DCT
1:25-cv-01539
Mirum Pharma Inc v. Zenara Pharma Pvt Ltd
Key Events
Complaint
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: Zenara Pharma Private Limited (India) and Biophore India Pharmaceuticals Private Limited (India)
- Plaintiff’s Counsel: Shaw Keller LLP
- Case Identification: 1:25-cv-01539, D. Del., 12/19/2025
- Venue Allegations: Plaintiffs allege venue is proper in Delaware based on Defendants' systematic business contacts in the state, their engagement in prior Hatch-Waxman litigation in the district without challenging jurisdiction, and the fact that Plaintiffs are Delaware corporations who will suffer injury in the state.
- Core Dispute: Plaintiffs allege that Defendants’ filing of an Abbreviated New Drug Application (ANDA) to market generic versions of Plaintiffs’ LIVMARLI® (maralixibat) drug product constitutes an act of infringement of eight U.S. patents covering methods of treating pediatric cholestatic liver diseases.
- Technical Context: The technology relates to pharmaceutical methods using Apical Sodium-dependent Bile Acid Transporter Inhibitors (ASBTIs) to treat rare and serious pediatric liver diseases by interrupting the recycling of bile acids in the gastrointestinal tract.
- Key Procedural History: The action was initiated under the Hatch-Waxman Act following Plaintiffs’ receipt of a Notice Letter dated November 22, 2025, in which Defendant Zenara informed Plaintiffs of its ANDA submission containing a Paragraph IV certification, asserting that the patents-in-suit are invalid, unenforceable, and/or will not be infringed by its proposed generic product.
Case Timeline
| Date | Event |
|---|---|
| 2010-05-26 | Priority Date for U.S. Patent No. 11,260,053 |
| 2011-10-28 | Priority Date for U.S. Patent Nos. 10,512,657; 11,229,661; 12,350,267; 11,376,251 |
| 2019-02-12 | Priority Date for U.S. Patent Nos. 11,229,647; 11,497,745; 11,918,578 |
| 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 |
| 2025-04-30 | Biophore India submits drug master file for maralixibat chloride |
| 2025-07-08 | U.S. Patent No. 12,350,267 Issued |
| 2025-11-22 | Zenara sends Paragraph IV Notice Letter to Plaintiffs |
| 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 addresses the lack of effective and less invasive treatments for pediatric cholestatic liver diseases, noting that existing options like liver transplantation are costly and that adult medications are often unsuitable for children due to issues with dosage form, taste, and side effects (’657 Patent, col. 1:18-42).
- The Patented Solution: The invention provides methods for treating or ameliorating these pediatric diseases by administering a non-systemically absorbed Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI). This approach works by inhibiting the recycling of bile acids in the gastrointestinal tract, thereby reducing the toxic accumulation of bile acids in the liver and blood that characterizes these diseases (’657 Patent, Abstract; col. 2:4-15).
- Technical Importance: The invention offers a non-systemic, targeted pharmacological intervention specifically adapted for pediatric patients, which may avoid the costs and risks of surgery while improving safety and compliance compared to repurposed adult medications (’657 Patent, col. 1:36-42).
Key Claims at a Glance
- The complaint asserts independent claims 1, 2, and 3 (Compl. ¶63, 70-72).
- Independent Claim 1: A method for treating or ameliorating pediatric progressive familial intrahepatic cholestasis type 2 (PFIC2) in a pediatric subject, comprising:
- administering to the pediatric subject an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI) or a pharmaceutically acceptable salt thereof;
- 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.
- Independent Claim 2: A method for treating or ameliorating pruritus in a pediatric subject suffering from PFIC2, comprising the same administration and efficacy steps as Claim 1.
- Independent Claim 3: A method for treating or ameliorating pediatric cholestasis in a pediatric subject having PFIC2, comprising the same administration and efficacy steps as Claim 1.
- The complaint alleges infringement of "one or more claims... including but not limited to independent claims 1-3" (Compl. ¶63).
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 identifies a need for treatments for pediatric cholestatic disorders that are linked to specific genetic mutations, particularly those affecting the Bile Salt Export Pump (BSEP) protein (’661 Patent, col. 6:29-31, col. 24:5-7, as cited in Compl. ¶92).
- The Patented Solution: The invention provides a method of using an ASBTI to treat pediatric disorders, such as PFIC2, that are specifically characterized by the presence of a non-truncating BSEP mutation. This represents a genetically targeted approach to therapy (’661 Patent, Claim 1).
- Technical Importance: This method moves beyond symptom-based treatment to a more precise, genotype-directed therapy, potentially offering improved outcomes for a specific subset of patients with cholestatic liver disease (’661 Patent, col. 84:50-67, as cited in Compl. ¶92).
Key Claims at a Glance
- The complaint asserts independent claim 1 (Compl. ¶84, 92).
- Independent Claim 1: A method for treating or ameliorating a pediatric disorder characterized by having a non-truncating BSEP mutation in a pediatric subject, comprising:
- wherein the pediatric disorder is selected from PFIC2, benign recurrent intrahepatic cholestasis 2 (BRIC2), and drug induced cholestasis;
- administering to the pediatric subject the claimed ASBTI or pharmaceutically acceptable salt thereof.
- The complaint alleges infringement of "one or more claims... including but not limited to independent claim 1" (Compl. ¶84).
U.S. Patent No. 12,350,267 - "Bile acid recycling inhibitors for treatment of pediatric cholestatic liver diseases"
- Technology Synopsis: This patent claims methods for treating or ameliorating progressive familial intrahepatic cholestasis (PFIC) and associated symptoms like pruritus in pediatric subjects by administering an ASBTI (’267 Patent, Claims 1, 2, 20).
- Asserted Claims: Independent claims 1, 2, and 20 (Compl. ¶104).
- Accused Features: The use of Zenara's ANDA Product for treating or ameliorating PFIC and pruritus in a pediatric subject, as allegedly instructed by the proposed product labeling (Compl. ¶112-113).
U.S. Patent No. 11,229,647 - "Methods for treating cholestasis"
- Technology Synopsis: This patent claims methods for treating Alagille syndrome (ALGS) in pediatric subjects by administering maralixibat within a specific dosage range of about 400 µg/kg/day to about 800 µg/kg/day (’647 Patent, Claims 1, 12).
- Asserted Claims: Independent claims 1 and 12 (Compl. ¶125).
- Accused Features: The use of Zenara's ANDA Product for treating ALGS in a pediatric subject at a dosage amount within the claimed range, as allegedly instructed by the proposed labeling (Compl. ¶134).
U.S. Patent No. 11,376,251 - "Bile acid recycling inhibitors for treatment of pediatric cholestatic liver diseases"
- Technology Synopsis: This patent claims methods of treating ALGS and associated pruritus in pediatric subjects by administering an ASBTI (’251 Patent, Claims 1, 14, 19).
- Asserted Claims: Independent claims 1, 14, and 19 (Compl. ¶146).
- Accused Features: The use of Zenara's ANDA Product as directed by its proposed labeling for treating ALGS and pruritus in pediatric subjects suffering from ALGS (Compl. ¶154-155).
U.S. Patent No. 11,497,745 - "Methods for treating cholestasis"
- Technology Synopsis: This patent claims a method of treating ALGS by administering maralixibat in a specific dosage range of 360 µg/kg/day to 880 µg/kg/day (’745 Patent, Claim 1).
- Asserted Claims: Independent claim 1 (Compl. ¶167).
- Accused Features: The use of Zenara's ANDA Product for treating ALGS at a dosage within the claimed range, as allegedly instructed by the proposed labeling (Compl. ¶176).
U.S. Patent No. 11,918,578 - "Methods for treating cholestasis"
- Technology Synopsis: This patent claims a method for treating cholestatic pruritus in a subject with ALGS by administering maralixibat in a specific dosage range (about 400 µg/kg/day to about 800 µg/kg/day) as a liquid pharmaceutical composition with a specific concentration (about 0.001 mg/mL to about 16 mg/mL) (’578 Patent, Claim 1).
- Asserted Claims: Independent claim 1 (Compl. ¶188).
- Accused Features: The use of Zenara's ANDA Product, a liquid composition, for treating cholestatic pruritus in subjects with ALGS at dosages and concentrations allegedly covered by the claim (Compl. ¶196).
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 claims a method for increasing the concentration of bile acids and salts in the distal gastrointestinal tract of an individual by administering an ASBTI to the distal ileum, colon, or rectum (’053 Patent, Claim 1).
- Asserted Claims: Independent claim 1 (Compl. ¶208).
- Accused Features: The use of Zenara's ANDA Product, which the LIVMARLI® label allegedly explains "decreases the reabsorption of bile acids... from the terminal ileum," thereby increasing the concentration of bile acids in the distal gastrointestinal tract (Compl. ¶210, 213).
III. The Accused Instrumentality
Product Identification
The accused instrumentality is "Zenara's ANDA Product," a proposed generic version of Mirum's LIVMARLI® (maralixibat chloride) Oral Solution, to be offered in concentrations of Eq. 9.5 mg Base/mL and 19 mg Base/mL (Compl. ¶2).
Functionality and Market Context
- The product is an oral solution containing maralixibat, an inhibitor of the Apical Sodium-dependent Bile Acid Transporter (ASBTI) (Compl. ¶71, 92). The complaint alleges that the proposed labeling for Zenara's ANDA Product is substantially identical to the label for LIVMARLI® and directs its use for treating cholestatic pruritus in patients with Alagille syndrome (ALGS) and progressive familial intrahepatic cholestasis (PFIC) (Compl. ¶32, 67, 88).
- The complaint alleges that Defendants seek FDA approval to market this product before the expiration of the Asserted Patents, which would directly compete with and displace sales of LIVMARLI® (Compl. ¶1, 28). 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... | Zenara's proposed label allegedly instructs and encourages the use of its ANDA product for treating PFIC, which includes the PFIC2 subtype, in pediatric patients. | ¶71 | col. 6:27-29 |
| ...comprising administering to the pediatric subject an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTI) or a pharmaceutical composition comprising the ASBTI, or a pharmaceutically acceptable salt thereof... | The ANDA Product is a maralixibat chloride solution, and maralixibat is identified as an ASBTI. | ¶2, ¶71 | col. 2:7-12 |
| ...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 the proposed labeling instructs and encourages a use where the ASBTI is effective for achieving this 20% decrease. | ¶71 | col. 4:26-30 |
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... | The proposed label allegedly instructs use for treating PFIC2, which the patent describes as being associated with BSEP mutations. The complaint alleges the label encourages use in this specific patient population. | ¶92 | col. 24:5-7 |
| ...wherein the pediatric disorder is selected from PFIC2, benign recurrent intrahepatic cholestasis 2 (BRIC2), and drug induced cholestasis... | The proposed label allegedly includes an indication for PFIC, which encompasses the claimed PFIC2 disorder. | ¶90, ¶92 | col. 1:12-14 |
| ...comprising administering to the pediatric subject the claimed ASBTI or pharmaceutically acceptable salt thereof. | The ANDA Product contains maralixibat, which is an ASBTI. | ¶2, ¶92 | col. 1:12-14 |
Identified Points of Contention
- Scope Questions: A central issue for all asserted method claims will be whether the Defendants' proposed label is found to actively induce infringement by encouraging or instructing physicians to perform each claimed step. For the ’661 Patent, this raises the question of whether a general instruction to treat PFIC2 is sufficient to induce infringement of a claim that requires the patient to have a specific "non-truncating BSEP mutation."
- Technical Questions: For the ’657 Patent, a key factual question may be what evidence supports the allegation that use of the ANDA Product as directed by the label is "effective for decreasing at least 20% of serum and/or hepatic bile acid levels." Defendants may argue their label makes no such guarantee, and thus they do not induce infringement of this functional limitation.
V. Key Claim Terms for Construction
The Term: "treating or ameliorating" (from '657 Patent, Claim 1 and '661 Patent, Claim 1)
- Context and Importance: This term's scope is critical, as the infringement case is built on the allegation that Defendants' label instructs a method of "treating." Practitioners may focus on whether the patent's own definition of the term encompasses the indications and outcomes described on the proposed label.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: Plaintiffs may point to language in the specification defining "treat" and "treatment" broadly to include "reducing the progression of a disease" or ameliorating symptoms like pruritus, which are indications on the LIVMARLI® label (Compl. ¶71; ’657 Patent, col. 83:66-84:16; col. 6:48-50).
- Evidence for a Narrower Interpretation: Defendants may argue that, in the context of claim 1 of the ’657 Patent, "treating" is implicitly limited by the functional requirement of "decreasing at least 20% of serum and/or hepatic bile acid levels," and that merely prescribing the drug for a relevant condition without instructing this specific outcome does not constitute induced infringement.
The Term: "a pediatric disorder characterized by having a non-truncating BSEP mutation" ('661 Patent, Claim 1)
- Context and Importance: This limitation defines the patient population by a specific genetic marker. The dispute will likely focus on whether the proposed label, by indicating treatment for PFIC2, necessarily induces infringement of this genetically-defined method.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: Plaintiffs may argue that the specification links PFIC2 directly to BSEP mutations and that instructing treatment for the disorder inherently covers patients with the mutation, thereby satisfying the claim element (Compl. ¶92; ’661 Patent, col. 24:5-7).
- Evidence for a Narrower Interpretation: Defendants could contend that their label does not instruct or require physicians to perform a genetic test to confirm the presence of a "non-truncating BSEP mutation" before prescribing the drug. They may argue that without such an instruction, they cannot be held liable for inducing infringement of a claim that requires this specific patient characteristic.
VI. Other Allegations
Indirect Infringement
The complaint is predicated on a theory of induced infringement under 35 U.S.C. § 271(b) and (e)(2). It alleges that Defendants, by filing an ANDA with a proposed label that is substantially identical to the LIVMARLI® label, intend to and will instruct and encourage healthcare professionals and patients to use the generic product in a manner that directly infringes the asserted method claims (Compl. ¶71, 76, 92). Knowledge of the patents is alleged based on their listing in the FDA's Orange Book and the act of filing a Paragraph IV certification against them (Compl. ¶79, 99).
Willful Infringement
Plaintiffs allege that Defendants have acted with full knowledge of the asserted patents and without a reasonable basis for believing they would not be liable for infringement. This allegation is based on Defendants' pre-suit knowledge of the patents via the Orange Book and their decision to file the ANDA. Plaintiffs request a declaration that the case is "exceptional" to support an award of attorneys' fees (Compl. ¶80, 100, 121; Prayer for Relief ¶G).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of inducement: Will the court determine that Defendants' proposed product label, by mirroring the indications of the branded drug, actively encourages medical professionals to perform all the specific steps of the asserted method claims, particularly for claims that recite specific genetic markers (e.g., "non-truncating BSEP mutation") or quantitative clinical outcomes (e.g., "decreasing at least 20% of serum... bile acid levels")?
- A key evidentiary question will be one of label scope: Does the alleged instruction on the proposed label to treat a general condition like "PFIC" sufficiently meet claim limitations directed to a specific subtype like "PFIC2," or will Defendants be able to argue that their label allows for substantial non-infringing uses, thereby negating the intent required for induced infringement?