United States Patent 9,050,311: Treprostinil Salt Claims, Patent Scope, Expiration, and Competitive Landscape

U.S. Patent No. 9,050,311 covers processes for producing crystalline pharmaceutically acceptable salts of treprostinil, including treprostinil sodium, treprostinil potassium, and treprostinil diethanolamine. Its principal commercial relevance is the manufacturing route and the resulting crystalline salt, rather than treprostinil itself as a chemical compound.

The patent does not broadly claim every treprostinil formulation or every method of treating pulmonary arterial hypertension. It targets a crystallization process that uses treprostinil, a solvent, a base, heat, cooling, and an antisolvent. The patent has a nominal 2031 term based on its filing timeline, subject to any patent-term adjustment shown in the USPTO patent-term records. The claims should be analyzed separately from FDA Orange Book listings and from later patents covering inhaled, oral, or dry-powder treprostinil products.

What does U.S. Patent 9,050,311 cover?

U.S. Patent 9,050,311 covers the production of crystalline treprostinil salts through a controlled solvent and antisolvent process.

The independent claims are:

Claim	Subject matter	Practical scope
1	Method of producing a pharmaceutically acceptable treprostinil salt by dissolving treprostinil, adding a base, heating, and cooling in an antisolvent to form a crystalline solid	Broad process claim
10	Crystalline treprostinil salt produced by the process of claim 1	Product-by-process claim
11	Pharmaceutical composition containing the salt produced by claim 1 and a pharmaceutically acceptable carrier	Composition claim tied to the patented production process

Claims 2 through 9 narrow claim 1 by specifying the type of base, solvent, and antisolvent.

The patent therefore has three layers of protection:

A manufacturing process.
A crystalline treprostinil salt made by that process.
A pharmaceutical composition containing that salt.

The claims do not expressly require a particular treprostinil indication, dosage strength, route of administration, device, or patient population.

How broad is claim 1 of U.S. Patent 9,050,311?

Claim 1 is the principal enforcement claim. It requires each of the following steps:

Treprostinil is dissolved in a solvent.
A base is added.
The mixture is heated.
The mixture is cooled in an antisolvent.
A pharmaceutically acceptable treprostinil salt is formed as a crystalline solid.

The claim is functional and process-oriented. It does not limit the claim to sodium, potassium, or diethanolamine. Those alternatives appear in dependent claims.

A process may fall within claim 1 even if it uses a different base, solvent system, or antisolvent, provided that the accused process satisfies the claim’s required operations. The key infringement questions would be:

Whether treprostinil is dissolved before salt formation.
Whether a base is added.
Whether heating occurs.
Whether cooling takes place in the presence of an antisolvent.
Whether the resulting salt is crystalline.
Whether the resulting salt is pharmaceutically acceptable.

The words “heating” and “cooling” are not limited in the supplied claim text to particular temperatures, durations, or rates. The absence of numerical process limits increases the apparent breadth of claim 1, but it also creates potential claim-construction issues concerning what qualifies as an antisolvent and what sequence of operations is required.

What treprostinil salts are specifically protected?

The dependent claims identify three commercially and technically important salt categories.

Claims	Salt or base category	Scope
2	Inorganic base	Covers the broader inorganic-base subset
3	Alkali-metal base	Narrows claim 2
4	Sodium or potassium	Specifically identifies treprostinil sodium and treprostinil potassium
5	Organic base	Covers organic-base processes
6	Diethanolamine	Specifically identifies treprostinil diethanolamine

Treprostinil sodium has the strongest commercial significance because treprostinil products such as Remodulin and Tyvaso have historically used treprostinil sodium as the active pharmaceutical ingredient. The patent’s claim language, however, is not limited to products sold under those brand names.

Claim 6 is narrower than claim 5 because it requires diethanolamine. Claims 7 and 8 further narrow the solvent environment to ethanol and water. Claim 9 identifies acetone as the antisolvent.

What formulations are protected by U.S. Patent 9,050,311?

Claim 11 covers a pharmaceutical composition containing a treprostinil salt produced under claim 1 and a pharmaceutically acceptable carrier.

The claim does not specify:

Inhalation versus injection.
Oral versus parenteral administration.
Liquid versus solid dosage form.
A particular excipient.
A specific concentration.
A nebulizer or inhaler.
A sustained-release matrix.
A dry-powder carrier.
A particular indication.

This creates potentially broad composition coverage, but the composition must contain a treprostinil salt “produced according to” the claimed process. That product-by-process limitation is central. An accused manufacturer may argue that its salt was made by a materially different process, even if the resulting material has the same chemical identity.

The claim is more relevant to the active ingredient and its solid-state form than to the design of a finished drug-delivery product. Later formulation patents may independently protect aerosol systems, oral extended-release tablets, inhalation powders, or device-specific delivery methods.

How do the product-by-process claims affect infringement analysis?

Claim 10 is a product-by-process claim. It claims a crystalline treprostinil salt produced by the process of claim 1 rather than defining the salt solely by chemical structure or solid-state parameters.

Under U.S. patent law, product-by-process language generally limits the claim to products possessing the recited process relationship for infringement analysis, even though patentability may focus on whether the product itself is distinct from known products. The Federal Circuit has treated product-by-process claims as product claims for validity purposes but as requiring the claimed process limitation for infringement purposes. Amgen Inc. v. F. Hoffman-La Roche Ltd., 580 F.3d 1340 (Fed. Cir. 2009).

For a generic or competing manufacturer, the critical evidence would include:

Batch records.
Solvent charging sequence.
Base addition records.
Heating and cooling parameters.
Antisolvent addition.
Crystallization observations.
Solid-form characterization.
Manufacturing instructions and development reports.

A salt with the same molecular formula may not automatically infringe claim 10 if it was produced through a noninfringing route. Conversely, changing the order of operations may not avoid infringement if the process still performs all limitations under the proper construction of the claim.

What is the patent expiration date for U.S. Patent 9,050,311?

U.S. Patent 9,050,311 issued on June 9, 2015. Its nominal patent term runs approximately 20 years from the relevant nonprovisional or international filing date, producing an expected expiration in 2031, subject to any patent-term adjustment recorded by the USPTO.

Event	Date or period
Patent grant	June 9, 2015
Nominal term	Approximately 20 years from the relevant filing date
Expected statutory expiration	2031
PTA/PTE effect	Any adjustment recorded by the USPTO controls
Post-expiration status	Process and composition claims generally become unenforceable after expiration

The grant date is not the expiration date. The controlling date is the statutory term calculated from the applicable filing history, including any priority, national-stage, continuation, terminal-disclaimer, and patent-term-adjustment data. A freedom-to-operate opinion should use the USPTO Patent Examination Data System and patent-term records rather than the grant date alone.

Is U.S. Patent 9,050,311 listed in the FDA Orange Book?

The Orange Book does not list every patent associated with an approved drug. FDA listing generally concerns patents claiming the drug substance, drug product, or an approved method of use. Pure manufacturing-process patents are ordinarily not eligible for Orange Book listing unless the patent claims fall within the statutory categories for approved products or uses. FDA’s Orange Book instructions address the distinction between drug substance, drug product, method-of-use, and process claims. (FDA, 2024a).

The supplied claims are principally manufacturing claims. Claim 10 may be characterized as a drug-substance claim because it covers a crystalline treprostinil salt, but its product-by-process wording can complicate listing and infringement analysis. Claim 11 is a composition claim, but it remains tied to production by the patented process.

The practical conclusion is that U.S. Patent 9,050,311 should not be treated as an automatic Orange Book barrier for every treprostinil product. Its relevance depends on:

Whether it is listed against Remodulin, Tyvaso, Orenitram, or another FDA-approved product.
The exact claim category accepted by FDA.
Whether a later abbreviated new drug application identifies the patent in a Paragraph IV certification.
Whether other later patents, rather than 9,050,311, provide the principal Orange Book protection.

The FDA Orange Book must be checked by application number and product-specific patent listing. Relevant treprostinil products include Remodulin injection, Tyvaso inhalation solution, Tyvaso DPI, and Orenitram extended-release tablets. (FDA, 2024b).

When does treprostinil lose regulatory exclusivity?

Regulatory exclusivity and patent exclusivity are separate.

Product	Sponsor or applicant	General regulatory framework
Remodulin	United Therapeutics	505(b)(1) new drug application
Tyvaso inhalation solution	United Therapeutics	505(b)(1) new drug application
Orenitram	United Therapeutics	505(b)(1) new drug application
Tyvaso DPI	United Therapeutics	Later product approval and device/formulation protection
Generic treprostinil	Potential ANDA applicant	Requires reference-product and patent certifications

Five-year new chemical entity exclusivity, three-year clinical-investigation exclusivity, pediatric exclusivity, orphan-drug exclusivity, and patent term operate under different rules. Treprostinil’s commercial barriers have primarily involved patents, formulation technology, delivery systems, and manufacturing know-how rather than the original compound exclusivity period.

The expiration of U.S. Patent 9,050,311 would not eliminate other patent barriers. A competitor may still face separate patents covering:

Inhaled treprostinil formulations.
Dry-powder treprostinil.
Oral extended-release formulations.
Nebulizer systems.
Device cartridges.
Specific dosing regimens.
Combination therapies.
Manufacturing specifications.
Crystalline forms or impurity profiles.

What Paragraph IV risks exist for a generic treprostinil manufacturer?

A Paragraph IV challenge to a listed treprostinil product would require a patent-by-patent analysis. For U.S. Patent 9,050,311, a challenger could develop several possible positions:

Noninfringement

The generic manufacturer could use:

A preformed treprostinil salt.
A salt made without an antisolvent.
A process that does not dissolve treprostinil before salt formation.
A process without a heating step.
A process in which crystallization occurs through evaporation rather than antisolvent cooling.
A different process that produces an amorphous rather than crystalline material.

The strength of these positions depends on the actual process, not merely on the final product label.

Invalidity

Potential validity arguments would focus on:

Anticipation by an earlier treprostinil salt or crystallization process.
Obviousness based on conventional salt formation and crystallization techniques.
Lack of written description or enablement for the full range of bases, solvents, and antisolvents.
Indefiniteness of “pharmaceutically acceptable,” “heating,” “cooling,” or “antisolvent.”
Whether the claimed crystalline product is adequately distinguished from the prior art.

The broad language of claim 1 may increase exposure to enablement and written-description arguments, while the specific examples and experimental data in the specification would determine the practical strength of those defenses.

Invalidity of the product-by-process claim

Claim 10 may be vulnerable if the crystalline salt itself was known before the patent, even if the process used to make it was new. The challenger would examine prior disclosures of treprostinil sodium, potassium, or diethanolamine salts and any solid-state characterization data.

Which companies are most exposed to this patent?

United Therapeutics is the primary commercial company associated with approved treprostinil products in the United States. The patent is therefore most relevant to:

United Therapeutics’ internal manufacturing.
Contract manufacturers producing treprostinil active ingredient.
Generic manufacturers developing treprostinil sodium.
Suppliers of treprostinil API.
Companies developing alternative inhaled, oral, or injectable treprostinil products.

Liquidia Technologies is a major competitive company in the treprostinil market, particularly through Yutrepia and related inhalation technologies. Its principal patent disputes with United Therapeutics have centered on inhalation products, particle engineering, and delivery technology rather than necessarily on the exact crystallization claims of U.S. Patent 9,050,311.

A competitor can avoid direct infringement of the manufacturing claims while still facing other patents covering the finished product or delivery system.

What patent litigation affects treprostinil products?

The major modern treprostinil patent disputes have involved United Therapeutics products and competing inhaled treprostinil technologies. Litigation involving Liquidia has included patents directed to inhaled treprostinil formulations and delivery systems. Those disputes are commercially important because they may delay or limit launch of competing inhaled products even when a competitor avoids an older API manufacturing patent.

There is no basis in the supplied claim text to treat U.S. Patent 9,050,311 as a patent claiming:

Yutrepia’s specific inhalation powder.
Tyvaso DPI’s inhaler architecture.
Orenitram’s extended-release tablet technology.
A particular nebulizer.
A treprostinil treatment regimen.

The patent should therefore be separated from later product-specific litigation.

How strong is the patent estate for treprostinil?

The treprostinil patent estate is layered rather than dependent on one patent.

Layer	Typical protected subject matter	Relevance of U.S. 9,050,311
Active ingredient	Treprostinil chemical entity	Limited; the patent does not claim treprostinil itself
Salt and solid state	Sodium, potassium, diethanolamine, crystalline forms	Direct relevance
API manufacturing	Solvent, base, heating, cooling, crystallization	Direct relevance
Injectable product	Formulation, concentration, container, stability	Possible overlap only if process-linked
Inhaled product	Aerosol formulation, particle size, device, dosing	Generally separate
Oral product	Extended-release matrix and dosage regimen	Generally separate
Method of use	Pulmonary arterial hypertension and related indications	Not expressly claimed
Device	Nebulizer, inhaler, cartridge, capsule	Not claimed

The patent is strongest against a manufacturer using the claimed salt-production sequence. It is weaker as a standalone barrier against a competitor that purchases API from an independent supplier or uses a documented noninfringing process.

What geographic coverage does U.S. Patent 9,050,311 provide?

The patent provides enforceable rights in the United States only. It does not automatically protect the same process in:

Europe.
Canada.
Japan.
China.
India.
Australia.
Brazil.

Equivalent foreign applications or patents must be reviewed separately. International patent families may contain different claim scope, prosecution amendments, expiration dates, and enforceability outcomes. A global launch assessment should not use the U.S. grant as a proxy for foreign coverage.

What generic launch scenarios are most plausible?

The principal launch scenarios are:

Independent API process: A generic manufacturer uses a different salt-formation route and avoids claims 1 through 9.
Licensed API supply: The manufacturer purchases treprostinil salt from a supplier that has resolved the patent risk.
Paragraph IV challenge: The applicant argues that the claims are invalid or not infringed.
Post-expiration launch: The applicant waits until the 2031 patent term ends while addressing other product patents separately.
Alternative dosage form: The applicant pursues a product with a distinct route, formulation, or device and evaluates the remaining Orange Book patents independently.

The highest-risk scenario is direct manufacture of crystalline treprostinil sodium using ethanol-water, an alkali-metal base, heat, and acetone-based antisolvent crystallization. That process maps closely to claims 1, 3, 4, 7, and 9.

Key Takeaways

U.S. Patent 9,050,311 is primarily a treprostinil salt manufacturing and crystallization patent.
Claim 1 is the broadest process claim and does not limit the base to sodium, potassium, or diethanolamine.
Claims 4, 7, and 9 create a particularly relevant combination for treprostinil sodium made with ethanol, water, and acetone.
Claim 10 is a product-by-process claim covering a crystalline treprostinil salt made by the claimed process.
Claim 11 extends the process-linked protection to pharmaceutical compositions.
The patent does not expressly claim treprostinil itself, a specific indication, inhaler, nebulizer, oral tablet, or dosing regimen.
The nominal expiration period is in 2031, subject to the USPTO’s final patent-term calculation.
Orange Book relevance must be assessed against the specific FDA-listed treprostinil product and patent category.
A noninfringing manufacturing route may avoid this patent while remaining exposed to later formulation, device, method-of-use, or delivery patents.
The strongest design-around strategy is a documented salt-production process that omits at least one required claim element, particularly the claimed antisolvent-cooling sequence.

FAQs About U.S. Patent 9,050,311

Does U.S. Patent 9,050,311 cover treprostinil sodium itself?

Not without qualification. Claim 10 covers a crystalline treprostinil salt produced by the process of claim 1. The patent does not broadly claim every treprostinil sodium material regardless of how it was manufactured.

Can a company avoid the patent by using potassium treprostinil instead of sodium treprostinil?

Not necessarily. Claim 4 expressly covers sodium or potassium in the claimed alkali-metal process. A different salt may avoid some product-specific exposure but can remain within claim 1 or claim 4 if the process limitations are met.

Does drying treprostinil after crystallization avoid the patent?

Drying alone does not determine infringement. The relevant issue is whether the full claimed sequence occurred, including dissolution, base addition, heating, cooling in an antisolvent, and formation of a crystalline salt.

Does the patent cover a treprostinil inhalation formulation?

Only potentially through claim 11, and only if the composition contains a treprostinil salt produced according to claim 1. The patent does not expressly claim a particular inhaler, nebulizer, aerosol particle, or inhalation dosing regimen.

Is a Paragraph IV certification automatically required for this patent?

No. The requirement depends on whether the patent is listed for the relevant reference product in the FDA Orange Book and whether the ANDA applicant must certify against it. A patent not listed for the relevant product does not create the same ANDA certification obligation.

References

U.S. Patent and Trademark Office. (2015). U.S. Patent No. 9,050,311, crystalline treprostinil salts and methods of making same. U.S. Department of Commerce.
U.S. Food and Drug Administration. (2024a). Approved drug products with therapeutic equivalence evaluations: Patent and exclusivity information. U.S. Department of Health and Human Services.
U.S. Food and Drug Administration. (2024b). Orange Book: Approved drug products with therapeutic equivalence evaluations. U.S. Department of Health and Human Services.
U.S. Food and Drug Administration. (2024c). Hatch-Waxman amendments: Abbreviated new drug applications and patent certifications. U.S. Department of Health and Human Services.
Amgen Inc. v. F. Hoffman-La Roche Ltd., 580 F.3d 1340 (Fed. Cir. 2009).

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Canada	2526534	⤷ Start Trial
Canada	2736406	⤷ Start Trial
Canada	2851309	⤷ Start Trial
Canada	2959852	⤷ Start Trial
China	100558351	⤷ Start Trial
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Details for Patent: 9,050,311

Summary for Patent: 9,050,311