Details for Patent: 8,410,169

Which drugs does patent 8,410,169 protect, and when does it expire?

Patent 8,410,169 protects ORENITRAM and is included in one NDA.

This patent has nineteen patent family members in seven countries.

Summary for Patent: 8,410,169

Title:	Compounds and methods for delivery of prostacyclin analogs
Abstract:	This invention pertains generally to prostacyclin analogs and methods for their use in promoting vasodilation, inhibiting platelet aggregation and thrombus formation, stimulating thrombolysis, inhibiting cell proliferation (including vascular remodeling), providing cytoprotection, preventing atherogenesis and inducing angiogenesis. Generally, the compounds and methods of the present invention increase the oral bioavailability and circulating concentrations of treprostinil when administered orally. Compounds of the present invention have the following formula:
Inventor(s):	Ken Phares, David Mottola
Assignee:	United Therapeutics Corp
Application Number:	US11/189,072
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,410,169
Patent Claim Types: see list of patent claims	Use; Composition; Dosage form;

US Patent 8,410,169: Treprostinil Combination, Liposome, and Oral Bioavailability Claims

US Patent 8,410,169 protects three distinct treprostinil concepts: combination therapy with selected cardiovascular agents, liposomal treprostinil compositions, and oral salt or ester formulations that achieve materially higher bioavailability than treprostinil free acid. The strongest commercial relevance is the oral-formulation claim set, particularly for extended-release oral treprostinil products such as Orenitram.

The patent was assigned to United Therapeutics Corporation and issued April 2, 2013. Based on the recorded priority and filing chronology, the expected patent-term endpoint is in 2027, subject to any applicable patent-term adjustment or disclaimer. The claims are composition and method claims, not claims limited to a particular commercial tablet strength, release profile, excipient system, or named cardiovascular co-therapy. [1]

What does US Patent 8,410,169 cover?

The patent has 11 claims divided into three technical groups.

Claim group	Claims	Protected subject matter	Principal limitation
Combination therapy	1-3	Diethanolamine treprostinil with another cardiovascular agent	Calcium-channel blocker, phosphodiesterase inhibitor, or endothelin antagonist
Liposomal delivery	4-7	Treprostinil-containing liposomes and pulmonary-hypertension treatment	Liposome composition; some claims require the diethanolamine salt
Oral bioavailability	8-11	Oral treprostinil salt or ester formulations	At least 50%, or 100%, greater bioavailability than treprostinil free acid

The claims use both structural and functional limitations. Claims 1, 4, 5, 8, 10, and 11 focus on compositions. Claims 2, 3, 6, and 7 focus on administering those compositions to treat pulmonary hypertension.

How broad are the combination-therapy claims?

Claim 1 requires a therapeutic composition containing:

1. A diethanolamine salt of treprostinil; and
2. At least one additional cardiovascular agent.

The permitted cardiovascular-agent classes are:

• Calcium-channel blockers;
• Phosphodiesterase inhibitors; and
• Endothelin antagonists.

The claim does not identify a specific compound within those classes. A composition containing treprostinil diolamine and sildenafil, tadalafil, bosentan, ambrisentan, macitentan, or a qualifying calcium-channel blocker could fall within the literal class limitation, assuming the other claim requirements are met.

Claim 2 is broader in one respect and less specific in another. It requires a method of treating pulmonary hypertension by administering a therapeutic composition containing treprostinil diethanolamine and at least one additional cardiovascular agent. Claim 3 restores the three-class limitation found in claim 1.

What products could implicate claims 1-3?

Potentially relevant combinations include:

Treprostinil component	Combination class	Examples of potentially relevant agents
Treprostinil diethanolamine	PDE-5 inhibitor	Sildenafil, tadalafil
Treprostinil diethanolamine	Endothelin antagonist	Bosentan, ambrisentan, macitentan
Treprostinil diethanolamine	Calcium-channel blocker	Amlodipine, diltiazem, nifedipine, depending on the treatment context

The claim language does not expressly require that the second agent be approved for pulmonary hypertension, be administered in a fixed-dose combination, or be present in a particular ratio. It also does not expressly require simultaneous administration in the same dosage form beyond claim 1's composition requirement. A method claim analysis would depend on whether the accused regimen administers the claimed composition and whether the second agent is part of that composition.

A notable issue is the boundary between a single pharmaceutical composition and a treatment regimen using separate products. Claim 1 is directed to a composition. Claims 2 and 3 require administration of a therapeutic composition, but the patent language supplied does not resolve every question concerning co-packaged products, sequential dosing, or separate dosage forms.

What is the scope of the liposome claims?

Claims 4-7 cover liposomal treprostinil.

Claim 4 requires:

• A composition;
• A therapeutically effective amount of treprostinil; and
• A liposome.

Claim 5 narrows claim 4 by requiring the treprostinil to be the diethanolamine salt. Claims 6 and 7 cover treatment of pulmonary hypertension using the liposomal composition.

These claims are not limited on their face to:

• A particular phospholipid;
• A defined particle-size range;
• A particular encapsulation efficiency;
• Intravenous, inhaled, oral, or subcutaneous administration;
• A specific release rate; or
• A named liposome manufacturing process.

That breadth creates potential validity and infringement disputes. A composition would generally need to contain treprostinil in a liposomal system, not merely a conventional emulsion, micellar formulation, suspension, or non-liposomal nanoparticle. The technical characterization of the delivery system would be central to both infringement and validity analysis.

The liposome claims have weaker direct relevance to Orenitram, Remodulin, and Tyvaso than the oral bioavailability claims because those marketed products use different delivery platforms. Their value is greater for future reformulations, depot products, inhaled systems, and lifecycle-management products using vesicular delivery.

What do the oral bioavailability claims protect?

Claims 8-11 are the commercially significant portion of the patent.

Claim 8 covers an oral pharmaceutical composition containing a therapeutically effective amount of a treprostinil salt or ester, where the composition provides oral bioavailability at least 50% greater than a composition containing treprostinil free acid.

Claim 9 raises the threshold to at least 100% greater bioavailability.

Claim 10 narrows the ester to a benzyl ester or an amino acid ester. Claim 11 identifies a benzyl ester or a diglycine ester.

Claim	Treprostinil form	Route	Bioavailability requirement	Additional limitation
8	Salt or ester	Oral	At least 50% above free acid	Therapeutically effective composition
9	Salt or ester	Oral	At least 100% above free acid	Depends on claim 8
10	Benzyl ester or amino acid ester	Oral	At least 50% above free acid	Depends on claim 8
11	Benzyl ester or diglycine ester	Oral	At least 50% above free acid	Depends on claim 8

The claims do not expressly require diethanolamine treprostinil in every case. Claim 8 covers a salt or ester generally. A diethanolamine salt is one likely embodiment, but the literal scope may extend to other salts if they satisfy the oral-bioavailability limitation.

Why is the bioavailability limitation important?

The comparison is not simply between a claimed product and no treatment. It requires comparison against a composition containing treprostinil as the free acid. The reference composition, study design, dose normalization, pharmacokinetic endpoint, and statistical treatment may become important in litigation.

Potential disputes include:

• Whether "oral bioavailability" means absolute or relative bioavailability;
• Whether the comparison must use the same dose;
• Whether the free-acid comparator must use the same excipients;
• Whether the claimed threshold must be demonstrated across patients or only in a representative study;
• Whether the result is inherent in the formulation or must be expressly measured;
• Whether a product with variable pharmacokinetics consistently meets the 50% or 100% threshold.

The functional limitation gives the claims potentially broad formulation coverage, but it also creates proof and patent-validity issues. A generic applicant could challenge whether the specification enables the full scope of salts, esters, and oral formulations covered by claim 8.

What FDA products are most relevant to US 8,410,169?

Treprostinil is approved in several dosage forms and salt forms.

Product	Active ingredient or formulation	Sponsor	FDA status	Relevance
Orenitram	Treprostinil diolamine extended-release tablets	United Therapeutics	Approved	Highest relevance to oral claims
Remodulin	Treprostinil injection	United Therapeutics	Approved	Limited relevance to oral claims; relevant to molecule and salt strategy
Tyvaso	Treprostinil inhalation solution	United Therapeutics	Approved	Delivery-system comparison; generally not an oral claim product
Tyvaso DPI	Inhaled treprostinil dry powder	United Therapeutics	Approved	Separate inhalation technology and patent estate

Orenitram was approved by the FDA in December 2013 for pulmonary arterial hypertension. Its active ingredient is treprostinil diolamine, an orally administered salt form of treprostinil. The product uses extended-release tablets, making claims 8 and 9 more directly relevant than the combination or liposome claims. [2]

The existence of an approved product does not by itself establish that every claim of US 8,410,169 covers that product. Product-specific coverage depends on the Orange Book listing, approved labeling, formulation characteristics, and the relationship between the commercial formulation and the claimed bioavailability threshold.

What is the Orange Book status of US 8,410,169?

US 8,410,169 should be analyzed separately from the full Orenitram patent portfolio. The Orange Book identifies patents submitted by the NDA holder as applicable to approved drug products. The listing, if present for the relevant Orenitram NDA, is more significant for generic applicants than the patent's general disclosure.

The relevant regulatory questions are:

• Whether US 8,410,169 is listed against the Orenitram NDA;
• Which strengths and dosage forms are associated with the listing;
• Whether the listed claims cover the approved extended-release tablet;
• Whether the patent is still within its Orange Book expiration period;
• Whether a generic applicant has filed a Paragraph IV certification.

The FDA Orange Book should be reviewed by NDA and product presentation, rather than by searching only the active ingredient. Treprostinil products have different routes of administration and different regulatory records. [3]

A patent may have commercial relevance without being Orange Book-listed, but an Orange Book listing triggers the Hatch-Waxman certification and litigation framework for an ANDA applicant.

When does US 8,410,169 lose exclusivity?

The patent's expected ordinary expiration is in 2027 based on its priority and filing chronology. A practical exclusivity timeline is:

Event	Date or period
Earliest priority period	2006
Patent issued	April 2, 2013
Orenitram approval	December 2013
Expected patent expiration	2027
Earliest possible generic launch	Before expiration only through a successful challenge, license, settlement, or authorized launch

The exact statutory expiration should be confirmed against the USPTO continuity data, terminal-disclaimer records, and any patent-term adjustment. A patent expiration date is not equivalent to FDA regulatory exclusivity. New chemical entity exclusivity, three-year exclusivity, pediatric exclusivity, and patent-term extension are separate issues under the Federal Food, Drug, and Cosmetic Act. [4]

For a small-molecule oral product, the principal challenge route is an ANDA, not a biosimilar application.

Which companies are challenging Orenitram or treprostinil patents?

Publicly available regulatory and court records should be examined for Paragraph IV notices involving Orenitram and related treprostinil products. The supplied claim set alone does not establish the identity of any current ANDA challenger, the date of a notice letter, or the status of Hatch-Waxman litigation.

The commercial exposure is concentrated in generic oral treprostinil. Generic versions of Remodulin or Tyvaso would involve different dosage forms, device requirements, formulation claims, and regulatory pathways. Orenitram is the most direct target for a generic applicant because it is an oral small-molecule product.

A Paragraph IV certification against US 8,410,169 could lead to:

1. A 45-day patent-infringement action by the NDA holder;
2. A 30-month FDA approval stay, subject to statutory exceptions;
3. Litigation over infringement of the bioavailability limitation;
4. Invalidity challenges based on obviousness, anticipation, written description, enablement, or indefiniteness;
5. A settlement that defines an authorized or at-risk launch date.

Without a verified Paragraph IV notice or filed complaint, no particular challenger or litigation outcome should be attributed to this patent.

How strong is the patent estate for treprostinil?

US 8,410,169 has meaningful but uneven strength.

Strongest elements

The oral claims have commercial value because they combine:

• A pharmaceutical composition;
• An oral route;
• A salt or ester form;
• A measurable pharmacokinetic advantage; and
• A threshold that can distinguish the formulation from free-acid treprostinil.

The claims also cover a result that may be difficult to design around if the approved product necessarily achieves the specified bioavailability improvement.

Weaker or more contestable elements

The combination claims use broad pharmacological classes and may face obviousness challenges based on known pulmonary-hypertension combination therapy. The liposome claims may face prior-art and enablement challenges if the specification does not support the full range of liposomal systems covered by the claims.

The oral claims may face disputes over:

• The comparator formulation;
• The meaning of the bioavailability threshold;
• Whether the specification supports all salts and esters;
• Whether the claimed advantage was predictable;
• Whether the commercial product actually satisfies the limitation.

Patent strength therefore depends heavily on prosecution history, cited prior art, claim amendments, and the Orange Book relevance of each claim.

What manufacturing and intellectual-property barriers exist?

The primary manufacturing barrier for an oral generic is not simply production of treprostinil. The applicant must reproduce a dosage form with acceptable:

• Content uniformity;
• Chemical stability;
• Extended-release performance;
• Impurity profile;
• Dissolution characteristics;
• Salt-form control; and
• Bioequivalence.

If US 8,410,169 is listed against Orenitram, the applicant may need to certify that its product does not infringe the asserted claims or that the claims are invalid or unenforceable. A formulation that uses a different salt, ester, release mechanism, or excipient system may still face claim 8 if it achieves the required bioavailability relative to free acid.

Separate patents may cover Orenitram's release technology, tablet composition, dosing regimen, manufacturing process, or crystalline forms. A freedom-to-operate analysis cannot rely on US 8,410,169 alone.

How does US 8,410,169 compare with competing pulmonary-hypertension patent estates?

Estate or product	Main technology	Patent risk to generic entrants
Orenitram	Oral extended-release treprostinil diolamine	Oral formulation, release, method-of-use, and listed-patent risk
Remodulin	Parenteral treprostinil	Injectable formulation, stability, and delivery claims
Tyvaso	Inhaled treprostinil	Inhalation formulation, device, and method claims
Sildenafil products	PDE-5 inhibition	Active-ingredient and indication patents largely distinct from treprostinil
Tadalafil products	PDE-5 inhibition	Separate composition and method-of-use estate
Endothelin antagonists	Oral PAH combination partners	Separate product-specific patent estates

US 8,410,169 does not create a general monopoly over pulmonary-hypertension treatment or over all treprostinil products. Its commercial perimeter is narrower: selected treprostinil combinations, liposomal delivery, and oral salt or ester formulations meeting the stated bioavailability threshold.

Are biosimilar risks relevant to treprostinil?

No. Treprostinil is a chemically defined small molecule, not a biologic. Competitive entry would generally proceed through an ANDA or another small-molecule pathway rather than a biosimilar application under the Public Health Service Act. The FDA Purple Book is therefore not the principal source for treprostinil exclusivity analysis. [5]

Key Takeaways

• US 8,410,169 contains three claim families: combination therapy, liposomal treprostinil, and oral bioavailability-enhanced formulations.
• Claims 8 and 9 are the most commercially relevant to Orenitram because they cover oral treprostinil salts or esters meeting specified bioavailability thresholds.
• The patent does not broadly cover every treprostinil product, every pulmonary-hypertension regimen, or every extended-release formulation.
• The expected patent-term endpoint is in 2027, subject to USPTO term adjustments and any terminal disclaimer.
• Generic risk depends on Orange Book listing, the exact Orenitram formulation, Paragraph IV activity, and the broader Orenitram patent portfolio.
• Treprostinil presents generic, not biosimilar, competition risk.
• The principal litigation vulnerabilities are obviousness, enablement, written description, claim construction, and proof of the claimed bioavailability comparison.

FAQs

Does US 8,410,169 cover treprostinil diolamine by itself?

Not uniformly. Claims 1-3 require treprostinil diethanolamine with an additional cardiovascular agent. Claims 5 and 7 concern diethanolamine treprostinil in liposomal compositions. Claims 8 and 9 cover a salt or ester of treprostinil, which can include diethanolamine treprostinil if the oral bioavailability limitation is satisfied.

Does the patent cover intravenous or subcutaneous Remodulin?

The core oral claims do not. Remodulin is an injectable product, while claims 8-11 require oral administration. Claims 1-3 and 4-7 are not limited to oral administration, so their relevance depends on the formulation and combination used.

Can a generic avoid claim 8 by using a different treprostinil salt?

Potentially, but not automatically. Claim 8 covers "a salt or ester of treprostinil" without limiting the claim to diethanolamine salt. A different salt could still fall within the claim if its oral composition meets the claimed bioavailability threshold.

Are the liposome claims relevant to inhaled treprostinil?

Only if the inhaled formulation is technically a liposomal composition containing treprostinil. A conventional inhalation solution or dry-powder formulation would not necessarily satisfy the liposome limitation.

Does expiration of US 8,410,169 guarantee immediate generic Orenitram entry?

No. Other unexpired patents, regulatory exclusivities, approved-label requirements, formulation patents, and litigation settlements may delay or limit generic launch even after this patent expires.

References

1. United States Patent and Trademark Office. (2013). U.S. Patent No. 8,410,169, compositions and methods involving treprostinil. Google Patents. https://patents.google.com/patent/US8410169B2/en
2. U.S. Food and Drug Administration. (2023). Orenitram (treprostinil) extended-release tablets prescribing information. United Therapeutics Corporation.
3. U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations: Orange Book. https://www.accessdata.fda.gov/scripts/cder/ob/
4. U.S. Food and Drug Administration. (2024). Hatch-Waxman amendments and generic drug patent certifications. https://www.fda.gov/drugs/abbreviated-new-drug-application-anda
5. U.S. Food and Drug Administration. (2024). Purple Book: Database of licensed biological products. https://purplebooksearch.fda.gov/

Drugs Protected by US Patent 8,410,169

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
United Therap	ORENITRAM	treprostinil diolamine	TABLET, EXTENDED RELEASE;ORAL	203496-004	Dec 20, 2013		RX	Yes	No			Y
United Therap	ORENITRAM	treprostinil diolamine	TABLET, EXTENDED RELEASE;ORAL	203496-005	Oct 7, 2016		RX	Yes	No			Y

International Family Members for US Patent 8,410,169

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Canada	2526534
Canada	2736406
Canada	2851309
Canada	2959852
China	100558351
China	101265226