United States Patent 5,980,867: Flunisolide HFA Aerosol Formulation Patent Analysis

United States Patent 5,980,867 covers hydrofluorocarbon-propelled flunisolide aerosol formulations, particularly flunisolide dissolved in ethanol and delivered through a metered-dose inhaler. The patent’s principal protection is formulation-based, not compound-based. Its broadest independent claim requires flunisolide, a specified HFA propellant, and 3% to 30% ethanol by weight.

The patent was granted on November 9, 1999, and its standard 20-year term ran from the earliest effective nonprovisional filing date. Public patent records associate the patent with Dey, L.P., the developer of Aerospan flunisolide HFA. The patent term has expired. It therefore does not create a current U.S. barrier to generic or competing flunisolide HFA products, although the claim structure remains relevant for historical litigation, freedom-to-operate analysis, and formulation design.

What does U.S. Patent 5,980,867 protect?

The patent protects solution-based flunisolide aerosol formulations using HFA-134a, HFA-227, or a mixture of both, with ethanol at a concentration sufficient to solubilize flunisolide.

Claim element	Scope
Active ingredient	Flunisolide
Flunisolide concentration	About 0.1% to about 0.9% by weight
Propellant	HFA-134a, HFA-227, or a mixture
Ethanol	About 3% to about 30% by weight
Physical state	Flunisolide in solution
Optional excipients	Water, sorbitan trioleate, cetylpyridinium chloride, flavoring agents, menthol
Delivery system	Metered-dose inhaler
Additional container protection	Inert resin coating, including epoxy resin, or glass canister
Therapeutic method	Inhalation treatment of bronchial asthma

HFA-134a is 1,1,1,2-tetrafluoroethane. HFA-227 is 1,1,1,2,3,3,3-heptafluoropropane. Both are hydrofluorocarbon propellants used as replacements for chlorofluorocarbon propellants.

The patent does not claim flunisolide as a chemical compound. It does not broadly cover every flunisolide inhaler, dry-powder product, nebulized formulation, nasal formulation, or formulation using a propellant outside the recited HFA group.

How broad is independent claim 1?

Claim 1 is the core formulation claim. A formulation must satisfy each of the following limitations:

Flunisolide is present.
Flunisolide is present at approximately 0.1% to approximately 0.9% by weight.
Flunisolide is in solution rather than merely suspended.
The propellant is HFA-134a, HFA-227, or a combination.
Ethanol is present at approximately 3% to approximately 30% by weight.
Ethanol is present in an amount effective to solubilize the flunisolide.

The claim does not require a particular canister, valve, actuator, particle-size distribution, dose strength, or inhalation device unless those features are added through dependent claims or the product is analyzed under another claim.

What does “in solution” mean?

The “in solution” limitation distinguishes the claimed product from a suspension formulation. A formulation in which flunisolide is dissolved in the ethanol-HFA vehicle falls within the technical center of the claim. A product containing undissolved flunisolide particles may avoid literal infringement if the product is not properly characterized as a solution.

The distinction would depend on formulation testing, including visual inspection, microscopy, solubility data, analytical assay, and the product’s approved chemistry, manufacturing, and controls documentation.

How do the concentration ranges affect infringement?

The concentration ranges are important design limitations:

Ingredient	Claimed range in claim 1	Narrower ranges in dependent claims
Flunisolide	About 0.1% to about 0.9%	About 0.2% to about 0.5%
Ethanol	About 3% to about 30%	About 10% to about 20%
Water	Not required	About 0.005% to about 1%
Sorbitan trioleate	Not required	About 0.001% to about 0.1%; narrower claims use 0.001% to 0.005%
Cetylpyridinium chloride	Not required	About 0.001% to about 0.2%
Menthol	Not required	About 0.3%

Because claim 1 uses “about,” small deviations from the numerical endpoints may still raise infringement questions. The practical risk depends on intrinsic evidence, prosecution history, analytical precision, and whether the formulation is materially outside the claimed range.

What do claims 2 through 14 cover?

Claims 2 through 14 narrow the formulation claim by specifying propellant identity, excipients, and narrower concentration ranges.

Claims	Subject matter
2	HFA-134a formulation
3	HFA-227 formulation
4	Mixture of HFA-134a and HFA-227
5	Formulation substantially free of chlorofluorocarbons
6	Addition of 0.005% to 1% water
7	Addition of 0.001% to 0.1% sorbitan trioleate
8	Addition of 0.001% to 0.2% cetylpyridinium chloride
9	Addition of a flavoring agent
10	Addition of approximately 0.3% menthol
11	Flunisolide, ethanol, and HFA-227 within narrower ranges
12	Claim 11 plus sorbitan trioleate at 0.001% to 0.005%
13	Flunisolide, ethanol, and HFA-134a within narrower ranges
14	Claim 13 plus sorbitan trioleate at 0.001% to 0.005%

Claims 11 and 13 are commercially important because they map the two principal HFA propellant alternatives. Claims 12 and 14 add a low concentration of sorbitan trioleate, likely directed to formulation stability, valve performance, suspension or solution behavior, or delivery characteristics.

A product falling outside a dependent claim may still infringe claim 1. For example, omission of sorbitan trioleate avoids claims 7, 12, and 14 but does not avoid claim 1 if all claim 1 elements remain present.

What do claims 15 through 19 protect?

Claims 15 through 19 extend protection beyond the bulk formulation.

Claim 15: asthma treatment method

Claim 15 covers treating bronchial asthma by administering an effective amount of the claim 1 formulation through inhalation.

The claim requires:

a formulation meeting claim 1;
administration by inhalation; and
treatment of bronchial asthma.

The method claim would be relevant to a product label that expressly directs use for bronchial asthma. Its historical enforcement value would depend on the labeled indication, product instructions, prescribing practices, and whether the asserted product formulation satisfied claim 1.

Claim 16: metered-dose inhaler

Claim 16 covers a metered-dose inhaler comprising:

an aerosol canister defining a formulation chamber; and
a claim 1 formulation contained in that chamber.

This claim combines the formulation with the inhaler container. It is broader than claims 17 through 19 because it does not require a particular canister material or coating.

Claims 17 and 18: coated canister

Claim 17 requires the formulation chamber to be coated with a resin inert to flunisolide. Claim 18 specifies epoxy resin.

These claims target compatibility problems between flunisolide formulations and canister surfaces. The relevant technical issue is whether the container or coating alters flunisolide concentration, adsorption, degradation, extractables, or delivered dose.

Claim 19: glass canister

Claim 19 requires an aerosol canister made of glass. A glass canister could avoid claims directed to metal canisters or coated metal canisters, but it remains within claim 16 if the contained formulation meets claim 1.

When did U.S. Patent 5,980,867 expire?

The patent’s standard term expired in 2017, based on the earliest relevant U.S. filing date reflected in public patent records. The patent is no longer an enforceable U.S. exclusion right.

Event	Date or status
Earliest U.S. filing priority	1996, according to public patent-family records
U.S. application filing	1997
Patent issued	November 9, 1999
Patent number	US 5,980,867
Standard term	20 years from the applicable nonprovisional filing date
U.S. status	Expired
Current infringement enforceability	None after expiration

Patent-term adjustment, patent-term extension, and pediatric exclusivity must be checked against the USPTO Patent Examination Data System and FDA regulatory records for a definitive term calculation. The public commercial history of Aerospan does not establish a currently enforceable term for this patent.

What is the Orange Book status of flunisolide HFA?

Flunisolide HFA was marketed in the United States as Aerospan, an inhaled corticosteroid product associated with Dey, L.P. FDA labeling identified Aerospan as a metered-dose inhaler containing flunisolide and using HFA propellant technology.[2]

The Orange Book relevance of US 5,980,867 was historical. Any listed patent would no longer block an ANDA through an enforceable patent term after expiration. FDA Orange Book entries should be evaluated by product, NDA, patent-listing date, and current marketing status rather than by patent number alone.[3]

Regulatory issue	Assessment
Product	Aerospan flunisolide HFA
Active ingredient	Flunisolide
Dosage form	Inhalation aerosol
Regulatory pathway	NDA for branded product; ANDA pathway for eligible generic products
Patent relevance	Historical formulation protection
Current patent barrier	None from US 5,980,867 because the patent has expired
Biosimilar pathway	Not applicable
Current competition	Depends on FDA-approved product status, commercial availability, and any later patents

Were there Paragraph IV challenges to this patent?

A Paragraph IV certification would have been the principal ANDA mechanism for challenging an unexpired listed patent covering a flunisolide HFA product. The applicant would have asserted that the patent was invalid, unenforceable, or not infringed.

For US 5,980,867, the practical significance of a Paragraph IV challenge ended when the patent expired. A current ANDA applicant would not need to overcome this patent through a Paragraph IV certification if the patent is no longer enforceable.

The available information does not establish a specific reported Paragraph IV litigation proceeding against US 5,980,867. No active U.S. litigation can be inferred from the patent’s historical association with Aerospan.

What litigation and settlement risks affected Aerospan?

The main historical litigation exposure would have involved:

an ANDA product containing flunisolide in solution;
HFA-134a, HFA-227, or a mixture;
ethanol within the claimed range;
a marketed metered-dose inhaler;
labeling for asthma or related inhaled corticosteroid use.

A generic manufacturer could have pursued several design-around positions:

use a non-HFA propellant;
use a suspension rather than a solution;
use an ethanol concentration below 3% or above 30%;
use a flunisolide concentration outside the claimed range;
develop a dry-powder inhaler;
use nebulization rather than a pressurized metered-dose inhaler;
rely on a different active corticosteroid;
use a formulation that lacks the claimed solubilization relationship.

No settlement agreement should be assumed solely from the existence of the patent. A settlement analysis requires a specific court docket, ANDA challenger, and agreement record.

How strong was the patent estate?

The patent estate was technically focused and commercially relevant during the transition from CFC to HFA inhalers. Its strength came from combining several limitations that described a practical product architecture:

flunisolide as the active ingredient;
solution formulation;
HFA propellant;
ethanol as a cosolvent;
metered-dose inhaler delivery;
optional container and excipient limitations.

Its limitations were equally clear. The patent did not control the flunisolide molecule, the entire inhaled corticosteroid market, or every delivery platform. It was vulnerable to formulation design-around strategies involving physical state, propellant, concentration, dosage form, and therapeutic product selection.

Patent-strength factor	Assessment
Compound coverage	None
Broad formulation coverage	Moderate within the defined HFA-ethanol solution space
Device coverage	Narrow, dependent on claim 16 architecture
Method-of-use coverage	Limited to administration of the claimed formulation for bronchial asthma
Design-around potential	Material
Current enforceability	None because the patent expired
Relevance to new products	Historical and technical, not blocking

What formulations are most exposed under the claims?

The highest historical risk profile would have been a product with the following characteristics:

flunisolide concentration between 0.2% and 0.5%;
ethanol concentration between 10% and 20%;
HFA-134a or HFA-227;
flunisolide fully dissolved;
metered-dose inhaler;
sorbitan trioleate at 0.001% to 0.005%;
asthma indication.

That profile corresponds closely to claims 11 through 14. Products using HFA-227 and the narrower concentration ranges would have required particular attention to claim 11 or claim 12. Products using HFA-134a would have required analysis of claim 13 or claim 14.

A product with HFA-227, 0.3% flunisolide, 15% ethanol, and 0.003% sorbitan trioleate would fall squarely within the numerical subject matter of claim 12, assuming the flunisolide is in solution and the remaining limitations are satisfied.

How does this patent compare with competing inhaled corticosteroid patents?

US 5,980,867 differs from patents covering other inhaled corticosteroids such as beclomethasone dipropionate, budesonide, fluticasone propionate, or mometasone furoate. Those products may have separate patents covering:

active pharmaceutical ingredients;
crystalline forms;
particle engineering;
device geometry;
dose counters;
suspension systems;
formulations;
manufacturing processes;
approved methods of use.

The patent should therefore be analyzed as a flunisolide HFA formulation patent, not as a general inhaled corticosteroid patent.

Product category	Relationship to US 5,980,867
Flunisolide HFA solution inhaler	Historically relevant
Flunisolide dry-powder inhaler	Generally outside the principal formulation claim
Flunisolide nebulizer	Generally outside the metered-dose aerosol claims
Beclomethasone inhaler	Different active ingredient
Budesonide inhaler	Different active ingredient
Fluticasone inhaler	Different active ingredient
Oral or injectable flunisolide	Outside the claimed aerosol format

What manufacturing and intellectual-property barriers remain?

The patent’s manufacturing concepts remain relevant even though the patent has expired. A developer of a flunisolide HFA product would still need to address:

flunisolide solubility in the ethanol-HFA vehicle;
formulation uniformity;
canister and valve compatibility;
adsorption to container surfaces;
extractables and leachables;
delivered-dose uniformity;
actuator performance;
stability under storage;
moisture control;
filling and crimping processes;
HFA supply and handling;
commercial-scale reproducibility.

Those issues can generate later patents that are separate from US 5,980,867. Later intellectual property may cover a specific valve, actuator, coating, manufacturing process, particle-control method, or stability improvement. The expired patent does not provide clearance for later patents.

What is the generic launch risk for flunisolide HFA?

The expired status of US 5,980,867 removes one historical patent obstacle, but generic launch risk depends on regulatory and commercial factors.

Risk category	Current assessment
US 5,980,867 patent infringement	No current risk from the expired patent
Paragraph IV litigation under this patent	No current blocking effect
Biosimilar litigation	Not applicable to flunisolide
ANDA approval	Depends on FDA product-specific requirements
Device comparability	Material for metered-dose inhalers
Formulation equivalence	Material where the reference product uses a solution system
Later patents	Must be independently cleared
Market size	Constrained by product availability and the status of branded flunisolide HFA
Commercial launch	Dependent on FDA approval, manufacturing capability, and payer demand

Flunisolide is a small molecule, so a generic applicant would generally use the ANDA framework rather than the biosimilar pathway. The major regulatory challenge is pharmaceutical equivalence and device performance, not biologic comparability.

What geographic coverage does the patent have?

US 5,980,867 provides rights only in the United States. Its expiration does not determine the status of corresponding foreign patents. Foreign family members must be reviewed separately by jurisdiction because filing dates, patent-term rules, lapses, maintenance payments, supplementary protection rights, and prosecution outcomes may differ.

The U.S. patent does not itself confer rights in Canada, Europe, Japan, Australia, or other markets. A global freedom-to-operate assessment must separate U.S. formulation claims from foreign family rights and later continuation patents.

Key Takeaways

US 5,980,867 covers flunisolide in solution with HFA-134a, HFA-227, or both, using 3% to 30% ethanol.
The patent’s strongest historical claims are claims 1, 11, and 13, with claims 12 and 14 adding sorbitan trioleate.
Claims 15 through 19 cover asthma treatment, metered-dose inhalers, inert resin coatings, epoxy coatings, and glass canisters.
The patent does not claim flunisolide generally or every flunisolide inhaler.
The U.S. patent term expired in 2017 and is no longer an enforceable U.S. barrier.
A current flunisolide HFA generic would face regulatory, device, formulation, and manufacturing requirements, but not an active exclusion right under this patent.
No biosimilar pathway applies because flunisolide is a small-molecule drug.
Later patents and foreign family members require separate clearance.

FAQs About US 5,980,867

Is US 5,980,867 still active?

No. The U.S. patent term expired in 2017 under the standard patent-term framework.

Does US 5,980,867 cover Aerospan?

The patent is associated with the flunisolide HFA formulation technology used for Aerospan. Product coverage depends on the formulation and device characteristics, not the brand name alone.

Can a generic use HFA-134a after expiration of the patent?

Yes. Expiration of US 5,980,867 removes the patent-based restriction on using the claimed HFA-134a flunisolide formulation in the United States. Later patents and FDA requirements remain separate issues.

Does the patent cover a flunisolide dry-powder inhaler?

The principal claims are directed to an aerosol formulation and a metered-dose inhaler. A dry-powder inhaler would generally fall outside those claim categories.

Is flunisolide subject to biosimilar approval?

No. Flunisolide is a small-molecule corticosteroid. A qualifying generic product would generally proceed through the ANDA pathway rather than the biologics license application and biosimilar pathway.

References

United States Patent and Trademark Office. (1999). Flunisolide aerosol formulation (U.S. Patent No. 5,980,867).
U.S. Food and Drug Administration. (2002). Aerospan (flunisolide) inhalation aerosol prescribing information.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations. Orange Book.
U.S. Code, 35 U.S.C. § 154. Patent term.
U.S. Code, 21 U.S.C. § 355(j). Abbreviated new drug applications and patent certifications.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	1098695	⤷ Start Trial
Australia	680967	⤷ Start Trial
Canada	2178473	⤷ Start Trial
Germany	69424181	⤷ Start Trial
Denmark	0735884	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,980,867

Summary for Patent: 5,980,867