Details for Patent: 10,821,108

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Which drugs does patent 10,821,108 protect, and when does it expire?

Patent 10,821,108 protects UPTRAVI and is included in one NDA.

Protection for UPTRAVI has been extended six months for pediatric studies, as indicated by the *PED designation in the table below.

This patent has forty-one patent family members in thirty-three countries.

Summary for Patent: 10,821,108

Title:	Pharmaceutical composition containing 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsulfonyl)acetamide
Abstract:	A stabilized solid preparation containing 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsulfonyl)acetamide is provided, namely, a solid preparation containing 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsulfonyl)acetamide and D-mannitol having a specific surface area of 1.0 m2/g or less.
Inventor(s):	Shouji FURUTA, Hironori MUKAI
Assignee:	Nippon Shinyaku Co Ltd
Application Number:	US15/777,711
Patent Claim Types: see list of patent claims	Use; Composition; Dosage form;

US Patent 10,821,108: Selexipag Solid-Preparation Claims, Patent Scope, and Generic Entry Risk

US Patent 10,821,108 protects specific solid oral formulations containing selexipag and D-mannitol with controlled particle-surface-area and concentration parameters. Its strongest protection is not directed to selexipag itself, but to tablets or granules using a defined mannitol grade, formulation ratio, and excipient system. The patent also contains method-of-treatment claims covering pulmonary arterial hypertension and multiple vascular, renal, pulmonary, and inflammatory conditions.

The principal commercial relevance is Uptravi, the selexipag product marketed by Actelion Pharmaceuticals, a Janssen Pharmaceutical Companies company. The patent is most relevant to formulation-level design-around analysis, abbreviated new drug application strategy, Orange Book review, and potential patent litigation involving selexipag tablets.

What drug and formulation does US Patent 10,821,108 cover?

The active pharmaceutical ingredient is selexipag, chemically identified in the claims as:

2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsulfonyl)acetamide.

Selexipag is an orally administered prostacyclin-receptor agonist approved in the United States for treatment of pulmonary arterial hypertension. Its active metabolite contributes substantially to pharmacologic activity. The FDA-approved product is Uptravi tablets and injection for intravenous use in specific clinical circumstances. The patent claims are directed to solid preparations, principally tablets and granules, rather than injectable products. (U.S. Food and Drug Administration, 2025a)

The patent requires D-mannitol with a specific surface area:

Parameter	Broad claim 1 requirement	Narrow claim 24 requirement
D-mannitol specific surface area	Greater than 0.2 m²/g and no more than 1.0 m²/g	Greater than 0.2 m²/g and less than 0.7 m²/g
Selexipag-to-mannitol ratio	5 to 10,000 parts mannitol per part selexipag	10 to 9,500 parts mannitol per part selexipag
Mannitol content by total formulation weight	10% to 99%	20% to 80%
Mannitol share of total diluents	At least 20%	At least 50%
Dosage form	Solid preparation	Tablet
Additional excipients	Optional under claim 1	Cornstarch and hydroxypropyl cellulose under claims 25 and 26

The claimed composition is therefore a low-dose drug product in which mannitol is a quantitatively significant diluent and its physical surface-area specification is a central limitation.

What are the independent claims in US Patent 10,821,108?

The patent has two principal independent claim categories.

Claim 1: solid preparation

Claim 1 requires:

1. Selexipag;
2. D-mannitol;
3. D-mannitol with a specific surface area above 0.2 m²/g and no more than 1.0 m²/g;
4. A mannitol-to-selexipag weight ratio of 5:1 to 10,000:1;
5. Mannitol at 10% to 99% of the total solid-preparation weight; and
6. Mannitol representing at least 20% of all diluents in the preparation.

The claim does not require a tablet. It covers a broader solid preparation, including tablets and granules, provided the composition meets the stated limitations.

Claim 9: method of treatment

Claim 9 repeats the formulation limitations of claim 1 and adds administration to a subject for treatment of one or more listed conditions. The conditions include:

• Pulmonary hypertension;
• Peripheral circulatory disturbance;
• Chronic arterial occlusion;
• Intermittent claudication;
• Scleroderma;
• Thrombosis;
• Myocardial infarction;
• Angina pectoris;
• Diabetic neuropathy;
• Diabetic gangrene;
• Glomerulonephritis;
• Diabetic nephropathy;
• Chronic renal failure;
• Bronchial asthma;
• Interstitial pneumonia;
• Pulmonary fibrosis;
• Chronic obstructive pulmonary disease;
• Tubulointerstitial nephritis;
• Inflammatory bowel disease; and
• Symptoms associated with spinal canal stenosis.

Claims 10 through 19 narrow the disease indications. Claims 19 through 26 narrow the treatment to pulmonary arterial hypertension and specify additional formulation features.

How do the dependent claims narrow the patent scope?

The dependent claims progressively move from a broad formulation concept to a narrow commercial-tablet profile.

Claim	Added limitation	Practical significance
2	Another diluent and a binder	Excludes formulations consisting only of selexipag and mannitol
3	Cornstarch, sucrose, or crystalline cellulose as additional diluent	Creates excipient-specific subclaims
4	Hydroxypropyl cellulose as binder	Protects a specific binder choice
5	Cornstarch, sucrose, or crystalline cellulose plus hydroxypropyl cellulose	Combines the excipient classes
6	Selexipag 0.1%-2%; mannitol 20%-80%; cornstarch 15%-40%; hydroxypropyl cellulose 1%-5%	Closely defines a commercial-style formulation
7	Selexipag Form I crystal	Adds solid-state protection
8	Tablet or granule	Limits the dosage form
10-19	Specific diseases	Narrows the treatment method
20-23	Pulmonary arterial hypertension plus excipients and tablet form	Connects disease use to formulation structure
24	Tablet; mannitol surface area below 0.7 m²/g; narrower mannitol ranges	One of the strongest formulation-specific claims
25	Additional diluent and hydroxypropyl cellulose	Narrows claim 24
26	Cornstarch, specified selexipag, cornstarch, and hydroxypropyl cellulose ranges	Most commercially specific claim set

Claim 6 is especially important because it defines a narrow quantitative formulation:

• Selexipag: 0.1% to 2%;
• D-mannitol: 20% to 80%;
• Cornstarch: 15% to 40%; and
• Hydroxypropyl cellulose: 1% to 5%.

Claim 26 similarly requires a tablet under claim 24 and adds cornstarch and hydroxypropyl cellulose. The supplied text appears to contain typographical errors, including “c f” and an incomplete reference to limitation “(f).” Claim construction would rely on the issued patent text, prosecution history, and any certificate of correction rather than the transcription supplied in the question. (U.S. Patent No. 10,821,108, 2020)

What formulation features are protected?

The patent protects four technical variables in combination.

D-mannitol surface area

The most distinctive limitation is the specific surface area of D-mannitol. The broad range is:

• Greater than 0.2 m²/g; and
• No more than 1.0 m²/g.

Claim 24 narrows the upper limit to less than 0.7 m²/g.

This limitation is likely directed to manufacturing performance, blend uniformity, compressibility, dissolution, or stability. A generic manufacturer cannot assess infringement from the ingredient list alone. It would need to characterize the exact mannitol grade and determine the measurement method used for specific surface area.

A formulation using mannitol outside the claimed range may avoid literal infringement, but the technical and legal outcome would depend on the measurement method, claim construction, and possible doctrine-of-equivalents analysis.

Mannitol concentration

Claim 1 requires mannitol to constitute 10% to 99% of the solid preparation and at least 20% of total diluents. Claim 24 raises the lower limit to 20% and requires mannitol to constitute at least 50% of total diluents.

These limitations make the patent less relevant to formulations in which mannitol is a minor excipient or is replaced by lactose, microcrystalline cellulose, dibasic calcium phosphate, sorbitol, or another principal diluent.

Selexipag Form I crystal

Claim 7 covers a formulation using Form I crystalline selexipag. This limitation may matter where the drug substance is manufactured in a defined polymorphic form. It does not necessarily cover all crystalline or amorphous forms of selexipag.

A product containing a different polymorph could present a potential design-around, although the analysis would require solid-state characterization and consideration of whether the Form I limitation is inherited by the relevant claim.

Excipient architecture

The principal excipient combinations are:

• D-mannitol plus cornstarch;
• D-mannitol plus sucrose;
• D-mannitol plus crystalline cellulose;
• D-mannitol plus hydroxypropyl cellulose; and
• D-mannitol plus one or two additional diluents and hydroxypropyl cellulose.

The patent therefore reaches beyond the active ingredient and into the manufacturing recipe. An alternative formulation using a different binder, a different diluent, or a different mannitol grade may reduce literal infringement risk.

How strong is the patent estate for selexipag?

US Patent 10,821,108 is a formulation patent, not the core compound patent. Its strength depends on the ability to prove that an accused product uses the claimed mannitol grade and meets the quantitative formulation limitations.

Risk category	Assessment
Core-molecule protection	Not provided by the supplied claims
Tablet formulation protection	Material, especially under claims 24-26
Granule protection	Covered under claim 8 if the composition satisfies claim 1 or another applicable dependent claim
Polymorph protection	Limited to Form I under claim 7
Method-of-use protection	Broad disease list, but tied to the claimed solid formulation
Detectability from public product labeling	Low to moderate for surface area and manufacturing composition
Design-around potential	Moderate, particularly through diluent substitution or mannitol-grade selection
Litigation leverage	Higher if the generic formulation closely copies the claimed excipient and particle specifications

The patent has stronger practical value against a close formulation copy than against a product designed around mannitol content, surface area, binder, or dosage-form limitations.

When does selexipag lose exclusivity?

Selexipag exclusivity must be analyzed separately for:

1. FDA regulatory exclusivity;
2. The original active-ingredient and formulation patents;
3. Orange Book-listed patents;
4. Pediatric exclusivity;
5. Patent-term adjustment or extension; and
6. Any settlement or license affecting generic launch.

The claims supplied for US Patent 10,821,108 do not establish the patent’s earliest effective filing date, patent-term adjustment, patent-term extension, or Orange Book listing status. Those dates must be taken from the USPTO patent record, the patent front page, FDA Orange Book data, and any relevant court or settlement records. The statutory patent term generally runs 20 years from the earliest effective nonprovisional filing date, subject to patent-term adjustment and other statutory provisions. (35 U.S.C. § 154)

The patent should not be treated as expiring 20 years after its issue date. US Patent 10,821,108 issued on November 3, 2020, but its expiration date is determined by the applicable priority and continuity chain, not by the grant date alone. (U.S. Patent No. 10,821,108, 2020)

What is the Orange Book status of US Patent 10,821,108?

The Orange Book status cannot be determined from the claim text alone. FDA Orange Book listing is product-specific and depends on whether the NDA holder submitted the patent for listing and whether FDA accepted it under the applicable statutory and regulatory criteria.

For Uptravi, the relevant Orange Book analysis should distinguish:

• Patents directed to selexipag or its active metabolite;
• Formulation patents covering tablets;
• Method-of-use patents;
• Patents covering specific polymorphs or manufacturing processes; and
• Patents that may be listed but are not necessarily infringed by every generic formulation.

An Orange Book-listed formulation patent can trigger a Paragraph IV certification and litigation under the Hatch-Waxman framework. A patent not listed in the Orange Book may still be enforceable, but it generally does not create the same automatic 30-month stay mechanism following a Paragraph IV notice. (FDA, 2025b)

Which companies are likely to challenge or defend the patent?

The commercial parties are expected to include:

Party type	Likely role
NDA holder and licensees	Defend Uptravi patents and pursue listing, litigation, or settlement
Generic drug applicants	File ANDAs with Paragraph IV certifications or seek non-infringement declarations
Contract manufacturers	Supply selexipag drug substance or tablets and manage formulation confidentiality
Specialty pharmaceutical companies	Evaluate licensing or regional commercialization rights
Patent challengers	Attack claim construction, written description, enablement, anticipation, or obviousness

The relevant branded product is Uptravi. Actelion developed selexipag and commercialized Uptravi; Actelion became part of Johnson & Johnson through the acquisition of Actelion by Janssen Pharmaceuticals. The identity of the current patent owner, exclusive licensee, and NDA holder should be confirmed from the latest USPTO assignment and FDA records before relying on ownership for a transaction or litigation position. (FDA, 2025a; U.S. Patent and Trademark Office, 2025)

What Paragraph IV challenges could target this patent?

A Paragraph IV challenge could attack the patent through several routes.

Anticipation

A challenger could argue that an earlier reference discloses:

• Selexipag in a solid dosage form;
• D-mannitol as a diluent;
• The claimed mannitol concentration;
• The claimed particle-surface-area range; and
• The specified excipient combination.

Anticipation would require a single reference to disclose all limitations, expressly or inherently.

Obviousness

Obviousness is likely to focus on whether a skilled formulator would have selected:

• D-mannitol instead of another diluent;
• The claimed surface-area range;
• The claimed mannitol percentage;
• Cornstarch and hydroxypropyl cellulose; and
• The Form I crystal.

The strongest validity issue may concern whether the surface-area range reflects an unexpected technical result or routine optimization. Evidence of improved tablet strength, dissolution, content uniformity, stability, or manufacturability would be important.

Enablement and written description

The claims cover broad numerical ranges and multiple diseases. A challenger could examine whether the specification supports the full combination of:

• Selexipag;
• Multiple mannitol grades;
• Broad concentration ranges;
• Multiple diluents;
• Multiple disease indications; and
• Both tablets and granules.

The narrower claims are more likely to have substantial support if the specification contains working examples matching the claimed ranges.

Indefiniteness and measurement methodology

Specific surface area is a potential claim-construction issue. The relevant questions include:

• What analytical method measures the surface area?
• Is the value based on BET analysis?
• What degassing conditions apply?
• How is lot-to-lot variation handled?
• Does the claim require a particular particle-size distribution or only the measured surface area?

If the patent does not define the analytical method adequately, a challenger may argue that the surface-area limitation lacks reasonable certainty. The viability of that argument depends on the specification, prosecution history, and technical practice at the relevant filing date.

What generic launch scenarios exist?

Scenario 1: Formulation outside the claimed mannitol range

A generic applicant could use no mannitol, use mannitol below 10% of total formulation weight, or use mannitol as less than 20% of all diluents. This would avoid the literal limitations of claim 1 if no other asserted claim applies.

Scenario 2: Different mannitol surface area

A formulation could use D-mannitol with a specific surface area of 0.2 m²/g or less, above 1.0 m²/g, or outside the narrower claim 24 range. This strategy would require reliable analytical control and documentation.

Scenario 3: Different excipient system

Replacing cornstarch, sucrose, crystalline cellulose, or hydroxypropyl cellulose may avoid claims 3-6, 20-22, and 25-26. This does not necessarily avoid claim 1 or claim 24 if the remaining composition still satisfies their limitations.

Scenario 4: Different solid-state form

Use of a non-Form I form may avoid claim 7, but it would not avoid the broader formulation claims unless the other limitations are also changed.

Scenario 5: Litigation or settlement

An ANDA applicant may certify Paragraph IV and litigate, seek a covenant not to sue, or enter a settlement providing a later launch date. The commercial outcome would depend on the complete Orange Book patent set, not US Patent 10,821,108 alone.

How does US Patent 10,821,108 compare with core selexipag patents?

Patent category	What it protects	Relevance to generic entry
Compound patent	Selexipag molecule or related chemical genus	Broadest product protection
Process patent	Synthesis, intermediates, purification, or crystallization	May affect API sourcing
Polymorph patent	Form I or another defined crystal form	Relevant if the generic uses the same form
Formulation patent	Tablet composition, mannitol grade, excipients, ratios	Relevant to the finished dosage form
Method-of-use patent	Treatment of pulmonary arterial hypertension or other conditions	Relevant to labeling and skinny-label strategy
Manufacturing patent	Granulation, compression, coating, or process parameters	May create production-stage infringement risk

US Patent 10,821,108 is most valuable as a formulation barrier. It does not, on the supplied claims, prevent every selexipag product. A generic may be able to commercialize a non-infringing formulation even while this patent remains in force, subject to other patents covering the active ingredient, polymorph, process, or method of use.

What manufacturing and IP barriers matter most?

The main technical barrier is not simply the presence of mannitol. It is the combination of mannitol identity, specific surface area, concentration, diluent share, and dosage form.

A generic developer should control:

• Supplier and grade of D-mannitol;
• BET or equivalent surface-area testing;
• Selexipag polymorphic form;
• Blend uniformity;
• Granulation conditions;
• Compression force;
• Dissolution profile;
• Tablet hardness and friability;
• Binder concentration;
• Cornstarch content;
• Batch records; and
• ANDA formulation disclosures.

The most important evidence in an infringement dispute may be manufacturing and development records rather than the commercial label. Discovery could include raw-material certificates, formulation-development reports, analytical methods, batch records, and supplier specifications.

What is the geographic coverage of the patent?

US Patent 10,821,108 provides protection in the United States only. Corresponding foreign applications or granted patents may exist in jurisdictions such as Japan, Europe, Canada, China, and other markets, but each family member has an independent claim set, prosecution history, term, and enforceability profile.

A global launch assessment therefore requires a jurisdiction-by-jurisdiction review of:

• Family members;
• National-phase status;
• Patent term;
• Supplementary protection certificates;
• Local formulation claims;
• Local regulatory linkage;
• Opposition or post-grant proceedings; and
• License or settlement restrictions.

The US claims should not be assumed to predict the scope of foreign equivalents.

Key Takeaways

• US Patent 10,821,108 is a selexipag formulation patent focused on solid preparations containing D-mannitol.
• Claim 1 requires a specific mannitol surface-area range, concentration, and share of total diluents.
• Claim 9 adds method-of-treatment protection but remains tied to the claimed formulation.
• Claims 24-26 provide the most commercially targeted tablet protection.
• Cornstarch, hydroxypropyl cellulose, and Form I selexipag are important narrowing limitations.
• The patent does not, based on the supplied claims, provide broad protection over every selexipag product.
• Generic design-around opportunities include changing the mannitol grade, diluent system, binder, polymorph, or mannitol concentration.
• Orange Book listing, patent-term expiration, Paragraph IV exposure, and litigation status cannot be established from the claim text alone.
• The commercial risk must be assessed against the full Uptravi patent family, not US Patent 10,821,108 in isolation.

FAQs About US Patent 10,821,108 and Selexipag

Does US Patent 10,821,108 cover Uptravi by name?

No. The claims identify selexipag by its chemical name and cover specified solid formulations. The patent does not claim the trademark Uptravi.

Can a generic use mannitol and avoid this patent?

Potentially. A generic may reduce risk by using a mannitol grade outside the claimed surface-area range or by changing the mannitol concentration and diluent ratio. The complete formulation must be tested against every asserted claim.

Does claim 7 cover every crystalline form of selexipag?

No. Claim 7 is limited to a formulation in which selexipag is Form I crystal. Other claims may apply regardless of crystal form.

Are pulmonary arterial hypertension method claims easy to avoid?

Not necessarily. Claims 19-23 and related claims tie pulmonary arterial hypertension treatment to the claimed formulation. A generic using a different formulation may reduce risk, but method-of-use and induced-infringement issues require analysis of the proposed label and marketing conduct.

Does the patent block injectable selexipag products?

The supplied claims are directed to solid preparations, including tablets and granules. They do not expressly cover an injectable dosage form, although separate patents or regulatory protections may apply to injectable products.

References

1. Food and Drug Administration. (2025a). Uptravi (selexipag) prescribing information. U.S. Department of Health and Human Services.

2. Food and Drug Administration. (2025b). Approved drug products with therapeutic equivalence evaluations: Orange Book. U.S. Department of Health and Human Services.

3. U.S. Patent No. 10,821,108. (2020). Solid preparation. United States Patent and Trademark Office.

4. U.S. Patent and Trademark Office. (2025). Patent Center and assignment search records. U.S. Department of Commerce.

5. 35 U.S.C. § 154. (2025). Contents and term of patent; provisional rights. United States Code.

Drugs Protected by US Patent 10,821,108

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Actelion	UPTRAVI	selexipag	TABLET;ORAL	207947-010	May 23, 2026		RX	Yes	No					Y
Actelion	UPTRAVI	selexipag	TABLET;ORAL	207947-011	May 23, 2026		RX	Yes	No					Y
Actelion	UPTRAVI	selexipag	TABLET;ORAL	207947-001	Dec 21, 2015	AB	RX	Yes	No					Y
Actelion	UPTRAVI	selexipag	TABLET;ORAL	207947-002	Dec 21, 2015	AB	RX	Yes	Yes					Y

Foreign Priority and PCT Information for Patent: 10,821,108

Foriegn Application Priority Data
Foreign Country	Foreign Patent Number	Foreign Patent Date
Japan	2015-236034	Dec 2, 2015

PCT Information
PCT Filed	December 01, 2016	PCT Application Number:	PCT/JP2016/085822
PCT Publication Date:	June 15, 2017	PCT Publication Number:	WO2017/098998

International Family Members for US Patent 10,821,108

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
Australia	2016366073
Brazil	112018009534
Canada	3005169
Chile	2018001464