DCT

1:25-cv-01537

Mirum Pharma Inc v. Annora Pharma Pvt Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:25-cv-01537, D. Del., 05/18/2026
  • Venue Allegations: Venue is asserted based on Defendants' regular and systematic business contacts within Delaware, purposeful availment of the forum, and the submission of an Abbreviated New Drug Application (ANDA) which constitutes a tortious act of infringement directed at the entire U.S. market, including Delaware.
  • Core Dispute: Plaintiffs allege that Defendants' filing of an ANDA to seek FDA approval for a generic version of Plaintiffs' drug LIVMARLI® (maralixibat) constitutes an act of infringement of nine patents covering the drug's composition and methods for treating rare pediatric cholestatic liver diseases.
  • Technical Context: The technology involves Apical Sodium-dependent Bile Acid Transporter (ASBTI) inhibitors, which are designed to treat certain liver diseases by blocking the reabsorption of bile acids in the intestine, thereby reducing their accumulation in the liver and bloodstream.
  • Key Procedural History: This case was initiated under the provisions of the Hatch-Waxman Act following Defendants' submission of ANDA No. 220669. The filing includes a Paragraph IV certification alleging that Plaintiffs' Orange Book-listed patents for LIVMARLI® are invalid, unenforceable, or will not be infringed by the proposed generic product.

Case Timeline

Date Event
2010-05-26 Earliest Priority Date (’053 Patent)
2011-10-28 Earliest Priority Date (’657, ’661, ’267, ’251 Patents)
2019-02-12 Earliest Priority Date (’647, ’745, ’578, ’602 Patents)
2019-12-24 ’657 Patent Issued
2022-01-25 ’661 Patent Issued
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
2025-07-08 ’267 Patent Issued
2025-11-20 Zydus Notice Letter Sent to Plaintiffs
2026-04-14 ’602 Patent Issued
2026-04-22 ’602 Patent listed in FDA Orange Book
2026-05-18 Complaint Filed

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 safe treatments for pediatric cholestatic liver diseases, which are rare but can lead to severe liver damage, need for liver transplantation, and mortality ( Compl. ¶39; ’657 Patent, col. 1:21-26). The patent notes that therapeutic options for the pediatric population are particularly limited, and adult treatments may be unsuitable due to side effects or difficulties with administration to children (’657 Patent, col. 1:29-38).
  • The Patented Solution: The patent discloses methods for treating these pediatric diseases by administering an Apical Sodium-dependent Bile Acid Transporter (ASBTI) inhibitor (’657 Patent, abstract). By inhibiting ASBTI in the gastrointestinal tract, the drug blocks the re-uptake of bile acids into the bloodstream, increasing their fecal excretion and lowering their concentration in the liver and serum, which is intended to ameliorate liver damage and symptoms like pruritus (intense itching) (’657 Patent, col. 17:1-9; ’657 Patent, col. 18:1-12). The invention focuses on non-systemically absorbed inhibitors to minimize side effects (’657 Patent, abstract).
  • Technical Importance: The development of a non-systemically absorbed inhibitor represented an approach to treating chronic pediatric liver conditions that could potentially offer a better safety profile for long-term use compared to systemically absorbed drugs (’657 Patent, col. 18:6-12).

Key Claims at a Glance

  • The complaint asserts independent claims 1, 2, and 3 (Compl. ¶73).
  • Independent Claim 1: A method of treating or ameliorating pediatric progressive familial intrahepatic cholestasis type 2 (PFIC2) in a pediatric subject by administering an ASBTI (maralixibat) that is effective for decreasing serum and/or hepatic bile acid levels by at least 20%.
  • Independent Claim 2: A method of treating or ameliorating pruritus in a pediatric subject suffering from PFIC2 by administering an ASBTI (maralixibat) that is effective for decreasing serum and/or hepatic bile acid levels.
  • Independent Claim 3: A method of treating or ameliorating a pediatric cholestatic liver disease (selected from a specific list including PFIC2) in a pediatric subject by administering an ASBTI (maralixibat).

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

The Invention Explained

  • Problem Addressed: As with the ’657 Patent, the technology addresses the unmet need for treating pediatric cholestatic liver diseases (’661 Patent, col. 2:20-33).
  • The Patented Solution: The ’661 patent claims methods for treating specific subsets of pediatric patients. The invention focuses on administering an ASBTI (maralixibat) to pediatric patients whose disorder is characterized by a "non-truncating BSEP mutation" or who have specific types of cholestasis like PFIC2 or Benign Recurrent Intrahepatic Cholestasis 2 (BRIC2) (’661 Patent, abstract; ’661 Patent, col. 19:1-9).
  • Technical Importance: This patent refines the treatment paradigm by identifying a specific genetic biomarker (non-truncating BSEP mutation) associated with the disease, potentially allowing for more targeted therapeutic intervention in a defined patient subpopulation (’661 Patent, col. 19:1-24).

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶94; Compl. ¶99).
  • Independent Claim 1: A method for treating or ameliorating a pediatric disorder characterized by having a non-truncating BSEP mutation in a pediatric subject, the disorder being selected from PFIC2 or BRIC2, by administering an ASBTI (maralixibat).

U.S. Patent No. 12,350,267 - Bile acid recycling inhibitors for the treatment of pediatric cholestatic liver diseases

  • Technology Synopsis: The patent claims methods of treating or ameliorating pruritus in pediatric subjects with cholestatic liver disease by administering an ASBTI inhibitor like maralixibat, including as part of a composition (’267 Patent, abstract). (Compl. ¶50).
  • Asserted Claims: Independent claims 1, 2, and 20 are asserted (Compl. ¶112).
  • Accused Features: The proposed use of the Zydus ANDA Product to treat pruritus in pediatric patients having PFIC is alleged to infringe (’267 Patent, col. 6:34-36; Compl. ¶120; Compl. ¶121).

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

  • Technology Synopsis: The patent claims methods for treating Alagille syndrome (ALGS) in pediatric subjects by administering maralixibat chloride in a specific dosage range (’647 Patent, abstract). (Compl. ¶54).
  • Asserted Claims: Independent claims 1 and 12 are asserted (Compl. ¶133).
  • Accused Features: The proposed use of Zydus's ANDA Product for treating ALGS at an administered amount of about 400 µg/kg/day to about 800 µg/kg/day is alleged to infringe (Compl. ¶140).

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

  • Technology Synopsis: The patent claims methods for treating or ameliorating ALGS in pediatric subjects by administering a composition containing an ASBTI inhibitor (’251 Patent, abstract). (Compl. ¶57).
  • Asserted Claims: Independent claims 1, 14, and 19 are asserted (Compl. ¶152).
  • Accused Features: The proposed use of Zydus's ANDA Product for treating ALGS in a pediatric subject is alleged to infringe (Compl. ¶160; Compl. ¶161).

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

  • Technology Synopsis: The patent claims methods of treating ALGS in a subject by administering maralixibat chloride in a specific dosage range, from about 360 µg/kg/day to 880 µg/kg/day (’745 Patent, abstract). (Compl. ¶61).
  • Asserted Claims: Independent claim 1 is asserted (Compl. ¶173).
  • Accused Features: The use of Zydus's ANDA Product as directed by its proposed labeling for treating ALGS is alleged to fall within the claimed dosage range (Compl. ¶180).

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

  • Technology Synopsis: This patent claims methods for treating cholestatic pruritus in a subject with ALGS by administering a pharmaceutical composition of maralixibat within a specific dosage and concentration range (’578 Patent, abstract). (Compl. ¶64).
  • Asserted Claims: Independent claim 1 is asserted (Compl. ¶192).
  • Accused Features: The proposed use and formulation of the Zydus ANDA Product, including administration of maralixibat at about 400 µg/kg/day to about 800 µg/kg/day, is alleged to infringe (Compl. ¶200).

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

  • Technology Synopsis: The patent claims methods for increasing the concentration of bile acids and salts in the distal gastrointestinal tract of an individual by administering an ASBTI inhibitor (’053 Patent, abstract). This mechanism is foundational to the therapeutic effect of maralixibat. (Compl. ¶67).
  • Asserted Claims: Independent claim 1 is asserted (Compl. ¶212).
  • Accused Features: The use of the Zydus ANDA Product is alleged to inherently practice the claimed method by decreasing reabsorption of bile acids, which in turn increases their concentration in the distal ileum (Compl. ¶214; Compl. ¶217).

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

  • Technology Synopsis: This patent claims a pharmaceutical composition as an oral solution comprising maralixibat, a sweetener, a flavoring agent, and a liquid carrier, for treating cholestatic pruritus in subjects with ALGS (’602 Patent, abstract). (Compl. ¶70).
  • Asserted Claims: Independent claim 1 is asserted (Compl. ¶229).
  • Accused Features: The Zydus ANDA Product is alleged to be an oral solution containing maralixibat, a sweetener, a flavoring agent, and a liquid carrier, thereby infringing the composition claim (Compl. ¶¶235-241).

III. The Accused Instrumentality

Product Identification

The accused instrumentality is "Zydus's ANDA Product," a generic version of LIVMARLI® (maralixibat chloride) oral solution for which Zydus FZE has filed Abbreviated New Drug Application No. 220669 with the U.S. Food and Drug Administration (FDA) (Compl. ¶¶1-2).

Functionality and Market Context

The Zydus ANDA Product is a proposed generic drug intended to be therapeutically equivalent to LIVMARLI®, which is approved for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS) and progressive familial intrahepatic cholestasis (PFIC) (Compl. ¶¶39-40; Compl. ¶77). As an ASBTI inhibitor, its function is to block bile acid reabsorption in the gut (Compl. ¶214). The complaint alleges that upon approval, Zydus's product will compete with and displace sales of LIVMARLI®, indicating its commercial importance as a lower-cost alternative to a branded orphan drug (Compl. ¶35).

No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint alleges that the filing of the ANDA is a technical act of infringement under 35 U.S.C. § 271(e)(2)(A), and that the future commercial manufacture, use, or sale of the Zydus ANDA Product will infringe the asserted patents. The infringement theory for the method-of-use claims is primarily one of induced infringement, based on the allegation that the proposed product labeling will instruct medical professionals to prescribe the drug for the patented methods (Compl. ¶81; Compl. ¶100).

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 in need thereof The proposed label for Zydus's ANDA Product instructs and encourages use for treating or ameliorating PFIC2, a form of cholestatic liver disease. ¶81 col. 23:23-28
comprising administering to the pediatric subject an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI) The Zydus ANDA Product is an ASBTI. Its proposed label instructs administration to pediatric subjects. ¶81 col. 1:40-47
wherein the ASBTI is [maralixibat structure], or a pharmaceutically acceptable salt thereof The Zydus ANDA Product is an oral solution of maralixibat chloride, a pharmaceutically acceptable salt of the claimed structure. ¶77 col. 146:20-43
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 use of Zydus's ANDA Product as directed by its proposed label is alleged to be effective for achieving this decrease in bile acid levels. ¶81 col. 3:1-9

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 disorder characterized by having a non-truncating BSEP mutation in a pediatric subject, wherein the pediatric disorder is selected from PFIC2, benign recurrent intrahepatic cholestasis 2 (BRIC2), and drug induced cholestasis, The proposed label for Zydus's ANDA Product instructs for use in treating PFIC2. The complaint alleges that treating PFIC2 inherently means treating a disorder characterized by a BSEP mutation. ¶100 col. 19:1-9
comprising administering to the pediatric subject the claimed ASBTI or a pharmaceutically acceptable salt thereof. The proposed label for the Zydus ANDA Product instructs its administration to pediatric subjects for treating PFIC2. ¶100 col. 1:1-8

Identified Points of Contention

  • Scope Questions: A potential point of contention for the method claims (e.g., in the '657 and '661 patents) is whether the instructions on Zydus's proposed label will be specific enough to induce infringement of every claim limitation. For example, for the '661 patent, the dispute may center on whether a general instruction to treat "PFIC2" is sufficient to induce infringement of a claim that requires treating a disorder "characterized by having a non-truncating BSEP mutation," or if a more specific instruction or patient selection criterion is needed.
  • Technical Questions: For the ’657 patent, a key question will be evidentiary: what proof is required to show that administering the accused generic product is "effective for decreasing at least 20% of serum and/or hepatic bile acid levels"? The dispute may involve whether the bioequivalence data in the ANDA is sufficient to meet this functional limitation, or if Zydus will contest that its product achieves this specific outcome.

V. Key Claim Terms for Construction

"pediatric subject"

  • Context and Importance: (e.g., ’657 Patent, claim 1) The patents are specifically directed to a pediatric population. The precise age range encompassed by "pediatric" is fundamental to the scope of the method claims, as it defines the eligible patient population.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification of the ’657 patent explicitly defines "pediatric" to include "a neonate, an infant, a toddler, a child, and an adolescent." It further defines "adolescent" as an individual from about 10 to about 18 years of age, providing a wide range (’657 Patent, col. 83:58-67; ’657 Patent, col. 7:5-15).
    • Evidence for a Narrower Interpretation: A defendant might argue that the specific examples and clinical data provided in the patent primarily support efficacy in a narrower age group within the pediatric population, and that the claims should be limited accordingly to what the patent actually demonstrates was enabled.

"non-truncating BSEP mutation"

  • Context and Importance: (’661 Patent, claim 1) This term defines the genetic characteristic of the patient population in claim 1 of the ’661 patent. Its definition is critical because infringement will depend on whether Zydus’s product is intended for patients with this specific type of genetic mutation.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: Plaintiffs may argue that the term should be given its plain and ordinary meaning as understood by a person of ordinary skill in genetics and hepatology. The patent itself links the term to the underlying cause of PFIC2, suggesting that treating PFIC2 often involves treating patients with such mutations (’661 Patent, col. 19:1-9).
    • Evidence for a Narrower Interpretation: The ’661 patent provides a table listing specific mutations identified in a clinical study (’661 Patent, Table 3, col. 121-122). A defendant could argue that the term should be construed as being limited to the types of non-truncating mutations explicitly disclosed and studied in the patent, rather than any and all conceivable non-truncating BSEP mutations.

VI. Other Allegations

Indirect Infringement

The complaint alleges induced infringement under 35 U.S.C. § 271(b) (Compl. ¶¶86-87). The basis for this allegation is that Defendants, by creating and seeking approval for a product with a label that is substantially identical to the LIVMARLI® label, know and intend for healthcare professionals to prescribe the generic product for the patented methods of treatment, thereby encouraging direct infringement by those professionals and their patients (Compl. ¶81; Compl. ¶100).

Willful Infringement

Plaintiffs allege that Defendants' infringement has been and will be willful (Compl. ¶90). This allegation is based on Defendants' alleged actual and constructive knowledge of the asserted patents, including from their listing in the FDA's Orange Book, prior to filing the ANDA (Compl. ¶89). The complaint posits that proceeding with the ANDA filing in the face of this knowledge constitutes an "exceptional case" warranting enhanced damages (Compl. ¶90).

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

  1. Label-Induced Infringement: A core issue will be whether the text of Zydus’s proposed product label is specific enough to actively encourage infringement of the detailed method-of-use claims. This will require the court to analyze if a general indication for a disease (e.g., PFIC2) is sufficient to induce infringement of claims that specify genetic subtypes (e.g., "non-truncating BSEP mutation") or functional outcomes (e.g., a "20% decrease" in bile acids).
  2. Patent Thicket Validity: Plaintiffs are asserting a large family of nine patents with overlapping subject matter and priority dates. A key battleground will likely be validity, with questions of whether the later-issued patents are non-obvious variations of the earlier-disclosed inventions. The court's analysis of obviousness-type double patenting and the patentability of claims directed to specific patient subpopulations, dosages, and formulations will be critical.
  3. Claim Scope and Patient Population: The case will likely turn on questions of claim construction, particularly the scope of the term "pediatric subject" and the definitions of the specific diseases and genetic markers recited in the claims. The extent to which the claims are limited to the specific populations and outcomes demonstrated in the patents' clinical examples, versus a broader interpretation, will be central to both infringement and validity determinations.
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