U.S. Patent 5,290,815: Salmeterol Late-Phase Asthma Claims, Scope, Expiration, and Patent Landscape

U.S. Patent No. 5,290,815 covers the use of salmeterol, including salmeterol xinafoate, to treat the late asthmatic reaction or late-phase asthma. The patent is a method-of-treatment patent, not a composition-of-matter, formulation, inhaler-device, or manufacturing patent. It was granted on March 1, 1994, and its ordinary pre-URAA patent term appears to have expired on March 1, 2011. The patent therefore does not create a current U.S. barrier to generic salmeterol entry.

What drug does U.S. Patent 5,290,815 protect?

The claimed active ingredient is salmeterol, formally identified in the claims as:

4-hydroxy-alpha1-[[[6-(4-phenylbutoxy)hexyl]amino]methyl]-1,3-benzenedimethanol.

Claim 3 specifically covers the 1-hydroxy-2-naphthalenecarboxylate salt, commonly called salmeterol xinafoate. Salmeterol xinafoate is the active pharmaceutical ingredient used in GlaxoSmithKline's Serevent products.[1]

Item	Analysis
Patent	U.S. Patent No. 5,290,815
Patent type	Method of treatment
Active ingredient	Salmeterol
Claimed salt	Salmeterol xinafoate
Therapeutic target	Late asthmatic reaction and late-phase asthma
Primary product association	Serevent
Grant date	March 1, 1994
Original applicant/assignee	Glaxo Group Limited
Expected ordinary expiration	March 1, 2011
Current blocking effect	None based on this expired patent

The claim language does not cover every use of salmeterol. It targets a defined therapeutic setting involving the late asthmatic reaction or late-phase asthma.

What are the claims of U.S. Patent 5,290,815?

The three claims divide into two broad categories.

Claims 1 and 2: broad late-asthma treatment claims

Claims 1 and 2 cover administering an effective amount of salmeterol, or a physiologically acceptable salt or solvate, to a mammal suffering from:

The late asthmatic reaction; or
Late-phase asthma.

The claims are materially similar but use different disease terminology. Claim 1 refers to the "late asthmatic reaction." Claim 2 refers to "late-phase asthma."

Both claims require proof of the following elements:

A mammalian patient, including a human.
The patient is suffering from the claimed late-phase condition.
An effective amount of salmeterol, or an acceptable salt or solvate, is administered.
The administration is for treatment of that condition.

Neither claim specifies:

A particular inhalation device.
A dose.
A dosing interval.
A route of administration.
A particle-size distribution.
A propellant.
A dry-powder carrier.
A particular formulation.
A particular clinical endpoint.

The absence of those limitations makes the claims technologically broad within the defined treatment indication. The claims could potentially read on different dosage forms and administration routes if the accused conduct satisfied the treatment and active-ingredient limitations.

Claim 3: salmeterol xinafoate

Claim 3 depends on claims 1 or 2 and narrows the active ingredient to salmeterol 1-hydroxy-2-naphthalenecarboxylate, or salmeterol xinafoate.

A product or method would need to satisfy both:

The late-phase asthma treatment limitations in claim 1 or 2; and
The salt limitation requiring salmeterol xinafoate.

Claim 3 does not independently cover salmeterol xinafoate for all respiratory diseases. It is limited to the claimed late-asthma treatment use.

How broad is the patent's legal scope?

The patent's scope is broad as a treatment-use patent but narrow compared with a composition patent.

Scope by subject matter

Subject matter	Covered by U.S. 5,290,815?
Salmeterol composition itself	No
Salmeterol xinafoate composition itself	No, based on the supplied claims
Use of salmeterol for late-phase asthma	Yes
Use of salmeterol for the late asthmatic reaction	Yes
Any use of salmeterol for COPD	No express coverage
Any use of salmeterol for exercise-induced bronchospasm	No express coverage
Specific inhaler device	No
Specific dry-powder formulation	No
Manufacturing salmeterol	No
Manufacturing salmeterol xinafoate	No
Administration by inhalation only	Not expressly required
Administration of another long-acting beta agonist	No

The critical limitation is the medical condition. A defendant would not infringe merely by making or selling salmeterol. The conduct would need to involve administration for the claimed late-phase asthma condition, or liability theories based on inducing or contributing to such use.

What does "effective amount" mean in these claims?

"Effective amount" is a functional treatment limitation. It generally requires an amount sufficient to produce the claimed therapeutic effect in the relevant patient population.

The patent does not provide a numerical dose limitation in the claims supplied. That creates flexibility for the patentee but can create proof issues in litigation. A claimant would generally need to establish that the administered dose was intended or capable of treating the late asthmatic reaction or late-phase asthma.

The phrase does not automatically cover every exposure to salmeterol. A subtherapeutic amount, accidental exposure, or administration for an unrelated purpose would be less likely to satisfy the limitation.

Does the patent cover Serevent and salmeterol xinafoate inhalers?

Serevent is associated with salmeterol xinafoate. The FDA-approved product has been supplied in inhalation formulations, including metered-dose and dry-powder presentations.[1]

The patent can be relevant to a Serevent-type product when the product labeling, prescribing instructions, or actual use directs treatment of the claimed late-phase asthma condition. The patent does not, however, claim the inhaler device or formulation architecture on the face of the supplied claims.

That distinction matters:

A product patent can block manufacture or sale of the product itself.
A formulation patent can block a particular pharmaceutical formulation.
A device patent can block a particular inhaler.
A method patent generally requires proof tied to the patented use.

U.S. Patent 5,290,815 falls into the fourth category.

When did U.S. Patent 5,290,815 expire?

The patent was granted on March 1, 1994. Because the application predates the effective transition to the modern twenty-year term for most U.S. applications, the ordinary term was seventeen years from grant. On that basis, the patent expired on March 1, 2011.[2]

Event	Date
Priority period	Before U.S. grant
U.S. grant	March 1, 1994
Ordinary seventeen-year term	March 1, 2011
Current status	Expired by term

No patent term extension or patent term adjustment appears to create a current enforceable term for this patent. The expiration date also predates the current generic salmeterol market.

What is the Orange Book status of U.S. Patent 5,290,815?

U.S. Patent 5,290,815 was historically relevant to FDA-listed salmeterol products, including Serevent. The Orange Book records patents and exclusivity information submitted for approved drug products, but an Orange Book listing does not extend an expired patent.[3]

The practical status is:

Historical relevance: significant.
Current enforceability: none after expiration.
Current ANDA blocking effect: none from this patent.
Current Paragraph IV litigation risk: none based solely on this expired patent.
Current 30-month stay potential: none based solely on this expired patent.

A historical ANDA applicant could have addressed a listed patent through a Paragraph IV certification if the patent was listed and unexpired at the relevant time. After expiration, the patent cannot support a new patent-based stay or prevent an otherwise approvable ANDA from receiving approval.

Were Paragraph IV challenges likely for salmeterol?

A Paragraph IV certification would have been the relevant pathway for an ANDA applicant asserting that a listed salmeterol patent was invalid, unenforceable, or would not be infringed. For U.S. Patent 5,290,815, the commercial value of such a challenge depended on the timing of the ANDA filing and the remaining patent term.

The patent presented several potential challenge issues:

Whether the late-phase asthma indication was adequately supported.
Whether the claimed disease terminology was definite.
Whether the prior art disclosed salmeterol for the claimed therapeutic use.
Whether an ANDA label would induce the claimed use.
Whether the claims covered the proposed product's labeled indications.
Whether the patent remained enforceable when the generic was approved.

Once the patent expired in 2011, these issues ceased to create a forward-looking patent barrier. A current generic applicant would not need to win a Paragraph IV dispute against this patent to launch after approval.

What other patent rights could affect generic salmeterol?

The main patent risks for salmeterol historically fell into four groups.

Composition-of-matter patents

Earlier salmeterol patents could have protected the molecule or related beta-agonist compounds. Those rights generally expired before or around the period when Serevent faced generic competition.

A composition patent is stronger than the claims in U.S. 5,290,815 because it can cover the active ingredient regardless of indication. The supplied patent does not have that scope.

Method-of-use patents

U.S. 5,290,815 is an example of a method-of-use patent. Other use patents could address:

Asthma prophylaxis.
Exercise-induced bronchospasm.
Chronic obstructive pulmonary disease.
Combination treatment with inhaled corticosteroids.
Particular dosing schedules.
Patient subgroups.

A generic label that omits the patented indication may reduce inducement risk, but label design does not eliminate all potential exposure if the product is promoted or distributed for the patented use.

Formulation patents

Formulation patents can cover:

Salmeterol xinafoate particle engineering.
Dry-powder blends.
Lactose carrier systems.
Metered-dose aerosol formulations.
Stabilizers and excipients.
Dose uniformity and aerosol performance.

The supplied claims do not include these limitations. Any separate formulation patents would need to be analyzed independently.

Device and manufacturing patents

Serevent Diskus and related inhalation products may implicate device, packaging, manufacturing, and process rights. Those rights are distinct from U.S. 5,290,815. The patent at issue does not claim a Diskus device or a process for manufacturing salmeterol xinafoate.

Does biosimilar risk apply to salmeterol?

No. Salmeterol is a chemically synthesized small-molecule drug, not a biologic. The relevant competitor pathway is an ANDA for a generic drug under section 505(j) of the Federal Food, Drug, and Cosmetic Act, not a biosimilar application under the Biologics Price Competition and Innovation Act.[4]

The principal regulatory issues for a generic salmeterol inhalation product are bioequivalence, device performance, delivered dose, particle-size distribution, product characterization, and therapeutic equivalence. Biosimilar interchangeability standards do not apply.

Which companies have commercial exposure to this patent?

The historical rights holder and commercial sponsor associated with salmeterol was Glaxo Group Limited and its successor commercial organization, GlaxoSmithKline. The patent's commercial value was linked to Serevent and salmeterol xinafoate products.

The patent's current revenue exposure is zero as a blocking right because the patent expired in 2011. Any present commercial exposure relates to the broader salmeterol product franchise, brand value, regulatory approvals, manufacturing capability, device technology, or separate intellectual-property rights, not to enforceable rights under U.S. 5,290,815.

No patent-specific royalty or licensing stream can be assigned to this patent from the claims and public patent record alone.

How strong was the patent estate for salmeterol?

U.S. Patent 5,290,815 was commercially meaningful because it targeted a clinically important use of the marketed drug and covered the xinafoate salt used in Serevent. Its strength was limited by its legal category and by its finite term.

Strength factor	Assessment
Active ingredient coverage	Weak; no composition claim in the supplied claims
Indication coverage	Strong within late-phase asthma
Formulation coverage	None in the supplied claims
Device coverage	None
Manufacturing coverage	None
Label-based enforcement potential	Potentially meaningful before expiration
Geographic reach	United States only
Current enforceability	None
Generic launch significance today	None

The patent was more valuable as an indication and product-label protection tool than as a complete market-exclusivity right.

What generic launch scenarios existed?

Before expiration, a generic manufacturer could have pursued several strategies:

Paragraph IV challenge: Assert invalidity, unenforceability, or noninfringement.
Section viii carve-out: Omit the patented late-phase asthma use if the remaining labeling supported approval.
Post-expiration launch: Wait for the patent term to end.
Alternative formulation or device: Avoid separate formulation or device claims while still addressing any method-use exposure.
Narrow commercial labeling: Limit promotion to non-patented indications where legally and regulatorily permissible.

After March 1, 2011, the patent no longer required a design-around. Any remaining launch barriers would have arisen from other patents, FDA requirements, manufacturing capacity, device compatibility, or market economics.

Key Takeaways

U.S. Patent 5,290,815 claims treating late asthmatic reaction or late-phase asthma with salmeterol.
Claim 3 narrows the invention to salmeterol xinafoate.
The patent does not claim salmeterol itself, an inhaler, a formulation, or a manufacturing process.
Its ordinary U.S. term ended on March 1, 2011.
The patent has no current blocking effect against generic salmeterol.
Paragraph IV risk was historically relevant but is no longer a current barrier based on this patent.
Biosimilar analysis does not apply because salmeterol is a small-molecule drug.
Any current freedom-to-operate assessment must focus on separate composition, formulation, device, manufacturing, or method-of-use patents.

FAQs

Does U.S. Patent 5,290,815 cover salmeterol for COPD?

No express claim covers COPD. The supplied claims are directed to the late asthmatic reaction and late-phase asthma.

Does the patent cover salbutamol or formoterol?

No. The claims identify salmeterol by its chemical structure. They do not cover other beta-2 agonists.

Is salmeterol xinafoate still patent protected in the United States?

U.S. Patent 5,290,815 no longer protects salmeterol xinafoate because its term expired. Separate later patents would require independent analysis.

Could a generic manufacturer launch salmeterol without a Paragraph IV challenge to this patent?

Yes. Because the patent expired in 2011, it does not require a current Paragraph IV challenge for launch.

Is a salmeterol inhaler automatically infringing because it contains salmeterol xinafoate?

No. The patent claims a method of treatment, not the product alone. Infringement would require satisfaction of the method limitations, including treatment of the claimed late-phase asthma condition, or a legally sufficient inducement or contributory-infringement theory.

References

U.S. Food and Drug Administration. (2010). Serevent Diskus prescribing information: Salmeterol xinafoate inhalation powder.
U.S. Patent No. 5,290,815. (1994). Treatment of asthma. United States Patent and Trademark Office.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations.
Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 355(j); Biologics Price Competition and Innovation Act, 42 U.S.C. § 262(l).

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
United Kingdom	8920235	Sep 07, 1989
United Kingdom	9011940	May 29, 1990

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Canada	2024789	⤷ Start Trial
European Patent Office	0416925	⤷ Start Trial
European Patent Office	1078629	⤷ Start Trial
United Kingdom	8920235	⤷ Start Trial
United Kingdom	9011940	⤷ Start Trial
Japan	H03178929	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,290,815

Summary for Patent: 5,290,815