United States Drug Patent 6,040,344: Claim Scope, Expiration, and Formoterol Tartrate Patent Landscape

U.S. Patent No. 6,040,344 covers crystalline R,R-formoterol L-(+)-tartrate, specified polymorphs, and pharmaceutical compositions containing that salt. The patent is distinct from the patents and Orange Book listings associated with marketed formoterol fumarate products. Its U.S. patent term has expired, eliminating current U.S. patent exclusivity under the patent.

The patent’s commercial relevance is concentrated in four areas: the protected salt form, polymorph control, lactose-reduced or lactose-free formulations, and dry-powder inhalation compositions.

What does U.S. Patent 6,040,344 cover?

U.S. Patent 6,040,344 covers a specific enantiomeric salt of formoterol: R,R-formoterol combined with L-(+)-tartaric acid. The claims do not broadly cover every formoterol salt, every formoterol stereoisomer, or every inhaled formoterol product.

The core coverage is:

Claim category	Claims	Subject matter
Chemical substance	1-4	Crystalline R,R-formoterol L-(+)-tartrate and defined solid or polymorphic forms
Pharmaceutical composition	5-6	Compositions containing the salt, including substantially lactose-free compositions
Aerosol formulation	7	Aerosol pharmaceutical composition containing the salt
Oral formulation	8-9	Oral compositions, including tablets, capsules, or syrups
Dry-powder inhalation	10	R,R-formoterol L-(+)-tartrate with a dry solid carrier having a mean particle size of 1 to 100 micrometers

The claims are product claims and composition claims. They do not expressly claim a method of treating asthma or chronic obstructive pulmonary disease, a manufacturing process, a device, or a specific dosage regimen.

What are the independent claims in Patent 6,040,344?

Claims 1 and 5 are the principal independent claims based on the claim set provided.

Claim 1: crystalline R,R-formoterol L-(+)-tartrate

Claim 1 covers the crystalline salt itself. A product would generally fall within the claim if it contains:

The R,R stereoisomer of formoterol;
L-(+)-tartrate as the counterion; and
A crystalline solid form.

The claim does not appear to require a particular melting point, polymorph, particle size, dosage form, or therapeutic use. Claims 2 through 4 narrow the subject matter by adding physical-property limitations.

The stereochemical limitation is important. A racemic formoterol salt, an S,S-formoterol salt, or a different salt such as formoterol fumarate would not satisfy claim 1 merely because the product has similar bronchodilator activity.

Claim 5: pharmaceutical composition

Claim 5 covers a pharmaceutical composition containing R,R-formoterol L-(+)-tartrate and a pharmaceutically acceptable carrier. The carrier limitation is broad and can encompass excipients used in oral, inhaled, aerosol, or other pharmaceutical preparations.

Claims 7 through 10 narrow claim 5 by specifying administration route, dosage form, or carrier particle size.

How do claims 2 through 4 protect formoterol polymorphs?

Claims 2 through 4 use physical properties to define solid forms.

Claim	Physical limitation	Practical scope
2	Solid R,R-formoterol L-(+)-tartrate with melting point greater than 179°C	Covers solids meeting the temperature threshold, subject to the underlying salt and solid-form limitations
3	Polymorph with DSC transition point of about 193°C and water solubility of about 15 mg/mL at 25°C	Targets a higher-transition, lower-solubility form
4	Polymorph with DSC transition point of about 180°C and water solubility greater than 25 mg/mL at 25°C	Targets a lower-transition, higher-solubility form

Melting-point and DSC limitations

Claim 2 uses a melting-point threshold. Claims 3 and 4 use differential scanning calorimetry, or DSC, transition points. These limitations may require analytical testing rather than reliance on a product label or ordinary chemical identity.

The phrase “about” introduces an issue of claim interpretation. Courts typically evaluate the term in the context of the specification, experimental methods, measurement variability, and the knowledge of a person skilled in the art. The relevant DSC instrument, heating rate, sample preparation, and hydration state can affect the reported transition point.

Solubility limitations

Claims 3 and 4 also require solubility values at 25°C:

Claim 3: about 15 mg/mL.
Claim 4: greater than 25 mg/mL.

Solubility depends on pH, buffer composition, ionic strength, equilibration time, particle size, solid-state history, and whether the measurement is performed on an anhydrous or hydrated form. A product challenge would therefore likely focus on the patent’s testing protocol and whether the accused material has the claimed physical characteristics under the proper analytical conditions.

Product-by-property claim risks

Claims 3 and 4 are product claims expressed partly through properties. A chemically different polymorph may avoid the claims if it does not have the claimed transition and solubility characteristics. Conversely, a manufacturer may infringe even if its internal manufacturing process is different if the resulting product has the claimed characteristics.

What formulations are protected by Patent 6,040,344?

The formulation claims extend beyond the isolated crystalline salt.

Lactose-free or substantially lactose-free formulations

Claim 6 covers a pharmaceutical composition under claim 5 in which the carrier is substantially lactose-free. The claim could be relevant to inhaled products using alternative carriers or excipient systems, including formulations designed to avoid lactose intolerance, lactose-related stability issues, or compatibility problems.

“Substantially lactose-free” is a quantitative and construction-sensitive limitation. The patent specification and prosecution history would control the permissible lactose level. A formulation containing trace lactose may not automatically fall outside the claim.

Aerosol compositions

Claim 7 covers an aerosol pharmaceutical composition containing the salt. The claim does not, based on the supplied language, require a specific propellant, valve, canister, metering system, particle-size distribution, or nominal dose.

Potentially relevant delivery systems include:

Pressurized metered-dose inhalers;
Solution aerosols;
Suspension aerosols; and
Other aerosolized preparations containing the claimed salt.

The presence of a different inhaler device would not necessarily avoid the claim if the pharmaceutical composition itself contains the claimed salt.

Oral compositions

Claims 8 and 9 cover oral formulations. Claim 9 specifically identifies tablets, capsules, and syrups. These claims are broader than the inhalation claim in route coverage but remain limited to the R,R-formoterol L-(+)-tartrate salt.

Dry-powder inhalation

Claim 10 requires:

R,R-formoterol L-(+)-tartrate;
A dry, solid carrier; and
A carrier mean particle size between 1 and 100 micrometers.

The claim is directed to carrier-based dry-powder inhalation formulations. The particle-size limitation creates a measurable technical boundary. A dry-powder product using a different carrier, a carrier outside the claimed mean particle-size range, or no dry solid carrier may require separate infringement analysis.

Does Patent 6,040,344 cover formoterol fumarate?

No. The patent claims the L-(+)-tartrate salt of R,R-formoterol. Marketed formoterol products in the United States generally use formoterol fumarate, commonly formoterol fumarate dihydrate, rather than formoterol L-(+)-tartrate.

The distinction is material:

Feature	Patent 6,040,344	Marketed U.S. formoterol products
Active stereoisomer	R,R-formoterol	R,R-formoterol component
Counterion	L-(+)-tartrate	Fumarate, commonly fumarate dihydrate
Solid-form focus	Tartrate crystal and polymorphs	Fumarate solid forms and formulations
Patent relevance	Directly relevant to tartrate products	Generally not directly applicable to fumarate products
Orange Book connection	No identified listing for this patent	Orange Book patents concern approved fumarate products and combinations

A product containing formoterol fumarate would not infringe merely because it contains the same pharmacologically active R,R-formoterol moiety.

When did U.S. Patent 6,040,344 expire?

U.S. Patent 6,040,344 has expired. The patent was issued on March 21, 2000. Its U.S. application was filed in 1998, and the ordinary patent term is generally 20 years from the earliest effective nonprovisional U.S. filing date under 35 U.S.C. § 154.

The ordinary U.S. term therefore ended in 2018, subject to any applicable patent-term adjustment or terminal disclaimer. Public patent records identify the patent as expired, and it does not provide current enforceable U.S. patent exclusivity. [1][2]

Event	Date or status
U.S. patent grant	March 21, 2000
Patent term framework	20 years from applicable U.S. filing date
Expected ordinary expiration	2018
Current status	Expired
Current blocking patent right	None under Patent 6,040,344

The expiration of this patent does not eliminate other patents that may have covered formoterol products, inhaler devices, combination products, manufacturing processes, or later-developed solid forms.

What is the Orange Book status of Patent 6,040,344?

Patent 6,040,344 is not identified as a current Orange Book patent for the principal FDA-approved formoterol products. The Orange Book listings for products such as Foradil Aerolizer, Perforomist, Symbicort, Dulera, Bevespi Aerosphere, and Breztri Aerosphere relate to approved products containing formoterol fumarate, often in combination with another active ingredient.

The Orange Book does not operate as a complete database of every patent that has ever related to a compound. A patent must meet FDA listing requirements and be relevant to the approved drug substance, drug product, or method of use. A patent directed to an unmarketed alternative salt may not be listed for a fumarate-based product. [3]

FDA regulatory relevance

The tartrate salt covered by Patent 6,040,344 is not the active salt used in the principal approved U.S. formoterol inhalers identified above. The patent therefore has limited direct importance to abbreviated new drug applications referencing currently approved formoterol fumarate products.

A sponsor seeking approval of a tartrate product would need to address the applicable FDA pathway, including drug substance characterization, dosage-form performance, safety, efficacy, and bioequivalence or clinical requirements. Patent expiration would remove the patent barrier but would not create FDA approval or establish substitutability.

Which companies are challenging Patent 6,040,344?

No material current Paragraph IV challenge to Patent 6,040,344 is identified. The principal reason is that the patent has expired. Paragraph IV litigation is ordinarily associated with an unexpired Orange Book-listed patent cited against an ANDA product.

The patent also does not appear to be the central U.S. patent in the generic disputes involving formoterol fumarate products. Those disputes have generally concerned product-specific patents, combination inhalers, inhaler devices, or other listed patents rather than the expired tartrate patent.

What patent landscape surrounds formoterol?

The relevant formoterol patent landscape is divided into several layers.

Formoterol compound and stereochemistry

Earlier patents and applications addressed formoterol itself, stereoisomer selection, preparation, and therapeutic use. These rights are generally expired or near historical expiration because formoterol was developed decades ago.

Salt and polymorph patents

Patent 6,040,344 occupies the salt and solid-state layer for R,R-formoterol L-(+)-tartrate. Other formoterol patent families may concern fumarate, hydrates, solvates, particle engineering, or alternative crystal forms.

Inhalation formulation patents

Later rights may cover:

Dry-powder carrier systems;
Metered-dose aerosol formulations;
Suspension or solution formulations;
Particle-size distributions;
Dose uniformity;
Moisture protection; and
Device-formulation combinations.

These patents may remain relevant even after an active-ingredient patent expires.

Combination-product patents

Current commercial risk is more likely to arise from patents covering combinations such as:

Budesonide/formoterol;
Mometasone/formoterol; and
Long-acting muscarinic antagonist/formoterol products.

These patents protect the combination, formulation, device, or method of use rather than the tartrate salt claimed in Patent 6,040,344.

Biologic and biosimilar risk

There is no biosimilar pathway issue for formoterol. Formoterol is a small-molecule active ingredient. Regulatory competition proceeds through generic-drug pathways, including ANDAs, rather than the biosimilar pathway under the Public Health Service Act.

How strong is the patent estate for R,R-formoterol L-(+)-tartrate?

As an enforceable U.S. estate, Patent 6,040,344 is no longer strong because it has expired. Historically, its strongest claims were claims 1, 3, and 4:

Claim 1 established direct protection for the crystalline salt.
Claims 3 and 4 targeted specific polymorphs through DSC and solubility properties.
Claim 10 addressed a commercially relevant dry-powder inhalation format.

The formulation claims were broader in dosage-form coverage but depended on use of the claimed tartrate salt. They would not ordinarily reach a fumarate-based formulation.

The estate’s principal historical vulnerabilities would have included:

Whether the claimed salt and polymorphs were novel and nonobvious over known formoterol salts;
Whether the DSC and solubility parameters adequately distinguished the claimed forms;
Whether “about” and “substantially lactose-free” provided definite boundaries;
Whether an accused product actually contained the L-(+)-tartrate salt; and
Whether the claimed physical properties were reproducible under the patent’s test methods.

What generic entry risks exist after expiration?

A generic or other sponsor can generally enter the U.S. market without infringing Patent 6,040,344 because the patent has expired. The remaining risks are regulatory, technical, and commercial rather than based on this patent.

Risk area	Relevance after expiration
Tartrate salt patent	No current exclusion under Patent 6,040,344
Fumarate product patents	May remain relevant depending on product and filing date
Combination patents	Relevant for combination inhalers
Device patents	Relevant where the product uses a patented inhaler
FDA exclusivity	Must be assessed separately from patent expiration
Formulation patents	May affect dry powder, aerosol, or carrier systems
Trade secrets	May affect manufacturing but are not visible in the patent record
Market access	Depends on FDA approval, labeling, pricing, and supply

A generic tartrate product would not automatically be therapeutically substitutable for an approved fumarate product. Salt selection can affect dose expression, stability, dissolution, inhalation performance, and regulatory comparability.

Are there licensing deals or settlements tied to Patent 6,040,344?

No material publicly identified licensing deal or settlement is associated specifically with U.S. Patent 6,040,344. The patent’s age, expiration, and limited connection to current FDA-approved fumarate products reduce its present licensing value.

Licensing and settlement activity in the broader formoterol market is more likely to concern:

Approved combination products;
Inhaler devices;
Formoterol fumarate formulations;
ANDA launches; and
Product-specific Orange Book patents.

Key Takeaways

U.S. Patent 6,040,344 covers crystalline R,R-formoterol L-(+)-tartrate.
Claims 3 and 4 target two polymorphs using DSC transition points and aqueous solubility.
Claims 5 through 10 cover pharmaceutical compositions, lactose-reduced formulations, aerosols, oral products, and dry-powder inhalation products.
The patent does not broadly cover formoterol fumarate, the salt used in major approved U.S. formoterol products.
The patent expired in 2018 under the ordinary U.S. patent-term framework.
It is not a current Orange Book barrier for approved formoterol fumarate products.
No current material Paragraph IV challenge or settlement involving this expired patent is identified.
Formoterol competition is now driven mainly by fumarate product patents, combination-product patents, device rights, formulation rights, FDA requirements, and commercial execution.
No biosimilar pathway applies because formoterol is a small-molecule drug.

FAQs

Can a company sell R,R-formoterol L-(+)-tartrate in the United States after Patent 6,040,344 expired?

Yes, patent expiration removes the exclusionary rights under this patent. FDA approval, product quality, labeling, and any other unexpired patent rights remain separate requirements.

Does a formoterol tartrate product infringe patents for Foradil or Perforomist?

Not automatically. Foradil and Perforomist contain formoterol fumarate. Infringement depends on the specific claims of the other patents, not merely on the shared R,R-formoterol active moiety.

Does claim 10 cover every dry-powder formoterol inhaler?

No. Claim 10 requires R,R-formoterol L-(+)-tartrate and a dry solid carrier with a mean particle size from 1 to 100 micrometers. A fumarate product or a formulation outside those limitations would not satisfy the claim as written.

Is R,R-formoterol L-(+)-tartrate interchangeable with formoterol fumarate?

Not automatically. The two salts can differ in physicochemical properties, dose calculations, stability, dissolution, manufacturing behavior, and regulatory comparability.

Could a later patent still block a formoterol tartrate product?

Yes. Patent 6,040,344 is expired, but later patents could potentially cover a specific formulation, inhaler device, manufacturing process, combination, dosage regimen, or later-developed solid form.

References

United States Patent and Trademark Office. (2000). U.S. Patent No. 6,040,344, crystalline R,R-formoterol L-(+)-tartrate.
United States Code. (2023). 35 U.S.C. § 154: Contents and term of patent; provisional rights.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	219047	⤷ Start Trial
Austria	259779	⤷ Start Trial
Australia	2705900	⤷ Start Trial
Australia	5175598	⤷ Start Trial
Australia	722859	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Summary for Patent: 6,040,344