DCT

1:25-cv-01541

Mirum Pharma Inc v. Zydus Lifesciences Global FZE

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:25-cv-01541, D. Del., 12/19/2025
  • Venue Allegations: Plaintiffs allege venue is proper in Delaware because all three plaintiff entities are incorporated there, and the alleged injury from the patent challenge is therefore suffered in Delaware. They further allege that Defendants conduct continuous and systematic business in the state and have purposefully availed themselves of its laws, such that they should reasonably anticipate being sued in the district.
  • Core Dispute: Plaintiffs allege that Defendants’ Abbreviated New Drug Application (ANDA) to market a generic version of LIVMARLI® (maralixibat) infringes eight U.S. patents related to methods of treating pediatric cholestatic liver diseases.
  • Technical Context: The patents relate to the use of Apical Sodium-dependent Bile Acid Transporter Inhibitors (ASBTIs) to treat rare and serious pediatric liver diseases by reducing the systemic accumulation of bile acids.
  • Key Procedural History: The action was initiated under the Hatch-Waxman Act following a Notice Letter dated November 20, 2025, in which Defendant Zydus FZE informed Plaintiffs of its ANDA filing with a Paragraph IV certification, asserting non-infringement, invalidity, or unenforceability of the patents-in-suit. The asserted patents are listed in the U.S. Food and Drug Administration's "Orange Book" for LIVMARLI®.

Case Timeline

Date Event
2010-05-26 Earliest Priority Date for '053 Patent
2011-10-28 Earliest Priority Date for '657, '661, '267, '647, '251, '745, '578 Patents
2019-12-24 U.S. Patent No. 10,512,657 Issued
2022-01-25 U.S. Patent No. 11,229,661 Issued
2022-01-25 U.S. Patent No. 11,229,647 Issued
2022-03-01 U.S. Patent No. 11,260,053 Issued
2022-07-05 U.S. Patent No. 11,376,251 Issued
2022-11-15 U.S. Patent No. 11,497,745 Issued
2024-03-05 U.S. Patent No. 11,918,578 Issued
2025-07-08 U.S. Patent No. 12,350,267 Issued
2025-11-20 Date of Zydus's Notice Letter
2025-12-19 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 describes that pediatric cholestatic liver diseases are difficult to treat, often requiring invasive and costly procedures like surgery or transplantation, and that medications formulated for adults are often unsuitable for children due to dosage issues, side effects such as diarrhea, and poor compliance (’657 Patent, col. 1:19-41).
  • The Patented Solution: The invention provides methods for treating these pediatric diseases through the non-systemic administration of an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI). By inhibiting the ASBTI in the gut, the drug prevents the reabsorption of bile acids, leading to their increased excretion in feces. This, in turn, is intended to lower the concentration of toxic bile acids in the liver and blood, thereby ameliorating the disease and its symptoms, like pruritus (itching) (’657 Patent, Abstract; col. 2:4-7). Figure 1 of the patent illustrates the inverse relationship between plasma bile acids (which decrease) and fecal bile acids (which increase) upon administration of an ASBTI (’657 Patent, Fig. 1).
  • Technical Importance: This therapeutic approach aims to treat a systemic liver condition with a non-systemically absorbed drug, which may reduce the risk of side effects associated with drugs that enter the bloodstream, a key consideration for pediatric patients (’657 Patent, col. 2:5-15).

Key Claims at a Glance

  • The complaint asserts independent claims 1-3 (Compl. ¶66).
  • Claim 1: A method for treating or ameliorating pediatric progressive familial intrahepatic cholestasis type 2 (PFIC2) in a pediatric subject, which involves administering an ASBTI that is effective for decreasing at least 20% of serum and/or hepatic bile acid levels compared to pre-administration levels.
  • Claim 2: A method for treating or ameliorating pruritus in a pediatric subject with PFIC2, which involves administering an ASBTI that is effective for decreasing at least 20% of serum and/or hepatic bile acid levels compared to pre-administration levels.
  • Claim 3: A method for treating or ameliorating PFIC2 in a pediatric subject, which involves administering a pharmaceutical composition containing an ASBTI that 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: The patent addresses the treatment of specific pediatric cholestatic liver disorders that are linked to particular genetic mutations in the Bile Salt Export Pump (BSEP) gene, such as certain forms of PFIC2 (Compl. ¶93, citing ’661 Patent, col. 6:29-31, 24:5-7).
  • The Patented Solution: The invention provides a method of treating a subset of pediatric disorders, including PFIC2, that are specifically characterized by the patient having a "non-truncating BSEP mutation." The treatment consists of administering a claimed ASBTI, targeting the therapy to a genetically defined patient sub-population (Compl. ¶93).
  • Technical Importance: This method represents a targeted therapeutic strategy, suggesting that treatment efficacy with an ASBTI may be correlated with the specific type of genetic mutation underlying the patient's liver disease (Compl. ¶93).

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶87).
  • Claim 1: A method of treating or ameliorating a pediatric disorder characterized by a non-truncating BSEP mutation in a pediatric subject, where the disorder is selected from a group including PFIC2, benign recurrent intrahepatic cholestasis 2 (BRIC2), and drug induced cholestasis. The method comprises administering a claimed ASBTI or a pharmaceutically acceptable salt thereof to the subject (Compl. ¶93).

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

  • Patent Identification: U.S. Patent No. 12,350,267, titled "Bile acid recycling inhibitors for treatment of pediatric cholestatic liver diseases," issued July 8, 2025 (the "’267 Patent") (Compl. ¶45).
  • Technology Synopsis: This patent, similar to the '657 Patent, relates to methods of treating pediatric cholestatic liver diseases, specifically Progressive Familial Intrahepatic Cholestasis (PFIC), and the symptom of pruritus in PFIC patients, by administering an ASBTI (Compl. ¶¶ 113-114).
  • Asserted Claims: Independent claims 1, 2, and 20 are asserted (Compl. ¶105).
  • Accused Features: The proposed use of Zydus's ANDA Product to treat PFIC and pruritus in pediatric subjects having PFIC is alleged to infringe (Compl. ¶¶ 113-114).

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

  • Patent Identification: U.S. Patent No. 11,229,647, titled "Methods for treating cholestasis," issued January 25, 2022 (the "’647 Patent") (Compl. ¶49).
  • Technology Synopsis: This patent claims methods for treating Alagille syndrome (ALGS) in a pediatric subject by administering an ASBTI (maralixibat) within a specific dosage range (Compl. ¶133).
  • Asserted Claims: Independent claims 1 and 12 are asserted (Compl. ¶126).
  • Accused Features: The proposed label for Zydus's ANDA Product is alleged to instruct and encourage the treatment of ALGS in a pediatric subject by administering the product in an amount of about 400 µg/kg/day and/or from about 400 µg/kg/day to about 800 µg/kg/day (Compl. ¶133).

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

  • Patent Identification: U.S. Patent No. 11,376,251, titled "Bile acid recycling inhibitors for treatment of pediatric cholestatic liver diseases," issued July 5, 2022 (the "’251 Patent") (Compl. ¶52).
  • Technology Synopsis: This patent is directed to methods of treating Alagille syndrome (ALGS) and associated pruritus in pediatric subjects by administering a claimed ASBTI (Compl. ¶¶ 153-154).
  • Asserted Claims: Independent claims 1, 14, and 19 are asserted (Compl. ¶145).
  • Accused Features: The proposed use of Zydus's ANDA Product for treating or ameliorating ALGS and pruritus in pediatric subjects suffering from ALGS is alleged to infringe (Compl. ¶¶ 153-154).

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

  • Patent Identification: U.S. Patent No. 11,497,745, titled "Methods for treating cholestasis," issued November 15, 2022 (the "’745 Patent") (Compl. ¶56).
  • Technology Synopsis: This patent claims methods for treating Alagille syndrome (ALGS) by administering maralixibat within a specific dosage range (Compl. ¶173).
  • Asserted Claims: Independent claim 1 is asserted (Compl. ¶166).
  • Accused Features: The use of Zydus's ANDA Product is alleged to infringe because its proposed label instructs administration to treat ALGS in an amount from 360 µg/kg/day to 880 µg/kg/day (Compl. ¶173).

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

  • Patent Identification: U.S. Patent No. 11,918,578, titled "Methods for treating cholestasis," issued March 5, 2024 (the "’578 Patent") (Compl. ¶59).
  • Technology Synopsis: This patent is directed to a method of treating cholestatic pruritus in a subject with Alagille syndrome (ALGS) by administering maralixibat within a specific dosage and concentration range (Compl. ¶193).
  • Asserted Claims: Independent claim 1 is asserted (Compl. ¶185).
  • Accused Features: The proposed labeling for Zydus's ANDA Product is alleged to instruct administration of maralixibat for treating cholestatic pruritus in ALGS subjects in an amount from about 400 µg/kg/day to about 800 µg/kg/day, as a liquid composition comprising about 0.001 mg/mL to about 16 mg/mL of maralixibat (Compl. ¶193).

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

  • Patent Identification: U.S. Patent No. 11,260,053, titled "Bile acid recycling inhibitors and satiogens for treatment of diabetes, obesity, and inflammatory gastrointestinal conditions," issued March 1, 2022 (the "’053 Patent") (Compl. ¶62).
  • Technology Synopsis: This patent describes a method for increasing the concentration of bile acids and salts in the distal gastrointestinal tract of an individual by administering a claimed ASBTI to the distal ileum, colon, or rectum (Compl. ¶210). This is the physiological effect of administering an ASBTI.
  • Asserted Claims: Independent claim 1 is asserted (Compl. ¶205).
  • Accused Features: The LIVMARLI® label states that maralixibat "decreases the reabsorption of bile acids...from the terminal ileum." The complaint alleges that using Zydus's ANDA Product according to its proposed label, which is substantially identical, will directly perform the claimed method of increasing bile acid concentration in the distal gastrointestinal tract (Compl. ¶¶ 207-210).

III. The Accused Instrumentality

Product Identification

The accused instrumentality is "Zydus's ANDA Product," identified as a generic version of Maralixibat Chloride Solution, Oral, Eq. 9.5 mg Base/mL and 19 mg Base/mL, for which Zydus FZE submitted ANDA No. 220669 to the FDA (Compl. ¶2).

Functionality and Market Context

The complaint alleges that Zydus's ANDA Product contains maralixibat, an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI) (Compl. ¶74). It is a proposed generic equivalent to Plaintiffs' branded drug, LIVMARLI®, which is indicated for the treatment of cholestatic pruritus associated with Alagille syndrome (ALGS) and progressive familial intrahepatic cholestasis (PFIC) (Compl. ¶¶ 1, 35). The complaint alleges that Zydus's proposed labeling is "substantially identical" to the LIVMARLI® label and will instruct and encourage healthcare professionals to prescribe the product for the indications covered by the patents-in-suit (Compl. ¶¶ 70, 74, 93). No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

'657 Patent Infringement Allegations

Claim Element (from Independent Claim 2) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for treating or ameliorating pruritus in a pediatric subject suffering from PFIC2... The proposed labeling for Zydus's ANDA Product allegedly instructs and encourages its use for treating pediatric subjects suffering from PFIC, a condition for which pruritus is a common symptom. ¶75 col. 6:48-50
...comprising administering to the pediatric subject the claimed ASBTI or pharmaceutically acceptable salt thereof... Zydus's ANDA Product is a formulation of maralixibat, which is a claimed ASBTI, and its proposed label instructs for its administration to pediatric subjects. ¶75 col. 2:4-7
...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 that use of Zydus's ANDA Product in accordance with its label will meet this efficacy limitation. ¶75 col. 84:9-16
  • Identified Points of Contention:
    • Scope Questions: A central question may be whether Zydus's proposed label, by indicating the product for the treatment of PFIC, actively induces infringement of a claim specifically directed to "treating or ameliorating pruritus." The analysis could turn on whether treating the underlying disease is legally equivalent to treating one of its primary symptoms as recited in the claim.
    • Technical Questions: The infringement allegation hinges on the claim's efficacy requirement ("effective for decreasing at least 20% of serum...bile acid levels"). This raises the question of what evidence Plaintiffs will need to prove that the administration of Zydus's generic product, as instructed by its label, will necessarily result in this clinical outcome in the target patient population.

'661 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of 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... The proposed labeling for Zydus's ANDA Product allegedly instructs and encourages its use for treating pediatric PFIC2. The complaint's theory is that by targeting the general PFIC2 population, the label necessarily induces treatment of the sub-population with this specific mutation. ¶93 col. 6:29-31
...comprising administering to the pediatric subject the claimed ASBTI or pharmaceutically acceptable salt thereof. Zydus's ANDA Product contains maralixibat, which is a claimed ASBTI, and its proposed label instructs for its administration to pediatric subjects for treating PFIC2. ¶93 col. 84:50-52
  • Identified Points of Contention:
    • Scope Questions: A key dispute may center on the requirements for induced infringement. Does a product label for a broad condition (PFIC2) induce infringement of a method claim directed to treating a specific genetic subset of that condition ("non-truncating BSEP mutation")? The court may need to determine if Zydus's label specifically encourages or instructs physicians to identify and treat this particular patient subgroup.
    • Technical Questions: The analysis may raise the evidentiary question of what proportion of the PFIC2 patient population has a non-truncating BSEP mutation. This could be relevant to determining whether the infringing use encouraged by the label is substantial.

V. Key Claim Terms for Construction

  • Term: "treating or ameliorating pruritus" (’657 Patent, Claim 2)
  • Context and Importance: This term is critical because the accused product's label is for the treatment of PFIC, not explicitly for pruritus. Defendants may argue that their label does not instruct the specific method of "treating pruritus," while Plaintiffs will likely contend that pruritus is a primary symptom of PFIC and treating the disease inherently involves treating the symptom.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent specification describes pruritus as one of the "one or more symptoms" characterizing cholestatic liver disease and PFIC2, suggesting that treating the disease encompasses treating its symptoms (’657 Patent, col. 6:48-50, 24:14-15).
    • Evidence for a Narrower Interpretation: The patent includes separate independent claims for treating PFIC2 (Claim 1) and for treating pruritus in a subject with PFIC2 (Claim 2). This structural separation, under the doctrine of claim differentiation, may suggest that "treating...PFIC2" and "treating...pruritus" are intended to be distinct and non-interchangeable actions.
  • Term: "a pediatric disorder characterized by having a non-truncating BSEP mutation" (’661 Patent, Claim 1)
  • Context and Importance: The infringement theory depends on whether Zydus’s general label for PFIC2 induces infringement of this specific, genetically-defined method. Practitioners may focus on whether "treating a disorder characterized by" a mutation requires the physician to have knowledge of the mutation, an act which the Zydus label does not instruct.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patent links PFIC2 with mutations in the BSEP gene, potentially supporting an argument that treating PFIC2 inherently involves treating a disorder characterized by such mutations (Compl. ¶93, citing ’661 Patent, col. 24:5-7).
    • Evidence for a Narrower Interpretation: The claim specifically recites a "non-truncating" BSEP mutation. This level of genetic specificity is not typically included in a general drug label. A defendant could argue that without an instruction to perform genetic testing to identify the specific mutation type, there can be no intent to induce infringement of this precise method.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement for all asserted patents. Inducement is based on the allegation that Defendants' proposed product label will instruct and encourage physicians and patients to perform the patented methods of treatment (Compl. ¶¶ 79, 97). Contributory infringement is based on the allegation that Zydus's ANDA Product has no substantial non-infringing uses (Compl. ¶¶ 81, 99).
  • Willful Infringement: Willfulness is alleged for all asserted patents. The complaint alleges that Defendants had actual and constructive knowledge of the patents prior to submitting the ANDA, at least because the patents are listed in the FDA's Orange Book for LIVMARLI® (Compl. ¶¶ 82, 100). The complaint alleges that Defendants' continued intent to market the generic product despite this knowledge constitutes willful infringement and makes the case "exceptional" under 35 U.S.C. § 285 (Compl. ¶¶ 83, 101).

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

  • A central issue will be one of induced infringement and intent: Can Plaintiffs demonstrate that Zydus's proposed label for general conditions like PFIC and ALGS meets the legal requirement of encouraging or promoting infringement of method claims that recite specific patient subsets (e.g., those with a "non-truncating BSEP mutation") or particular clinical outcomes (e.g., "decreasing at least 20% of serum...bile acid levels")?
  • A key evidentiary question will be one of mapping the label to the claims: The case will likely examine the extent to which the instructions in the proposed generic label must mirror the specific steps and patient characteristics recited in the method claims. This will be particularly relevant for claims involving specific dosage ranges or genetic markers that are not explicitly mentioned on the accused product's proposed label.
  • A further question will be one of claim scope and differentiation: The dispute may involve whether treating a disease as a whole (e.g., "PFIC2") is legally distinct from treating a primary symptom of that disease (e.g., "pruritus"), particularly where the asserted patent claims these methods in separate independent claims.