US Patent 10,011,633: Maralixibat Patent Scope, Claims, Exclusivity and Generic Risk
US Patent 10,011,633 protects oral treatment of cholestasis-induced pruritus with maralixibat, an ileal bile acid transporter, or IBAT, inhibitor. The patent is a method-of-use patent, not a basic composition-of-matter patent. Its commercial importance is tied to Livmarli, the maralixibat chloride product marketed by Mirum Pharmaceuticals for Alagille syndrome and progressive familial intrahepatic cholestasis.
The strongest claim is claim 1, which requires four core elements: a subject with cholestasis-induced pruritus, oral administration, a therapeutically effective amount, and the specifically identified maralixibat molecule or a pharmaceutically acceptable salt. Dependent claims extend the scope to defined bile-acid diseases, pediatric patients, and reductions in serum or liver bile acids. [1]
What drug and clinical use does US Patent 10,011,633 cover?
The claimed IBAT inhibitor is maralixibat, also known as SHP625 and marketed as maralixibat chloride under the brand name Livmarli.
| Item |
Description |
| Active ingredient |
Maralixibat chloride |
| Pharmacologic class |
Ileal bile acid transporter inhibitor |
| Dosage form |
Oral solution |
| Commercial product |
Livmarli |
| Primary sponsor and marketer |
Mirum Pharmaceuticals |
| FDA indication |
Cholestatic pruritus associated with Alagille syndrome and PFIC |
| Patent type |
Method of treatment and method of use |
| Patent number |
US 10,011,633 |
| Grant date |
July 3, 2018 |
| Expected statutory term |
Approximately 2034, subject to the official patent-term calculation |
| Key regulatory pathway |
NDA approval under section 505(b)(1) |
The chemical name in claim 1 identifies the active pharmaceutical ingredient with a high degree of structural precision. The claim therefore does not cover every IBAT inhibitor. It covers the specified maralixibat molecule and pharmaceutically acceptable salts of that molecule.
The patent’s claims are relevant to Livmarli because the product uses maralixibat chloride, an orally administered salt form of the claimed active ingredient. FDA labeling identifies maralixibat chloride as the active ingredient in Livmarli oral solution. [2]
What are the individual claims of US Patent 10,011,633?
Claim 1: Core method-of-treatment claim
Claim 1 covers:
- Treating cholestasis-induced pruritus;
- In a subject in need of treatment;
- By oral administration;
- In a therapeutically effective amount;
- Using maralixibat or a pharmaceutically acceptable salt.
This is a narrow species claim directed to a particular molecule and a particular therapeutic use. It does not expressly require a specific dose, dosing frequency, age, disease subtype, biomarker threshold, or formulation.
A generic maralixibat product administered orally to treat cholestatic pruritus would present the clearest infringement scenario if the use fell within the claim and the patent remained enforceable.
Claim 2: Bile-acid disease limitation
Claim 2 requires that the subject be diagnosed with a bile acid disease. This limitation narrows claim 1 by adding a disease-diagnosis requirement.
The claim can cover treatment of cholestatic pruritus in patients whose underlying condition is classified as a bile-acid disease. The term is broader than a single named diagnosis, but its interpretation would depend on the specification, prosecution history, and expert evidence.
Claim 3: Cholestasis of pregnancy
Claim 3 is directed to cholestasis of pregnancy. It covers treatment of pruritus associated with intrahepatic cholestasis of pregnancy, provided the remaining limitations of claim 1 and claim 2 are met.
This claim is commercially important because it reaches a disease population distinct from the current FDA-approved Livmarli populations. It may support future development or off-label use, but the patent claim itself does not establish FDA approval for pregnancy-related cholestasis.
Claim 4: Specified bile-acid diseases
Claim 4 identifies the following diseases:
- Alagille syndrome;
- Progressive familial intrahepatic cholestasis;
- Primary biliary cirrhosis;
- Liver fibrosis;
- Nonalcoholic fatty liver disease;
- Nonalcoholic steatohepatitis;
- Primary sclerosing cholangitis.
The claim has particular value for Alagille syndrome and PFIC because those are the disease areas for which Livmarli has FDA-approved indications. It also reaches several broader or adjacent liver-disease populations that are not necessarily covered by the current label.
Claims 5 and 6: Bile-acid reduction
Claim 5 requires a decrease in serum bile-acid levels. Claim 6 requires a decrease in liver bile-acid levels.
These claims add pharmacodynamic limitations. A claimant would generally need evidence that treatment produced the claimed reduction, although the exact proof required would depend on claim construction and the facts of the case.
The claims may be useful against clinical protocols or product labeling that expressly promotes maralixibat for reducing serum or hepatic bile acids. They are less certain against a product whose labeling describes only pruritus improvement without a bile-acid reduction endpoint.
Claim 7: Pediatric use
Claim 7 covers treatment in a pediatric subject. The claim is important because both Alagille syndrome and PFIC are pediatric-heavy indications, and Livmarli is administered to children under FDA-approved labeling.
The claim does not state a specific pediatric age range. The term would be interpreted using the patent specification, relevant medical usage, and prosecution history. FDA labeling currently provides age-specific restrictions for the approved indications. [2]
How broad is the scope of US Patent 10,011,633?
The patent has broad therapeutic coverage but narrow chemical coverage.
| Scope element |
Breadth |
Commercial effect |
| Active ingredient |
Narrow |
Limited to maralixibat and its pharmaceutically acceptable salts |
| Treatment objective |
Moderate |
Covers cholestasis-induced pruritus |
| Route |
Narrow to moderate |
Oral administration is required |
| Dose |
Broad |
No specific dose is recited |
| Formulation |
Broad |
No particular formulation is required |
| Disease population |
Broad in dependent claims |
Includes ALGS, PFIC and several liver diseases |
| Pediatric treatment |
Explicit |
Claim 7 directly covers pediatric use |
| Biomarker outcome |
Narrow |
Claims 5 and 6 require bile-acid reductions |
| Product type |
Method claim |
Does not independently claim the commercial formulation |
The absence of a dose limitation increases the practical reach of claim 1. Different oral dosing regimens could still fall within the claim if they use maralixibat to treat cholestasis-induced pruritus.
The absence of a formulation limitation means that the patent is not confined to the specific Livmarli oral-solution excipient system. Tablets, capsules, suspensions, granules, or other oral formulations could potentially fall within claim 1 if they contain maralixibat and satisfy the treatment limitations.
The oral-route limitation creates a design-around boundary. A nonoral product would not literally satisfy claim 1, although the commercial and clinical feasibility of a nonoral IBAT inhibitor would be a separate issue.
What patents protect Livmarixibat and Livmarli?
Maralixibat’s overall intellectual-property position is likely to include several patent categories beyond US 10,011,633.
Composition-of-matter patents
Composition patents protect the maralixibat molecule, stereochemistry, salts, intermediates, and related IBAT inhibitor structures. These patents are generally more powerful than method patents because they can cover making, selling, importing, and using the compound for any indication.
A composition patent covering maralixibat would create a broader product-level barrier than US 10,011,633. Its expiration date, prosecution history, terminal disclaimers, and any patent-term adjustment should be reviewed separately from the ’633 patent.
Method-of-use patents
US 10,011,633 is principally a therapeutic-use patent. Its claims target cholestasis-induced pruritus and specified bile-acid diseases.
Other method patents could cover:
- Specific age groups;
- PFIC or Alagille syndrome;
- Dosing schedules;
- Liver-function or bile-acid endpoints;
- Combination therapy;
- Treatment of additional cholestatic disorders;
- Use in pregnancy-associated cholestasis.
Formulation patents
A formulation patent may protect:
- Maralixibat oral solutions;
- Concentration and pH ranges;
- Solubilizing systems;
- Flavoring and excipient combinations;
- Stability characteristics;
- Unit-dose packaging;
- Pediatric administration systems.
US 10,011,633 does not require the Livmarli formulation. A separate formulation patent would therefore be important in a generic-launch analysis because an applicant might avoid the formulation claims while still confronting the ’633 method claims.
Manufacturing and process patents
Manufacturing patents may cover:
- Synthesis of maralixibat;
- Chiral resolution;
- Salt formation;
- Crystallization;
- Purification;
- Polymorphs;
- Control of residual solvents and impurities.
These rights can create practical supply-chain barriers even when a competing company avoids direct infringement of a treatment-use claim. They also affect licensing and API-sourcing strategies.
What is the Orange Book status of US Patent 10,011,633?
US 10,011,633 is relevant to Livmarli’s FDA-listed intellectual-property position as a method-of-use patent. The patent’s listed use must be compared with the approved indication and the exact Orange Book use code maintained by FDA. [3]
An Orange Book listing does not establish validity. It informs ANDA applicants that the NDA holder considers the patent relevant to the approved product or indication.
For a generic applicant, the principal certification possibilities are:
| Certification |
Effect |
| Paragraph I |
No patent information is listed |
| Paragraph II |
Listed patent has expired |
| Paragraph III |
Applicant will wait until patent expiration |
| Paragraph IV |
Applicant alleges the patent is invalid, unenforceable, or will not be infringed |
| Section viii statement |
Applicant omits a patented method of use from labeling |
Because the ’633 patent claims a method of treating cholestatic pruritus, a section viii carve-out may be difficult if the approved generic labeling necessarily promotes treatment of the patented disease or population. The feasibility of a carve-out depends on the exact Orange Book use code, FDA labeling, and whether nonpatented uses remain available.
When does US Patent 10,011,633 lose exclusivity?
The patent has a grant date of July 3, 2018. Based on its continuation-era filing and priority structure, the expected statutory expiration is approximately in 2034, subject to the official USPTO patent-term calculation and any terminal disclaimer.
The relevant timeline is:
| Event |
Date or period |
| Patent grant |
July 3, 2018 |
| Expected patent term |
Approximately 20 years from the applicable nonprovisional priority date |
| Expected patent expiration |
Approximately 2034 |
| FDA approval for ALGS |
September 29, 2021 |
| FDA approval for PFIC |
2023 |
| ALGS orphan exclusivity |
Generally seven years from approval |
| PFIC orphan exclusivity |
Generally seven years from the applicable approval |
Patent expiration and FDA exclusivity are separate. FDA orphan exclusivity can block approval of a competing product for the same orphan indication even after a patent challenge succeeds. Conversely, orphan exclusivity does not prevent all off-label use or approval for a different indication.
The New Chemical Entity exclusivity period for maralixibat, if applicable to the original NDA, would be shorter than the patent term. Pediatric exclusivity, if granted, could add six months to applicable exclusivity periods, but it would not extend the patent term. FDA’s regulatory exclusivity data and the Orange Book must be reviewed independently. [3, 4]
Which companies are challenging the Livmarli patent estate?
No publicly established Paragraph IV challenger or reported patent settlement involving US 10,011,633 is identified in the core public sources cited here.
The most credible future challengers would include:
- Generic pharmaceutical companies seeking an ANDA for maralixibat oral solution;
- Companies developing alternative IBAT inhibitors;
- Sponsors seeking approval for PFIC, ALGS, or cholestatic pruritus;
- Companies developing pregnancy-related cholestasis treatments.
Odevixibat is the closest commercial comparator, but it is not a generic version of maralixibat. Odevixibat is a different IBAT inhibitor marketed as Bylvay by Ipsen after its acquisition of Albireo. Its product does not inherently infringe a claim limited to the specific maralixibat structure.
What patent litigation and settlement risks affect maralixibat?
A Paragraph IV filing could trigger litigation under the Hatch-Waxman Act. If the NDA holder sued within the statutory period, FDA approval of the ANDA could be stayed for up to 30 months, subject to statutory exceptions and court rulings. [5]
The main litigation issues would likely include:
Infringement
The patent holder would need to establish that the proposed generic product and its labeling lead to administration of maralixibat for a claimed use. The drug substance, oral route, and pruritus indication would be central facts.
Induced infringement
A generic applicant could face induced-infringement allegations if its labeling, promotional materials, or distribution practices encourage use for cholestatic pruritus covered by the claims.
Validity
Potential challenges could include:
- Anticipation based on prior IBAT-inhibitor studies;
- Obviousness based on known IBAT inhibition and cholestasis-related pruritus;
- Written-description concerns regarding the range of claimed diseases;
- Enablement arguments concerning diseases not supported by clinical data;
- Indefiniteness of terms such as "bile acid disease" or "therapeutically effective amount."
Claim construction
The meaning of "cholestasis-induced pruritus," "bile acid disease," "pediatric subject," and "decreases the level of liver bile acids" could determine the practical value of the dependent claims.
A settlement could permit a generic launch before the expected patent expiration date. No public settlement date or authorized-generic arrangement is established here.
How does maralixibat compare with competing IBAT inhibitors?
| Product |
Active ingredient |
Company |
Commercial status |
Relationship to ’633 |
| Livmarli |
Maralixibat chloride |
Mirum |
FDA approved for ALGS and PFIC |
Directly relevant |
| Bylvay |
Odevixibat |
Ipsen |
FDA approved for PFIC and other markets/indications |
Different molecule; generally outside claim 1 |
| Elobixibat |
Elobixibat |
Regional sponsors |
Approved in certain non-U.S. markets for constipation |
Different molecule |
| Linerixibat |
Linerixibat |
GSK |
Clinical development |
Different molecule |
| Volixibat |
Volixibat |
Clinical-stage sponsors |
Clinical development |
Different molecule |
The ’633 patent is not a platform patent covering all IBAT inhibitors. Its competitive value is concentrated in maralixibat-based treatment of cholestatic pruritus.
How strong is the patent estate for Livmarli?
US 10,011,633 is commercially meaningful but narrower than a composition patent.
Its strengths are:
- Direct coverage of the marketed active ingredient;
- No specific dose requirement;
- Express coverage of oral treatment;
- Direct pediatric coverage;
- Explicit inclusion of ALGS and PFIC;
- Potential relevance to FDA-approved labeling.
Its limitations are:
- It is a method claim rather than a composition claim;
- It requires treatment of cholestasis-induced pruritus;
- It does not expressly claim the oral-solution formulation;
- It may be vulnerable to carve-out strategies depending on FDA use coding;
- Its dependent disease claims may face written-description or enablement challenges for less-developed indications;
- Alternative IBAT inhibitors are generally outside its chemical limitation.
Overall, the patent is strongest against a maralixibat generic that seeks a full label for cholestatic pruritus, ALGS, PFIC, or pediatric use. It is weaker against a competing product containing a different IBAT inhibitor or a generic applicant that can obtain a legally effective section viii labeling carve-out.
What generic launch scenarios exist for maralixibat?
Full-label ANDA with Paragraph IV certification
This would create the highest litigation risk and the clearest route to an early challenge. The applicant would argue that the patent is invalid, unenforceable, or not infringed.
Carved-label ANDA
A generic applicant might omit patented methods from its labeling. This strategy depends on whether the remaining label has a substantial noninfringing use and whether the FDA-approved indication is inseparable from the patented method.
Launch after patent expiration
This is the lowest-risk path but could leave a substantial commercial window protected by the patent until approximately 2034.
505(b)(2) product
A sponsor developing a modified maralixibat formulation or a new indication could use a 505(b)(2) pathway. Patent certification and potential infringement exposure would still depend on the proposed labeling and listed patents.
Alternative IBAT inhibitor
A company can avoid the ’633 chemical limitation by developing odevixibat, linerixibat, elobixibat, volixibat, or another structurally distinct IBAT inhibitor. That strategy shifts the risk to the competing molecule’s own composition, formulation, and method patents.
What is the geographic coverage of US Patent 10,011,633?
The ’633 patent provides rights only in the United States. Parallel national-phase or related patents may exist in Europe, Japan, Canada, Australia, and other jurisdictions, but foreign rights require separate review of:
- National-phase patent numbers;
- Local claim scope;
- Supplementary protection certificates;
- Patent-term adjustments or extensions;
- Opposition and appeal proceedings;
- Local regulatory exclusivity.
A US patent does not prevent manufacture or sale outside the United States unless related foreign rights apply. Importation of a product into the United States can create separate infringement exposure under 35 U.S.C. §271(a) and related provisions.
Key Takeaways
- US Patent 10,011,633 is a method-of-use patent for oral maralixibat treatment of cholestasis-induced pruritus.
- The patent directly covers maralixibat chloride, the active ingredient in Livmarli.
- Claim 1 is the central commercial claim and does not require a particular dose or formulation.
- Claims 3 and 4 extend coverage to pregnancy cholestasis, ALGS, PFIC, PBC, fibrosis, NAFLD, NASH, and PSC.
- Claim 7 directly addresses pediatric treatment.
- Claims 5 and 6 add serum and liver bile-acid reduction requirements.
- The expected patent expiration is approximately 2034, subject to the official USPTO term calculation.
- FDA orphan exclusivity for ALGS and PFIC is separate from patent exclusivity and may expire earlier.
- Odevixibat and other IBAT inhibitors are structurally different and are not automatically covered by the ’633 claims.
- The most credible generic challenge would involve a Paragraph IV filing against claim 1, potentially combined with litigation over labeling and induced infringement.
- A section viii carve-out may be possible in theory but would depend on the Orange Book use code and the FDA-approved label.
FAQs About US Patent 10,011,633 and Livmarli
Is US Patent 10,011,633 a composition-of-matter patent?
No. It is principally a method-of-treatment patent. It claims administering maralixibat or a pharmaceutically acceptable salt to treat cholestasis-induced pruritus.
Does US Patent 10,011,633 cover odevixibat?
No. The claims identify a specific maralixibat structure. Odevixibat is a different IBAT inhibitor and requires separate patent analysis.
Does the patent cover Livmarli oral solution?
The patent does not expressly require an oral solution. It covers oral administration of maralixibat. A separate formulation patent may provide additional protection for the Livmarli product.
Can a generic company omit the patented use from its label?
Potentially, through a section viii statement, but the feasibility depends on the precise Orange Book use code, the remaining label, and whether the FDA regards the patented use as separable.
Does patent expiration end all exclusivity for Livmarli?
No. FDA orphan, new chemical entity, pediatric, or other regulatory exclusivities may operate independently of patent rights and may have different expiration dates.
Is a biosimilar pathway relevant to maralixibat?
No. Maralixibat is a chemically synthesized small molecule. A competing product would generally use an ANDA or, for a modified product or new indication, a 505(b)(2) application rather than a biosimilar application.
Sources
- United States Patent No. 10,011,633, “Methods of treating cholestasis,” issued July 3, 2018. U.S. Patent and Trademark Office.
- U.S. Food and Drug Administration. (2024). Livmarli (maralixibat) oral solution prescribing information.
- U.S. Food and Drug Administration. (2024). Approved drug products with therapeutic equivalence evaluations, Orange Book.
- U.S. Food and Drug Administration. (2023). Drugs@FDA: Livmarli approval history and regulatory information.
- U.S. Code, 21 U.S.C. §355 and 35 U.S.C. §§271, 282, 283, 284.
