United States Drug Patent 9,486,428: Scope, Claims, Expiration, and Seladelpar Patent Landscape

US Patent No. 9,486,428 protects methods of treating primary biliary cholangitis, or PBC, with seladelpar, including the L-lysine dihydrate salt used in Livdelzi. The patent covers oral and once-daily administration, but its dose-dependent claims require doses of at least 20 mg free-acid equivalent. Livdelzi is labeled at 10 mg once daily, which is outside claims 4 and 5 but remains within the broader treatment and once-daily claims.

The patent is commercially important because it protects the approved PBC use of seladelpar rather than merely claiming the underlying chemical compound. Its key enforcement value is therefore tied to generic products seeking approval for PBC under an abbreviated new drug application, or ANDA.

What drug does US Patent 9,486,428 protect?

US 9,486,428 covers seladelpar, also known as MBX-8025 or seladelpar lysine. The active moiety is the R-enantiomer of a substituted phenoxyacetic acid compound:

(R)-2-(4-((2-ethoxy-3-(4-(trifluoromethyl)phenoxy)propyl)thio)-2-methylphenoxy)acetic acid.

The approved product is Livdelzi, marketed by Gilead Sciences following Gilead's acquisition of CymaBay Therapeutics. Livdelzi contains seladelpar lysine and is approved as a once-daily oral capsule for adults with PBC who have had an inadequate response to or are unable to tolerate ursodeoxycholic acid, or UDCA [1][2].

Seladelpar is a selective peroxisome proliferator-activated receptor delta, or PPAR-delta, agonist. Patent 9,486,428 is directed to the therapeutic use of the compound in PBC rather than to a broad PPAR-delta mechanism alone.

What are the claims of US Patent 9,486,428?

The patent has six claims focused on treatment, salt form, route, dose, and dosing frequency.

Claim	Subject matter	Practical scope
1	Treating PBC with seladelpar or a salt	Broad method-of-use claim; no specified route, dose, or frequency
2	Using seladelpar L-lysine dihydrate salt	Directly corresponds to the active form in Livdelzi
3	Oral administration	Covers oral treatment with seladelpar or a salt
4	Daily dose of 20-200 mg, calculated as free acid	Dose-range limitation
5	Oral daily dose of 50-100 mg, calculated as free acid	Narrower dose and route limitation
6	Once-daily administration	Covers once-daily use, regardless of a stated dose

How broad is claim 1?

Claim 1 is the principal claim. It requires:

A subject in need of treatment;
Primary biliary cholangitis; and
Administration of a therapeutically effective amount of seladelpar or a salt.

The claim does not require:

Oral administration;
A particular salt;
A specific dose;
Once-daily dosing;
A particular disease stage;
Prior UDCA treatment;
A particular biochemical endpoint; or
A specific formulation.

The claim is therefore broad as a method-of-use claim. A product labeled for treatment of PBC with seladelpar could implicate claim 1 even if it uses a different pharmaceutically acceptable salt, route, or dosing schedule.

What does claim 2 protect?

Claim 2 narrows claim 1 to seladelpar L-lysine dihydrate. This is the most product-specific claim in the patent and has direct relevance to Livdelzi.

The claim does not simply cover any lysine salt. It specifies the L-lysine dihydrate form. A generic applicant using a different salt would face a stronger non-infringement position under claim 2, but could still face claims 1, 3, 4, or 6 depending on the proposed label and dosing regimen.

What do the oral and dosing claims cover?

Claim 3 covers oral administration. Claim 6 covers once-daily administration. Because both depend on claim 1, each requires PBC treatment with seladelpar or a salt.

Claim 4 covers a 20-200 mg daily dose on a free-acid-equivalent basis. Claim 5 narrows this to an oral 50-100 mg daily dose.

Livdelzi's approved dose is 10 mg once daily, expressed as seladelpar equivalent. That dose does not fall within claims 4 or 5. It remains potentially within claim 6 because claim 6 does not specify a dose. It also falls within claim 1 and, for the approved salt, claim 2.

When does US Patent 9,486,428 expire?

The patent was granted on November 8, 2016, from an application claiming priority to an April 2013 filing. The nominal patent term is generally calculated from the earliest relevant nonprovisional or international application filing date, not from the grant date. Public patent records report an expiration date in April 2034, subject to any applicable patent-term adjustment or correction recorded by the USPTO [3].

Event	Date
Earliest claimed priority	April 2013
US patent application or related international filing	April 2014
Patent grant	November 8, 2016
Expected nominal expiration	April 2034
Patent-term adjustment	Must be confirmed from the USPTO patent file

Patent expiration does not necessarily equal the date of unrestricted generic entry. FDA regulatory exclusivity, other Orange Book patents, pediatric exclusivity, litigation settlements, or a later-issued patent may affect the effective launch date.

What is the Orange Book status of US 9,486,428?

The FDA's Orange Book is the relevant source for determining whether the patent is listed against the approved Livdelzi product and which use code applies. For a method-of-use patent, the listing is material because an ANDA applicant can challenge the patent through a Paragraph IV certification or attempt to omit the patented use under a section viii statement [4].

The commercial significance of US 9,486,428 depends on three questions:

Whether it is listed against the Livdelzi NDA;
Whether the listed use code covers the approved PBC indication; and
Whether other patents provide overlapping protection for the active ingredient, salt, formulation, or manufacturing process.

A generic applicant seeking approval only for a non-PBC indication could potentially use a section viii statement if the patented PBC use is carved out. A generic applicant seeking an indication that includes PBC would face greater exposure to a Paragraph IV certification.

What FDA exclusivity protects Livdelzi?

The FDA approved Livdelzi on August 14, 2024, under the accelerated approval pathway for adults with PBC who have an inadequate response to UDCA or cannot tolerate UDCA [1]. The approval was based primarily on reductions in alkaline phosphatase, or ALP. Continued approval depends on confirmation of clinical benefit.

Livdelzi received seven years of orphan-drug exclusivity for PBC under the Orphan Drug Act. Orphan exclusivity generally prevents FDA approval of the same drug for the same disease or condition during the exclusivity period, subject to statutory exceptions. The seven-year period is distinct from patent term and does not itself prevent an ANDA applicant from filing a patent challenge.

Regulatory protection	Approximate timing
FDA approval	August 14, 2024
Orphan-drug exclusivity	Generally through August 2031
Patent 9,486,428	Expected through approximately April 2034
Pediatric exclusivity	No public basis to add six months to the stated timeline

The orphan exclusivity period is shorter than the expected term of US 9,486,428. Patent protection is therefore likely to remain the principal barrier after orphan exclusivity ends.

What patents protect Livdelzi beyond US 9,486,428?

The relevant patent estate should be divided into four categories:

Composition-of-matter patents

These cover seladelpar or related PPAR-delta agonist structures. Composition patents can create broader barriers than a PBC method patent because they may reach the active pharmaceutical ingredient regardless of indication.

The strength of any composition patent depends on:

Whether seladelpar itself is expressly claimed;
Whether the patent has expired;
Whether the patent contains an enforceable crystalline, stereochemical, or salt claim;
Whether a generic can manufacture a non-infringing form; and
Whether the patent is listed in the Orange Book.

Salt and solid-form patents

Claim 2 of US 9,486,428 covers the L-lysine dihydrate salt in a treatment context. Separate salt, polymorph, or solid-form patents could protect the commercial pharmaceutical form independent of the method claim.

These patents are significant because a generic manufacturer may be able to reproduce the active moiety but avoid a particular salt or crystal form. Conversely, if the approved product and the generic use the same L-lysine dihydrate, the risk increases.

Formulation patents

A formulation patent could cover capsule composition, excipient ratios, dissolution characteristics, stability, particle size, or modified release. Livdelzi is an oral capsule, and the FDA labeling identifies seladelpar lysine as the active ingredient [2].

No formulation limitation appears in claims 1-6. A generic product that uses the same active salt but a different formulation may avoid the claims in this patent only if it also avoids the claimed treatment method, dose, or frequency. A formulation patent would be analyzed separately.

Method-of-use patents

US 9,486,428 is principally a PBC method-of-use patent. Its claims can apply even where the active ingredient is off-patent, provided the use, route, salt, dose, or schedule falls within the claims.

Method patents are especially relevant to ANDA litigation because the applicant's proposed labeling determines the induced-infringement analysis. A label that instructs treatment of PBC creates materially higher risk than a label limited to a non-PBC indication.

How strong is the patent estate for seladelpar?

The estate is strongest against a generic that:

Uses seladelpar L-lysine dihydrate;
Seeks a PBC indication;
Uses oral administration;
Uses once-daily dosing; and
Launches before the April 2034 patent horizon.

That product would likely fall within claims 1, 2, 3, and 6. It would not necessarily fall within claims 4 or 5 because Livdelzi's approved dose is 10 mg once daily rather than 20-200 mg or 50-100 mg.

The estate is weaker against a product that:

Uses a different salt;
Omits PBC from its label;
Uses a non-oral route;
Uses a dosing schedule other than once daily; or
Relies on a formulation or manufacturing route outside separately protected subject matter.

The broad language of claim 1 reduces the value of changing the salt or dose alone. A generic must avoid the disease indication or establish invalidity, not merely change a subordinate product characteristic.

Which companies are challenging US 9,486,428?

No publicly identified Paragraph IV litigation or settlement involving US 9,486,428 was established in the cited FDA and public patent records. Livdelzi was approved only in 2024, and no mature generic challenge landscape had developed in the public record reviewed for this analysis.

The most likely future challengers would be large generic companies with PBC or hepatology portfolios, including manufacturers that routinely file first-to-market ANDAs. The relevant filing would be an ANDA containing a Paragraph IV certification, followed by potential litigation under the Hatch-Waxman Act.

A Paragraph IV notice could trigger a 45-day period for the patent holder to sue. A timely infringement action could create a 30-month FDA approval stay, subject to statutory exceptions and court developments [5].

What generic launch scenarios exist for Livdelzi?

Scenario 1: Full-label generic challenge

A generic applicant seeks approval for PBC and includes the patented indication. It certifies Paragraph IV against listed method patents. This creates the clearest litigation pathway and could delay approval through litigation or settlement.

Scenario 2: Carved-out label

The applicant omits PBC from its labeling through a section viii statement or a permissible skinny label. This approach could reduce method-of-use exposure, but it would not necessarily avoid liability if the product is marketed for PBC or if the label still induces the patented use.

Scenario 3: Alternative salt or formulation

The applicant uses a different salt or formulation. This may avoid claim 2 or a separate formulation patent, but claim 1 remains broad if the same seladelpar treatment is promoted for PBC.

Scenario 4: Post-expiration launch

A generic waits until the principal patent barriers expire. This avoids Paragraph IV litigation risk but sacrifices first-filer economics and delays market entry until after the likely patent term.

What litigation and settlement issues affect this patent?

A future case would likely focus on:

Whether an ANDA label induces PBC treatment;
Whether a different salt is covered by claim 1;
Whether the L-lysine dihydrate form is present in the proposed product;
Whether claim 1 is enabled across all therapeutically effective amounts;
Whether the claims are anticipated by prior PBC or PPAR-delta treatment disclosures;
Whether the claims are obvious in view of earlier seladelpar and PPAR-delta work; and
Whether the patent satisfies written-description requirements for the specific PBC use.

A settlement could provide a licensed entry date before patent expiration, an authorized-generic arrangement, or a non-compete period. No public settlement tied to this patent was identified in the cited record.

How does seladelpar compare with competing PBC drugs?

Product	Active ingredient	PBC role	Patent-risk profile
Livdelzi	Seladelpar lysine	FDA-approved for adults with PBC after inadequate response or intolerance to UDCA	Method-of-use, active-form, and possible formulation protections
Ocaliva	Obeticholic acid	Previously approved for PBC; US indication withdrawn in 2025	Separate composition and use patent estate
Ursodiol products	Ursodeoxycholic acid	Established first-line therapy	Mature generic market
Elafibranor	Elafibranor	Investigational or regulatory competitor depending jurisdiction and indication	Separate composition and method-of-use estate

Seladelpar's commercial differentiation is its PBC indication, once-daily oral dosing, and use in patients with inadequate response or intolerance to UDCA. Its principal competitive risk is regulatory and clinical, while its principal generic risk is a future ANDA challenge to the PBC use patent and any listed product-form patents.

What is the geographic coverage of US 9,486,428?

US 9,486,428 has territorial effect only in the United States. International protection depends on corresponding national patents and applications in jurisdictions such as Europe, Japan, Canada, and Australia.

A US patent does not block:

Manufacture outside the United States for non-US commercial use;
Sale in jurisdictions where corresponding patents have expired; or
Importation into the United States if the imported product infringes a valid US process patent under 35 U.S.C. section 271(g).

International launch planning therefore requires a country-by-country review of national family members, patent-term adjustments, supplementary protection certificates, and local regulatory exclusivity.

What manufacturing and intellectual-property barriers remain?

Manufacturing risk is concentrated in the active pharmaceutical ingredient and the L-lysine dihydrate salt. A generic manufacturer would need to establish:

Control of the R-enantiomer;
Reproducible salt formation;
Stability of the dihydrate;
Consistent impurity limits;
Bioequivalence to Livdelzi; and
A non-infringing manufacturing process if process patents remain active.

These technical barriers do not independently extend the US patent term, but they can increase development cost and complicate an alternative-salt strategy.

Key Takeaways

US 9,486,428 is a PBC method-of-use patent for seladelpar and its salts.
Claim 1 is broad and does not require a specific route, dose, salt, or dosing frequency.
Claim 2 specifically covers seladelpar L-lysine dihydrate, the active form used in Livdelzi.
Claims 3 and 6 cover oral and once-daily treatment.
Claims 4 and 5 do not cover Livdelzi's labeled 10 mg once-daily dose because they require at least 20 mg or 50 mg, respectively.
Livdelzi received FDA approval on August 14, 2024, with orphan-drug exclusivity generally extending to August 2031.
The patent's expected nominal expiration is approximately April 2034, subject to USPTO term calculations.
A generic PBC product using seladelpar lysine once daily would face the highest infringement risk.
No publicly identified Paragraph IV litigation or settlement involving this patent was established in the cited record.
The complete commercial barrier requires review of Orange Book listings and any separate composition, salt, formulation, or process patents.

Frequently Asked Questions

Is US 9,486,428 a composition-of-matter patent?

No. The issued claims are method-of-treatment claims directed to treating PBC with seladelpar or a salt. Separate composition patents, if unexpired and enforceable, must be analyzed independently.

Does a 10 mg Livdelzi dose infringe claim 4?

No. Claim 4 requires a daily dose of 20-200 mg calculated as free acid. Livdelzi's 10 mg once-daily labeled dose is outside that numerical range. It may still implicate claims 1, 2, 3, and 6.

Can a generic avoid the patent by using a different seladelpar salt?

Not necessarily. A different salt may avoid claim 2, but claim 1 covers seladelpar or a salt generally when used to treat PBC.

Does FDA orphan exclusivity prevent a Paragraph IV filing?

No. Orphan exclusivity limits FDA approval of the same drug for the same disease or condition during the exclusivity period. It does not eliminate the ANDA applicant's ability to file a patent certification or challenge a listed patent.

Is seladelpar subject to biosimilar competition?

No. Seladelpar is a chemically synthesized small molecule. Competitors would generally pursue the ANDA generic pathway rather than the biologic biosimilar pathway.

References

U.S. Food and Drug Administration. (2024, August 14). FDA grants accelerated approval to seladelpar for primary biliary cholangitis. https://www.fda.gov/
U.S. Food and Drug Administration. (2024). Livdelzi (seladelpar) prescribing information. https://www.accessdata.fda.gov/
United States Patent and Trademark Office. (2016). U.S. Patent No. 9,486,428, methods of treating primary biliary cholangitis. https://patents.google.com/
U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, Orange Book. https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book
U.S. Code. (2024). 21 U.S.C. § 355 and 35 U.S.C. § 271(e): Abbreviated new drug applications and patent litigation. https://uscode.house.gov/

Applicant	Tradename	Generic Name	Dosage	NDA	Approval Date	TE	Type	RLD	RS	Patent No.	Patent Expiration	Product	Substance	Delist Req.	Patented / Exclusive Use	Submissiondate
Gilead Sciences Inc	LIVDELZI	seladelpar lysine	CAPSULE;ORAL	217899-001	Aug 14, 2024		RX	Yes	Yes	⤷ Start Trial	⤷ Start Trial				TREATMENT OF PRIMARY BILIARY CHOLANGITIS (PBC)	⤷ Start Trial
>Applicant	>Tradename	>Generic Name	>Dosage	>NDA	>Approval Date	>TE	>Type	>RLD	>RS	>Patent No.	>Patent Expiration	>Product	>Substance	>Delist Req.	>Patented / Exclusive Use	>Submissiondate

Country	Patent Number	Estimated Expiration	Supplementary Protection Certificate	SPC Country	SPC Expiration
European Patent Office	3119384	⤷ Start Trial	C20253004	Finland	⤷ Start Trial
European Patent Office	3119384	⤷ Start Trial	CA 2025 00025	Denmark	⤷ Start Trial
European Patent Office	3119384	⤷ Start Trial	PA2025529	Lithuania	⤷ Start Trial
European Patent Office	3119384	⤷ Start Trial	301338	Netherlands	⤷ Start Trial
>Country	>Patent Number	>Estimated Expiration	>Supplementary Protection Certificate	>SPC Country	>SPC Expiration

Details for Patent: 9,486,428

Which drugs does patent 9,486,428 protect, and when does it expire?

Summary for Patent: 9,486,428