United States Drug Patent 6,352,684: Scope, Claims, Expiration, and HFA Aerosol Patent Landscape

U.S. Patent No. 6,352,684 protected medicinal aerosol formulations using 1,1,1,2-tetrafluoroethane, commonly known as HFA-134a, combined with a more polar compound such as ethanol. The claims covered both suspension and solution inhalers, including formulations containing salbutamol sulfate, sodium cromoglycate, and beclomethasone dipropionate.

The patent is expired. Its practical value is historical and analytical rather than exclusionary. It does not currently block generic or branded inhaler development, although its claim structure remains relevant to freedom-to-operate reviews involving HFA propellants, ethanol, surfactants, micronized particles, and solution formulations.

What does U.S. Patent 6,352,684 cover?

The patent covers pharmaceutical aerosol formulations that satisfy a defined combination of compositional and functional limitations:

Required element	Scope of claim 1
Medicament	0.01% to 5% by weight
Primary propellant	At least 50% HFA-134a by weight
Surface-active agent	Less than 5% by weight
Polar component	At least one compound more polar than HFA-134a
Excluded materials	Chlorofluorocarbons, CHClF2, CH2F2, and CF3CH3
Dosage form	Medicinal aerosol formulation

The patent is directed to chlorofluorocarbon-free metered-dose inhalers developed during the transition from CFC propellants to hydrofluoroalkane propellants. Its technical focus is the use of HFA-134a with a polar cosolvent or additive to improve formulation performance.

The claims do not cover every HFA-134a inhaler. A potentially infringing formulation would need to satisfy all limitations of at least one unexpired claim. Because claim 1 is the principal independent claim, a formulation outside any one required limitation would not literally fall within that claim.

How broad is independent claim 1?

Claim 1 is compositionally broad but technically constrained. It requires four central quantitative or qualitative features:

The active ingredient must constitute 0.01% to 5% of the formulation by weight.
HFA-134a must constitute at least 50% by weight.
The formulation must contain less than 5% surface-active agent.
The formulation must contain at least one compound more polar than HFA-134a.

The formulation must also exclude several alternative propellants and all chlorofluorocarbons.

Quantitative boundaries

The lower and upper concentration limits matter:

A formulation containing less than 0.01% medicament would fall outside claim 1.
A formulation containing more than 5% medicament would fall outside claim 1.
HFA-134a at exactly 50% appears to satisfy the "at least 50%" limitation.
A surface-active agent at exactly 5% would not satisfy "less than 5%."
The claim does not impose a minimum concentration for the higher-polarity compound.

The absence of a minimum polar-compound concentration gives claim 1 a potentially broad reach. A formulation could theoretically include a relatively small amount of ethanol or another qualifying compound, subject to the claim’s construction and any applicable prosecution-history limitations.

Excluded propellants

Claim 1 expressly excludes:

Chlorofluorocarbons
CHClF2, chlorodifluoromethane
CH2F2, difluoromethane
CF3CH3, 1,1,1,2,2-pentafluoroethane

The exclusion is important because the claim is framed around HFA-134a formulations that avoid older or alternative volatile propellants. A formulation containing HFA-134a and a listed excluded propellant could fall outside the literal scope of claim 1, depending on the amount and legal construction of the exclusion.

What formulations are protected by claims 2 through 17?

The dependent claims progressively narrow the formulation by administration route, physical form, additive identity, concentration ratio, surfactant identity, and active ingredient.

Claim	Additional limitation
2	Suitable for oral or nasal inhalation
3	Suspension of medicament particles with median particle size below 10 microns
4	Solution formulation
5	Higher-polarity compound selected from specified hydrocarbons and other compounds
6	More specific additive list, including ethanol, isopropyl alcohol, pentanes, and isopropyl myristate
7	HFA-134a concentration of 60% to 95%
8	HFA-134a-to-polar-compound ratio of 50:50 to 99:1
9	Ratio of 70:30 to 98:2
10	Ratio of 85:15 to 95:5
11	Specified surface-active agents
12	Surface-active-agent-to-medicament ratio of 1:100 to 10:1
13	Specified active ingredients
14	Higher-polarity compound comprises ethanol
15	Micronized salbutamol sulfate suspension
16	Micronized sodium cromoglycate suspension
17	Beclomethasone dipropionate solution

Claims 15 through 17 are the most product-relevant claims because they connect particular actives with defined HFA-134a and ethanol formulation architectures.

How does claim 17 protect beclomethasone dipropionate inhalers?

Claim 17 requires the limitations of claims 14 and 11, as well as claim 2 and claim 1 through dependency. Its scope therefore includes:

An aerosol suitable for oral or nasal inhalation;
HFA-134a at not less than 50% by weight;
Less than 5% surface-active agent;
A higher-polarity compound comprising ethanol;
A surface-active agent from the claim 11 list;
Beclomethasone dipropionate in solution form;
The specified medicament and propellant concentration limits of claim 1.

A beclomethasone dipropionate inhaler would not necessarily infringe claim 17 merely because it uses HFA-134a and ethanol. The formulation would also need to satisfy the surface-active-agent requirement and the other incorporated limitations.

A formulation using ethanol but no surface-active agent would be a particularly important design-around candidate for claim 17, subject to the patent’s claim construction and any other applicable patent rights.

What is the significance of claims 15 and 16 for salbutamol and sodium cromoglycate?

Claims 15 and 16 target micronized suspension formulations:

Claim 15 covers micronized salbutamol sulfate.
Claim 16 covers micronized sodium cromoglycate.

Both claims require ethanol through claim 14 and a listed surface-active agent through claim 11. They also inherit the particle-size limitation only if claim 3 is incorporated through the dependency chain. Claims 15 and 16 depend on claim 14, which depends on claim 11, but neither claim expressly depends on claim 3. Accordingly, the less-than-10-micron median particle-size limitation in claim 3 is not automatically imported into claims 15 or 16.

This distinction matters in claim charting. A micronized suspension may satisfy the ordinary technical description of the formulation without satisfying claim 3 unless the particle-size limitation is independently required by the asserted claim.

What does "higher polarity than HFA-134a" mean?

The phrase is a comparative chemical limitation. It requires the selected compound to have a higher polarity than HFA-134a. The claim lists alcohols, hydrocarbons, esters, and other materials, including:

Ethanol
Isopropyl alcohol
Propane
Butane
Isobutane
Pentane
Isopentane
Neopentane
Isopropyl myristate
Other listed mixtures

The list creates potential interpretive issues. Several listed hydrocarbons have low polarity in ordinary chemical terminology. The claim may therefore depend on the specification’s definition, comparative measurement, or technical context rather than a simple textbook polarity ranking.

Claim 6 also contains the phrase "ethyl alcohols," which appears grammatically irregular. In context, the intended compound is likely ethyl alcohol, or ethanol. A court could examine the patent specification and prosecution history to determine whether the wording is a typographical error, an indefinite expression, or a broader reference.

What is the scope of the surfactant claims?

Claim 11 lists a broad group of surface-active agents and related excipients. The list includes:

Sorbitan esters;
Polyoxyethylene sorbitan esters;
Lecithins;
Polyoxyethylene ethers;
Block copolymers of oxyethylene and oxypropylene;
Oleic acid;
Ethyl oleate;
Isopropyl myristate;
Glyceryl esters;
Fatty alcohols;
Polyethylene glycol 400;
Cetyl pyridinium chloride;
Vegetable oils.

Claim 12 adds a surface-active-agent-to-medicament ratio from 1:100 to 10:1. This is a wide range. At the low end, the surfactant can be only 1% of the medicament weight. At the high end, it can be ten times the medicament weight, while still remaining subject to claim 1’s less-than-5%-by-weight limitation.

A formulation may therefore satisfy claim 12 only when both ratio conditions are met:

The surfactant is less than 5% of total formulation weight; and
The surfactant-to-medicament ratio is between 1:100 and 10:1.

When does U.S. Patent 6,352,684 lose exclusivity?

U.S. Patent 6,352,684 has expired. The patent issued on March 5, 2002. Based on the applicable twenty-year patent term measured from the earliest relevant nonprovisional filing or international filing date, the enforceable term ended in 2015, absent a valid patent-term extension or other term adjustment.

Public patent records identify the patent as part of an HFA medicinal-aerosol patent family associated with Glaxo Group Limited. The patent’s term should be confirmed against the USPTO Patent Center record, including any patent-term adjustment, terminal disclaimer, reexamination certificate, or patent-term extension entry.[1][2]

Event	Date or status
Subject matter	HFA-134a medicinal aerosol formulations
Patent number	U.S. 6,352,684
Issue date	March 5, 2002
Patent term	Expired
Approximate end of enforceable term	2015
Current blocking effect	None from this patent alone
Relevant regulatory pathway today	ANDA for small-molecule generic inhalers, not biosimilar approval

The expired status eliminates current infringement liability under this patent. It does not eliminate risk from later patents covering inhaler devices, valve systems, particle engineering, crystalline forms, manufacturing processes, dose counters, or specific approved products.

What is the Orange Book status of U.S. Patent 6,352,684?

U.S. Patent 6,352,684 is a formulation platform patent rather than a currently enforceable product patent. Its patent number should not be treated as a current Orange Book barrier without a product-specific listing.

The FDA Orange Book lists patents and exclusivity information in connection with approved drug products. A formulation patent can be absent from the current Orange Book, can have been listed historically against a particular product, or can have been listed under a related patent number or patent family member. The Orange Book does not convert an expired patent into an enforceable right.[3]

For present-day generic entry analysis:

No Paragraph IV certification against an expired patent creates a current launch barrier.
The patent cannot support a new thirty-month stay.
A generic applicant would still need to address any later-expiring patents listed for the reference listed drug.
Device patents and drug-delivery patents may be relevant even where the formulation patent has expired.

Are there Paragraph IV challenges or litigation involving this patent?

An expired patent cannot support a current Paragraph IV challenge in the ordinary ANDA sense. Paragraph IV certifications address patents listed for an approved reference product that remain relevant to approval and potential enforcement.

The available public patent record does not establish an active infringement case involving U.S. Patent 6,352,684. Historical litigation, if any, would need to be separated from current enforceability. Patent litigation databases and PACER records should be read together with USPTO status data because a case may have ended before expiration through settlement, dismissal, judgment, or a consent order.[1][4]

There is no basis to treat this patent as an active litigation asset without a current case docket, asserted-claim order, or settlement agreement.

Which companies challenged or competed around HFA inhaler patents?

The commercial competition surrounding this patent involved companies developing CFC-free metered-dose inhalers, including:

Glaxo Group Limited and related GlaxoSmithKline entities;
3M and 3M Drug Delivery Systems;
AstraZeneca;
Boehringer Ingelheim;
Chiesi;
Teva;
Cipla;
generic inhaler manufacturers and contract device suppliers.

The relevant competition was not limited to active-ingredient patents. It extended across:

HFA-134a and HFA-227 propellant systems;
Ethanol-containing solutions;
Suspension stability;
Surfactant selection;
Valve compatibility;
Canister coating;
Micronized particle production;
Dose uniformity;
Moisture control;
Metered-dose inhaler assembly.

A competitor could avoid this patent while still encountering later patents covering the same commercial inhaler.

How strong was the patent estate?

The estate was technically meaningful during the CFC-to-HFA transition but is weak as a current exclusionary asset because the patent has expired.

Factor	Assessment
Claim breadth	Moderate to broad at claim 1 level
Composition specificity	High for claims 11 through 17
Formulation relevance	High for HFA-134a and ethanol inhalers
Design-around potential	Moderate to high
Current enforceability	None
Orange Book value	Historical or product-specific only
Manufacturing barrier	Limited from this patent alone
Geographic coverage	U.S. only for this patent
Biosimilar relevance	None
Current generic-entry risk	None from this patent

The main technical vulnerabilities would have involved the meaning of "higher polarity," the scope of the listed compounds, the relationship between "surface active agent" and excipients, and whether the specification enabled the full breadth of the Markush groups. Those issues no longer determine current commercial freedom to operate because the patent term has ended.

What generic launch scenarios exist after expiration?

A generic developer can generally pursue an HFA-134a inhaler without concern under U.S. Patent 6,352,684. Commercial launch risk instead depends on:

Patents listed for the reference product;
Device and actuator patents;
Dose-counter and valve patents;
Later formulation patents;
Active-ingredient or polymorph patents;
FDA comparative-performance requirements;
Manufacturing scale-up and suspension uniformity;
State and federal product-liability exposure.

For a salbutamol or albuterol HFA inhaler, the relevant FDA pathway is generally an ANDA or another abbreviated pathway applicable to the specific product and presentation. For beclomethasone dipropionate or sodium cromoglycate, regulatory strategy depends on the reference product, dosage form, and FDA requirements applicable at the time of filing. These products are small-molecule inhalation products, not biologics, so biosimilar litigation is not the appropriate risk framework.[3][5]

How does this patent compare with later HFA inhaler patents?

U.S. Patent 6,352,684 is an early platform patent. It claims the formulation concept at a relatively high level: HFA-134a, a more polar compound, a medicament, and controlled surfactant content.

Later patent families generally moved toward narrower commercial features:

Patent category	Typical protection
Formulation patents	Specific drug, ethanol level, propellant ratio, and excipient
Suspension patents	Particle-size distribution, crystal habit, density, and aggregation control
Solution patents	Solubility, chemical stability, pH, and cosolvent concentration
Device patents	Valve, actuator, canister, dose counter, and spray geometry
Manufacturing patents	Filling, homogenization, micronization, and moisture control
Product patents	Approved drug-device combination and presentation

The expired patent therefore has greater importance as prior art and as evidence of the state of HFA inhaler technology than as a current patent barrier.

What is the commercial and revenue exposure?

The patent itself creates no current royalty or infringement exposure. Historical products may have used formulations within the claim set, particularly CFC-free inhalers containing HFA-134a and ethanol. Attribution of product revenue to this patent would require a product-by-product mapping of approved labels, historical patent listings, formulation disclosures, and sales data.

The current revenue risk lies with later patents and regulatory exclusivities covering specific inhaler products. A company evaluating an HFA generic should not rely on the expiration of U.S. 6,352,684 as a complete freedom-to-operate conclusion.

Key Takeaways

U.S. Patent 6,352,684 covers CFC-free medicinal aerosols using HFA-134a and a more polar compound, especially ethanol.
Claim 1 is broad but requires every listed composition and exclusion limitation.
Claims 11 through 17 narrow the scope to specified surfactants and actives, including salbutamol sulfate, sodium cromoglycate, and beclomethasone dipropionate.
The patent issued March 5, 2002 and expired approximately in 2015.
It creates no current Paragraph IV, Orange Book, settlement, or infringement barrier by itself.
It has no biosimilar relevance because the claimed products are small-molecule inhalation formulations.
Current generic-entry risk depends on later formulation, device, manufacturing, and product-specific patents.
The patent remains relevant as prior art and as a historical marker in the development of HFA metered-dose inhalers.

FAQs

Can a company launch an HFA-134a inhaler after U.S. Patent 6,352,684 expired?

Yes, this patent alone does not prevent launch. The company must still assess later patents, FDA requirements, device rights, and patents listed for the applicable reference product.

Does using ethanol automatically infringe this patent?

No. Ethanol is only one element of the claimed combination. The formulation must also satisfy the HFA-134a concentration, medicament concentration, surfactant, dosage-form, and exclusion limitations of the asserted claim.

Does claim 3 require every claim in the patent to use particles below 10 microns?

No. Claim 3 adds the particle-size limitation only to claims that depend on claim 3. Claims 15 and 16 do not automatically include the less-than-10-micron limitation merely because they refer to micronized suspensions.

Is U.S. Patent 6,352,684 a biologic or biosimilar patent?

No. It concerns small-molecule aerosol formulations. The relevant regulatory and litigation framework is generic-drug and inhalation-product regulation, not biosimilar approval.

Can the patent still be cited against a new HFA formulation?

Yes. Although it is expired, it can remain relevant as prior art in patentability analysis. It may also affect the validity analysis of later patent claims directed to HFA-134a, ethanol, surfactants, and inhaled drug suspensions.

References

United States Patent and Trademark Office. (n.d.). Patent Center: U.S. Patent No. 6,352,684. https://patentcenter.uspto.gov/
Google Patents. (n.d.). U.S. Patent No. 6,352,684, medicinal aerosol formulation. https://patents.google.com/
U.S. Food and Drug Administration. (2025). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book
Administrative Office of the U.S. Courts. (n.d.). PACER: Public Access to Court Electronic Records. https://pacer.uscourts.gov/
U.S. Food and Drug Administration. (n.d.). Abbreviated new drug application (ANDA). https://www.fda.gov/drugs/types-applications/abbreviated-new-drug-application-anda

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	88284773	Dec 06, 1988

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	4595689	⤷ Start Trial
Australia	631155	⤷ Start Trial
Canada	2004598	⤷ Start Trial
Canada	2303601	⤷ Start Trial
Germany	68904300	⤷ Start Trial
Germany	68924540	⤷ Start Trial
Denmark	595789	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 6,352,684

Summary for Patent: 6,352,684