US Patent 10,898,494: Treprostinil Dry-Powder Inhaler Claims, Expiration, and Patent Landscape
US Patent 10,898,494 protects specific methods for treating pulmonary hypertension with inhaled dry-powder treprostinil. Its strongest commercial coverage is directed to high-dose administration over one to four inhalations, capsule-based delivery, molded particles containing treprostinil and excipients, and dosing schedules aligned with Tyvaso DPI. The patent was issued to United Therapeutics Corp. on January 26, 2021, and has a nominal expiration date in 2037, subject to any patent-term adjustment or disclaimer recorded by the USPTO.[1]
The patent is a method-of-use patent, not a broad composition-of-matter patent. It does not independently prevent all manufacture or sale of treprostinil. Its infringement value depends on whether a competing product uses the claimed dry-powder formulation, dose range, inhalation burden, capsule system, and pulmonary-hypertension treatment regimen.
What does US Patent 10,898,494 claim?
The independent claims cover three related treatment formats:
| Independent claim |
Core subject matter |
Principal limitations |
| Claim 1 |
Treatment method using inhaled dry powder |
100-300 micrograms treprostinil over one to four breaths |
| Claim 10 |
Capsule and inhaler treatment method |
At least 100 micrograms per capsule; inhalation in one to two breaths |
| Claim 12 |
Particle-based dose method |
100-300 micrograms over one to four breaths; defined excipient classes |
| Claim 13 |
Daily treatment regimen |
400-1,200 micrograms over four to 16 breaths per day |
The claims are cumulative. Claims 2-9 narrow claim 1. Claims 11 and 14-16 narrow claims 10 and 13. Claims 17-19 add a comparative tolerability limitation against a nebulized 54-microgram treprostinil dose.
The patent therefore covers both the product-use interface and the clinical dosing protocol. A competing product could avoid literal infringement by changing the dose per breath, requiring more inhalations, using a different formulation architecture, or labeling the product for a different treatment method. Those changes may not avoid infringement if the doctrine of equivalents applies.
What formulations are protected by US 10,898,494?
The formulation limitations are directed to molded or uniform dry particles containing treprostinil and a defined excipient system. Claim 4 identifies five functional excipient categories:
- A non-reducing sugar.
- A wetting agent.
- A hydrophobicity-modifying agent.
- A pH-modifying agent.
- A buffer.
Claim 5 provides a highly specific solids composition:
| Component |
Approximate percentage by solids |
| Treprostinil sodium |
0.581% |
| Trehalose |
92.32% |
| Polysorbate 80 |
2.19% |
| L-leucine |
4.39% |
| Sodium citrate |
0.26% |
| Sodium chloride |
0.25% |
This claim is narrower than the broader particle claims. It offers stronger product-identification value but a smaller infringement target. A competing manufacturer using treprostinil free acid, a different sugar, a different surfactant, or a different particle-engineering system may avoid claim 5 while remaining exposed under claims 1, 4, 10, or 12.
Why the excipient categories matter
The claims do not merely require treprostinil in a dry powder. They require a particle system designed to address powder flow, dispersibility, wetting, surface characteristics, pH, and buffering. L-leucine is commonly used to modify particle surface properties and improve aerosolization. Trehalose functions as a stabilizing and bulking excipient. Polysorbate 80 supports wetting and dispersion.
The functional categories create infringement questions. A generic or competing product may use an excipient that performs the same function without being described in the same technical category. Claim construction could determine whether an excipient must be expressly identified by formulation role or whether its objective function is sufficient.
How do the dose and inhalation limits operate?
The central commercial limitation is dose delivery in a low number of breaths.
| Claim |
Treprostinil dose |
Breath limitation |
| 1 |
100-300 micrograms |
One to four breaths |
| 2 |
More than 50 micrograms per breath |
Depends on claim 1 |
| 3 |
No more than approximately 30 mg dry powder per breath |
Depends on claim 1 |
| 8 |
100-300 micrograms per day |
Four breaths over a day |
| 9 |
100-600 micrograms per day |
Four to 16 breaths per day |
| 13 |
400-1,200 micrograms per day |
Four to 16 breaths |
| 14 |
Approximately 400 micrograms |
Eight breaths or fewer |
| 15 |
Approximately 800 micrograms |
Eight breaths or fewer |
| 16 |
Approximately 1,200 micrograms |
16 breaths or fewer |
Claims 13-16 are important because they extend beyond the 100-300 microgram single-dose range and capture daily dosing of approximately 400, 800, or 1,200 micrograms.
A product delivering 300 micrograms over five breaths would likely fall outside the literal scope of claim 1, assuming the five-breath administration is material. It could still fall within claim 9 or claim 13 if the daily dose and breath count satisfy those claims.
When does US Patent 10,898,494 expire?
The patent has a nominal 20-year term measured from the applicable nonprovisional priority framework, with a publicly reported expiration date in 2037.[1] The operative date should be determined from the USPTO Patent Center record, including any patent-term adjustment, terminal disclaimer, or other recorded term event.
| Milestone |
Date |
| Patent |
US 10,898,494 |
| Issue date |
January 26, 2021 |
| Applicant/patent holder |
United Therapeutics Corp. |
| Technology |
Inhaled dry-powder treprostinil |
| Nominal expiration |
2037 |
| Product most directly associated |
Tyvaso DPI |
The patent is not a basic treprostinil compound patent. Earlier treprostinil patents and regulatory exclusivities do not automatically determine the expiration of this patent. The relevant barrier for a dry-powder competitor is the surviving term of this patent and related continuation patents.
What is the Orange Book status of US 10,898,494?
US 10,898,494 is associated with Tyvaso DPI, the dry-powder inhaled formulation of treprostinil approved by FDA under NDA 214324.[2] Tyvaso DPI received FDA approval on May 23, 2022, for the treatment of pulmonary arterial hypertension and pulmonary hypertension associated with interstitial lung disease.[3]
The Orange Book listing is commercially important because it can support patent certification obligations for an abbreviated or hybrid application referencing the listed drug. A listed method-of-use patent may carry a use code that limits the statutory effect of a Paragraph IV challenge to the patented indication or dosing method.
Tyvaso DPI is not an ordinary small-molecule generic opportunity. A competing treprostinil inhalation product may require a 505(b)(2) application rather than a conventional ANDA if the dosage form, device, formulation, or clinical reliance differs materially from the reference product.
Are Paragraph IV challenges available against this patent?
Yes. A filer seeking approval for a competing treprostinil inhalation product could submit a Paragraph IV certification if the patent is listed in the Orange Book and the applicant asserts that the patent is invalid, unenforceable, or will not be infringed.
The principal challenge theories would likely include:
- Lack of written description for broad particle and dose combinations.
- Lack of enablement across the full 100-300 microgram and 400-1,200 microgram ranges.
- Obviousness based on known nebulized treprostinil dosing, dry-powder inhalation technology, and conventional excipient systems.
- Indefiniteness involving terms such as “about,” “uniform particles,” “fewer side effects,” and functional excipient categories.
- Non-infringement based on breath count, dose per capsule, particle composition, or labeling.
- Double-patenting issues involving continuation or divisional patents.
The strongest invalidity target is likely the combination of known treprostinil therapy with conventional dry-powder engineering. The patent holder’s counterargument would focus on the claimed high delivered dose in a low number of breaths, particle uniformity, capsule performance, and reduced side effects compared with nebulized treprostinil.
How vulnerable are the comparative side-effect claims?
Claims 17-19 require that the dry-powder composition induce fewer side effects than a nebulized 54-microgram dose. These claims may provide commercial protection, but they present proof and claim-construction issues.
A patent owner would need to establish:
- The identity and dose of the comparator nebulized product.
- The relevant side effects.
- The patient population.
- The measurement period.
- The statistical or clinical basis for the comparison.
- Whether “fewer side effects” means fewer events, lower severity, or lower incidence.
The phrase is potentially vulnerable to indefiniteness if the specification does not define the comparison protocol with sufficient precision. It may also create an infringement problem because a competing product’s label may not make an express comparative side-effect statement. Method-of-treatment infringement, however, can arise from the actual instructed use rather than only from promotional language, depending on the application and conduct.
How does this patent compare with other Tyvaso DPI protections?
Tyvaso DPI is protected by a layered estate rather than a single patent. The relevant categories include:
| Protection category |
Typical subject matter |
Commercial significance |
| Method-of-use patents |
Pulmonary-hypertension treatment and dose schedules |
Can delay labeled competitive use |
| Formulation patents |
Treprostinil particles and excipients |
Directly targets product composition |
| Device patents |
Dry-powder inhalers and capsule handling |
Can block substantially identical delivery systems |
| Manufacturing patents |
Particle formation, drying, and process controls |
Raises supply-chain substitution costs |
| Regulatory exclusivity |
FDA approval-based exclusivity |
Operates independently of patent validity |
US 10,898,494 is strongest where a competitor closely follows the Tyvaso DPI dosing pattern: approximately 100-300 micrograms delivered over one to four breaths, using capsules or particles with the claimed excipient architecture.
It is weaker against a product that uses a different device, a different formulation, a larger number of breaths, or a different dosing schedule. Related United Therapeutics patents must be analyzed separately because a product can avoid one patent and still infringe another.
Which companies are challenging the treprostinil inhalation franchise?
Liquidia Technologies is the principal publicly identified competitor in inhaled dry-powder treprostinil. Its Yutrepia program targets pulmonary arterial hypertension and pulmonary hypertension associated with interstitial lung disease using a dry-powder inhalation approach.[4]
The competitive question is not limited to whether Liquidia’s product contains treprostinil. The decisive issues include:
- Whether the product uses the same or equivalent particle composition.
- Whether the dose is delivered within the one-to-four-breath limitation.
- Whether its label instructs the same daily regimen.
- Whether its FDA application is an ANDA, 505(b)(2), or another pathway.
- Whether United Therapeutics asserts Orange Book patents in district court.
- Whether the parties reach a settlement defining an authorized launch date.
Public development of Yutrepia creates a meaningful litigation and settlement risk for the Tyvaso franchise. A regulatory approval does not eliminate patent exposure. A court may permit approval while restraining commercial launch until patent disputes are resolved, or the parties may agree to an earlier license date.
What generic launch risks exist?
A competing product has four principal launch scenarios.
Early launch after a successful challenge
The competitor prevails on invalidity or non-infringement and launches before the 2037 nominal expiration date. This scenario creates the greatest revenue risk for Tyvaso DPI.
Launch after litigation settlement
The parties agree to a licensed entry date. The settlement may include restrictions on formulation, labeling, manufacturing, or launch timing. Settlement terms may remain confidential, while the effective launch date becomes commercially visible.
Launch after patent expiration
The competitor waits until the relevant patents expire. This minimizes litigation exposure but sacrifices the commercial value of an early entry.
Carve-out launch
The competitor removes a patented indication or dosing instruction from its label. This strategy depends on whether the remaining non-patented use is commercially viable and whether actual marketing induces the patented use.
How strong is the patent estate for US 10,898,494?
The estate is commercially meaningful but technically narrow.
| Strength factor |
Assessment |
| Product specificity |
Strong against close copies of the Tyvaso DPI particle system |
| Dose coverage |
Strong for high-dose, low-breath administration |
| Broad composition coverage |
Moderate |
| Method-of-use coverage |
Moderate to strong |
| Obviousness exposure |
Material |
| Indefiniteness exposure |
Concentrated in “about,” “uniform,” and comparative side-effect language |
| Design-around potential |
Meaningful |
| Regulatory leverage |
High if listed in the Orange Book |
| Biosimilar relevance |
None |
The claims are more difficult to design around when combined with other United Therapeutics patents covering the inhaler, capsule, manufacturing process, or formulation. The principal commercial value therefore lies in the patent family as a portfolio, not in claim 1 alone.
Does biosimilar risk apply to treprostinil?
No. Treprostinil is a chemically synthesized small molecule, not a biologic. A competing product would generally pursue a generic or 505(b)(2) pathway rather than a biosimilar pathway under the Public Health Service Act.
The absence of biosimilar substitution rules does not eliminate competitive risk. It shifts the dispute to patent certifications, device equivalence, formulation comparison, clinical bridging, and labeling.
What is the likely revenue exposure?
Tyvaso is one of United Therapeutics’ core commercial products. The company reported Tyvaso franchise revenue of approximately $1.6 billion in 2023, with growth driven by Tyvaso DPI and the broader treprostinil inhalation franchise.[5] Revenue exposure to US competition depends on whether a challenger can offer:
- Comparable dose delivery in fewer breaths.
- Equivalent convenience to Tyvaso DPI.
- Coverage for both pulmonary arterial hypertension and interstitial lung disease-associated pulmonary hypertension.
- Payer access and specialty-pharmacy distribution.
- A device with acceptable patient handling.
- A launch date before 2037.
The economic risk is higher for a close dry-powder substitute than for a conventional nebulized treprostinil product because the dry-powder format directly targets the convenience advantage of Tyvaso DPI.
Key Takeaways
- US 10,898,494 is a United Therapeutics method-of-use patent covering inhaled dry-powder treprostinil for pulmonary hypertension.
- The core protected concept is 100-300 micrograms delivered over one to four breaths.
- Claims 10-12 add capsule use and a defined particle excipient system.
- Claims 13-16 cover daily doses of approximately 400-1,200 micrograms.
- Claim 5 identifies a specific treprostinil sodium, trehalose, polysorbate 80, L-leucine, citrate, and sodium chloride formulation.
- The patent is associated with Tyvaso DPI and has a nominal expiration date in 2037.
- Paragraph IV or 505(b)(2) challenges would likely focus on obviousness, enablement, written description, indefiniteness, and non-infringement.
- Liquidia’s Yutrepia is the main visible competitive threat in dry-powder treprostinil.
- Biosimilar law is not relevant because treprostinil is a small molecule.
- The patent is strongest against a close Tyvaso DPI copy and weaker against materially different dose, breath-count, particle, capsule, or device designs.
FAQs
What drug is protected by US Patent 10,898,494?
The patent protects treatment methods using inhaled dry-powder treprostinil or a pharmaceutically acceptable salt, including treprostinil sodium.
Is US 10,898,494 a composition-of-matter patent?
No. It is principally a method-of-treatment patent with formulation, particle, capsule, and dosing limitations.
Can a competitor avoid US 10,898,494 by using a nebulizer?
A nebulized product may avoid the dry-powder and inhalation limitations, but it may face other treprostinil patents and regulatory requirements.
Does claim 5 cover every treprostinil dry-powder formulation?
No. Claim 5 is limited to an approximate solids composition containing the listed ingredients and percentages. Broader claims may still apply to alternative formulations.
What is the difference between Tyvaso and Tyvaso DPI for patent analysis?
Tyvaso is a nebulized treprostinil product, while Tyvaso DPI uses a dry-powder inhaler. US 10,898,494 is primarily directed to the dry-powder dosing and particle technology associated with Tyvaso DPI.
References
- United States Patent and Trademark Office. (2021). US Patent No. 10,898,494, methods of treating pulmonary hypertension.
- U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book.
- U.S. Food and Drug Administration. (2022, May 23). FDA approves new inhaled treatment for pulmonary hypertension.
- Liquidia Technologies, Inc. (2024). Yutrepia clinical and regulatory development materials.
- United Therapeutics Corporation. (2024). 2023 annual report.
