United States Patent 4,594,359: Salbutamol Liquid Formulation Claims, Scope, Expiration, and Patent Landscape

U.S. Patent No. 4,594,359 protects aqueous oral salbutamol compositions stabilized with specified cellulose derivatives. Its strongest commercial embodiment is an oral liquid containing salbutamol or a physiologically acceptable salt, hydroxypropyl methylcellulose or another listed cellulose derivative, and a defined viscosity and concentration profile. The patent issued June 10, 1986, and, under the pre-Uruguay Round patent term applicable to the patent, expired in 2003. It therefore does not create current U.S. blocking exclusivity for generic salbutamol products.

What does U.S. Patent 4,594,359 protect?

The patent covers a pharmaceutical composition, not salbutamol as an active pharmaceutical ingredient. The core invention is the use of a cellulose derivative in an aqueous salbutamol formulation at a concentration effective to stabilize salbutamol.

The independent claim requires four principal elements:

An aqueous dispersion.
Salbutamol and/or a physiologically acceptable salt.
A qualifying cellulose derivative.
A stabilizing-effective amount of that cellulose derivative.

The qualifying cellulose derivatives include alkyl and hydroxyalkyl cellulose ethers, carboxymethylcellulose, and carboxymethylcellulose salts. The claim is drafted with the transitional term "comprising," so additional excipients do not avoid infringement if all required elements remain present.

In the United States, salbutamol is generally called albuterol. The patent therefore has practical relevance to oral albuterol solutions and syrups, including formulations using albuterol sulfate expressed on a salbutamol free-base-equivalent basis.

How do the claims of U.S. Patent 4,594,359 operate?

Claim 1: Broad composition claim

Claim 1 is the principal scope-bearing claim. It covers an aqueous salbutamol composition containing one or more specified cellulose derivatives in a stabilizing-effective amount.

The claim does not require:

A particular salbutamol salt;
A specific cellulose derivative;
A stated pH;
A stated viscosity;
A stated salbutamol concentration;
Oral administration;
A particular preservative, sweetener, flavor, buffer, or container.

The functional phrase "salbutamol stabilizing effective amount" is central. A cellulose derivative is not necessarily within the claim merely because it is present. The composition must contain enough of the derivative to stabilize salbutamol. In litigation, that limitation would likely require evidence from formulation testing, stability data, specifications, or expert analysis.

Claims 2 through 5: Cellulose concentration and preferred polymers

Claim 2 narrows claim 1 by requiring at least 0.1% w/v of the cellulose derivative or derivatives. This limitation corresponds to at least 1 gram per liter.

Claim 3 limits the derivative to an alkyl and/or hydroxyalkyl ether of cellulose. Claim 4 lists specific compounds:

Ethyl cellulose;
Methyl cellulose;
Ethylmethyl cellulose;
Hydroxymethyl cellulose;
Hydroxyethyl cellulose;
Hydroxypropyl cellulose;
Hydroxyethyl methylcellulose;
Hydroxypropyl methylcellulose;
Hydroxyethyl ethylcellulose;
Carboxymethylcellulose;
Salts of carboxymethylcellulose.

Claim 5 narrows the composition to hydroxypropyl methylcellulose, commonly abbreviated HPMC. HPMC is commercially significant because it can provide both viscosity control and formulation stabilization in oral liquid products.

Claims 6 through 10: Oral liquid dosage form

Claim 6 requires a liquid preparation suitable for oral administration. This limitation excludes nonoral compositions, including inhalation aerosols, dry powders, tablets, and injectable products.

Claim 7 requires a viscosity from 5 to 10,000 centipoises. Claim 8 narrows that range to 10 to 100 centipoises. The narrower range is commercially more consistent with pourable oral syrups and solutions rather than highly viscous suspensions or gels.

Claim 9 requires 1 mg to 4 mg of salbutamol, expressed as free base, per 5 mL. Claim 10 narrows the concentration to 2 mg per 5 mL. The 2 mg/5 mL strength is a recognizable pediatric oral-solution concentration and is likely the most commercially relevant dependent-claim embodiment.

Claims 11 through 14: pH and chemical-substitution limits

Claim 11 requires a pH of 3.5. Claim 13 covers a broader pH range of 2.5 to 7. A formulation at pH 3.5 would fall within both claims if it satisfies the other limitations.

Claim 12 requires hydroxyethyl cellulose. Claim 14 limits the alkyl group and alkyl moiety to one through four carbon atoms. This limitation captures common lower-alkyl and hydroxyalkyl cellulose ethers while excluding longer-chain alkyl variants.

What are the strongest and weakest claim elements?

Claim element	Scope	Enforcement significance
Aqueous dispersion	Broad within liquid aqueous products	Excludes dry and nonaqueous dosage forms
Salbutamol or physiologically acceptable salt	Broad	Covers salbutamol sulfate and other acceptable salts
Listed cellulose derivative	Moderate to broad	Requires a qualifying polymer, not any excipient
Stabilizing-effective amount	Functional	Likely requires technical proof
At least 0.1% w/v	Narrower	Provides an objective concentration threshold
Oral liquid	Narrower	Focuses commercial exposure on syrups and oral solutions
5 to 10,000 cP	Moderate	Can reach highly viscous products
10 to 100 cP	Narrow	Targets conventional pourable liquids
1 to 4 mg/5 mL	Narrow	Relevant to pediatric and standard oral strengths
2 mg/5 mL	Very narrow	High relevance only for the specific strength
pH 3.5	Very narrow	Requires tight analytical matching
pH 2.5 to 7	Moderate	Broadens the pH coverage substantially
HPMC	Narrow but commercially important	Common formulation polymer
C1-C4 alkyl groups	Narrow chemical limitation	Limits the ether-substitution scope

The broadest practical risk arises under claim 1, particularly for an aqueous oral albuterol product containing HPMC, hydroxyethyl cellulose, methylcellulose, or carboxymethylcellulose. The stabilizing-effective-amount limitation may be the principal technical issue.

When did U.S. Patent 4,594,359 expire?

U.S. Patent 4,594,359 issued on June 10, 1986. For a patent governed by the pre-Uruguay Round patent term, the term was generally 17 years from grant. On that basis, the patent expired on June 10, 2003, absent an unusual term adjustment or extension. The patent’s age and 1986 issue date place it outside the current period of enforceable U.S. patent exclusivity.

Event	Date
U.S. patent grant	June 10, 1986
Expected term basis	17 years from grant
Expected expiration	June 10, 2003
Current enforceability	Expired
Current generic blocking effect	None from this patent

Patent expiration eliminates the right to prevent practicing the claimed invention in the United States. It does not eliminate the patent’s historical value as prior art or its relevance to freedom-to-operate analyses involving continuation, divisional, foreign, or related family patents.

What is the Orange Book status of U.S. Patent 4,594,359?

The patent should not be treated as a current Orange Book barrier solely because it covers a salbutamol formulation. Orange Book listing is product-specific and depends on submission by the applicable New Drug Application holder and FDA acceptance of the patent information for an approved drug product. A patent number alone does not establish current listing status.

The patent is also expired. An expired patent cannot provide current patent-based delay against an ANDA applicant, even if it appeared in historical patent records. Any Paragraph IV strategy directed specifically to U.S. Patent 4,594,359 would therefore have little present commercial value unless a related unexpired patent were also asserted.

FDA Orange Book analysis for albuterol products should distinguish among:

Drug substance patents;
Drug product or formulation patents;
Method-of-use patents;
Device or delivery-system patents;
Exclusivity periods unrelated to patent term;
Historical listings that have since expired or been delisted.

Does U.S. Patent 4,594,359 cover inhalers or nebulizers?

No. The issued claims are directed to aqueous compositions and, in the narrower claims, oral liquid preparations. They do not claim:

Metered-dose inhalers;
Dry-powder inhalers;
Nebulizer devices;
Aerosol propellants;
Inhalation methods;
Device architecture;
Pulmonary delivery systems.

An inhaled albuterol product would generally fall outside claims 6 through 10 because those claims require a liquid preparation suitable for oral administration. Claim 1 is broader than claims 6 through 10 but still requires the claimed aqueous salbutamol-cellulose composition. A formulation used in a nebulizer could raise a separate claim-construction question under claim 1, but the patent does not expressly claim inhalation delivery.

What formulations are protected by the patent?

The clearest covered formulation is an oral liquid with the following profile:

Parameter	Representative patented embodiment
Active ingredient	Salbutamol or salbutamol salt
U.S. active-ingredient terminology	Albuterol or albuterol sulfate
Dosage form	Aqueous oral liquid
Stabilizer	HPMC, hydroxyethyl cellulose, or another listed derivative
Polymer level	At least 0.1% w/v for claim 2 coverage
Viscosity	5 to 10,000 cP under claim 7
Narrow viscosity range	10 to 100 cP under claim 8
Strength	1 to 4 mg/5 mL under claim 9
Specific strength	2 mg/5 mL under claim 10
pH	2.5 to 7 under claim 13; 3.5 under claim 11

The claims do not require a particular sugar system, preservative, flavor, buffer, colorant, or sweetener. A generic manufacturer could potentially design around the patent by using a nonlisted stabilizer, a nonaqueous vehicle, or a dosage form that does not satisfy the oral-liquid limitations. Those design choices would require separate evaluation against claim 1, which remains broader than the dependent claims.

What generic entry risks existed before patent expiration?

Before June 2003, a generic applicant marketing a matching oral liquid could have faced infringement allegations if its product contained:

Albuterol or an acceptable salbutamol salt;
Water as an aqueous vehicle;
A listed cellulose derivative;
The derivative at a stabilizing-effective level.

A Paragraph IV certification would have been relevant only if the patent were listed for the reference drug and remained unexpired at the time of the ANDA certification. The commercial impact would have depended on the reference product, listed patent status, claim interpretation, and whether the generic product used the claimed polymer and concentration.

The patent was less relevant to generic inhaler competition because its issued claims focus on liquid compositions and oral administration. It also had limited reach over formulations that used alternative stabilizers, provided those formulations did not contain a qualifying cellulose derivative in a stabilizing-effective amount.

How strong was the patent estate?

The patent appears to have been a focused formulation patent rather than a broad salbutamol platform patent.

Strengths

Claim 1 covers multiple cellulose derivative classes.
The composition claim does not require oral administration.
The claims cover both salbutamol and physiologically acceptable salts.
Dependent claims identify commercially plausible HPMC and oral-liquid embodiments.
The 2 mg/5 mL limitation maps to a known oral-liquid strength.

Limitations

The patent does not claim salbutamol itself.
It does not cover inhaler devices or inhaled delivery methods.
The functional stabilization limitation may require comparative testing.
Many dependent claims are narrow and analytically testable.
The patent expired in 2003.
Any continuing commercial relevance depends on related patents, not this patent alone.

The estate’s historical value was strongest for oral albuterol liquids using cellulose-based stabilizers. Its current value is limited to prior-art analysis, historical product review, and assessment of related family rights.

Which companies challenged or licensed the patent?

The provided claim text does not establish a particular Paragraph IV litigation, settlement, or licensing agreement. The patent number alone does not support attributing a challenge or license to a specific company.

The original patent holder is associated with the Allen & Hanburys salbutamol product-development history. Allen & Hanburys was part of the Glaxo organization, later incorporated into GlaxoSmithKline’s historical respiratory business. Ownership, assignment, licensing, and enforcement must be confirmed through USPTO assignment records, court dockets, and product-specific regulatory filings.

No current licensing restriction can arise from an expired U.S. patent. A separate license could still matter for confidential know-how, trademarks, regulatory data, or unexpired related patents, but those rights are not established by the claims supplied.

What manufacturing and intellectual-property barriers remain?

The expired patent does not prevent manufacture of the claimed compositions. Remaining barriers may include:

FDA approval or ANDA requirements;
Demonstration of pharmaceutical equivalence;
Stability and preservative-effectiveness data;
Control of viscosity and polymer substitution levels;
Microbial limits for aqueous oral liquids;
Labeling and pediatric-use requirements;
Trademark constraints involving branded albuterol products;
Unexpired patents covering specific products, devices, processes, or uses;
Manufacturing know-how not disclosed in the patent.

The patent’s technical disclosure may still assist formulation development because it identifies cellulose derivatives as stabilizing excipients for aqueous salbutamol systems. That disclosure can also limit the patentability of later claims directed broadly to the same formulation concept.

How does this patent compare with albuterol inhaler patent estates?

Issue	U.S. Patent 4,594,359	Typical inhaler patent estate
Product type	Oral aqueous liquid	Metered-dose or dry-powder inhaler
Active ingredient	Salbutamol/albuterol	Albuterol or another bronchodilator
Main technology	Cellulose-based stabilization	Device, aerosol, formulation, or dose metering
Key claim variables	Polymer, viscosity, pH, concentration	Actuator, propellant, particle size, dose delivery
Orange Book relevance	Product-specific and historical	Often product- and device-specific
Current enforceability	Expired	Depends on individual patents
Biosimilar relevance	None	None
Generic pathway	ANDA for oral liquid	ANDA or applicable complex-product pathway

Biosimilar risk is not relevant. Salbutamol is a small molecule, and competing products are generally evaluated through generic-drug pathways rather than the biologic licensing pathway.

Key Takeaways

U.S. Patent 4,594,359 covers aqueous salbutamol compositions stabilized with specified cellulose derivatives.
The commercially important embodiment is an oral albuterol liquid containing HPMC or a related cellulose polymer.
Claim 1 is broadest; claims 7 through 10 target viscosity and concentration profiles associated with oral syrups.
Claim 11 requires pH 3.5, while claim 13 covers pH 2.5 to 7.
The patent issued June 10, 1986, and expired on the expected 17-year term in 2003.
It does not cover salbutamol as a compound, inhaler devices, dry powders, or inhalation methods.
Current Orange Book significance cannot be inferred from the patent number and, in any event, an expired patent cannot block current generic entry.
No biosimilar pathway applies because albuterol is a small-molecule drug.
Any present freedom-to-operate risk must come from unexpired related patents, product-specific listings, device rights, regulatory exclusivity, trademarks, or manufacturing know-how.

Frequently Asked Questions

Does U.S. Patent 4,594,359 cover albuterol sulfate?

Yes, if the albuterol sulfate is present in an aqueous composition with a qualifying cellulose derivative in a salbutamol-stabilizing effective amount. The claims cover salbutamol and physiologically acceptable salts, while the concentration limitations are expressed as salbutamol free base.

Can a generic company use hydroxypropyl methylcellulose in an albuterol syrup today?

This patent does not prevent that use because it expired in 2003. A separate unexpired patent would need to be identified before concluding that the formulation is free of all patent risk.

Is the 2 mg/5 mL albuterol syrup specifically claimed?

Yes. Claim 10 covers a composition within claim 9 containing 2 mg of salbutamol, expressed as free base, per 5 mL of liquid, subject to the underlying composition and cellulose-derivative requirements.

Does the patent cover carboxymethylcellulose sodium?

Claim 4 expressly includes carboxymethylcellulose and salts of carboxymethylcellulose. A formulation using a salt may fall within the claim if the other limitations are met.

Is U.S. Patent 4,594,359 relevant to current albuterol inhaler launches?

Generally, no. The patent is expired and its narrower claims focus on oral liquid preparations. Current inhaler analysis should focus on inhaler formulation, device, dose-metering, and product-specific patent rights.

References

United States Patent and Trademark Office. (1986). U.S. Patent No. 4,594,359, Pharmaceutical compositions containing salbutamol. https://patents.google.com/patent/US4594359
United States Patent and Trademark Office. (n.d.). Patent term adjustment and patent term information. https://www.uspto.gov/patents/laws/patent-term-calculator
U.S. Food and Drug Administration. (2025). Approved drug products with therapeutic equivalence evaluations. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book
U.S. Food and Drug Administration. (2024). Approved drug product and patent information. https://www.fda.gov/drugs/development-approval-process-drugs/orange-book-data-files
U.S. Food and Drug Administration. (2024). Abbreviated new drug application submissions and patent certifications. https://www.fda.gov/drugs/abbreviated-new-drug-application-anda/abbreviated-new-drug-application-anda-submissions-questions-and-answers

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	8215502	May 27, 1982

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	390191	⤷ Start Trial
Austria	A195283	⤷ Start Trial
Australia	1503983	⤷ Start Trial
Australia	567675	⤷ Start Trial
Belgium	896870	⤷ Start Trial
Canada	1203176	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 4,594,359

Summary for Patent: 4,594,359