Mirum Pharma Inc v. Sandoz Inc

I. Executive Summary and Procedural Information

• Parties & Counsel:
  • Plaintiff: Mirum Pharmaceuticals, Inc. (Delaware); Satiogen Pharmaceuticals, Inc. (Delaware); and Shire Human Genetic Therapies, Inc. (Delaware)
  • Defendant: Sandoz Inc. (Delaware)
  • Plaintiff's Counsel: Shaw Keller LLP; Cooley LLP; Patterson Belknap Webb & Tyler LLP
• Case Identification: 1:25-cv-01538, D. Del., 05/18/2026
• Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant Sandoz Inc. is a Delaware corporation, conducts systematic business in the state, and has purposefully availed itself of the protections of Delaware law.
• Core Dispute: Plaintiffs allege that Defendant's submission of an Abbreviated New Drug Application (ANDA) to the FDA, seeking to market a generic version of Plaintiffs' LIVMARLI® (maralixibat) oral solution, constitutes an act of infringement of six U.S. patents.
• Technical Context: The technology relates to pharmaceutical methods for treating rare cholestatic liver diseases, such as Alagille syndrome (ALGS), by administering an Apical Sodium-dependent Bile Acid Transporter (ASBT) inhibitor to reduce the accumulation of bile acids.
• Key Procedural History: This is a Hatch-Waxman action triggered by a notice letter dated November 14, 2025, in which Sandoz notified Plaintiffs of its ANDA filing with a Paragraph IV certification, asserting that the patents-in-suit are invalid, unenforceable, or will not be infringed by its proposed generic product. All asserted patents are listed in the FDA's "Orange Book" for LIVMARLI®.

Case Timeline

Date	Event
2010-05-26	Priority Date for '053 Patent
2012-05-06	Priority Date for '251 Patent
2019-11-07	Earliest Priority Date for '647, '745, '578, and '602 Patents
2022-01-25	'647 Patent Issued
2022-03-01	'053 Patent Issued
2022-07-05	'251 Patent Issued
2022-11-15	'745 Patent Issued
2024-03-05	'578 Patent Issued
2025-11-14	Sandoz sends Paragraph IV Notice Letter
2026-04-14	'602 Patent Issued
2026-04-22	'602 Patent listed in the Orange Book
2026-05-18	Complaint Filed

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 11,229,647 - "Methods for treating cholestasis"

The Invention Explained

• Problem Addressed: The patent addresses cholestatic liver diseases, which are characterized by impaired bile secretion and the resulting accumulation of toxic levels of bile acids in the liver, leading to liver injury (e.g., cirrhosis, liver failure) and severe symptoms like pruritus (itching) '647 Patent, col. 1:26-34
• The Patented Solution: The invention provides a method for treating cholestasis, and specifically Alagille Syndrome (ALGS), by administering maralixibat, an Apical Sodium-dependent Bile Acid Transporter (ASBT) inhibitor '647 Patent, abstract As illustrated in Figure 1 of the patent, maralixibat interrupts the enterohepatic circulation of bile acids by blocking their reuptake from the intestine, which increases their fecal excretion and reduces their concentration in the liver '647 Patent, FIG. 1 '647 Patent, col. 7:31-38
• Technical Importance: The invention provides a targeted molecular therapy for ALGS, a rare genetic disorder with limited treatment options that often leads to progressive liver damage.

Key Claims at a Glance

• The complaint asserts independent claims 1 and 12 Compl. ¶51
• Independent Claim 1:
  • A method for treating Alagille Syndrome (ALGS) in a subject in need of such treatment.
  • The method comprises administering maralixibat (or a pharmaceutically acceptable salt thereof).
  • The maralixibat is administered in an amount of from about 400 µg/kg/day to about 800 µg/kg/day.
• Independent Claim 12:
  • A method for treating Alagille Syndrome (ALGS) in a pediatric subject in need of such treatment.
  • The method comprises administering maralixibat chloride.
  • The maralixibat chloride is administered in an amount of about 400 µg/kg/day.
• The complaint reserves the right to assert additional claims Compl. ¶51

U.S. Patent No. 11,376,251 - "Bile acid recycling inhibitors for treatment of pediatric cholestatic liver diseases"

The Invention Explained

• Problem Addressed: The patent describes the significant morbidity associated with pediatric cholestatic liver diseases and the lack of effective and safe treatments, particularly for pediatric patients who are vulnerable to systemic side effects '251 Patent, col. 1:33-41
• The Patented Solution: The patent claims methods of treating or ameliorating pediatric cholestatic liver diseases, including ALGS and associated pruritus, by administering a non-systemically or minimally absorbed ASBT inhibitor, specifically maralixibat '251 Patent, abstract The minimal systemic absorption is intended to reduce the risk of side effects while still providing therapeutic benefit by acting locally in the gastrointestinal tract to inhibit bile acid reuptake '251 Patent, col. 18:31-41
• Technical Importance: This approach offers a targeted treatment for pediatric liver diseases that is designed to be safer by minimizing the drug's presence in the rest of the body.

Key Claims at a Glance

• The complaint asserts independent claims 1, 14, and 19 Compl. ¶72
• Independent Claim 1:
  • A method for treating or ameliorating Alagille syndrome (ALGS) in a pediatric subject.
  • The method comprises administering a therapeutically effective amount of an ASBT inhibitor (ASBTi), specifically the compound of Formula I (maralixibat) or a salt thereof.
• Independent Claim 14:
  • A method for treating or ameliorating pruritus in a pediatric subject suffering from ALGS.
  • The method comprises administering a therapeutically effective amount of an ASBTi, specifically the compound of Formula I (maralixibat) or a salt thereof.
• Independent Claim 19:
  • A method for treating or ameliorating pruritus in a pediatric subject suffering from ALGS.
  • The method comprises administering an ASBTi which is maralixibat, or a salt thereof.
• The complaint reserves the right to assert additional claims Compl. ¶72

U.S. Patent No. 11,497,745 - "Methods for treating cholestasis"

• Technology Synopsis: This patent claims methods for treating ALGS by administering maralixibat within a specific dosage range. The invention is directed at providing an effective therapeutic window for treating the disease '745 Patent, abstract '745 Patent, col. 134:2-10
• Asserted Claims: Independent claim 1 Compl. ¶93
• Accused Features: The complaint alleges that Sandoz's proposed product label instructs administering maralixibat for treating ALGS in a subject at a dosage of 360 µg/kg/day to 880 µg/kg/day, which falls within the claimed range Compl. ¶102

U.S. Patent No. 11,918,578 - "Methods for treating cholestasis"

• Technology Synopsis: This patent covers a method for treating cholestatic pruritus in ALGS patients by administering a specific liquid pharmaceutical composition of maralixibat. The invention focuses on the specific formulation and dosage for effective treatment '578 Patent, abstract '578 Patent, col. 136:7-17
• Asserted Claims: Independent claim 1 Compl. ¶114
• Accused Features: The complaint alleges that Sandoz's proposed product is a liquid oral solution of maralixibat and that its label will instruct administration for treating cholestatic pruritus in ALGS subjects within the claimed dosage range of about 400 µg/kg/day to about 800 µg/kg/day Compl. ¶122

U.S. Patent No. 11,260,053 - "Bile acid recycling inhibitors and satiogens for treatment of diabetes, obesity, and inflammatory gastrointestinal conditions"

• Technology Synopsis: This patent is directed to methods of increasing the concentration of bile acids in the distal gastrointestinal tract by administering an ASBT inhibitor, which is delivered to the distal ileum, colon, and/or rectum. This mechanism is described as useful for treating various metabolic and gastrointestinal disorders '053 Patent, abstract '053 Patent, col. 1:18-28
• Asserted Claims: Independent claim 1 Compl. ¶134
• Accused Features: The complaint alleges that the proposed label for Sandoz's ANDA Product, which contains the ASBTI maralixibat, instructs a use that necessarily results in increasing the concentration of bile acids in the distal gastrointestinal tract as claimed Compl. ¶141

U.S. Patent No. 12,599,602 - "Methods for treating cholestasis"

• Technology Synopsis: This patent claims a method for treating cholestatic pruritus in ALGS patients using a liquid pharmaceutical composition containing maralixibat, a sweetener, a flavoring agent, and a liquid carrier, administered at a specific dosage. The invention focuses on a particular formulation for oral delivery '602 Patent, abstract '602 Patent, col. 137:1-8
• Asserted Claims: Independent claim 1 Compl. ¶153
• Accused Features: The complaint alleges Sandoz's ANDA product is an oral solution containing maralixibat, a sweetener, and a flavoring agent, and that its proposed label instructs administration for treating cholestatic pruritus at a dosage that meets the claim limitations Compl. ¶¶159-164

III. The Accused Instrumentality

Product Identification

• Sandoz's ANDA No. 220714 product, a proposed generic version of LIVMARLI® (maralixibat) Oral Solution, 9.5 mg/mL ("Sandoz's ANDA Product") Compl. ¶2

Functionality and Market Context

• The accused instrumentality is a proposed generic drug product that has not yet been marketed. The act of infringement is the submission of the ANDA to the FDA seeking approval to market this product prior to the expiration of the Asserted Patents Compl. ¶1 The complaint alleges that the proposed product is a liquid oral solution containing maralixibat as the active ingredient Compl. ¶3 Compl. ¶30 It is intended to be a lower-cost, bioequivalent version of Plaintiffs' branded drug, LIVMARLI®, which is indicated for the treatment of cholestatic pruritus in patients with ALGS Compl. ¶29 Compl. ¶56 This figure provides a schematic diagram illustrating the physiological mechanism by which maralixibat interrupts the recirculation of bile acids to treat cholestasis '647 Patent, FIG. 1

IV. Analysis of Infringement Allegations

11,229,647 Patent Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
A method for treating Alagille Syndrome (ALGS) in a subject in need of such treatment	The proposed label for Sandoz's ANDA Product indicates the drug for "the treatment of cholestatic pruritus in patients... with Alagille syndrome (ALGS)," which Plaintiffs allege constitutes treating ALGS as defined in the patent (Compl. ¶56; Compl. ¶60).	¶56; ¶60	col. 21:8-21
comprising administering to the subject maralixibat, or a pharmaceutically acceptable salt thereof,	Sandoz's ANDA Product is an oral solution containing maralixibat Compl. ¶2 Compl. ¶3	¶2; ¶3	col. 137:5-7
wherein maralixibat is administered in an amount of from about 400 µg/kg/day to about 800 µg/kg/day.	The complaint alleges, on information and belief, that Sandoz's proposed labeling instructs and encourages administration in an amount of "about 400 µg/kg/day and/or from about 400 µg/kg/day to about 800 µg/kg/day" (Compl. ¶60).	¶60	col. 137:8-10

11,376,251 Patent Infringement Allegations

Claim Element (from Independent Claim 1)	Alleged Infringing Functionality	Complaint Citation	Patent Citation
A method for treating or ameliorating Alagille syndrome (ALGS) in a pediatric subject in need thereof,	The proposed labeling for Sandoz's ANDA product is for treating cholestatic pruritus in pediatric subjects with ALGS, which the complaint alleges meets the "treating or ameliorating" limitation (Compl. ¶77; Compl. ¶80).	¶77; ¶80	col. 85:19-38
the method comprising administering to the pediatric subject a therapeutically effective amount of an Apical Sodium-dependent Bile Acid Transporter inhibitor (ASBTi)... wherein the ASBTi is a compound of Formula I...	Sandoz's ANDA Product contains maralixibat, which is the ASBTi compound of Formula I, and the proposed label directs administration to pediatric subjects (Compl. ¶76; Compl. ¶80).	¶76; ¶80	col. 147:15-46

Identified Points of Contention

• Scope Questions: A central dispute may arise over the interpretation of "treating Alagille Syndrome" (e.g., in the '647 patent). The court will likely need to determine whether a product label indicating treatment for "cholestatic pruritus in patients with... Alagille syndrome" Compl. ¶56 meets a claim limitation for "treating Alagille Syndrome" itself. Sandoz may argue that treating a symptom is not the same as treating the underlying disease, while Plaintiffs will likely argue the patent's definition of "treating" is broad enough to cover symptom alleviation.
• Technical Questions: For all asserted patents, the infringement allegation relies on the instructions in Sandoz's proposed product label. The factual question will be whether the specific language of that label, once finalized by the FDA, directs users to perform all steps of the claimed methods. Any discrepancy between the final approved label and the claimed methods (e.g., in dosage, patient population, or stated indication) could form the basis of a non-infringement defense.

V. Key Claim Terms for Construction

"treating" or "treating or ameliorating"

• Context and Importance: This term is critical because Sandoz's proposed label is for treating "cholestatic pruritus in patients... with Alagille syndrome" Compl. ¶56, whereas several key claims are for "treating Alagille Syndrome" (e.g., '647 Patent, claim 1). The outcome of the infringement analysis may depend on whether treating a major symptom of a disease is construed as "treating" the disease itself under the patent's terms.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The specifications provide an explicit definition. For example, the '647 Patent states the term ""treating" or "treatment"... refers to an action that obtains a desired pharmacologic and/or physiologic effect... The effect may be prophylactic... or it may be therapeutic... For purposes of the present invention, beneficial or desired clinical results include, but are not limited to, relieving, reducing or alleviating one or more signs, symptoms, or causes of a disease or condition" '647 Patent, col. 21:8-21 This language may support Plaintiffs' view that alleviating pruritus (a sign/symptom) constitutes "treating" ALGS.
  • Evidence for a Narrower Interpretation: Sandoz may point to the fact that some patents-in-suit, like the '251 Patent, contain separate independent claims directed to "treating or ameliorating Alagille syndrome" (Claim 1) and "treating or ameliorating pruritus" (Claim 14). Practitioners may focus on this distinction to argue that the patentee treated these as separate concepts, suggesting "treating ALGS" requires more than just addressing pruritus.

"pediatric subject"

• Context and Importance: Multiple claims are limited to use in a "pediatric subject" (e.g., '251 Patent, claim 1). Sandoz's proposed label is for patients "3 months of age and older" Compl. ¶56 The construction of "pediatric subject" will be necessary to determine the extent of overlap between the claimed patient population and the population covered by the accused label.
• Intrinsic Evidence for Interpretation:
  • Evidence for a Broader Interpretation: The '251 Patent provides a definition: "The term "pediatric" is used to refer to a subject who is a neonate, an infant, a child, or an adolescent" and further defines "child" as a subject between 2 and 11 years old and "adolescent" as between 12 and 18 years old '251 Patent, col. 85:12-18 This broad definition appears to cover a significant portion of the patient population in Sandoz's proposed label.
  • Evidence for a Narrower Interpretation: A defendant could potentially argue for a narrower construction based on the specific age ranges of patients included in the clinical trials described in the specification. For example, if the data supporting efficacy was primarily from a narrower age band within the pediatric range, Sandoz might contend the claims should be limited to that demonstrated scope, though this is often a difficult argument to win against an explicit definition in the specification.

VI. Other Allegations

Indirect Infringement

• The complaint alleges induced infringement under 35 U.S.C. § 271(b). The basis for this allegation is that Sandoz's proposed product label will actively instruct and encourage healthcare professionals and patients to administer the generic drug in a manner that directly infringes the method claims of the asserted patents Compl. ¶64 Compl. ¶85 Compl. ¶106 Compl. ¶126 Compl. ¶145 Compl. ʻ168

Willful Infringement

• The complaint alleges that Sandoz's infringement has been and will be willful. This is based on Sandoz's alleged knowledge of the asserted patents, evidenced by the patents' listing in the FDA Orange Book and, most directly, by Sandoz's submission of a Paragraph IV notice letter acknowledging the patents' existence Compl. ¶67 Compl. ¶88 The complaint further alleges Sandoz acted without a reasonable basis for believing it would not be liable for infringement Compl. ¶68 Compl. ¶89

VII. Analyst's Conclusion: Key Questions for the Case

• A core issue will be one of definitional scope: can the claim term "treating Alagille Syndrome" be construed to cover a product label indicating treatment for "cholestatic pruritus in patients with Alagille syndrome"? The court's interpretation of "treating" in the context of the patent's own definitions and claim differentiation arguments will be pivotal.
• A second key question will be one of infringement by labeling: does the specific language in Sandoz's proposed ANDA label-governing dosage, patient population, and formulation-contain instructions that fall squarely within the boundaries of the asserted method claims? As this is a Hatch-Waxman case, the entire infringement analysis rests on this comparison between the patent claims and the paper record of the proposed drug label.
• A final dispositive issue will be patent validity: Sandoz has asserted in its Paragraph IV notice letter that the patents are invalid and/or unenforceable Compl. ¶3 While the complaint does not detail Sandoz's invalidity theories, these challenges (e.g., based on obviousness or lack of written description) will be a central battleground in the litigation, running in parallel to the infringement analysis.