United States Patent 5,225,183: Claim Scope, Expiration, and Aerosol Formulation Patent Landscape

U.S. Patent No. 5,225,183 covers pressurized metered-dose aerosol formulations using 1,1,1,2-tetrafluoroethane, commonly known as HFA-134a, together with a surfactant and a solubility-enhancing co-component. The patent targets CFC-free replacement formulations for inhaled medicines. It issued on July 6, 1993, and its ordinary 17-year patent term expired on July 6, 2010. The patent therefore presents no current U.S. blocking right, Orange Book exclusivity, or Paragraph IV litigation risk.

What does U.S. Patent 5,225,183 cover?

The patent covers a formulation combination rather than a particular inhaler device, manufacturing process, or single active ingredient.

The independent claim requires all of the following:

Required element	Claim requirement
Medicament	A therapeutically effective amount
Propellant	A propellant substantially free of chlorofluorocarbons
Required propellant component	1,1,1,2-tetrafluoroethane, or HFA-134a
Surface-active agent	An amount sufficient to stabilize the formulation or lubricate a metering-valve stem
Co-component	At least one specified compound that is miscible with HFA-134a
Solubility function	The co-component must increase the amount of surfactant soluble in the formulation compared with HFA-134a alone

The claim uses “comprising,” which generally makes it open-ended. A formulation containing the listed components may still fall within the claim if it also contains additional propellants, excipients, stabilizers, or other ingredients.

The patent addresses the technical difficulty of using HFA-134a as a CFC replacement. HFA-134a has different solvency and compatibility characteristics from chlorofluorocarbon propellants. The claimed co-component improves surfactant solubility and supports formulation stability or valve lubrication. [1]

What is the scope of claim 1?

Claim 1 has four principal limitations.

HFA-134a must be present

A formulation using only HFA-227ea, HFA-152a, nitrogen, carbon dioxide, or another propellant would not satisfy the express HFA-134a requirement. A mixed-propellant formulation containing HFA-134a could satisfy this element if the other limitations are met.

The claim does not require HFA-134a to be the only propellant. The phrase “comprising 1,1,1,2-tetrafluoroethane” permits additional propellant components, subject to the requirement that the overall propellant be substantially free of CFCs.

The formulation must be substantially free of CFCs

The claim is directed to CFC-replacement formulations. “Substantially free” is a qualitative limitation rather than a fixed numerical concentration in the claim. The term would ordinarily be interpreted in light of the specification, prosecution history, technical context, and relevant regulatory standards.

A formulation containing a material CFC concentration would create a substantial non-infringement position. Trace contamination or residual quantities could present a more fact-dependent issue.

A surface-active agent is mandatory

The claim does not cover every HFA-134a aerosol formulation. It requires a surface-active agent, such as a surfactant, in an amount sufficient either to:

Stabilize the aerosol formulation; or
Lubricate a valve stem in a metering valve.

A formulation without a surface-active agent would fall outside claim 1. A formulation containing a surfactant at a concentration that performs neither claimed function would also present a potential non-infringement position, although functional claim language may require technical evidence.

Compound (d) must perform a defined solubility function

The claim requires at least one compound selected from the listed group. The compound must both:

Be miscible with HFA-134a; and
Increase the amount of surfactant soluble in the formulation compared with HFA-134a alone.

This is a functional limitation. Merely including ethanol or another listed compound is not necessarily enough. The accused formulation must satisfy the miscibility and comparative surfactant-solubility requirements.

The supplied claim text lists “isopropyl, and myristate.” The chemically coherent reading is “isopropyl myristate.” A claim chart should use the issued patent text and prosecution record to confirm the exact wording before relying on that portion of the claim.

What compounds are listed in claim 1?

The claimed compound group includes:

Ethyl alcohol, or ethanol
Isopropyl alcohol
n-Pentane
Isopentane
Neopentane
Isopropyl myristate, subject to confirmation against the issued document

Ethanol is commercially significant because it is widely used as a cosolvent in HFA pressurized metered-dose inhalers. Pentane isomers and isopropyl myristate are less common in currently marketed inhalation products but are relevant to the literal claim language.

The list is a Markush group. A formulation using one listed compound may satisfy the compound-selection limitation; use of a compound outside the list generally would not satisfy that limitation unless a doctrine-of-equivalents theory were available. That theory would be difficult to deploy against an expired patent and would require a separate legal analysis.

How does claim 2 narrow claim 1?

Claim 2 adds a weight-ratio limitation:

HFA-134a to compound (d) in the range of 50:50 to 99:1.

The ratio is inclusive on its face. Examples within the stated range include:

HFA-134a	Compound (d)	Ratio
50%	50%	50:50
75%	25%	75:25
90%	10%	90:10
99%	1%	99:1

A formulation at 99.5:0.5 would fall outside claim 2, although it could still fall within claim 1 because claim 1 does not specify a numerical ratio.

The ratio must be calculated on the basis used by the patent, normally weight-to-weight. Formulation records, batch manufacturing instructions, and analytical data would be relevant to determining compliance.

What drugs are expressly covered by claim 3?

Claim 3 limits the medicament to one of the following:

Listed medicament	Therapeutic category or historical use
Salbutamol	Short-acting beta-2 agonist; known as albuterol in the United States
Beclomethasone dipropionate	Inhaled corticosteroid
Disodium cromoglycate	Mast-cell stabilizer
Pirbuterol	Short-acting beta agonist
Isoprenaline	Beta-adrenergic agonist; known as isoproterenol in the United States
Adrenaline	Epinephrine
Rimiterol	Bronchodilator
Ipratropium bromide	Anticholinergic bronchodilator

Claim 3 is dependent on claim 1. It therefore inherits every limitation of claim 1 and adds the closed medicament list. A formulation containing budesonide, fluticasone, formoterol, tiotropium, or another active ingredient would not satisfy claim 3, although it could potentially implicate claim 1 because claim 1 broadly recites “a medicament.”

The claim does not expressly require a particular salt, particle size, dose strength, suspension concentration, device, or administration schedule. Those limitations may appear in the specification or other family members but are not apparent from the supplied claims.

What formulations are protected by U.S. Patent 5,225,183?

The strongest literal claim scenario is a CFC-free pressurized metered-dose inhaler formulation containing:

HFA-134a;
A therapeutic inhaled medicine;
A surfactant;
Ethanol or another listed co-component; and
A demonstrated increase in surfactant solubility compared with HFA-134a alone.

A formulation containing HFA-134a and ethanol but no surfactant would not meet claim 1. A formulation containing a surfactant and HFA-134a but using propylene glycol instead of a listed compound would not satisfy the express compound-selection limitation. A formulation using only HFA-227ea would lack the required HFA-134a component.

The patent is therefore technically broad in its choice of medicament but narrower than a general HFA inhaler patent because it requires a surfactant and a specified solubility-enhancing compound.

When did U.S. Patent 5,225,183 lose exclusivity?

The patent issued on July 6, 1993. For a U.S. utility patent filed before the June 8, 1995 transition to the current patent-term regime, the ordinary term was 17 years from grant. On that basis, U.S. Patent 5,225,183 expired on July 6, 2010. [1, 2]

Event	Date
U.S. patent grant	July 6, 1993
Ordinary term basis	17 years from grant
Expiration	July 6, 2010
Current status	Expired

No current license, settlement, continuation, or terminal-disclaimer issue can restore the expired patent’s enforceability. A patent expiration analysis should still check whether a reissue or related continuation presents a separate right, but the claims supplied here do not create an active U.S. exclusionary right.

What is the Orange Book status of U.S. Patent 5,225,183?

The patent is not a current Orange Book barrier because it expired in 2010. Orange Book listing and patent enforceability are separate questions. A patent may historically have been submitted for a drug product, while an expired patent no longer supports a current period of patent-based generic delay.

The FDA Orange Book records approved products, listed patents, regulatory exclusivity, and therapeutic-equivalence information. It does not convert every formulation patent into a listed patent, and the absence of a current listing does not determine whether a patent once appeared in a historical submission. [3]

For present commercial purposes:

The patent cannot support a new 30-month stay under Hatch-Waxman.
A Paragraph IV certification against this patent would have no practical current effect.
The patent cannot block an ANDA applicant from launching a product.
Any surviving market protection would need to arise from another unexpired patent, regulatory exclusivity, pediatric exclusivity, orphan exclusivity, device right, trade secret, or commercial agreement.

How does this patent relate to Paragraph IV challenges?

A Paragraph IV certification asserts that a patent is invalid, unenforceable, or will not be infringed by the proposed generic product. The statutory framework applies to patents submitted for an approved reference-listed drug. [4]

Because U.S. Patent 5,225,183 expired on July 6, 2010, it is not a meaningful target for a current Paragraph IV launch strategy. A generic applicant would focus on unexpired patents listed for the relevant reference product, including later formulation, device, method-of-use, or manufacturing patents.

The patent could have affected historical generic strategies during its term. A product matching HFA-134a, surfactant, and a listed co-component would have required an infringement analysis. That historical issue does not create a current launch restriction.

Which companies are challenging or relying on this patent?

There is no current challenge necessary to clear this patent because it is expired. The patent’s original commercial significance arose from the transition from CFC propellants to HFA-based inhalers, which affected innovator manufacturers, generic developers, valve suppliers, and formulation licensors.

The patent’s claim structure indicates a platform-technology use case. It could support products containing several different bronchodilators or corticosteroids, but the patent alone would not establish ownership of:

A specific inhaler brand;
A specific active pharmaceutical ingredient;
A metering-valve design;
A manufacturing process;
A particle-engineering method;
A later formulation using a different cosolvent or surfactant.

Current competitive analysis should therefore treat the patent as historical background and review later patent families associated with individual products.

How strong is the patent estate for HFA inhaler formulations?

U.S. Patent 5,225,183 had meaningful historical breadth but limited present value.

Factor	Assessment
Technical breadth	Broad across medicaments in claim 1
Excipient breadth	Limited to a listed compound group
Propellant coverage	Requires HFA-134a
Surfactant requirement	Narrows claim scope
Claim 2 breadth	Narrower because of the 50:50 to 99:1 ratio
Claim 3 breadth	Narrower because of the closed drug list
Current enforceability	None after expiration
Current generic risk	None from this patent
Historical design-around potential	Material
Orange Book value today	None as an enforceable patent right

Potential historical design-arounds included removing the surfactant, using a non-listed cosolvent, using a different propellant system, changing the surfactant chemistry, or developing a formulation in which the comparative solubility limitation could not be demonstrated.

What manufacturing and intellectual-property barriers remain?

The expired patent does not eliminate technical barriers to HFA inhaler development. A current developer may still need to address:

Valve compatibility and extractables;
Container corrosion and coating integrity;
Suspension stability;
Particle-size distribution;
Dose uniformity;
Etching or aggregation of the active ingredient;
Propellant vapor pressure;
Filling-process controls;
Device performance over shelf life;
FDA combination-product requirements.

These issues may be protected by later patents or controlled through know-how rather than by U.S. Patent 5,225,183. The most relevant surviving rights are likely to concern specific formulations, valve systems, actuator geometries, manufacturing controls, particle engineering, and approved methods of use.

What generic launch scenarios exist?

A generic company can launch without clearing U.S. Patent 5,225,183. The principal scenarios are:

An ANDA product that uses a different formulation architecture and avoids unexpired product patents.
An authorized generic or licensed product using the reference formulation.
A 505(b)(2) product with a differentiated device, formulation, or clinical positioning.
A product using HFA-134a and ethanol that relies on freedom to operate against later patents, not this expired patent.
A formulation using another HFA or low-global-warming propellant, subject to FDA and product-performance requirements.

The regulatory pathway depends on the reference product, dosage form, active ingredient, device, and extent of formulation difference. FDA approval does not itself resolve every patent issue, while expiration of this patent does remove one historical barrier.

Key Takeaways

U.S. Patent 5,225,183 covers CFC-free aerosol formulations containing HFA-134a, a surfactant, and a specified co-component.
Claim 1 is open-ended because it uses “comprising,” but it requires every listed technical element.
Claim 2 narrows the formulation to an HFA-134a-to-co-component weight ratio of 50:50 to 99:1.
Claim 3 limits the medicament to eight expressly listed drugs.
The patent issued July 6, 1993, and expired July 6, 2010.
It creates no current U.S. patent, Orange Book, Paragraph IV, or generic-launch barrier.
Current freedom-to-operate analysis must focus on later HFA inhaler formulation, device, process, and method-of-use patents.

FAQs About U.S. Patent 5,225,183

Does U.S. Patent 5,225,183 cover albuterol inhalers?

Yes, claim 3 expressly lists salbutamol, the international name for albuterol. The formulation must also satisfy all limitations inherited from claim 1.

Does the patent cover an HFA-134a inhaler without ethanol?

Potentially, if the formulation uses another listed compound, such as isopropyl alcohol or a qualifying pentane isomer. An HFA-134a formulation without any listed compound would not meet claim 1.

Can this patent block a generic albuterol HFA product?

No. The patent expired on July 6, 2010, so it cannot currently block a generic albuterol HFA product.

Does claim 1 cover HFA-227ea inhalers?

Not by itself. Claim 1 requires HFA-134a. An HFA-227ea-only formulation lacks that required element, while a blend containing both HFA-227ea and HFA-134a could require further analysis.

Is “isopropyl myristate” correctly stated in the claim?

The supplied text appears to omit “myristate” after “isopropyl.” The issued patent and prosecution record should control the definitive construction. The chemically coherent reading is “isopropyl myristate.”

References

United States Patent No. 5,225,183. (1993). Aerosol formulations. United States Patent and Trademark Office.
United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term information. https://www.uspto.gov/
U.S. Food and Drug Administration. (n.d.). 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
U.S. Food and Drug Administration. (n.d.). Abbreviated new drug application submissions: Patent certifications and 30-month stays. https://www.fda.gov/drugs/abbreviated-new-drug-application-anda/anda-submissions-content-and-format/paragraph-iv-certifications-and-30-month-stays

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	8828477	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
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,225,183

Summary for Patent: 5,225,183