United States Drug Patent 5,508,269: Scope, Claims, Expiration, and Patent Landscape

U.S. Patent No. 5,508,269 covers an aerosolized aminoglycoside formulation, particularly 300 mg of tobramycin in 5 mL of 0.225% sodium chloride at approximately pH 6.0, delivered through a jet or ultrasonic nebulizer producing predominantly 1-5 micron particles. The patent is associated with TOBI, or tobramycin inhalation solution. It expired on December 21, 2013, and does not create current U.S. exclusivity for generic tobramycin inhalation solution.[1,2]

The claims combine four technical limitations: drug quantity, diluent concentration, pH, and pulmonary delivery parameters. The independent claims also include either a therapeutic outcome or a treatment method directed to endobronchial infection, especially infection caused by Pseudomonas aeruginosa.

What does U.S. Patent 5,508,269 cover?

The patent covers aerosol delivery of an aminoglycoside into the endobronchial space using a narrowly defined formulation and nebulizer performance profile.

Claim element	Scope
Active ingredient	Aminoglycoside in claims 1 and 13; tobramycin in claims 5 and 9
Dose	About 200-400 mg for the broad aminoglycoside claims; about 300 mg for the tobramycin claims
Fill volume	About 5 mL
Diluent	0.225% sodium chloride
pH	About 5.5-6.5; dependent claims specify approximately 6.0
Delivery route	Aerosolization into the endobronchial space
Nebulizer	Jet or ultrasonic nebulizer
Particle size	Predominantly 1-5 microns
Infection	Endobronchial infection, with specific claims directed to P. aeruginosa
Functional limitation	Suppression or inhibition of at least 95% of susceptible bacteria

The patent is narrower than a general patent on inhaled tobramycin. A product or treatment would need to satisfy the claimed formulation and delivery limitations, not merely contain tobramycin and use inhalation.

How many independent claims does Patent 5,508,269 have?

The patent has four independent claims: claims 1, 5, 9, and 13.

Claims 1 and 5 are formulation or aerosol claims. Claims 9 and 13 are method-of-treatment claims.

Claim 1: broad aminoglycoside aerosol

Claim 1 covers an aerosol formulation containing approximately 200-400 mg of an aminoglycoside in approximately 5 mL of 0.225% sodium chloride. The formulation must have a pH between approximately 5.5 and 6.5 and be administered with a jet or ultrasonic nebulizer producing predominantly 1-5 micron particles.

The claim also requires suppression or inhibition of at least 95% of susceptible bacteria in the endobronchial space. That language narrows the claim to a formulation and delivery system capable of producing the specified biological result.

The claim is not limited to tobramycin. It potentially reaches other aminoglycosides if the formulation, delivery system, infection setting, and functional result are satisfied.

Claim 5: tobramycin formulation

Claim 5 is the principal species claim. It requires:

Approximately 300 mg of tobramycin;
Approximately 5 mL of solution;
0.225% sodium chloride;
pH between approximately 5.5 and 6.5;
A jet or ultrasonic nebulizer;
Predominantly 1-5 micron aerosol particles; and
Suppression or inhibition of at least 95% of P. aeruginosa bacteria in the endobronchial space.

This claim tracks the commercial formulation of tobramycin inhalation solution marketed as TOBI. The FDA-approved TOBI presentation contains 300 mg of tobramycin in a 5 mL single-use ampule and is administered twice daily through a PARI LC PLUS reusable nebulizer.[2]

Claim 9: tobramycin treatment method

Claim 9 covers treating a patient with a P. aeruginosa endobronchial infection using the same 300 mg/5 mL tobramycin formulation and aerosol parameters.

Unlike claim 5, claim 9 is directed to conduct: providing the formulation to a patient in need of treatment. In an infringement analysis, the relevant conduct would include the formulation used, the nebulizer, particle-size distribution, treatment indication, and administration method.

Claim 13: broad aminoglycoside treatment method

Claim 13 extends the method category to approximately 200-400 mg of an aminoglycoside in the claimed saline formulation. It is broader as to active ingredient than claim 9 but remains tied to P. aeruginosa endobronchial infection and the specified aerosol delivery conditions.

What do the dependent claims add?

Claims 2-4, 6-8, and 10-12 narrow the independent claims by specifying pH or nebulizer type.

Dependent claims	Added limitation
2	pH approximately 6.0
3	Jet nebulizer
4	Ultrasonic nebulizer
6	pH approximately 6.0
7	Jet nebulizer
8	Ultrasonic nebulizer
10	pH approximately 6.0
11	Jet nebulizer
12	Ultrasonic nebulizer
14	pH approximately 6.0
15	Jet nebulizer
16	Ultrasonic nebulizer

The dependent claims do not add a new active ingredient or a different disease. They create narrower combinations that may be relevant if a broader independent claim is challenged.

What formulation is protected by Patent 5,508,269?

The core formulation is a low-volume, preservative-free or substantially simple saline solution containing 300 mg of tobramycin in 5 mL of 0.225% sodium chloride, with a pH near 6.0.

The formulation is materially different from a generic inhaled solution containing tobramycin at a different concentration, a different saline concentration, a materially different pH, or a different fill volume, although infringement would depend on claim construction and equivalents analysis.

The patent does not claim every tobramycin inhalation formulation. It claims a specific combination of:

Tobramycin quantity;
Fill volume;
Sodium chloride concentration;
pH;
Nebulizer class; and
Aerosol particle-size range.

The 1-5 micron particle requirement is important because it links the formulation to deposition in the lower respiratory tract and endobronchial region. A formulation with the same drug and dose but a delivery system producing a materially different particle distribution may fall outside the literal claim scope.

What is the scope of the 95% bacterial suppression limitation?

The 95% language is a functional limitation. It does not simply identify tobramycin as an antibacterial agent. It requires the claimed formulation and administration system to suppress or inhibit at least 95% of susceptible bacteria in the endobronchial space.

For claim interpretation, the key issues would include:

What constitutes a “susceptible” bacterium;
Whether the 95% result must be demonstrated clinically or may be established through laboratory or pharmacologic data;
Whether the result is measured after one administration or a treatment course;
What bacterial burden and sampling method apply; and
Whether “inhibition” includes bacteriostatic effects or requires bactericidal activity.

The claim language also contains drafting irregularities, including “about 400” without an explicit unit in the supplied text and inconsistent capitalization of “pH.” Those errors do not automatically invalidate the claims. The specification, prosecution history, and ordinary technical meaning would control construction.

When did U.S. Patent 5,508,269 expire?

Patent term

U.S. Patent 5,508,269 expired on December 21, 2013, based on its earliest effective U.S. filing date. The patent therefore cannot presently block commercial manufacture, sale, or use of a product that practices its claims.[1]

Event	Date
Earliest effective U.S. filing date	December 21, 1993
Patent issued	April 16, 1996
Patent expiration	December 21, 2013
Current status	Expired

The expiration date is separate from FDA regulatory exclusivity. A drug may lose patent protection before or after regulatory exclusivity ends, but neither type of exclusivity remains available under this patent.

What was the Orange Book status of Patent 5,508,269?

Patent 5,508,269 was listed in FDA patent information associated with TOBI, tobramycin inhalation solution, 300 mg/5 mL. The Orange Book identifies patents submitted by NDA sponsors for approved drug products and records patent term information and expiration data.[3]

The patent’s listing was commercially significant while it remained unexpired because an ANDA applicant seeking approval for a therapeutically equivalent tobramycin inhalation solution could have been required to address the patent through a Paragraph IV certification or wait for expiration.

After December 21, 2013, the patent ceased to provide an operative patent barrier. Any historical Orange Book listing does not restore enforceability after expiration.

Did Patent 5,508,269 create Paragraph IV risk for generic tobramycin?

Yes. Before expiration, a generic applicant seeking approval for a product referencing TOBI could have faced Paragraph IV certification risk if the ANDA product was alleged to infringe the patent or if the applicant asserted that the patent was invalid or unenforceable.

A Paragraph IV certification states that a listed patent is invalid, unenforceable, or will not be infringed by the proposed generic product. The filing can trigger patent litigation under the Hatch-Waxman Act and, if the NDA holder sues within the statutory period, an automatic FDA approval stay of up to 30 months.[4]

The practical risk ended when the patent expired. Current generic entrants do not need to defeat an expired patent, although they must still satisfy FDA requirements for pharmaceutical equivalence, bioequivalence, device compatibility, labeling, and manufacturing quality.

Which companies challenged or competed with TOBI?

The relevant competitive field included branded tobramycin inhalation products, generic tobramycin inhalation solution, and dry-powder inhalation products.

Company or product	Technology	Relationship to Patent 5,508,269
PathoGenesis, later Novartis	TOBI inhalation solution	Original commercial product associated with the patent
Teva Pharmaceuticals	Generic tobramycin inhalation solution	Competes after patent and regulatory barriers declined
Novartis	TOBI Podhaler	Dry-powder inhalation product with a separate device and formulation estate
PARI	LC PLUS nebulizer	Delivery device used with TOBI labeling
Other inhaled anti-infective developers	Nebulized or dry-powder products	Compete through alternative formulations, devices, or active ingredients

TOBI Podhaler is not simply a reformulation of the 5,508,269 product. It uses inhaled dry powder and a proprietary inhaler platform, creating different technical and patent questions from those applicable to a 300 mg/5 mL nebulized solution.

How does the patent compare with later tobramycin patents?

Patent 5,508,269 is an early foundational patent focused on the combination of tobramycin dose, saline vehicle, pH, nebulization, and particle size. Later patents in the TOBI and TOBI Podhaler portfolios generally addressed narrower improvements or alternative product architectures, including:

Dry-powder formulations;
Inhaler devices;
Powder engineering;
Dose delivery;
Treatment schedules;
Pharmacokinetic exposure;
Manufacturing processes; and
Device-formulation combinations.

Later patents could have extended commercial exclusivity for particular products even after the 5,508,269 patent expired. They did not extend the term of Patent 5,508,269 itself.

How strong was the patent estate?

Technical strength

The patent had strong product coverage for a formulation closely matching the commercial TOBI nebulized solution. The combination of 300 mg tobramycin, 5 mL, 0.225% sodium chloride, pH near 6.0, and 1-5 micron aerosol delivery was commercially specific.

Claim breadth

The broad aminoglycoside claims had greater potential breadth but also greater vulnerability to prior-art and enablement challenges. Claims limited to tobramycin were narrower and more closely aligned with the marketed product.

Validity pressure points

Potential legal pressure points included:

Prior art on aerosolized aminoglycosides;
Earlier nebulized antibiotic formulations;
Obviousness of selecting tobramycin, saline concentration, pH, and particle size;
Definiteness of the 95% suppression limitation;
Meaning of “predominantly” 1-5 micron particles;
Enablement across the full 200-400 mg aminoglycoside range; and
Whether the claims adequately describe all aminoglycosides within the broad genus.

The patent’s commercial value came from its product fit and timing, rather than from unrestricted coverage of inhaled antibiotics.

What generic launch scenarios existed?

Before expiration, a generic manufacturer had three principal pathways:

Wait-and-launch: Enter after patent expiration and any applicable regulatory exclusivity.
Paragraph IV launch: Challenge validity, enforceability, or infringement and risk litigation.
Design-around: Use a materially different formulation, concentration, pH, delivery device, or particle-size profile.

After expiration, the first pathway became available without needing to overcome this patent. A current generic launch still faces FDA approval requirements and potential infringement exposure from separate, unexpired patents covering devices, formulations, manufacturing methods, or dosing regimens.

What geographic coverage did the patent have?

U.S. Patent 5,508,269 provided rights only in the United States. Parallel patent families could have existed in Europe, Canada, Japan, and other jurisdictions, but foreign members had separate filing dates, prosecution histories, claim scope, and expiration dates.

Expiration in the United States did not automatically terminate foreign rights. Conversely, a foreign patent expiration did not affect U.S. freedom to operate.

What manufacturing and intellectual-property barriers remain?

The expired patent no longer blocks manufacture of the claimed product. Current barriers may remain in:

Sterile inhalation-solution manufacturing;
Low-volume aseptic filling;
Control of pH and osmolality;
Stability and impurity control;
Nebulizer compatibility;
Aerosol particle-size characterization;
Device supply and qualification;
FDA ANDA requirements; and
Separate patents covering inhalers, dry-powder formulations, processes, or dosing regimens.

The most material post-expiration barrier is therefore regulatory and operational rather than Patent 5,508,269 itself.

What is the current commercial exposure?

The patent’s direct revenue exposure was concentrated in TOBI inhalation solution during the period before expiration. Once generic competition became possible, price erosion and substitution reduced the value of the original nebulized-solution franchise.

The remaining branded value shifted toward differentiated products such as dry-powder inhalers, device combinations, convenience, adherence, and other protected product attributes. Patent 5,508,269 no longer supports a royalty claim or exclusivity premium in the United States.

Key Takeaways

U.S. Patent 5,508,269 covers aerosolized aminoglycoside therapy for endobronchial infection.
Its core commercial embodiment is 300 mg of tobramycin in 5 mL of 0.225% sodium chloride at approximately pH 6.0.
The claims require jet or ultrasonic nebulization and predominantly 1-5 micron aerosol particles.
Claims 5 and 9 are the principal tobramycin formulation and treatment claims.
Claims 1 and 13 are broader as to aminoglycoside identity but remain limited by dose, saline, pH, aerosol, infection, and functional-result requirements.
The patent expired on December 21, 2013.
It no longer creates U.S. patent exclusivity or a current Paragraph IV barrier.
Separate patents may have protected later dry-powder products, devices, manufacturing processes, or dosing methods.
Current market entry risk is primarily regulatory, manufacturing, device-related, and dependent on unexpired patents outside this patent.

FAQs

Is Patent 5,508,269 still enforceable against a tobramycin inhalation solution?

No. The patent expired on December 21, 2013.

Does Patent 5,508,269 cover all inhaled aminoglycosides?

No. Claims 1 and 13 use broader aminoglycoside language, but they also require specific dose, saline, pH, aerosol particle, nebulizer, infection, and functional-result limitations.

Does a tobramycin nebulizer product infringe if it uses a different saline concentration?

It may avoid literal infringement of the listed claims if the saline concentration is materially different, but the complete formulation and delivery system must be analyzed, including potential equivalents.

Does the patent cover the PARI LC PLUS nebulizer itself?

No. The patent claims aerosol administration using a jet or ultrasonic nebulizer with the required particle-size profile. It does not, based on the supplied claims, claim ownership of the PARI LC PLUS device as a standalone product.

Can a generic manufacturer rely on expiration of this patent alone?

No. Expiration removes this patent barrier, but a generic applicant must still satisfy FDA approval requirements and assess other unexpired patents covering the referenced product, delivery device, manufacturing process, formulation, or treatment regimen.

References

United States Patent and Trademark Office. (1996). Aerosol formulation of aminoglycosides, U.S. Patent No. 5,508,269.
U.S. Food and Drug Administration. (2023). TOBI (tobramycin inhalation solution) prescribing information. Novartis Pharmaceuticals Corporation.
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: The Orange Book.
U.S. Food and Drug Administration. (2024). Hatch-Waxman amendments and abbreviated new drug applications.

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Austria	183080	⤷ Start Trial
Australia	3952295	⤷ Start Trial
Australia	688166	⤷ Start Trial
Canada	2179305	⤷ Start Trial
Germany	69511374	⤷ Start Trial
Denmark	0734249	⤷ Start Trial
European Patent Office	0734249	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 5,508,269

Summary for Patent: 5,508,269