
A different amorphous form;
A different binder or stabilizer instead of PVP;
A formulation outside the claimed PVP range; or
A dosage form other than the claimed tablet.

The design-around would still need to satisfy FDA bioequivalence and product-quality requirements.

What geographic coverage did the patent provide?

US 5,482,963 provided US protection only. It did not directly block sales in Europe, Japan, Canada, or other markets.

Equivalent foreign applications may have existed in the same patent family, but each jurisdiction required separate analysis of:

National-phase status;
Grant and lapse status;
Patent-term adjustment;
Supplementary protection certificate availability;
Claim amendments;
Opposition or revocation proceedings; and
Local infringement standards.

The US expiration date cannot be applied automatically to foreign family members.

What manufacturing and intellectual-property barriers remained?

After expiration, the primary barriers shifted from patent exclusion to execution:

Reproducible control of zafirlukast solid state;
Prevention of unwanted crystallization during granulation and storage;
Demonstration of dissolution comparability;
Stability of the amorphous form;
Control of particle size and content uniformity;
Selection of excipients compatible with the formulation; and
FDA approval of the ANDA.

The expired patent remains technically useful as prior art and as a source of formulation knowledge. It does not confer enforceable exclusivity, but its disclosure may inform freedom-to-operate analysis for later patents directed to manufacturing controls, improved stability, new dosage forms, or alternative delivery systems.

Key Takeaways

US Patent 5,482,963 covers a specific amorphous form of zafirlukast combined with polyvinylpyrrolidone.
Claim 1 is narrow because it requires the claimed amorphous form, substantial absence of other forms, eight specified infrared peaks, and PVP.
Claims 2 through 7 add carriers, concentration ranges, processing aids, and tablet limitations.
Claim 8 covers use of the claimed composition to antagonize leukotriene activity.
The patent issued January 9, 1996, and its ordinary 17-year term expired January 9, 2013.
The patent no longer blocks US generic entry.
Historical Paragraph IV risk would have centered on solid-state characterization and the presence of PVP.
The patent was a formulation and solid-state right, not a broad zafirlukast compound patent.
Foreign family members require separate country-by-country analysis.
Current commercial barriers are regulatory, manufacturing, and market-based rather than enforceable rights under US 5,482,963.

FAQs

Is US Patent 5,482,963 still enforceable against a zafirlukast generic?

No. The patent’s ordinary US term expired January 9, 2013, absent an unusual term adjustment or other legally operative extension.

Does the patent cover crystalline zafirlukast?

The supplied claims do not cover crystalline zafirlukast. Claim 1 requires an amorphous physical form substantially free of other physical forms.

Does zafirlukast without PVP infringe claim 1?

A composition lacking PVP would not meet the express PVP limitation in claim 1. It would also need to be assessed against other patents, regulatory requirements, and possible equivalents theories applicable during the patent term.

Can a generic use a different amorphous form of zafirlukast?

A different amorphous form may provide a non-infringement position if it lacks the claimed infrared profile or otherwise fails a claim limitation. Analytical testing and claim construction would control the assessment.

Is zafirlukast subject to biosimilar approval requirements?

No. Zafirlukast is a chemically synthesized small molecule. Generic products are approved through the ANDA pathway, not the biosimilar pathway under the Public Health Service Act.

References

United States Patent and Trademark Office. (1996). US Patent No. 5,482,963, Pharmaceutical compositions. https://patents.google.com/patent/US5482963
U.S. Food and Drug Administration. (1996). Accolate (zafirlukast) tablets prescribing information.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	9027014	Dec 12, 1990
United Kingdom	9115107	Jul 12, 1991

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
African Regional IP Organization (ARIPO)	285	⤷ Start Trial
African Regional IP Organization (ARIPO)	9100340	⤷ Start Trial
Austria	131048	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,482,963

Summary for Patent: 5,482,963