DCT

1:25-cv-01538

Mirum Pharma Inc v. Sandoz Inc

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Key Events
Complaint

I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:25-cv-01538, D. Del., 12/19/2025
  • Venue Allegations: Venue is asserted based on Defendant Sandoz Inc. being a corporation organized under the laws of Delaware. The complaint further alleges that Sandoz conducts regular and systematic business in the district, and that Plaintiffs, as Delaware corporations, will suffer the alleged patent infringement injury in Delaware.
  • Core Dispute: Plaintiffs allege that Defendant’s submission of an Abbreviated New Drug Application (ANDA) to market a generic version of Plaintiffs’ LIVMARLI® (maralixibat) oral solution infringes five patents related to methods of treating cholestatic liver diseases.
  • Technical Context: The technology concerns pharmacological methods for treating rare and serious liver diseases, particularly in children, by inhibiting the body's recycling of bile acids.
  • Key Procedural History: The lawsuit was initiated under the Hatch-Waxman Act following a November 14, 2025 Notice Letter from Sandoz, which informed Plaintiffs of its ANDA filing containing a Paragraph IV certification. This certification asserts that the patents-in-suit are invalid, unenforceable, and/or not infringed. All asserted patents are listed in the U.S. Food and Drug Administration's "Orange Book" for LIVMARLI®.

Case Timeline

Date Event
2010-05-26 U.S. Patent No. 11,260,053 Priority Date
2011-10-28 U.S. Patent No. 11,376,251 Priority Date
2019-02-12 U.S. Patent Nos. 11,229,647, 11,497,745, and 11,918,578 Priority Date
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
2025-11-14 Sandoz sends Paragraph IV Notice Letter
2025-12-19 Complaint Filed

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

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 on January 25, 2022.

The Invention Explained

  • Problem Addressed: The patent describes cholestatic liver diseases, which are associated with impaired bile secretion and result in the accumulation of bile acids in the liver, leading to hepatocellular injury (’647 Patent, col. 2:28-34). It notes a need for effective and safe medication for these conditions (’647 Patent, col. 2:53-56).
  • The Patented Solution: The invention provides a method for treating cholestasis by administering an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI), specifically maralixibat, which interrupts the recirculation of bile acid from the intestine back to the liver (’647 Patent, col. 2:57-65). This interruption increases the fecal excretion of bile acids, thereby reducing the overall bile acid load on the liver, as illustrated in the patent's Figure 1 (’647 Patent, Fig. 1).
  • Technical Importance: This approach provides a targeted, non-surgical method for managing bile acid levels in patients with rare cholestatic diseases such as Alagille Syndrome (ALGS) (’647 Patent, col. 17:62-67).

Key Claims at a Glance

  • The complaint asserts independent claims 1 and 12 (Compl. ¶44).
  • Independent Claim 1:
    • A method for treating Alagille Syndrome (ALGS) in a pediatric subject in need of such treatment
    • comprising administering to the subject maralixibat chloride,
    • wherein maralixibat chloride 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
    • comprising administering to the subject maralixibat chloride,
    • wherein maralixibat chloride is administered in an amount of about 400 µg/kg/day.

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 on July 5, 2022.

The Invention Explained

  • Problem Addressed: The patent background explains that pediatric patients have unique therapeutic needs and that conventional adult dosage forms can be problematic due to difficulty swallowing, unpleasant taste, and potential side effects, leading to safety and compliance issues (’251 Patent, col. 1:30-43).
  • The Patented Solution: The invention provides methods for treating pediatric cholestatic liver diseases by administering a non-systemically absorbed ASBTI in a "pediatric dosage form." The solution is designed to be effective and acceptable for children, thereby addressing compliance challenges specific to this patient population (’251 Patent, col. 2:10-14; Abstract).
  • Technical Importance: This technology focuses on the critical need for child-friendly formulations to enable long-term, effective management of chronic liver diseases in pediatric patients (’251 Patent, col. 1:43-46).

Key Claims at a Glance

  • The complaint asserts independent claims 1, 14, and 19 (Compl. ¶65).
  • Independent Claim 1:
    • A method for treating or ameliorating Alagille syndrome in a pediatric subject
    • comprising administering to the pediatric subject an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI),
    • wherein the ASBTI is maralixibat, or a pharmaceutically acceptable salt, solvate, or prodrug thereof.
  • Independent Claim 14:
    • A method for treating or ameliorating pruritus in a pediatric subject suffering from Alagille syndrome
    • comprising administering to the pediatric subject an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI),
    • wherein the ASBTI is maralixibat, or a pharmaceutically acceptable salt, solvate, or prodrug thereof.
  • Independent Claim 19:
    • A method for treating or ameliorating pruritus in a pediatric subject suffering from a pediatric cholestatic liver disease
    • comprising administering to the pediatric subject a pharmaceutical composition comprising an ASBTI, or a pharmaceutically acceptable salt thereof,
    • wherein the ASBTI is maralixibat.

Multi-Patent Capsule: 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 on November 15, 2022.
  • Technology Synopsis: This patent, similar to the ’647 Patent, is directed to methods of treating cholestasis, specifically ALGS, in a subject by administering the ASBTI maralixibat. The claimed method specifies a particular dosage range for this treatment (’745 Patent, Abstract; col. 135:1-8).
  • Asserted Claims: Independent claim 1 (Compl. ¶86).
  • Accused Features: The complaint alleges that Sandoz's proposed label for its generic maralixibat product will instruct and encourage its administration for treating ALGS in an amount of "from 360 µg/kg/day to 880 µg/kg/day," which corresponds to the patented method (Compl. ¶95).

Multi-Patent Capsule: 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 on March 5, 2024.
  • Technology Synopsis: This patent is directed to methods of treating cholestasis by administering the ASBTI maralixibat within a specific dosage range and as a liquid pharmaceutical composition with a specified concentration range. This patent covers a particular formulation aspect of the treatment method (’578 Patent, Abstract; col. 2:57-65).
  • Asserted Claims: Independent claim 1 (Compl. ¶107).
  • Accused Features: The complaint alleges infringement based on Sandoz's product being a liquid oral solution of maralixibat. The proposed label allegedly instructs its use for treating cholestatic pruritus in ALGS patients by administering a dose of "from about 400 µg/kg/day to about 800 µg/kg/day," with the maralixibat concentration being "about 0.001 mg/mL to about 16 mg/mL" (Compl. ¶115).

Multi-Patent Capsule: 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 on March 1, 2022.
  • Technology Synopsis: This patent relates to methods of using an ASBTI to increase the concentration of bile acids in the distal gastrointestinal tract by delivering a therapeutically effective amount to the distal ileum, colon, or rectum. This mechanism of action is claimed as a method of treatment (’053 Patent, col. 8:62-col. 9:4).
  • Asserted Claims: Independent claim 1 (Compl. ¶127).
  • Accused Features: The complaint alleges that Sandoz's proposed label instructs that maralixibat "decreases the reabsorption of bile acids (primarily the salt forms) from the terminal ileum," which Plaintiffs allege infringes the claimed method of increasing bile acid concentration in the distal gastrointestinal tract and delivering the ASBTI to the distal ileum (Compl. ¶¶131, 134).

III. The Accused Instrumentality

Product Identification

  • Defendant Sandoz's generic Maralixibat Oral Solution, 9.5 mg/mL, which is the subject of ANDA No. 220714 (Compl. ¶2).

Functionality and Market Context

  • The accused product is a generic version of Plaintiffs' LIVMARLI® drug and contains maralixibat chloride as its active ingredient (Compl. ¶¶1, 48). Maralixibat functions as an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI), which works by decreasing the reabsorption of bile acids from the terminal ileum (Compl. ¶131).
  • The complaint alleges, on information and belief, that the proposed label for Sandoz's product will be "substantially identical" to the FDA-approved label for LIVMARLI® (Compl. ¶¶48, 69). This label allegedly instructs for its use in treating "cholestatic pruritus in patients 3 months of age and older with Alagille syndrome (ALGS)" (Compl. ¶¶49, 70, 91).
  • The product is positioned to enter the market as a lower-cost generic alternative to LIVMARLI® prior to the expiration of the patents-in-suit (Compl. ¶¶1, 4).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

U.S. Patent No. 11,229,647 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for treating Alagille Syndrome (ALGS) in a pediatric subject in need of such treatment... Sandoz's proposed label allegedly instructs and encourages the use of its product for the treatment of ALGS in a pediatric subject. ¶53 col. 21:4-21
...comprising administering to the subject maralixibat chloride... The accused ANDA product is a maralixibat chloride oral solution, and its proposed label allegedly directs its administration. ¶¶2, 51 col. 2:16-23
...wherein maralixibat chloride is administered in an amount of from about 400 µg/kg/day to about 800 µg/kg/day. The proposed labeling for Sandoz's product allegedly instructs administration in a dosage amount that falls within the claimed range. ¶53 col. 83:41-45
  • Identified Points of Contention:
    • Scope Questions: The complaint alleges the proposed label will direct "treatment of ALGS" (Compl. ¶53), while elsewhere referencing the branded drug's indication for "treatment of cholestatic pruritus in patients...with Alagille syndrome" (Compl. ¶49). A potential dispute may arise over whether treating a primary symptom of ALGS (pruritus) constitutes "treating Alagille Syndrome" as required by the claim.
    • Technical Questions: Since infringement is predicated on the content of a proposed label not included as an exhibit, a central evidentiary question will be whether Sandoz’s ANDA and proposed labeling, once produced in discovery, actually instruct or encourage administration of the product in a manner that satisfies each limitation of the asserted claims.

U.S. Patent No. 11,376,251 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method for treating or ameliorating Alagille syndrome in a pediatric subject... Sandoz's proposed label allegedly instructs and encourages the use of its product for treating or ameliorating ALGS in a pediatric subject. ¶73 col. 1:24-29
...comprising administering to the pediatric subject an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI)... The accused product is an ASBTI (maralixibat), and its label allegedly instructs administration to patients. ¶73 col. 2:5-9
...wherein the ASBTI is [maralixibat structure], or a pharmaceutically acceptable salt, solvate, or prodrug thereof. The accused product is maralixibat chloride, a pharmaceutically acceptable salt of the claimed ASBTI. ¶¶2, 73 col. 31:4-24
  • Identified Points of Contention:
    • Scope Questions: Claims 1 and 14 are directed to "treating or ameliorating" ALGS or pruritus in a pediatric subject. As with the ’647 Patent, a definitional question may arise as to whether the product's labeled indication for treating a symptom of ALGS falls within the scope of "treating or ameliorating" the syndrome itself.
    • Technical Questions: The infringement theory for all asserted claims in this patent depends on the specific instructions that will be included in Sandoz's proposed label for its generic product. The key factual question is whether the label will, as alleged, direct healthcare professionals and patients to administer the maralixibat solution to pediatric ALGS patients.

V. Key Claim Terms for Construction

  • The Term: "treating Alagille Syndrome" (from ’647 Patent, Claim 1)

    • Context and Importance: This term is critical because the accused product's alleged indication is for a symptom ("cholestatic pruritus") in patients with Alagille Syndrome (Compl. ¶49), not necessarily for the syndrome as a whole. Practitioners may focus on this term because its construction will determine whether treating a key symptom is sufficient to meet the claim limitation of treating the underlying syndrome.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patent specification provides a broad definition for "treating," which includes "ameliorating the underlying disease or condition" as well as "relieving the symptoms of the disease or condition" (’647 Patent, col. 21:4-21). This language may support an interpretation where treating a significant symptom like pruritus constitutes "treating" the syndrome.
      • Evidence for a Narrower Interpretation: The specification describes ALGS as a multi-system disorder affecting not only the liver but also the heart, skeleton, and eyes (’647 Patent, col. 17:62–col. 18:15). A defendant may argue that "treating Alagille Syndrome" requires an effect on more than just the pruritus symptom to distinguish it from mere palliative care.

  • The Term: "pediatric dosage form" (from ’251 Patent, Claim 19 refers to a "pharmaceutical composition," but the patent's focus is on pediatric formulations)

    • Context and Importance: The ’251 patent's inventive concept is tied to creating formulations suitable for children. The accused product is an oral solution. The definition of "pediatric dosage form" will be central to determining if a simple liquid solution falls within the scope of what the patent claims to have invented.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The specification explicitly lists "solutions" and "oral solutions" as examples of pediatric dosage forms that are contemplated by the invention (’251 Patent, col. 103:22-26). This provides strong intrinsic support for construing the term to include the accused product.
      • Evidence for a Narrower Interpretation: The Background section emphasizes the problems with adult medications for children, such as swallowing pills and unpleasant taste (’251 Patent, col. 1:30-43). A defendant may argue that the true invention lies in more complex, specialized formulations also mentioned, such as "gummy candy," "chewable tablet," or "sprinkle oral powder" (’251 Patent, col. 103:22-26), and that a standard oral solution does not embody the novel aspects of the patent.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that Sandoz will induce infringement by providing a product with a proposed label that instructs and encourages healthcare professionals to prescribe, and patients to use, the generic product in a manner that practices the claimed methods (Compl. ¶¶57, 78, 99, 119, 138). The complaint also alleges contributory infringement on the basis that Sandoz's product will lack substantial non-infringing uses (Compl. ¶¶59, 80, 101, 121, 140).
  • Willful Infringement: Willfulness is alleged based on Sandoz’s purported pre-suit knowledge of the patents-in-suit. The complaint asserts that Sandoz had actual and constructive knowledge because the patents are listed in the FDA’s Orange Book for LIVMARLI® (Compl. ¶¶60, 81, 102, 122, 141). The complaint further alleges that Sandoz acted "without a reasonable basis for believing" it would not be liable, making the case "exceptional" under 35 U.S.C. § 285 (Compl. ¶¶61, 82, 103, 123, 142).

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

  • A core issue will be one of definitional scope: can the method of "treating Alagille Syndrome," as claimed in the '647 and '745 patents, be construed to cover the accused product's alleged labeled indication for treating "cholestatic pruritus" in patients with the syndrome, or does the claim require a broader therapeutic effect on the underlying multi-system disorder?
  • A central question will be one of evidentiary proof: as this is an ANDA action where infringement hinges on future conduct, the case will depend on whether Plaintiffs can prove that Sandoz's proposed product label will in fact instruct and encourage physicians and patients to perform all steps of the claimed methods, including administration to the specified patient populations at the claimed dosages.
  • A further point of contention may arise from the mechanism of action claimed in the '053 patent. The dispute will likely focus on whether the accused product's function of decreasing bile acid reabsorption from the terminal ileum inherently and necessarily results in "increasing the concentration of bile acids and salts thereof in the distal gastrointestinal tract" as required by the claim.