US Patent 5,676,930: Ipratropium HFA Aerosol Formulation Scope, Expiration, and Patent Landscape

US Patent 5,676,930 protects stabilized aerosol solution formulations containing ipratropium bromide, a hydrofluorocarbon propellant, ethanol or another cosolvent, and an acid stabilizer. Its central commercial relevance was the transition of ipratropium inhalers from chlorofluorocarbon propellants to HFA-134a and HFA-227. The patent was granted on October 14, 1997 and its enforceable US term has expired. It no longer blocks generic formulation, manufacture, or sale in the United States.

The patent remains relevant as a formulation precedent and as part of the historical intellectual-property estate associated with Atrovent HFA and related ipratropium products.

What does US Patent 5,676,930 cover?

The patent covers two related subject groups:

Aerosol solution compositions containing ipratropium bromide, an HFC propellant, ethanol or another organic cosolvent, and ascorbic or citric acid.
Methods for stabilizing ipratropium aerosol solutions by adding an organic acid, plus a broader claim directed to an inorganic-acid-stabilized medicament formulation.

The principal composition claim is claim 1. A product must contain all of the following elements to fall within its literal scope:

Required element	Claim 1 scope
Active ingredient	Ipratropium bromide
Concentration	About 0.001% to about 10% weight/weight
Propellant	A hydrofluorocarbon
Cosolvent	Ethyl alcohol
Stabilizer	Ascorbic acid or citric acid
Dosage form	Aerosol solution formulation

The claim is composition-based. It does not require a particular canister, valve, actuator, dose strength, particle-size distribution, or treatment indication.

How do claims 1 through 12 define the formulation scope?

Claims 1 through 12 establish two HFC branches.

HFA-134a formulations

Claim 2 narrows claim 1 to 1,1,1,2-tetrafluoroethane, commonly known as HFA-134a.

Claim 3 requires ethanol at approximately 1% to 50% weight/weight.

Claims 4 and 5 narrow the acid stabilizer:

Ascorbic acid: approximately 0.0045 to 5.0 mg/mL.
Citric acid: approximately 0.0039 to 27.7 mg/mL.

Claims 6 through 8 identify three specific ipratropium bromide concentrations in citric-acid formulations:

Claim	Ipratropium bromide concentration
6	About 0.0187% w/w
7	About 0.0374% w/w
8	About 0.0748% w/w

These concentrations correspond to progressively higher delivered-dose formulations when combined with a suitable metered-dose inhaler system. The claim language concerns concentration in the formulation, not necessarily the emitted or delivered dose.

HFA-227 formulations

Claim 9 narrows the propellant to 1,1,1,2,3,3,3-heptafluoropropane, commonly known as HFA-227 or HFC-227ea.

Claims 10 through 12 repeat the ethanol and acid ranges applicable to the HFA-227 branch. The patent therefore covers either of the two principal pharmaceutical HFC propellants used in early CFC-replacement development.

What do claims 13 through 15 protect?

Claims 13 and 14 are process claims directed to stabilization rather than merely to the final composition.

Claim 13 covers adding ascorbic acid or citric acid to an ipratropium aerosol solution containing:

0.001% to 10% ipratropium bromide;
HFA-134a; and
a cosolvent.

Claim 14 covers the corresponding HFA-227 process.

Claim 15 narrows claim 14 by specifying ethyl alcohol as the cosolvent. Based on the supplied claim text, claim 15 is described as a method of treatment, although its dependency and operative language are directed to the stabilization method. The patent record should control if the claim text is being used for litigation or freedom-to-operate analysis.

The process claims require more than the presence of acid in a finished product. A potential infringement theory would need to establish the claimed addition or stabilization step, depending on the accused activity and applicable claim-construction principles.

What is the scope of claim 16?

Claim 16 is materially broader in one respect and narrower in another.

It covers:

a medicament;
an HFC propellant;
an organic cosolvent; and
an inorganic acid present in an amount effective to provide chemical stability.

Unlike claims 1 through 15, claim 16 is not limited to ipratropium bromide, ascorbic acid, or citric acid. It also does not identify a specific inorganic acid or concentration.

The important limitations are the functional requirements that the acid be inorganic and present in an amount effective to provide chemical stability. The claim could therefore raise claim-construction issues concerning:

what qualifies as an inorganic acid;
what level of chemical stability is required;
the relevant degradation pathway;
the duration and test conditions for stability; and
whether the accused formulation contains the acid for stabilization or for another formulation purpose.

Claim 16 is not a broad claim to every HFC medicament aerosol. It still requires an organic cosolvent and an inorganic acid that performs the claimed stabilizing function.

What formulation technology did US 5,676,930 address?

The patent addressed chemical instability associated with replacing CFC propellants with HFC propellants in metered-dose inhalers.

The relevant formulation architecture is:

Component	Technical function
Ipratropium bromide	Anticholinergic bronchodilator
HFA-134a or HFA-227	Propellant
Ethanol or organic cosolvent	Solubilizes or assists dispersion of active and excipients
Citric or ascorbic acid	Stabilizes the active formulation
Canister and valve	Meter and deliver the aerosol dose

The patent is directed to aerosol solutions rather than conventional dry-powder inhalers or aqueous nebulizer solutions. A formulation that uses a suspension rather than a solution could fall outside the literal composition language, although the specification, prosecution history, and doctrine-of-equivalents analysis would remain relevant in an actual dispute.

When did US Patent 5,676,930 lose exclusivity?

The patent was granted on October 14, 1997. Its US patent term has expired, and the patent no longer provides an enforceable exclusionary right.

Milestone	Date or status
US patent grant	October 14, 1997
Patent term basis	Post-1995 US patent term measured from the relevant nonprovisional filing date
Current status	Expired
Current formulation blocking risk	None from this patent alone

The expiration removes the patent's ability to block a competing formulation that meets claims 1 through 16. It does not eliminate the possibility that later patents could cover a particular canister, valve, actuator, manufacturing process, excipient system, dose regimen, or combination product.

What is the Orange Book status of the patent?

US Patent 5,676,930 was associated with the historical HFA ipratropium product landscape, including the CFC-to-HFA transition relevant to Atrovent HFA. Atrovent HFA was approved by FDA under NDA 020648. FDA approval records identify ipratropium bromide inhalation aerosol as an HFA metered-dose inhaler product. [1][2]

The practical Orange Book position is:

any historical listing of US 5,676,930 does not create a current blocking patent right;
the patent's expiration cannot support a current Paragraph IV litigation strategy;
a generic applicant would evaluate any remaining listed patents separately from this expired patent;
FDA listing status and enforceability are distinct issues.

An expired patent can remain visible in historical patent records or product documentation. Its appearance in a patent database does not mean that it remains enforceable.

What Paragraph IV challenges and litigation affected the patent?

Because US 5,676,930 has expired, it cannot support a current Paragraph IV challenge or a new infringement action based solely on its claims.

The historical risk period was the period before expiration, when an ANDA applicant seeking approval for an ipratropium HFA aerosol could have faced:

a patent certification issue under Hatch-Waxman;
a 30-month stay if the NDA holder filed timely patent litigation;
formulation comparison based on HFA propellant, ethanol, acid, and ipratropium concentration;
disputes over whether an accused product was an aerosol solution or suspension;
process-claim issues concerning acid addition and stabilization.

Public FDA and Orange Book records should be used to identify the exact historical listing and any associated litigation docket. The present commercial conclusion is straightforward: US 5,676,930 is not a live Paragraph IV barrier.

How strong was the patent estate?

The patent was technically significant but commercially narrow after the HFA transition matured.

Strengths

The claims had several features that could make them effective during their term:

They targeted the complete formulation rather than a single excipient.
They covered both HFA-134a and HFA-227.
They recited broad ipratropium concentration ranges.
They covered both citric acid and ascorbic acid.
They included method claims directed to stabilization.
Claim 16 attempted to reach inorganic-acid stabilization beyond the specific organic acids in the earlier claims.

Limitations

The claims also had meaningful design-around characteristics:

A competitor could investigate non-acid stabilization systems.
A competitor could use a different cosolvent.
A suspension formulation could present a nonliteral route around solution claims.
A different active ingredient would avoid claims 1 through 15.
Different propellant systems could avoid the specific HFC branches, subject to claim 1's broader HFC language.
A formulation outside the stated concentration ranges could avoid the literal claims.
Device-only innovations would not be covered.

The strongest historical claims were likely the formulation claims covering an HFA propellant, ethanol, ipratropium bromide, and citric acid at commercially relevant concentrations. The process claims were more dependent on proving how the formulation was made and stabilized.

What generic launch risks exist now?

The patent itself creates no current generic launch risk. A company developing an ipratropium HFA product would instead assess the following patent categories:

Risk category	Current relevance
US 5,676,930 formulation claims	Expired
Later formulation patents	Product-specific review required
Metered-dose valve patents	Potentially relevant
Canister and actuator patents	Potentially relevant
Manufacturing and filling patents	Potentially relevant
Combination-product patents	Relevant for ipratropium/albuterol products
Method-of-use patents	Depends on indication and label
FDA exclusivity	Must be checked by NDA and product
Biosimilar risk	Not applicable to ipratropium bromide

Ipratropium bromide is a small-molecule drug, not a biologic. Biosimilar approval pathways do not apply. Competition proceeds through the ANDA pathway for therapeutically equivalent generic products, subject to FDA requirements for device performance, delivered dose, aerodynamic performance, and equivalence.

How does this patent compare with competing ipratropium product estates?

Product or platform	Active ingredient	Delivery system	Relationship to US 5,676,930
Atrovent HFA	Ipratropium bromide	HFA metered-dose aerosol	Historical commercial context
Atrovent CFC	Ipratropium bromide	CFC aerosol	Earlier propellant technology
Combivent HFA	Ipratropium plus albuterol	HFA aerosol	Combination-product estate
Combivent Respimat	Ipratropium plus albuterol	Soft-mist inhaler	Different delivery technology
Ipratropium nebulizer solution	Ipratropium bromide	Nebulizer	Outside aerosol solution claims
Generic ipratropium products	Ipratropium bromide	Product-specific	Evaluate later patents and FDA requirements

The patent's competitive focus was the HFA aerosol solution platform. It did not generally control nebulizer solutions, dry-powder inhalers, or soft-mist inhalers.

What manufacturing and geographic barriers remain?

The patent's expired status removes the US manufacturing barrier created by the claimed formulation. Manufacturing barriers may still arise from:

HFA-compatible pressure vessels;
metering valves and elastomer compatibility;
control of ethanol and acid concentrations;
low-level impurity and degradation control;
pressure and fill-weight specifications;
suspension or solution homogeneity;
actuator geometry;
extractables and leachables;
device assembly and filling infrastructure.

Geographic rights must be assessed separately. Expiration in the United States does not prove expiration in every country. The relevant international family members, national-phase filings, supplementary protection certificates, and local patent-term adjustments must be reviewed jurisdiction by jurisdiction. The US patent itself cannot be used to block conduct outside US territorial jurisdiction.

What licensing deals are associated with the patent?

No current licensing requirement follows from US 5,676,930 because the patent has expired. Historical commercial arrangements involving Boehringer Ingelheim, ipratropium products, inhaler platforms, or combination products may have included broader confidential rights, trademarks, manufacturing know-how, or later patents. Those arrangements cannot be inferred from the expired patent alone.

An expired formulation patent has no standalone licensing value for US commercialization. Commercial rights could still attach to trademarks, regulatory data, device technology, trade secrets, or unexpired improvement patents.

Key Takeaways

US Patent 5,676,930 covers stabilized ipratropium bromide HFA aerosol solutions.
Claims 1 through 15 focus on HFA-134a or HFA-227, ethanol or a cosolvent, and ascorbic or citric acid.
Claim 16 covers a broader medicament formulation using an HFC, organic cosolvent, and inorganic acid.
The patent was granted October 14, 1997 and is expired.
It creates no current US Paragraph IV, litigation, or generic-launch barrier.
The patent does not cover every ipratropium product. Nebulizer solutions, dry-powder inhalers, soft-mist inhalers, device components, and later combination-product patents require separate analysis.
Ipratropium is a small molecule, so biosimilar risk is not applicable.
Current freedom-to-operate risk is more likely to arise from later device, formulation, manufacturing, or combination-product patents.

FAQs

Does US 5,676,930 cover Atrovent HFA?

It is part of the historical patent landscape for HFA ipratropium aerosol products, including the technology transition associated with Atrovent HFA. The patent is expired and no longer blocks the product.

Can a generic use citric acid in an ipratropium HFA inhaler?

Yes, US 5,676,930 no longer prevents that formulation in the United States. Later patents and FDA product requirements must be evaluated independently.

Does the patent cover ipratropium nebulizer solution?

No. The claims are directed to aerosol solution formulations containing an HFC propellant. A conventional aqueous nebulizer solution does not satisfy that propellant limitation.

Is claim 16 limited to ipratropium bromide?

No. Claim 16 recites a medicament rather than expressly requiring ipratropium bromide. It requires an HFC propellant, an organic cosolvent, and an effective amount of an inorganic acid for chemical stability.

Are biosimilars relevant to ipratropium bromide?

No. Ipratropium bromide is a chemically synthesized small molecule. Generic competition uses the ANDA pathway rather than the biosimilar pathway.

References

U.S. Food and Drug Administration. (n.d.). Orange Book: Approved drug products with therapeutic equivalence evaluations. https://www.accessdata.fda.gov/scripts/cder/ob/
U.S. Food and Drug Administration. (n.d.). Drugs@FDA: FDA-approved drugs. https://www.accessdata.fda.gov/scripts/cder/daf/
United States Patent and Trademark Office. (1997). U.S. Patent No. 5,676,930, Stable aerosol formulations. https://patents.google.com/patent/US5676930
U.S. Food and Drug Administration. (2004). Atrovent HFA prescribing information. Boehringer Ingelheim Pharmaceuticals, Inc.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	177941	⤷ Start Trial
Australia	5740594	⤷ Start Trial
Australia	6048694	⤷ Start Trial
Australia	680227	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,676,930

Summary for Patent: 5,676,930