U.S. Patent 5,817,028: Claim Scope, Expiration, Orange Book Status, and Inhaled Mannitol Patent Landscape

U.S. Patent No. 5,817,028 protected methods for administering a respirable dry powder that increases airway-surface-liquid osmolarity and then either measures airway narrowing or increases mucociliary clearance or sputum production. The patent covered dry powders such as sodium chloride, potassium chloride, mannitol and dextrose, including unit doses in rupturable hard capsules.

The patent issued October 6, 1998, and expired October 6, 2015 under the pre-Uruguay Round patent-term regime. Its claims are no longer enforceable. The patent did not claim mannitol as a composition of matter, a proprietary inhaler, or a product label standing alone. Its principal commercial relevance was as a method patent supporting inhaled mannitol bronchial-challenge products, including Aridol.

What does U.S. Patent 5,817,028 cover?

The patent has two independent claim groups.

Claim group	Independent claim	Protected activity	Principal commercial relevance
Airway challenge	1	Inhaling an osmolarity-increasing dry powder and measuring airway resistance or narrowing	Bronchial provocation testing
Mucociliary clearance and sputum	12	Inhaling an osmolarity-increasing dry powder to increase mucociliary clearance or induce sputum	Respiratory clearance therapy and sputum induction

Claims 2-11 depend from claim 1. Claims 13-21 depend from claim 12.

The core technical concept is the delivery of a dry, respirable osmotic agent directly into the airway. The inhaled particles increase the osmolarity of airway surface liquid. In the challenge-test claims, the resulting airway response is measured. In the clearance claims, the intended result is increased mucociliary clearance or induced sputum.

The claims require the substance to be a dry dispersible powder. They expressly exclude a dry powder dissolved in a liquid. This limitation separates the claimed technology from conventional nebulized hypertonic saline and other liquid aerosol systems.

How broad are the independent claims?

Claim 1: airway-narrowing challenge

Claim 1 requires all of the following:

A subject inhales an effective amount of a substance.
The substance is capable of increasing airway-surface-liquid osmolarity.
The substance is a dry dispersible powder.
The powder contains an effective proportion of respirable particles.
The subject’s airway resistance or another parameter indicative of airway narrowing is measured.

The claim is functional in several respects. It does not require a specific chemical compound, inhaler, particle-generation process or clinical threshold. Instead, the substance must increase airway-surface-liquid osmolarity, and the particles must be respirable in an amount effective for the claimed result.

The phrase “attempting to provoke airway narrowing” broadens the claimed method relative to a claim requiring a confirmed bronchoconstrictive response. A method may fall within the claim even if the subject does not ultimately experience a clinically meaningful decline, provided the method is performed to provoke narrowing and includes the required inhalation and measurement steps.

Claim 9 narrows the measurement step to a reduction in forced expiratory volume in one second, or FEV1. This limitation corresponds closely to standard bronchial challenge testing, where a decline in FEV1 is used to determine airway hyperresponsiveness.

Claim 12: mucociliary clearance and sputum induction

Claim 12 omits the airway-resistance measurement requirement. It requires inhalation of an osmolarity-increasing dry powder for the purpose of increasing mucociliary clearance or inducing sputum.

This claim group is commercially broader in one respect because it does not require measurement of bronchoconstriction. It is narrower in another respect because the intended therapeutic or diagnostic result must relate to mucociliary clearance or sputum induction.

The distinction matters for infringement analysis. A dry-powder product used only for airway challenge is principally analyzed under claim 1. A product used for mucus clearance or sputum induction may implicate claim 12 even if no FEV1 measurement occurs.

What substances and formulations are protected?

Claims 4-6 identify the principal chemical classes and compounds:

Claim limitation	Covered substances
Claim 4	Mineral salts, sugars and sugar alcohols
Claim 5	Sodium or potassium salts, hexose and pentose sugars, and corresponding sugar alcohols
Claim 6	Sodium chloride, potassium chloride, mannitol and dextrose

The claims are not limited to mannitol. Mannitol is one expressly listed embodiment among several osmotic agents.

Claims 7 and 18 require an effective quantity of dry particles having a maximum dimension of 7 microns. Claims 8 and 19 require at least 10% by weight of respirable-size particles, with preferred levels of at least 25%, 40% and 50%.

These limitations create two different particle-size concepts:

A maximum-dimension limitation for an effective quantity of particles.
A minimum weight fraction of particles having respirable size.

The claims do not define respirable size solely by a single aerodynamic diameter. In practice, particle morphology, density, aerodynamic behavior and dispersion performance would affect whether a powder meets the limitation.

Claims 10, 11, 20 and 21 cover packaging in a rupturable hard capsule, with a capsule fill weight of 1-100 mg and a preferred range of 5-40 mg.

The patent therefore reaches a product-use configuration involving:

An osmotic dry powder;
A respirable particle fraction;
A unit-dose capsule;
A dose suitable for inhalation through a dry-powder device.

The claims do not require a particular capsule material, inhaler design, blister format or capsule-piercing mechanism.

What is the patent’s claim hierarchy?

Claim	Scope
1	Dry osmotic powder inhaled to provoke airway narrowing and measure airway response
2	Claim 1, pulmonary airway
3	Claim 1, nasal airway
4	Claim 1, mineral salts, sugars or sugar alcohols
5	Claim 4, specified salt and sugar classes
6	Claim 5, sodium chloride, potassium chloride, mannitol or dextrose
7	Claim 1, particles with maximum dimension of 7 microns
8	Claim 1, at least 10% respirable particles, with higher preferences
9	Claim 1, FEV1 reduction as the measured parameter
10	Claim 1, rupturable hard capsule
11	Claim 10, 1-100 mg, preferably 5-40 mg
12	Dry osmotic powder inhaled to increase clearance or induce sputum
13	Claim 12, pulmonary airway
14	Claim 12, nasal airway
15	Claim 12, mineral salts, sugars or sugar alcohols
16	Claim 15, specified salt and sugar classes
17	Claim 16, sodium chloride, potassium chloride, mannitol or dextrose
18	Claim 12, particles with maximum dimension of 7 microns
19	Claim 12, at least 10% respirable particles, with higher preferences
20	Claim 12, rupturable hard capsule
21	Claim 20, 1-100 mg, preferably 5-40 mg

The patent has substantial claim redundancy. Claims 1 and 12 establish the two functional use cases. The dependent claims narrow the powder chemistry, particle properties, administration site, measurement method and packaging.

When did U.S. Patent 5,817,028 lose exclusivity?

U.S. Patent 5,817,028 expired on October 6, 2015. It was granted before the change to the current 20-year term measured from the earliest effective nonprovisional filing date. The patent was therefore governed by the former 17-year term from grant, subject to applicable statutory adjustments. The U.S. Patent and Trademark Office patent record identifies the grant date and term status. (USPTO, 2024; U.S. Patent No. 5,817,028, 1998)

No enforceable patent rights remain under the claims. A manufacturer can no longer be sued for practicing claims 1-21 solely because the practice falls within the expired patent.

Expiration does not eliminate the patent’s relevance to freedom-to-operate analysis for later patents. It can remain relevant as prior art against continuation, improvement or follow-on applications, and as evidence of technical disclosure.

What is the Orange Book status of U.S. Patent 5,817,028?

The patent is not a current source of Orange Book exclusivity because it expired in 2015. Any historical listing associated with an FDA-approved inhaled mannitol product could not extend the patent term after expiration.

The FDA approved Aridol, an inhaled mannitol bronchial challenge product, in December 2010 under NDA 022054. The approved use is assessment of bronchial hyperresponsiveness in patients aged 6 years and older who do not have clinically apparent asthma. The product is a diagnostic challenge agent, not a chronic mucus-clearance therapy. (FDA, 2010)

An Orange Book listing does not create a new patent term. It can identify patents submitted by an NDA holder, but the enforceability of each listed patent still depends on its statutory term and other legal conditions.

What FDA products were commercially connected to the patent?

Aridol

Aridol is an inhaled mannitol product used to provoke bronchoconstriction during bronchial challenge testing. Its clinical protocol uses serial inhaled doses and FEV1 measurements. That use maps closely to claim 1 and claim 9.

The relationship is functional rather than product-claim based. The patent claims a method of using a dry osmotic powder. They do not claim “Aridol” by name, nor do they claim mannitol as a chemical compound.

Bronchitol

Bronchitol is an inhaled mannitol product developed for mucus clearance in cystic fibrosis. Its therapeutic objective maps more closely to claim 12, which covers increasing mucociliary clearance or inducing sputum.

Bronchitol was approved by FDA in 2020 for improving pulmonary function in adults with cystic fibrosis. The product uses inhaled mannitol powder administered through a dedicated inhalation system. (FDA, 2020)

The earlier patent did not provide continuing U.S. exclusivity for Bronchitol because it expired before the product’s FDA approval. Any current protection for Bronchitol must therefore arise from later patents, regulatory exclusivity, manufacturing know-how, device rights, or other intellectual-property rights.

What later patents and IP rights matter for inhaled mannitol?

The post-2015 landscape is separate from the expired patent and generally falls into four categories.

Formulation and particle-engineering patents

Later patent families may address:

Mannitol particle morphology;
Crystalline form;
Moisture control;
Powder flow and dispersibility;
Aerodynamic particle-size distribution;
Excipient selection;
Stability during storage;
High-dose capsule filling.

These patents can create meaningful barriers even when the active ingredient is an old compound. Their value depends on whether a competing product can use a different particle-generation process or formulation while retaining adequate lung deposition.

Device and capsule patents

Dry-powder inhaler patents may cover:

Capsule piercing;
Powder deaggregation;
Airflow resistance;
Dose containment;
Device geometry;
Dose-counting systems;
Protection from humidity.

A competitor may avoid the expired method patent but still face device or capsule patents if it uses a materially similar inhaler architecture.

Method-of-use patents

Later patents may cover:

Treatment of cystic fibrosis;
Treatment of bronchiectasis;
Treatment of chronic obstructive pulmonary disease;
Sputum induction protocols;
Pretreatment with a bronchodilator;
Dose escalation and tolerability procedures;
Patient-selection criteria.

Method-of-use claims are especially important because the active ingredient is established and cannot ordinarily support new composition-of-matter exclusivity.

Manufacturing and trade-secret barriers

Commercial inhaled mannitol products require consistent control over:

Particle-size distribution;
Residual moisture;
Powder cohesion;
Capsule fill uniformity;
Device emptying;
Delivered-dose uniformity;
Microbiological quality;
Packaging-barrier performance.

These controls may be protected by process patents or retained as confidential know-how. They can delay competition even where patent claims are narrow or expired.

Are there Paragraph IV challenges to U.S. Patent 5,817,028?

No current Paragraph IV challenge can create a live dispute over U.S. Patent 5,817,028 because the patent expired in 2015. A Paragraph IV certification is directed to a listed patent associated with an abbreviated new drug application. An expired patent does not provide an operative patent barrier to generic approval or launch.

For inhaled powders, the more important regulatory obstacle is often product sameness rather than the expired method patent. An ANDA applicant may need to establish equivalence involving:

Delivered dose;
Aerodynamic particle-size distribution;
Device performance;
Capsule or container configuration;
In vitro deposition;
Formulation sameness or permissible difference;
Labeling and clinical-use instructions.

Where the reference product is a complex dry powder, FDA may require substantial comparative characterization. Those requirements can raise development costs without restoring exclusivity to the expired patent.

Which companies are exposed to the patent landscape?

The relevant competitive groups are:

Participant type	Exposure
NDA holder or licensee	Later formulation, device, method and regulatory rights
Generic dry-powder manufacturer	Equivalence, device design and later patent risk
Inhaler-device company	Device patents and engineering know-how
Mannitol supplier	Pharmaceutical-grade material and particle-processing capability
Diagnostic testing company	Airway-challenge method and labeling requirements
Cystic-fibrosis therapeutics company	Mucus-clearance indication, clinical data and reimbursement

The expired patent removes one historical barrier, but it does not make inhaled mannitol a simple commodity. Respiratory delivery performance, high-dose powder handling and clinical labeling remain commercially important.

How strong was the patent estate around U.S. Patent 5,817,028?

The patent was strong against the specific combination of:

A dry osmotic powder;
Respirable particles;
Direct airway administration;
Airway narrowing measurement, mucociliary clearance or sputum induction.

Its weaknesses were equally clear:

It did not claim mannitol itself.
It did not claim a proprietary device.
It did not require a single formulation.
It did not cover liquid hypertonic aerosols.
It expired before current commercial expansion of inhaled mannitol therapy.
Its functional language could create proof issues concerning osmolarity, respirable fraction and intended use.

During its term, a product using sodium chloride, potassium chloride, mannitol or dextrose in a qualifying dry-powder format could have faced infringement risk even if the product used a different device. After expiration, those same facts have historical rather than exclusionary significance.

What generic launch scenarios exist after expiration?

The main launch scenarios are:

A dry-powder mannitol product using a different inhaler and formulation, relying on the expired patent as prior art but avoiding later active patents.
A product using another osmotic agent, such as sodium chloride, with a different clinical indication.
A liquid hypertonic-saline product, outside the dry-powder limitation.
A capsule-free multidose inhaler, potentially avoiding the capsule-dependent claims while still requiring analysis of claims 1 or 12 during the patent term.
A reformulated product protected by later particle, device or manufacturing patents.

For current U.S. launches, the dominant risks are later Orange Book-listed patents, FDA product-classification requirements, device equivalence and manufacturing reproducibility.

Key Takeaways

U.S. Patent 5,817,028 covers methods using respirable dry osmotic powders in airway challenge, mucociliary clearance and sputum induction.
The principal compounds include sodium chloride, potassium chloride, mannitol and dextrose.
Claims 1-11 focus on airway narrowing and FEV1-based bronchial challenge.
Claims 12-21 focus on mucociliary clearance and sputum induction.
The patent covers dry powders, not liquid nebulized formulations.
Particle-size, respirable-fraction and capsule-dose limitations materially narrow the dependent claims.
The patent expired October 6, 2015 and cannot support current patent enforcement or a present Paragraph IV barrier.
Aridol’s bronchial challenge use maps primarily to claim 1 and claim 9.
Bronchitol’s mucus-clearance use maps primarily to claim 12.
Current competition depends on later formulation, device, manufacturing and method-of-use rights rather than this expired patent.

FAQs

Does U.S. Patent 5,817,028 claim mannitol itself?

No. Mannitol appears as one covered substance in dependent claims 6 and 17. The patent claims methods of inhaling an osmolarity-increasing dry powder, not mannitol as a composition of matter.

Does the patent cover nebulized hypertonic saline?

No. The claims require a dry dispersible powder and exclude a dry powder dissolved in a liquid. A conventional liquid nebulizer is outside that express limitation.

Does the patent cover nasal administration?

Yes. Claims 3 and 14 expressly extend the methods to a nasal airway. The independent claims are not limited to pulmonary administration.

Could a product infringe without using a capsule?

Yes, during the patent term. Capsule use is required only by claims 10, 11, 20 and 21. Claims 1 and 12 do not require a rupturable hard capsule.

Is Bronchitol protected by U.S. Patent 5,817,028 today?

No. The patent expired in 2015, before Bronchitol received FDA approval. Any current Bronchitol protection must arise from later patents, regulatory exclusivity, device rights, manufacturing rights or other commercial protections.

References

U.S. Food and Drug Administration. (2010). Aridol (mannitol) inhalation powder: Prescribing information and approval materials. U.S. Department of Health and Human Services.
U.S. Food and Drug Administration. (2020). Bronchitol (mannitol) inhalation powder: Prescribing information and approval materials. U.S. Department of Health and Human Services.
U.S. Patent No. 5,817,028. (1998). Method for inducing bronchoconstriction and increasing mucociliary clearance. United States Patent and Trademark Office.
United States Patent and Trademark Office. (2024). Patent Center and patent term information for U.S. Patent No. 5,817,028. U.S. Department of Commerce.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. U.S. Department of Health and Human Services.

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Australia	PM4114	Feb 25, 1994

PCT Information
PCT Filed	February 23, 1995	PCT Application Number:	PCT/AU95/00086
PCT Publication Date:	August 31, 1995	PCT Publication Number:	WO95/22993

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	0748228	⤷ Start Trial	11C0002	France	⤷ Start Trial
European Patent Office	0748228	⤷ Start Trial	SPC/GB11/004	United Kingdom	⤷ Start Trial
Austria	474583	⤷ Start Trial
Australia	1748295	⤷ Start Trial
Australia	682756	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,817,028

Summary for Patent: 5,817,028