DCT

1:25-cv-01539

Mirum Pharma Inc v. Zenara Pharma Pvt Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:25-cv-01539, D. Del., 12/19/2025
  • Venue Allegations: Plaintiffs allege venue is proper in Delaware because Defendants regularly conduct business in the state, have placed their products into the stream of commerce with the expectation they will be purchased by consumers in Delaware, and will derive substantial revenue from sales within the district.
  • Core Dispute: Plaintiffs allege that Defendants' submission of an Abbreviated New Drug Application (ANDA) to the FDA, seeking approval to market a generic version of Plaintiffs' LIVMARLI® (maralixibat) oral solution, constitutes an act of patent infringement under the Hatch-Waxman Act.
  • Technical Context: The lawsuit concerns pharmaceutical methods for treating rare, serious pediatric cholestatic liver diseases by inhibiting the Apical Sodium-dependent Bile Acid Transporter (ASBTI) to reduce bile acid levels.
  • Key Procedural History: The case was triggered by a November 22, 2025 notice letter from Defendant Zenara to Plaintiffs, informing them of the submission of ANDA No. 220917 with a Paragraph IV certification against the asserted patents. This certification asserts that the patents are invalid, unenforceable, or will not be infringed by the manufacture and sale of the proposed generic product.

Case Timeline

Date Event
2010-05-26 Earliest Priority Date (’053 Patent)
2011-10-28 Earliest Priority Date (’267 Patent; ’251 Patent)
2011-12-28 Earliest Priority Date (’661 Patent)
2012-03-06 Earliest Priority Date (’657 Patent)
2018-11-09 Earliest Priority Date (’647 Patent)
2019-02-12 Earliest Priority Date (’578 Patent)
2019-11-07 Earliest Priority Date (’745 Patent)
2019-12-24 Issue Date: U.S. Patent No. 10,512,657
2022-01-25 Issue Date: U.S. Patent No. 11,229,661
2022-01-25 Issue Date: U.S. Patent No. 11,229,647
2022-03-01 Issue Date: U.S. Patent No. 11,260,053
2022-07-05 Issue Date: U.S. Patent No. 11,376,251
2022-11-15 Issue Date: U.S. Patent No. 11,497,745
2024-03-05 Issue Date: U.S. Patent No. 11,918,578
2025-07-08 Issue Date: U.S. Patent No. 12,350,267
2025-11-22 Date of Defendants' Paragraph IV Notice Letter
2025-12-19 Complaint Filing Date

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

U.S. Patent No. 10,512,657 - "Bile Acid Recycling Inhibitors for Treatment of Pediatric Cholestatic Liver Diseases"

The Invention Explained

  • Problem Addressed: The patent identifies a need for effective and acceptable treatments for pediatric cholestatic liver diseases, which are rare but can lead to severe complications, including the need for liver transplantation (Compl. ¶32; ’657 Patent, col. 1:15-26). Existing therapeutic options are limited and may carry significant side effects or compliance challenges in pediatric populations (’657 Patent, col. 1:27-39).
  • The Patented Solution: The invention provides a method for treating specific pediatric liver diseases by administering an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI) (’657 Patent, abstract). By inhibiting ASBTI, the drug blocks the reabsorption of bile acids from the intestine back to the liver, leading to their increased excretion (’657 Patent, col. 17:1-18:11). This reduction in circulating bile acids is intended to alleviate liver damage and symptoms associated with these diseases (’657 Patent, abstract).
  • Technical Importance: This technology offers a targeted pharmacological intervention for rare pediatric liver diseases, potentially providing a non-surgical alternative or adjunctive therapy where options were previously scarce.

Key Claims at a Glance

  • The complaint asserts independent claim 1 and dependent claims 2 and 3 (Compl. ¶63; Compl. ¶71; Compl. ¶72).
  • The core elements of independent claim 1 are:
    • A method for treating or ameliorating pediatric progressive familial intrahepatic cholestasis type 2 (PFIC2) in a pediatric subject.
    • The method comprises administering to the subject an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI).
    • The ASBTI is a specific compound (maralixibat) or a pharmaceutically acceptable salt thereof.
    • The ASBTI is effective for decreasing at least 20% of serum and/or hepatic bile acid levels compared to pre-administration levels.

U.S. Patent No. 11,229,661 - "Bile acid recycling inhibitors for treatment of pediatric cholestatic liver diseases"

The Invention Explained

  • Problem Addressed: Similar to the ’657 patent, the ’661 patent addresses the lack of effective and suitable medical treatments for a small percentage of children affected by pediatric cholestatic liver diseases (’661 Patent, col. 1:19-41).
  • The Patented Solution: The patent claims methods of treating a specified group of pediatric cholestatic liver diseases by administering an ASBTI, specifically the compound maralixibat (’661 Patent, abstract). The underlying mechanism of inhibiting bile acid recycling is consistent with the related patents, but this patent claims a different scope of treatable diseases (’661 Patent, col. 1:42-53).
  • Technical Importance: The invention broadens the potential therapeutic application of ASBTI inhibitors to additional specific pediatric cholestatic conditions, expanding the market and treatment landscape for this class of drugs.

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶84; Compl. ¶91).
  • The core elements of independent claim 1 are:
    • A method for treating or ameliorating a pediatric cholestatic liver disease in a pediatric subject.
    • The disease is selected from the group consisting of PFIC2, benign recurrent intrahepatic cholestasis 2 (BRIC2), and drug induced cholestasis.
    • The method comprises administering to the subject an ASBTI.
    • The ASBTI is a specific compound (maralixibat) or a pharmaceutically acceptable salt thereof.

Multi-Patent Capsule: U.S. Patent No. 12,350,267

  • Patent Identification: U.S. Patent No. 12,350,267, "Bile Acid Recycling Inhibitors for Treatment of Pediatric Cholestatic Liver Diseases," issued July 8, 2025.
  • Technology Synopsis: The ’267 patent covers methods of treating or ameliorating cholestatic pruritus in pediatric patients suffering from progressive familial intrahepatic cholestasis (PFIC) by administering an ASBTI (maralixibat) (’267 Patent, abstract).
  • Asserted Claims: Independent claims 1, 2, and 20 (Compl. ¶104).
  • Accused Features: The complaint alleges that the proposed labeling for Zenara's ANDA Product instructs and encourages the use of the product for treating or ameliorating PFIC in a pediatric subject, thereby infringing the claims (Compl. ¶112).

Multi-Patent Capsule: U.S. Patent No. 11,229,647

  • Patent Identification: U.S. Patent No. 11,229,647, "Methods for treating cholestasis," issued January 25, 2022.
  • Technology Synopsis: The ’647 patent is directed to methods of treating cholestasis in a subject with a liver disease by administering an ASBTI (maralixibat) at a specific dosage range of about 400 µg/kg/day to about 800 µg/kg/day (’647 Patent, abstract).
  • Asserted Claims: Independent claims 1 and 12 (Compl. ¶125).
  • Accused Features: The complaint alleges that the proposed label for Zenara's ANDA Product instructs administration for treating Alagille syndrome (ALGS), which the complaint asserts is a form of cholestasis, at a dosage that meets the claimed range (Compl. ¶134).

Multi-Patent Capsule: U.S. Patent No. 11,376,251

  • Patent Identification: U.S. Patent No. 11,376,251, "Bile acid recycling inhibitors for treatment of pediatric cholestatic liver diseases," issued July 5, 2022.
  • Technology Synopsis: The ’251 patent claims methods of treating or ameliorating pruritus in a pediatric subject suffering from Alagille syndrome (ALGS) by administering an ASBTI (maralixibat) (’251 Patent, abstract).
  • Asserted Claims: Independent claims 1, 14, and 19 (Compl. ¶146).
  • Accused Features: The complaint alleges that Zenara's proposed label directs the use of its maralixibat product for treating pruritus in pediatric subjects with ALGS, infringing the patent (Compl. ¶154; Compl. ¶155).

Multi-Patent Capsule: U.S. Patent No. 11,497,745

  • Patent Identification: U.S. Patent No. 11,497,745, "Methods for treating cholestasis," issued November 15, 2022.
  • Technology Synopsis: The ’745 patent covers methods for treating cholestasis in a subject with ALGS by administering maralixibat in a specific amount of from about 380 µg/kg/day to 880 µg/kg/day (’745 Patent, abstract).
  • Asserted Claims: Independent claim 1 (Compl. ¶167).
  • Accused Features: The complaint alleges that the proposed label for the Zenara product instructs its use for treating ALGS in a manner that falls within the claimed dosage range (Compl. ¶176).

Multi-Patent Capsule: U.S. Patent No. 11,918,578

  • Patent Identification: U.S. Patent No. 11,918,578, "Methods for treating cholestasis," issued March 5, 2024.
  • Technology Synopsis: The ’578 patent relates to methods for treating cholestasis in a subject with a liver disease, where the method includes administering an ASBTI (maralixibat) as a liquid pharmaceutical composition (’578 Patent, abstract).
  • Asserted Claims: Independent claim 1 (Compl. ¶188).
  • Accused Features: The complaint alleges infringement based on the proposed use of Zenara's liquid maralixibat formulation for treating cholestatic pruritus in subjects with ALGS (Compl. ¶196).

Multi-Patent Capsule: U.S. Patent No. 11,260,053

  • Patent Identification: U.S. Patent No. 11,260,053, "Bile acid recycling inhibitors and satiogens for treatment of diabetes, obesity, and inflammatory gastrointestinal conditions," issued March 1, 2022.
  • Technology Synopsis: The ’053 patent describes methods of utilizing an ASBTI to increase the concentration of bile acids in the distal gastrointestinal tract to treat various conditions (’053 Patent, abstract).
  • Asserted Claims: Independent claim 1 (Compl. ¶208).
  • Accused Features: The complaint alleges that Zenara's ANDA Product label directs that the product decreases the reabsorption of bile acids from the terminal ileum, which is part of the distal gastrointestinal tract, thus infringing the claimed method (Compl. ¶210; Compl. ¶213).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is "Zenara's Maralixibat Chloride Solution, Oral, Eq. 9.5 mg Base/mL and 19 mg Base/mL," referred to as "Zenara's ANDA Product" (Compl. ¶2). This is a generic drug for which Defendants are seeking FDA approval via ANDA No. 220917 (Compl. ¶2).

Functionality and Market Context

  • The Zenara ANDA Product is a proposed generic equivalent to Plaintiffs' LIVMARLI® product (Compl. ¶1). In this Hatch-Waxman context, the infringing functionality is defined by the intended use described on the product's proposed labeling (Compl. ¶63). The complaint alleges this proposed label is substantially identical to the approved label for LIVMARLI® and instructs its use for treating cholestatic pruritus in patients with specific liver diseases like PFIC and ALGS (Compl. ¶67; Compl. ¶109). The filing of the ANDA itself is the statutory act of infringement, predicated on the allegation that the eventual marketing and use of the product as directed by its label would infringe the asserted patents (Compl. ¶74).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

U.S. Patent No. 10,512,657 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for treating or ameliorating pediatric progressive familial intrahepatic cholestasis type 2 (PFIC2) in a pediatric subject The proposed label for Zenara's ANDA Product allegedly instructs and encourages its use for treating or ameliorating pediatric PFIC, which includes PFIC2. ¶71 col. 83:66-84:16
comprising administering to the pediatric subject an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI) The proposed label allegedly instructs administering maralixibat, which is an ASBTI, to pediatric subjects. ¶71 col. 1:40-45
wherein the ASBTI is [maralixibat] or a pharmaceutically acceptable salt thereof Zenara's ANDA Product is a maralixibat chloride solution, which is a pharmaceutically acceptable salt of the claimed ASBTI. ¶2 col. 146:49-62
wherein the ASBTI is effective for decreasing at least 20% of serum and/or hepatic bile acid levels in the pediatric subject as compared to bile acid levels prior to administration of the ASBTI. The complaint alleges on information and belief that the use of Zenara's ANDA Product as directed by its label will be effective in decreasing serum and/or hepatic bile acid levels by at least 20%. ¶71; ¶72 col. 3:1-12

U.S. Patent No. 11,229,661 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for treating or ameliorating a pediatric cholestatic liver disease in a pediatric subject in need thereof, wherein the pediatric cholestatic liver disease is selected from the group consisting of PFIC2, benign recurrent intrahepatic cholestasis 2 (BRIC2), and drug induced cholestasis, The proposed label for Zenara's ANDA Product allegedly instructs its use for treating or ameliorating pediatric PFIC, which includes PFIC2, a claimed disease. ¶92 col. 1:19-21; col. 24:5-20
comprising administering to the pediatric subject an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI), The proposed label allegedly instructs administering maralixibat, an ASBTI, to pediatric patients. ¶92 col. 22:21-25
wherein the ASBTI is [maralixibat] or a pharmaceutically acceptable salt thereof. Zenara's ANDA Product is identified as maralixibat chloride solution, which is a salt of the claimed ASBTI. ¶2; ¶88 col. 74:28-40
  • Identified Points of Contention:
    • Scope Questions: A central question will be whether the indication for "PFIC" on the proposed label is sufficient to meet the more specific claim limitation of "progressive familial intrahepatic cholestasis type 2 (PFIC2)" in the ’657 and ’661 patents. The complaint alleges that the LIVMARLI® label, which Zenara's is said to mimic, explains that PFIC is a "heterogeneous disease ... with different PFIC subtypes" including PFIC2, which may support the plaintiffs' infringement theory (Compl. ¶69; Compl. ¶90).
    • Technical Questions: For the ’657 patent, a key question will be whether the use as directed by the proposed label necessarily results in "decreasing at least 20% of serum and/or hepatic bile acid levels." Because this is an ANDA case based on bioequivalence, Plaintiffs will likely argue this efficacy is inherent in the approved use, while Defendants may argue that their ANDA submission does not concede this specific quantitative therapeutic outcome for all patients as required by the claim.

V. Key Claim Terms for Construction

  • The Term: "treating or ameliorating" (from Claim 1 of the ’657 and ’661 patents)

    • Context and Importance: The definition of this term is fundamental in a method-of-treatment claim. The infringement allegation hinges on the assertion that the instructions on the Defendants' proposed label direct a method of "treating or ameliorating" the claimed diseases (Compl. ¶71; Compl. ¶92). The breadth of this term will be critical to determining if the intended use constitutes infringement.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The ’657 patent provides an explicit, broad definition, stating the term includes "inhibiting or reducing symptoms, reducing or inhibiting the underlying cause of the disease," "arresting the development of the disease," and "preventing the recurrence" of the disease (’657 Patent, col. 83:66-84:16). This language could support a finding of infringement even if the drug only manages symptoms.
      • Evidence for a Narrower Interpretation: Defendants may argue that, in the context of the claims and examples, "treating" requires a specific, clinically significant outcome beyond mere symptom management, potentially pointing to the quantitative reduction of bile acids in claim 1 of the ’657 patent as a required objective measure of treatment.

  • The Term: "pediatric subject" (from Claim 1 of the ’657 and ’661 patents)

    • Context and Importance: The patents are specifically directed to a pediatric population. The complaint alleges the accused product's label directs use in pediatric patients (Compl. ¶109). Whether the patient population covered by the label aligns with the claimed "pediatric subject" is essential for infringement.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The ’657 patent defines "pediatric" or "pediatric patient" as including "a neonate, an infant, a child, or an adolescent" (’657 Patent, col. 83:21-23). It further provides specific age ranges, such as "a child (ages 2 to 11 years)" and "an adolescent (ages 12 to 18 years)" (’657 Patent, col. 83:24-25).
      • Evidence for a Narrower Interpretation: While the definition is broad, a defendant could potentially argue that the clinical data presented in the patent only supports efficacy in a narrower subset of the pediatric population. For example, if the data primarily involves children and not infants, a defendant might argue the claims should be limited to the populations for which efficacy was actually demonstrated in the specification, although this is generally a difficult argument against an explicit definition.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges induced infringement under 35 U.S.C. § 271(b). The factual basis is the allegation that Defendants, with knowledge of the patents, will market their ANDA Product with a proposed label that specifically instructs and encourages physicians and patients to perform the patented methods of treatment (Compl. ¶¶76, 96, 117, 138, 159, 180, 200, 217).
  • Willful Infringement: The complaint alleges willful infringement. The basis for this allegation is Defendants' alleged knowledge of the asserted patents, which are listed in the FDA's Orange Book for the reference listed drug, LIVMARLI® (Compl. ¶79; Compl. ¶99). The complaint asserts that Defendants' decision to file an ANDA with a Paragraph IV certification, despite this knowledge and without a reasonable basis for believing their product would not infringe, makes this an exceptional case warranting enhanced damages and attorneys' fees (Compl. ¶80; Compl. ¶100).

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

  • A core issue will be one of claim scope versus label indication: Does the language of the Defendants' proposed generic drug label, particularly its description of the diseases to be treated (e.g., "PFIC," "ALGS") and the patient population, fall squarely within the specific limitations of the asserted method claims (e.g., "PFIC2," "pediatric subject")?
  • A second key question will be one of demonstrating efficacy: For claims that require a specific therapeutic outcome (e.g., "decreasing at least 20% of serum...bile acid levels" in the '657 patent), will the court find that infringement is met simply by the act of filing an ANDA for a bioequivalent drug with an infringing label, or will Plaintiffs need to present further evidence that the instructed use will necessarily achieve that claimed result?
  • A final central issue will revolve around claim construction: How will the court define functional terms such as "treating or ameliorating"? The outcome of this construction will likely determine whether the uses described on the proposed generic label constitute direct infringement by the end-users, which is a prerequisite for finding induced infringement by the Defendants.
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