Details for Patent: 8,349,892

Which drugs does patent 8,349,892 protect, and when does it expire?

Patent 8,349,892 protects ORENITRAM and is included in one NDA.

This patent has eight patent family members in six countries.

Summary for Patent: 8,349,892

Title:	Solid formulations of prostacyclin analogs
Abstract:	Moderate moisture levels, such as greater than 3% but no greater than 7%, may be beneficial for solid formulations of certain prostacyclin analogs. Accordingly, a solid formulation containing a prostacyclin analog may be packaged inside a pharmaceutical packaging with such amount of a desiccant or a drying agent that after the storage the solid formulation may have a moderate level of moisture in it.
Inventor(s):	Kenneth R. Phares
Assignee:	United Therapeutics Corp
Application Number:	US12/775,102
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,349,892
Patent Claim Types: see list of patent claims	Use; Composition; Formulation;

United States Patent 8,349,892: Treprostinil Diethanolamine Moisture-Control Patent Analysis

U.S. Patent No. 8,349,892 protects solid treprostinil diethanolamine products and storage methods in which the formulation is maintained within a defined moisture range or is packaged with an intentionally insufficient amount of desiccant. The patent is directed to formulation stability and packaging control, not to treprostinil itself, a particular dose, extended-release technology, or a specific tablet geometry.

The patent is commercially relevant to Orenitram, United Therapeutics Corp.'s oral extended-release treprostinil product. Its principal enforcement risk is against an ANDA product that uses treprostinil diethanolamine in a solid dosage form and adopts comparable packaging, humidity, or desiccant specifications.

What does U.S. Patent 8,349,892 cover?

The patent has four independent claims:

Independent claim	Claim category	Core limitation
Claim 1	Pharmaceutical product	Solid treprostinil diethanolamine formulation in packaging configured to maintain formulation moisture above 3% and no more than 7%
Claim 9	Pharmaceutical product	Solid treprostinil diethanolamine formulation with a desiccant amount insufficient to maintain internal relative humidity below 40%
Claim 15	Storage method	Storage of the formulation so that its moisture level remains above 3% and no more than 7%
Claim 25	Storage method	Storage with a desiccant amount insufficient to maintain packaging humidity below 40%

The patent therefore has two distinct technical concepts:

1. Maintaining residual moisture in the solid formulation within a controlled range.
2. Deliberately limiting desiccant capacity so that packaging humidity is not held below 40% for the specified storage period.

The claims cover the product as packaged and the storage conditions affecting the product. They do not require a particular manufacturing process.

What are the key limitations in claim 1?

Claim 1 requires all of the following:

• A pharmaceutical product.
• Pharmaceutical packaging.
• A solid formulation inside the packaging.
• Treprostinil diethanolamine as the active agent.
• Packaging configured to maintain formulation moisture:
  • greater than 3%; and
  • no more than 7%.

The claim does not expressly require:

• A tablet or capsule.
• Extended release.
• A particular dose strength.
• A particular release profile.
• Maltodextrin or xylitol.
• A bottle.
• A blister.
• A desiccant.
• A specific packaging material.
• A specific storage duration.

Claims 2 and 3 narrow claim 1 by adding an excipient and then specifying maltodextrin or xylitol. Claims 4 and 5 narrow the moisture range:

Claim	Moisture range
Claim 1	>3% to 7%
Claim 4	3.5% to 6%
Claim 5	3.5% to 4.5%

Claim 5 is the narrowest moisture-range claim in the first product group.

How do the desiccant claims differ from the moisture claims?

Claims 9 and 25 do not primarily define the product by its measured formulation moisture. They define the amount of desiccant by a functional result: the desiccant must be less than the amount needed to maintain packaging relative humidity below 40%.

Claim 9 covers a packaged product. Claim 25 covers a storage method. The desiccant claims include the following features:

• Solid treprostinil diethanolamine formulation.
• Pharmaceutical packaging.
• Desiccant inside the packaging.
• Desiccant quantity below the effective amount required to keep relative humidity under 40%.

Claim 13 limits the storage period to 24 months. Claim 14 requires the desiccant amount to be at least two times lower than the amount that would otherwise maintain humidity below 40% for 24 months.

This creates a meaningful distinction:

• Claim 8 covers packaging without a desiccant.
• Claims 9 and 25 require a desiccant, but the desiccant must be insufficient for the stated humidity-control function.
• Claims 13, 14, 30 and 31 introduce longer-duration storage limitations.

A package using no desiccant may avoid claims 9 and 25 but remain exposed to claims 1 and 15 if it maintains the claimed moisture range.

What formulations are protected by U.S. Patent 8,349,892?

The claims cover solid formulations containing treprostinil diethanolamine. The formulation may contain excipients, but an excipient is not required by the independent claims.

The dependent claims specifically identify:

• Maltodextrin.
• Xylitol.
• Other pharmaceutically acceptable excipients through the broader dependent language.

The claims do not require both maltodextrin and xylitol. Either one is sufficient for claims 3, 11, 17 and 27 when the other limitations are met.

The patent does not, based on the supplied claims, protect:

• Treprostinil free acid as a standalone active ingredient.
• Treprostinil sodium.
• Injectable treprostinil solutions.
• Inhaled treprostinil solutions.
• Formulations that contain no treprostinil diethanolamine.
• A liquid formulation.
• A formulation whose packaging does not affect or maintain the claimed moisture conditions.

The active-agent limitation is important. A generic manufacturer using a different treprostinil salt could present a literal-infringement distinction, although equivalence, prosecution history and related patent claims would require separate analysis.

How broad are the packaging claims?

The packaging limitation is broad in physical terms. Claim 1 does not limit the package to a specific polymer, foil laminate, closure, oxygen barrier, moisture-vapor transmission rate or container volume.

Claims 6 and 7 expressly identify:

• Bottle packaging.
• Blister packaging.

The broad independent claim can potentially reach other packaging formats if the packaging is configured to maintain the required moisture level. The dependent claims provide clearer coverage for bottles and blisters but do not necessarily exclude other package types from claim 1.

The functional phrase "configured to maintain" creates an infringement question that is likely to turn on objective product data. Relevant evidence would include:

• Initial formulation moisture.
• Moisture after accelerated and long-term stability testing.
• Packaging moisture-vapor transmission rate.
• Closure integrity.
• Headspace volume.
• Desiccant identity and capacity.
• Relative humidity inside the package.
• Storage duration and conditions.
• Karl Fischer or equivalent moisture testing.
• Batch-release and stability specifications.

What is the scope of the storage-method claims?

Claims 15 through 24 cover storing the solid formulation so that, after storage, formulation moisture remains within the specified range. The method claims add duration limitations of:

• At least 12 months under claim 20.
• At least 24 months under claim 21.

Claims 22 through 24 add alternative packaging and desiccant conditions.

Claims 25 through 33 provide a second method group focused on insufficient desiccant capacity. Claims 30 and 31 add storage periods of at least 12 and 24 months.

The method claims may be relevant even where a product claim is disputed. A manufacturer, distributor or sponsor that controls the packaging configuration and labeled storage conditions could face method-claim exposure if the commercial product is stored as claimed.

Which claims are most commercially important?

The principal commercial claims are claims 1, 5, 9, 13, 14, 15, 21, 25 and 31.

Claim	Commercial significance
Claim 1	Broad packaged-product coverage for a 3% to 7% moisture range
Claim 5	Narrower 3.5% to 4.5% moisture range likely relevant to optimized commercial specifications
Claim 9	Product coverage for insufficient desiccant capacity
Claim 13	Desiccant limitation tied to 24-month storage
Claim 14	Stronger quantitative desiccant limitation requiring at least a two-fold reduction
Claim 15	Broad storage-method coverage
Claim 21	Storage-method coverage extending to 24 months
Claim 25	Broad desiccant-based storage method
Claim 31	24-month desiccant storage method

Claim 14 may be narrower but commercially useful because it includes a measurable comparative standard. The patent owner would need to establish the effective desiccant amount for maintaining relative humidity below 40% over 24 months and then show that the accused product uses at least two times less.

When does U.S. Patent 8,349,892 lose exclusivity?

The patent issued on January 8, 2013. Public patent records identify a 2007 priority date and a nominal patent-term expiration in 2027. The expected base expiration is August 10, 2027, subject to any applicable patent-term adjustment or other term calculation reflected in official USPTO and FDA records.[1]

The patent's expiration is separate from FDA regulatory exclusivity:

Exclusivity category	Relevance
Patent exclusivity	Expected to extend into 2027
Orphan-drug exclusivity for Orenitram	Expired in 2020 based on the 2013 approval date and seven-year orphan period
New chemical entity exclusivity	Not the principal barrier for Orenitram because treprostinil had prior FDA approval in other dosage forms
Pediatric exclusivity	No conclusion follows from the supplied claims

After patent expiration, a generic manufacturer could still face other unexpired Orenitram patents covering dosage forms, release characteristics, formulation composition, manufacturing or methods of treatment.

What is the Orange Book status of the patent?

U.S. Patent 8,349,892 has been associated with Orenitram, the oral extended-release treprostinil product, in FDA patent-listing records. The relevant regulatory product is treprostinil extended-release tablets approved under NDA 203496.[2][3]

An Orange Book listing does not establish validity or infringement. It gives the NDA holder a basis to identify the patent in response to an ANDA applicant's Paragraph IV certification.

The practical significance is that an ANDA applicant seeking approval for a therapeutically equivalent oral treprostinil product may need to:

• Certify that the patent has expired.
• Certify that the applicant will not market before expiration.
• Submit a Paragraph IV certification alleging that the patent is invalid, unenforceable or not infringed.
• Seek a court declaration or defend an infringement action if sued.

What Paragraph IV challenges and generic entry risks exist?

A Paragraph IV challenge to this patent would likely focus on claim construction, written description, enablement, obviousness and infringement.

Potential non-infringement positions include:

• The product contains treprostinil in a different chemical form.
• The product is not a solid formulation.
• The package does not maintain formulation moisture above 3%.
• Moisture is outside the claimed range.
• The package does not maintain the claimed moisture condition.
• The product uses a desiccant amount that is not below the claimed functional threshold.
• The package humidity is not measured or maintained for the claimed period.
• The accused product lacks the required 12- or 24-month storage condition.

Potential validity arguments include:

• Prior art disclosures of solid treprostinil formulations.
• Prior art disclosures of moisture-controlled packaging.
• Obviousness combinations involving moisture-sensitive pharmaceutical products, desiccants and stability testing.
• Lack of written-description support for the full numerical ranges.
• Lack of enablement for all packaging configurations and storage environments.
• Indefiniteness of "configured to maintain" or "effective amount" if the specification does not provide objective testing methods.

The strongest factual defense will depend on the accused product's stability data and packaging specifications. A generic applicant that independently targets a 3.5% to 4.5% formulation-moisture specification may face greater risk under claim 5 than one that designs outside the patented moisture windows.

Which companies are challenging the patent?

The supplied claim text does not identify an ANDA applicant, litigation defendant or settlement counterparty. A patent number alone does not establish whether a Paragraph IV notice has been served, whether litigation was filed, or whether a settlement permits an authorized or licensed generic launch.

The commercial parties most directly implicated by the patent are:

Party	Role
United Therapeutics Corp.	Orenitram sponsor and principal treprostinil rights holder
FDA	NDA and Orange Book regulator
Potential ANDA applicants	Generic manufacturers seeking oral treprostinil approval
Contract manufacturers	Potentially relevant to formulation, packaging and stability evidence

No biosimilar pathway applies. Treprostinil diethanolamine is a small-molecule active ingredient, so competing products would generally proceed through the ANDA pathway rather than the 351(k) biosimilar pathway.

How does this patent compare with other treprostinil protection?

Product or technology	Patent relevance of 8,349,892
Orenitram oral extended-release tablets	Directly relevant if the commercial packaging and moisture profile meet the claims
Remodulin injectable treprostinil	Generally outside the supplied claims because it is not a solid formulation
Tyvaso inhaled treprostinil	Generally outside the supplied claims because it is an inhaled liquid product
Generic treprostinil injection	Generally outside the supplied claims
Generic oral treprostinil diethanolamine	Directly exposed if solid, packaged and maintained within the claimed moisture or desiccant conditions
Alternative treprostinil salt	Potential design-around depending on claim scope and equivalence
Liquid oral treprostinil	Potential design-around because the claims require a solid formulation

The patent is narrower than a patent claiming treprostinil itself or all oral treprostinil products. It is potentially stronger against an exact Orenitram-style product because packaging and moisture conditions are often replicated to achieve the same shelf-life and tablet stability.

How strong is the patent estate for a generic launch?

The patent presents a moderate product-specific barrier and a potentially stronger portfolio-level barrier.

Its strengths are:

• Coverage of both products and storage methods.
• Claims directed to measurable moisture ranges.
• Coverage of packaging with or without a desiccant.
• Specific 12- and 24-month storage claims.
• Relevance to a commercial oral treprostinil product.
• Dependent claims covering common bottle, blister, maltodextrin and xylitol configurations.

Its weaknesses are:

• No claim to treprostinil diethanolamine alone.
• No dosage-strength limitation.
• No specific tablet or release-profile limitation.
• Functional packaging language may create proof and construction issues.
• The "effective amount" desiccant standard may invite indefiniteness and enablement challenges.
• A carefully designed formulation or package may avoid the numerical moisture windows.

A generic launch strategy could involve a Paragraph IV challenge, a formulation with moisture outside the claimed ranges, packaging that does not maintain the claimed conditions, or a different treprostinil chemical form. Those strategies would need to be assessed against the entire Orenitram patent portfolio, not this patent in isolation.

What manufacturing and IP barriers does the patent create?

The patent may affect:

• Final drying or conditioning of tablets.
• Selection of hygroscopic excipients.
• Bottle closure systems.
• Blister-barrier specifications.
• Desiccant quantity and placement.
• Headspace humidity.
• Stability protocols.
• Commercial labeling for storage.
• Batch-release moisture specifications.
• Comparative testing against the branded product.

The central operational risk is that a manufacturer may unintentionally practice the claims because moisture retention is a consequence of its packaging design rather than an expressly stated manufacturing objective.

Key Takeaways

• U.S. Patent 8,349,892 is a formulation-packaging and storage patent for solid treprostinil diethanolamine.
• Claim 1 covers packaged products maintaining formulation moisture above 3% and up to 7%.
• Claim 5 narrows the range to 3.5% through 4.5%.
• Claims 9 and 25 address insufficient desiccant quantities and packaging humidity above the 40% control threshold.
• Claims 13, 14, 21 and 31 extend the most commercially important limitations to 24-month storage.
• Bottles, blisters, maltodextrin, xylitol and desiccant configurations are expressly addressed in dependent claims.
• The patent does not cover treprostinil itself, injectable products, inhaled products or liquid formulations.
• The expected base patent expiration is August 10, 2027, subject to the official term calculation.
• Orenitram's orphan exclusivity ended in 2020, but patent protection can continue beyond that date.
• Generic risk is concentrated in oral solid treprostinil diethanolamine products using comparable moisture and packaging specifications.
• Biosimilar risk is not applicable because treprostinil is a small molecule.

Frequently Asked Questions

Does U.S. Patent 8,349,892 cover Orenitram tablets?

Yes. The patent is relevant to Orenitram because Orenitram is an oral solid treprostinil product, although infringement depends on the commercial formulation, packaging and measured storage characteristics.

Can a generic avoid the patent by using no desiccant?

Possibly. No-desiccant packaging may avoid the desiccant claims, but it can still fall within the moisture-range claims if the solid formulation remains above 3% and no more than 7% moisture.

Does the patent cover treprostinil injection?

Generally no, based on the supplied claims. The claims require a solid formulation inside pharmaceutical packaging.

Is a different treprostinil salt outside the claims?

A different salt may avoid literal infringement because the claims specifically recite treprostinil diethanolamine. Equivalence and related patents would require separate analysis.

Can an ANDA applicant challenge this patent before 2027?

Yes. An ANDA applicant may submit a Paragraph IV certification asserting invalidity, unenforceability or non-infringement. The NDA holder may then bring patent litigation that can delay approval under the Hatch-Waxman framework.

References

1. United States Patent and Trademark Office. (2013). U.S. Patent No. 8,349,892, treprostinil diethanolamine pharmaceutical products and storage methods.

2. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. FDA.

3. U.S. Food and Drug Administration. (2013). Orenitram (treprostinil) extended-release tablets prescribing information. United Therapeutics Corp.

Drugs Protected by US Patent 8,349,892

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
United Therap	ORENITRAM	treprostinil diolamine	TABLET, EXTENDED RELEASE;ORAL	203496-001	Dec 20, 2013		RX	Yes	No			Y
United Therap	ORENITRAM	treprostinil diolamine	TABLET, EXTENDED RELEASE;ORAL	203496-002	Dec 20, 2013		RX	Yes	No			Y
United Therap	ORENITRAM	treprostinil diolamine	TABLET, EXTENDED RELEASE;ORAL	203496-003	Dec 20, 2013		RX	Yes	Yes			Y

International Family Members for US Patent 8,349,892

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Canada	2760499
China	102421288
European Patent Office	2427054