US Patent 5,362,755: Scope, Claim Analysis, Expiration, and Levalbuterol Patent Landscape

US Patent 5,362,755 covers chronic treatment of asthma with substantially pure R(-)-albuterol, now known as levalbuterol, to produce bronchodilation while reducing adverse effects associated with racemic albuterol. The patent issued on November 8, 1994, and its ordinary 17-year term expired on November 8, 2011. The patent is therefore no longer an enforceable barrier to generic levalbuterol products, although it remains important as the foundational patent for the R-enantiomer therapeutic concept.

The patent is a method-of-treatment patent. It does not broadly claim the levalbuterol molecule, a pharmaceutical composition, a device, or every use of R-albuterol. Its enforceable scope was limited to specified clinical administration methods involving asthma, chronic dosing, bronchodilation, reduced side effects, and, in dependent claims, purity, dose, route, and combination therapy.

What invention does US Patent 5,362,755 protect?

US Patent 5,362,755 protects the use of optically pure or highly enriched R(-)-albuterol for chronic asthma treatment. The patent distinguishes R(-)-albuterol from racemic albuterol, which contains approximately equal quantities of the R(−) and S(+) enantiomers.

The core theory is that the R enantiomer produces bronchodilation while avoiding or reducing undesirable effects attributed to chronic exposure to racemic albuterol. The R enantiomer is now generally referred to as levalbuterol, while racemic albuterol is commonly called albuterol or salbutamol.

The patent does not claim:

Every administration of levalbuterol.
Treatment of every respiratory disease.
A composition containing any amount of R-albuterol.
A device or nebulizer.
A specific salt, such as levalbuterol hydrochloride, as a standalone composition.
Manufacturing of R-albuterol.
A broad pharmaceutical formulation claim.

The patent claims conduct by a healthcare provider or other party administering the drug to an asthma patient.

How many independent claims does US Patent 5,362,755 contain?

The patent contains two independent method claims: claims 1 and 6.

Claim	Claim type	Principal limitation
1	Independent method claim	Chronic administration of substantially pure R(-)-albuterol to treat asthma while reducing side effects associated with chronic racemic albuterol
2	Dependent	R-albuterol exceeds approximately 90% by weight
3	Dependent	R-albuterol exceeds 99% by weight
4	Dependent	Inhaled dose of approximately 30 to 90 mcg per dose
5	Dependent	Oral dose of 1 to 8 mg, administered two to four times daily
6	Independent method claim	Claim 1 treatment combined with at least one additional drug from specified classes
7	Dependent	Additional analgesic is aspirin, acetaminophen, or ibuprofen

Claim 1 is the central commercial claim. Claim 6 creates a separate combination-treatment pathway but incorporates the principal limitations of claim 1.

What does claim 1 require?

Claim 1 requires each of the following elements:

An individual with asthma.
Treatment with albuterol.
Chronic administration.
Administration of the R(-) isomer.
The R isomer is substantially free of the S(+) isomer.
The administered quantity is sufficient to produce bronchodilation.
Administration simultaneously reduces undesirable side effects associated with chronic racemic albuterol.

The claim is narrower than a simple “use of levalbuterol” claim. A potential infringement analysis would examine both the drug administered and the clinical use.

Chronic administration

“Chronically administering” distinguishes maintenance treatment from a single rescue dose or isolated acute administration. The patent does not establish a single universal minimum duration in the claims. The term would likely be interpreted in the context of the specification, treatment regimen, and ordinary clinical meaning.

A short-term emergency use of levalbuterol would present a weaker claim 1 infringement case than repeated maintenance administration. A recurring inhaled regimen for persistent asthma would more closely match the claim language.

Substantially free of the S(+) isomer

The phrase requires meaningful enrichment in R(-)-albuterol but does not itself specify a numerical purity threshold. Claims 2 and 3 provide express benchmarks:

More than approximately 90% R(-)-albuterol.
More than 99% R(-)-albuterol.

The term “substantially free” in claim 1 should not automatically be treated as identical to the greater-than-99% limitation in claim 3. Claim 3 narrows the claim by adding a specific purity requirement.

Reduced side effects

The side-effect limitation is functional. The method must reduce undesirable effects associated with chronic racemic albuterol while maintaining bronchodilation. The claim therefore contains a therapeutic outcome component, not merely a product identity requirement.

Potentially relevant adverse effects include tachycardia, tremor, nervousness, hypokalemia, and related beta-adrenergic effects. The patent’s claim language does not require reduction of every side effect or identify one exclusive adverse event.

What do claims 2 and 3 protect?

Claims 2 and 3 narrow claim 1 based on enantiomeric purity.

Claim 2 requires more than approximately 90% R(-)-albuterol by weight of total albuterol. This limitation would generally cover a high-enantiomeric-excess product but would not necessarily require pharmaceutical-grade optical purity.

Claim 3 requires more than 99% R(-)-albuterol by weight. This is the narrower purity claim and is closer to the purity profile associated with a highly purified levalbuterol active ingredient.

Purity level	Approximate R/S relationship	Claim relevance
Racemic albuterol	50% R / 50% S	Outside the express purity limitations
More than 90% R	Less than 10% S	Claim 2
More than 99% R	Less than 1% S	Claim 3

The claims use weight percentage language. An infringement analysis would need to address the measurement method, whether the percentage refers to the active ingredient fraction, and whether impurities other than the S enantiomer are included in the denominator.

What doses and routes are covered by claims 4 and 5?

Claim 4 covers inhaled administration of approximately 30 to approximately 90 micrograms of R(-)-albuterol per dose.

Claim 5 covers oral administration of 1 to 8 mg of R(-)-albuterol two to four times daily.

Claim	Route	Dose	Frequency
4	Inhalation	Approximately 30-90 mcg per dose	Not specified
5	Oral	1-8 mg	Two to four times daily

Claim 4 is directed to inhaled dosing, while claim 5 is directed to oral dosing. A product administered by nebulization, metered-dose inhaler, or another inhalation system could fall within claim 4 if the delivered dose and other claim 1 requirements were met.

The marketed Xopenex product line later included inhalation solution and inhalation aerosol presentations. FDA labeling identifies levalbuterol hydrochloride inhalation solution in 0.31 mg, 0.63 mg, and 1.25 mg per 3 mL strengths, and Xopenex HFA as a 45 mcg-per-actuation inhaler. Those labeled strengths do not map mechanically onto the 30-90 mcg limitation in claim 4 because nebulizer vial strength and inhaler actuation dose are different dosing concepts. The actual delivered dose, rather than the vial concentration alone, would be relevant to a claim analysis. (U.S. Food and Drug Administration, 2015, 2017)

What does claim 6 protect?

Claim 6 covers chronic administration of R(-)-albuterol together with at least one additional drug selected from:

Bronchodilators.
Antihistamines.
Analgesics.

The claim retains the central asthma, chronic administration, bronchodilation, reduced-side-effect, and R-isomer limitations from claim 1. The additional drug requirement creates a combination-treatment limitation.

Claim 6 does not require one drug from every listed class. “At least one additional drug selected from” the group means that a single qualifying bronchodilator, antihistamine, or analgesic can satisfy the combination element.

The additional drug does not need to be physically co-formulated with levalbuterol based on the claim language. Separate administration can potentially satisfy the claim if the treatment regimen uses both drugs.

What combinations are expressly covered by claim 7?

Claim 7 narrows claim 6 by identifying the analgesic as one of three drugs:

Aspirin.
Acetaminophen.
Ibuprofen.

The claim does not cover every analgesic under this dependent limitation. A combination involving an opioid, naproxen, or another analgesic would not satisfy claim 7 solely on that basis, although it could potentially implicate claim 6 if the broader analgesic category were met.

When did US Patent 5,362,755 expire?

US Patent 5,362,755 issued on November 8, 1994. Because it was filed before the June 8, 1995 transition to the modern 20-year-from-earliest-effective-filing-date term, its ordinary term was generally 17 years from issuance. The ordinary expiration date was November 8, 2011. (U.S. Patent No. 5,362,755, 1994)

Event	Date
Patent issued	November 8, 1994
Ordinary patent term	17 years from issue
Ordinary expiration	November 8, 2011
Current enforcement status	Expired

A patent-term adjustment or extension must be confirmed from the official patent record before asserting a different expiration date. The publicly cited term for this patent is November 8, 2011.

The expiration eliminates the patent as a current generic-entry barrier. It does not invalidate the patent’s historical role in supporting the original Xopenex regulatory and commercial strategy.

What was the FDA status of levalbuterol and Xopenex?

Levalbuterol was developed as the pharmacologically active R enantiomer of albuterol. The FDA approved Xopenex inhalation solution under NDA 20-837 in 1999. Xopenex HFA was later approved as a metered-dose inhalation product. FDA labeling identifies levalbuterol hydrochloride as the active ingredient. (U.S. Food and Drug Administration, 1999, 2017)

Levalbuterol is regulated as a small-molecule drug. Generic competition proceeds through the abbreviated new drug application pathway under section 505(j) of the Federal Food, Drug, and Cosmetic Act, not through the biosimilar pathway.

There is no biosimilar risk associated with US Patent 5,362,755. The relevant competitive risk is generic levalbuterol, including inhalation solution, inhalation aerosol, and potentially other dosage forms approved through ANDA or 505(b)(2) pathways.

What was the Orange Book status of US Patent 5,362,755?

The patent was historically associated with the Xopenex product and its levalbuterol indication. Its relevance to Orange Book exclusivity ended when the patent expired.

Orange Book listing does not itself determine the scope of infringement. It provides FDA patent-listing information for approved products and is relevant to ANDA certification and regulatory timing. Once the patent expired, a Paragraph IV challenge to that patent no longer provided a meaningful basis for a delayed generic launch.

The principal regulatory consequences were:

During the patent term, an ANDA applicant could certify that the patent was invalid, unenforceable, or not infringed under Paragraph IV.
A Paragraph IV notice could trigger patent litigation and, if suit was filed within the statutory period, a 30-month FDA approval stay.
After expiration, applicants could rely on a Paragraph III certification or otherwise proceed without treating the expired patent as a remaining barrier.
The patent’s expiration did not remove other formulation, device, or method patents that might have covered particular products.

Were there Paragraph IV challenges and generic-launch risks?

The principal historical Paragraph IV risk involved generic levalbuterol products seeking approval before expiration of the foundational method patent or other listed Xopenex patents. The commercial effect depended on:

Whether the proposed generic label included the patented asthma use.
Whether the product used R(-)-albuterol at the claimed purity.
Whether the proposed dose and route fell within claims 4 or 5.
Whether the applicant used a “skinny label” excluding a patented method of use.
Whether other Orange Book-listed patents remained in force.

After November 8, 2011, US Patent 5,362,755 could no longer independently prevent launch. Generic entry could still be delayed by other patents, regulatory deficiencies, manufacturing issues, device equivalence, or settlement terms relating to separate patents.

Publicly available FDA materials document generic levalbuterol approvals and product labeling, but a complete historical litigation chronology cannot be derived from the patent claims alone. The patent record should be distinguished from separate district-court litigation involving later formulation or device patents.

What other patents protect levalbuterol formulations and devices?

The foundational patent should be separated from later product-specific rights.

IP category	Relevance to levalbuterol	Status relative to US 5,362,755
Enantiomer therapeutic method	Chronic asthma treatment with R(-)-albuterol	Foundational patent; expired
Inhalation formulation	Stability, concentration, excipients, pH, preservatives, or delivery characteristics	May have had separate patent protection
Nebulizer product	Unit-dose presentation and administration system	Potentially separate patents and regulatory exclusivities
HFA aerosol	Propellant, canister, valve, actuator, and suspension formulation	Separate product and device rights
Manufacturing	Resolution, purification, salt formation, or crystallization	Separate process patents
Method of use	Particular patient population, dosing schedule, or combination	Separate method patents

US Patent 5,362,755 does not claim the Xopenex HFA device or a specific nebulizer formulation. A competitor could avoid the patent by using a different formulation only if the resulting use also fell outside the method claims. Conversely, a product could avoid the expired patent but still face a later formulation or device patent during that patent’s term.

How strong was the patent estate for levalbuterol?

Historically, the patent had meaningful commercial strength because it linked three elements:

A differentiated active ingredient, R(-)-albuterol.
A clinically relevant asthma indication.
A claimed reduction in side effects associated with racemic therapy.

Its limitations were equally important. The claims were method claims and required chronic asthma treatment plus a functional reduction in undesirable effects. They did not provide a broad composition monopoly over all levalbuterol products.

The estate’s historical strength was highest against products marketed for chronic asthma treatment with substantially pure R-albuterol. It was weaker against:

Racemic albuterol products.
Acute or one-time administration.
Non-asthma respiratory indications.
Products outside the claimed dose ranges.
Products with labels omitting the patented use.
Products covered only by later formulation or device patents.

The estate’s current strength is zero as an enforceable patent barrier because the patent expired in 2011.

What licensing and ownership issues affected the commercial landscape?

Sepracor was the original commercial developer and patent holder associated with levalbuterol and Xopenex. Dainippon Sumitomo Pharma acquired Sepracor in 2010, integrating the Xopenex business into its portfolio. This transaction changed corporate ownership and commercialization responsibility but did not extend the statutory term of US Patent 5,362,755.

The patent itself should be analyzed separately from commercial licenses involving:

Product commercialization.
Regional distribution.
Manufacturing.
Device supply.
Later formulation rights.
Regulatory rights for specific dosage forms.

An acquisition or license cannot revive an expired patent. It can, however, transfer rights in unexpired continuation patents, formulation patents, trademarks, regulatory data, and manufacturing know-how.

What generic entry scenarios applied after patent expiration?

The principal post-expiration scenarios were:

Immediate conventional generic entry

A generic sponsor could seek approval for levalbuterol inhalation solution or another dosage form after satisfying FDA requirements for pharmaceutical equivalence, bioequivalence where applicable, quality, labeling, and manufacturing.

Skinny-label entry

A generic applicant could omit a patented method of use from its labeling if the remaining labeling supported approval and the omission complied with FDA requirements. This strategy was more relevant while method patents remained in force.

Formulation or device differentiation

A company could develop a product with a different formulation, container, actuator, or delivery system. That approach could create separate patent issues even after expiration of the foundational method patent.

505(b)(2) competition

A sponsor with a new formulation, route, or clinical use could pursue a 505(b)(2) application and potentially obtain separate regulatory exclusivity or patent protection. That pathway does not create biosimilar exposure because levalbuterol is not a biologic.

Key Takeaways

US Patent 5,362,755 covers chronic asthma treatment with substantially pure R(-)-albuterol, or levalbuterol.
Claims 1 and 6 are the two independent claims.
Claims 2 and 3 address greater than 90% and greater than 99% R-isomer purity.
Claim 4 covers inhaled doses of approximately 30-90 mcg per dose.
Claim 5 covers oral doses of 1-8 mg two to four times daily.
Claims 6 and 7 address combination therapy with bronchodilators, antihistamines, and specified analgesics.
The patent issued November 8, 1994, and expired November 8, 2011, under its ordinary 17-year term.
It is no longer an enforceable barrier to generic levalbuterol.
Later formulation, device, manufacturing, or method patents had to be analyzed separately.
Generic competition involved ANDA and, in some cases, 505(b)(2) pathways, not biosimilar regulation.
The patent’s historical commercial importance exceeded its present legal value because the patent term has ended.

FAQs About US Patent 5,362,755 and Levalbuterol Exclusivity

Does US Patent 5,362,755 cover racemic albuterol?

No. The claims require the R(-) isomer to be substantially free of the S(+) isomer. Racemic albuterol contains both enantiomers and does not satisfy the express R-isomer purity limitations in claims 2 and 3.

Does US Patent 5,362,755 cover Xopenex HFA?

Historically, the patent could have been relevant to the use of substantially pure R-albuterol delivered by inhalation. It did not claim the Xopenex HFA device, canister, valve, actuator, or propellant formulation as such.

Is levalbuterol a biologic subject to biosimilar competition?

No. Levalbuterol is a small-molecule drug. Generic competition is governed principally by the ANDA pathway, not the FDA biosimilar pathway.

Could a generic launch before November 8, 2011?

Potentially, but early launch would have required addressing the patent through a Paragraph IV certification, a litigation settlement, a license, or another legally recognized pathway. The expiration date removed the patent barrier after November 8, 2011.

Does patent expiration eliminate all intellectual-property risk for generic levalbuterol?

No. Expiration eliminated this patent as a barrier but did not eliminate potentially unexpired formulation, device, manufacturing, trademark, regulatory, or separate method-of-use rights.

References

U.S. Patent No. 5,362,755. (1994). Method of treating asthma using R-albuterol. U.S. Patent and Trademark Office.
U.S. Food and Drug Administration. (1999). Xopenex (levalbuterol hydrochloride) inhalation solution: Approval history and prescribing information. FDA.
U.S. Food and Drug Administration. (2015). Xopenex (levalbuterol hydrochloride) inhalation solution prescribing information. FDA.
U.S. Food and Drug Administration. (2017). Xopenex HFA (levalbuterol tartrate) inhalation aerosol prescribing information. FDA.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, commonly known as the Orange Book. FDA.
U.S. Patent and Trademark Office. (2024). Patent term adjustment and patent term information. USPTO.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	135908	⤷ Start Trial
Australia	7174191	⤷ Start Trial
Canada	2073181	⤷ Start Trial
Germany	69118359	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,362,755

Summary for Patent: 5,362,755