DCT
1:25-cv-01017
Bow River LLC v. Alembic Pharma Ltd
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: Bow River LLC (Wyoming)
- Defendant: Alembic Pharmaceuticals Ltd (India) and Alembic Pharmaceuticals, Inc. (Delaware)
- Plaintiff’s Counsel: Potter Anderson & Corroon LLP
- Case Identification: 1:25-cv-01017, D. Del., 08/13/2025
- Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant Alembic Inc. is incorporated in Delaware, and Defendant Alembic Ltd. allegedly has persistent and continuous business contacts within the state.
- Core Dispute: Plaintiff alleges that Defendants' submission of an Abbreviated New Drug Application (ANDA) to the FDA for a generic version of the cancer drug VITRAKVI® constitutes an act of infringement of two patents related to methods for safely administering the drug after a patient has been treated with a strong CYP3A inhibitor.
- Technical Context: The case concerns the management of drug-drug interactions (DDIs), a critical safety issue in pharmacology, specifically involving drugs metabolized by the CYP3A4 enzyme, a common pathway for many pharmaceuticals.
- Key Procedural History: This action was filed under the Hatch-Waxman Act following a notice letter from Alembic regarding its ANDA submission. The complaint states that the asserted patents are listed in the FDA's "Approved Drug Products with Therapeutic Equivalence Evaluations" (the "Orange Book") in connection with VITRAKVI®, which statutorily links the patents to the approved drug product.
Case Timeline
| Date | Event |
|---|---|
| 2017-05-16 | ’967 and ’998 Patents Priority Date |
| 2022-05-24 | ’967 Patent Issue Date |
| 2024-05-07 | ’998 Patent Issue Date |
| 2025-06-30 | Alembic sends ANDA Notice Letter to Bow River |
| 2025-08-13 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 11,337,967 - "Methods of Treatment"
- Issued: May 24, 2022
The Invention Explained
- Problem Addressed: Certain drugs, like the cancer therapeutic larotrectinib, are metabolized by the CYP3A4 enzyme in the liver. When a patient is also taking a strong CYP3A4 inhibitor, such as the antifungal posaconazole, the metabolism of larotrectinib is blocked, causing its concentration in the body to rise to potentially dangerous levels. While medical guidance warns against taking these drugs simultaneously, the patent’s background section notes a lack of guidance on how long the inhibitory effect of posaconazole persists after a patient stops taking it (’967 Patent, col. 2:48-64).
- The Patented Solution: The inventors discovered that the inhibitory effects of posaconazole last significantly longer than previously understood, particularly in certain patient populations (’967 Patent, col. 2:14-21). The patented solution is a method of treatment that involves a "washout period": after a patient stops taking the CYP3A4 inhibitor, the physician must delay administering the CYP3A4 substrate drug for a specific period (e.g., at least 9 days) to allow the inhibitor to clear from the patient's system, thereby avoiding a dangerous drug-drug interaction (’967 Patent, col. 2:21-30; Abstract).
- Technical Importance: This method provides a specific, data-driven safety protocol for managing a known but previously unquantified post-treatment DDI risk, enabling safer transitions between essential medications for vulnerable patients, such as those being treated for cancer (’967 Patent, col. 1:16-24).
Key Claims at a Glance
- The complaint asserts infringement of one or more claims of the ’967 Patent, with Claim 1 being the first independent claim (Compl. ¶ 29).
- Essential Elements of Claim 1:
- A method of treating a patient in need thereof with a strong CYP3A4 substrate drug.
- The patient has previously been treated with a strong CYP3A4 inhibitor treatment.
- The method comprises stopping the CYP3A4 inhibitor treatment.
- Then, delaying administering, for at least 9 days after stopping the inhibitor, a dose of the CYP3A4 substrate drug.
- The CYP3A4 substrate drug is selected from a specified group including larotrectinib.
- The complaint does not explicitly reserve the right to assert dependent claims but makes a general allegation against "one or more claims" (Compl. ¶ 43).
U.S. Patent No. 11,974,998 - "Methods of Treatment"
- Issued: May 7, 2024
The Invention Explained
- Problem Addressed: The ’998 Patent addresses the same technical problem as the ’967 Patent: the risk of life-threatening side effects if a CYP3A4 substrate drug is administered too soon after a patient ceases a regimen of a strong CYP3A4 inhibitor like posaconazole (’998 Patent, col. 2:8-20).
- The Patented Solution: The solution is also a method of treatment involving a "washout period." This patent, however, claims a different methodology, which may include shorter delay periods (e.g., at least 3 days) or administering a reduced dose of the CYP3A4 substrate drug "as soon as it is safe to do so" after stopping the inhibitor regimen (’998 Patent, Abstract; col. 2:32-42).
- Technical Importance: This patent provides alternative or more flexible dosing regimens for managing the same DDI risk identified in the ’967 Patent, potentially allowing for tailored treatment based on patient-specific factors (’998 Patent, col. 2:62-67).
Key Claims at a Glance
- The complaint asserts infringement of one or more claims of the ’998 Patent, with Claim 1 being the first independent claim (Compl. ¶ 32).
- Essential Elements of Claim 1:
- A method of treating a patient with a CYP3A4 substrate drug.
- The patient is treated with posaconazole.
- The method involves the patient stopping the posaconazole treatment.
- The patient waits for at least 3 days.
- The patient is then treated with the CYP3A4 substrate drug as soon as it is safe to do so.
- The complaint makes a general allegation against "one or more claims" of the ’998 Patent (Compl. ¶ 49).
III. The Accused Instrumentality
Product Identification
- The "Alembic ANDA Products," which are generic versions of VITRAKVI® (larotrectinib) capsules in 25 mg and 100 mg strengths, for which Alembic seeks FDA approval under ANDA No. 220639 (Compl. ¶¶ 2, 33).
Functionality and Market Context
- The accused instrumentality is the future commercial manufacture, use, and sale of a generic version of larotrectinib, a first-in-class cancer drug for treating solid tumors with a specific NTRK gene fusion (Compl. ¶¶ 20-21). The act of infringement alleged in the complaint is the filing of the ANDA itself, which seeks approval to market the generic drug with a proposed label that allegedly instructs medical professionals and patients to perform the patented methods of treatment (Compl. ¶¶ 42-43, 48-49).
- The complaint alleges that Alembic's proposed prescribing information is "substantially identical" to that of the branded VITRAKVI® Capsules, and that this labeling will instruct users on how to administer the drug in a manner that directly infringes the asserted patents (Compl. ¶ 37). The complaint alleges that the methods claimed in the patents are so essential for safe administration that they must be included on the label for larotrectinib products (Compl. ¶ 26).
No probative visual evidence provided in complaint.
IV. Analysis of Infringement Allegations
’967 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of treating a patient in need thereof with a...CYP3A4 substrate drug...wherein the CYP3A4 substrate drug is larotrectinib... | Alembic's proposed prescribing information will instruct medical practitioners to treat patients with larotrectinib for cancer, which is a use covered by the patent. | ¶¶ 43-44 | col. 205:22-24 |
| wherein the patient has previously been treated with a strong CYP3A4 inhibitor treatment... | The proposed label will allegedly contain instructions for administering larotrectinib to patients who have been taking strong CYP3A4 inhibitors. | ¶¶ 24, 43 | col. 2:21-23 |
| comprising the steps of: (a) stopping the strong CYP3A4 inhibitor treatment; and then | The proposed label will instruct stopping the CYP3A4 inhibitor before starting larotrectinib. | ¶¶ 25, 43 | col. 205:15-16 |
| (b) delaying administering, for at least 9 days after stopping the strong CYP3A4 inhibitor treatment, a dose of the CYP3A4 substrate drug... | The proposed label will allegedly instruct a specific delay period post-cessation of the CYP3A4 inhibitor before administering larotrectinib. | ¶¶ 25, 43 | col. 205:16-19 |
’998 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| A method of treating a patient with a CYP3A4 substrate drug, wherein the patient is treated with posaconazole... | Alembic's proposed prescribing information will direct the administration of larotrectinib, a CYP3A4 substrate drug, to patients who have been treated with posaconazole. | ¶¶ 49-50 | col. 3:1-5 |
| wherein the method comprises: the patient stops posaconazole treatment... | The proposed label will instruct stopping posaconazole treatment before initiating or adjusting the larotrectinib dose. | ¶¶ 25, 49 | col. 3:5-7 |
| the patient waits for at least 3 days... | The proposed label will allegedly instruct a specific waiting period of at least three days after stopping posaconazole. | ¶¶ 25, 49 | col. 3:7-8 |
| and then is treated with the CYP3A4 substrate drug as soon as it is safe to do so. | The proposed label will instruct administering the larotrectinib after the specified waiting period, based on safety considerations. | ¶¶ 26, 49 | col. 3:8-9 |
Identified Points of Contention
- Evidentiary Questions: The central issue will be factual and evidentiary: what does Alembic’s proposed label actually say? The complaint proceeds on the "information and belief" that the label is "substantially identical" to the VITRAKVI® label and will instruct the claimed methods. A key question for the court will be whether the specific language of Alembic's proposed label meets the legal standard for inducing infringement of each claim limitation.
- Scope Questions: The claims require specific actions, such as "delaying...for at least 9 days" (’967 Patent) or waiting "at least 3 days" and treating when it is "safe to do so" (’998 Patent). A point of contention may be whether the instructions on the proposed label are merely informational warnings about drug interactions or rise to the level of specific encouragement or instruction to perform these claimed steps.
V. Key Claim Terms for Construction
The Term: "delaying administering, for at least 9 days" (’967 Patent, Claim 1)
- Context and Importance: The precise duration of the "washout period" is a core limitation of the claim. The infringement analysis will depend on whether the proposed label instructs a delay meeting this specific temporal requirement. Practitioners may focus on this term because the difference between a general warning and a specific instruction for a minimum duration is often outcome-determinative in pharmaceutical method patent cases.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification provides a range of delay periods, describing embodiments where the delay is between about 2-42 days, which might be used to argue that "at least 9 days" is just one example of a broader inventive concept of a delay (’967 Patent, col. 2:23-27).
- Evidence for a Narrower Interpretation: Claim 2, a dependent claim, specifies a delay of "9 days," and Claim 3 specifies "10 days," suggesting that the "at least 9 days" in Claim 1 is a specific and limiting threshold, not merely an example (’967 Patent, col. 205:25-28). The detailed description provides specific data supporting delays of this magnitude (’967 Patent, col. 72:55-65).
The Term: "as soon as it is safe to do so" (’998 Patent, Claim 1)
- Context and Importance: This term introduces a subjective, condition-based element to the method step. Its construction will be critical, as it may be argued as indefinite under 35 U.S.C. § 112 or, for infringement, may require a specific type of instruction on the proposed label regarding safety assessment.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification describes safety in terms of achieving blood plasma levels that "outweigh risks of elevated exposure," which could be interpreted broadly as any clinical judgment made by a physician (’998 Patent, col. 3:49-53).
- Evidence for a Narrower Interpretation: The patent provides a detailed table (Table 1) of "target safe levels" for various CYP3A4 substrate drugs, defining safety by specific pharmacokinetic parameters like AUC and Cmax. This could support a narrower construction where "safe" requires meeting objective, quantifiable criteria rather than just a physician's general judgment (’998 Patent, col. 57:1-68:53).
VI. Other Allegations
- Indirect Infringement: The complaint alleges that Alembic will actively induce infringement by patients and medical practitioners because its proposed prescribing information will instruct them to perform the steps of the patented methods (Compl. ¶¶ 43, 49). The complaint also alleges contributory infringement by asserting there are no "substantial non-infringing uses" for the Alembic ANDA Products other than in the claimed methods (Compl. ¶¶ 45, 51).
- Willful Infringement: The complaint alleges that Alembic had "actual and constructive knowledge" of the asserted patents prior to filing its ANDA, in part because the patents are listed in the FDA's Orange Book, and was aware that filing the ANDA constituted an act of infringement (Compl. ¶¶ 45, 51).
VII. Analyst’s Conclusion: Key Questions for the Case
- A primary issue will be one of induced infringement: does the specific language in Alembic's proposed product labeling rise to the level of actively encouraging or instructing physicians and patients to perform the precise, multi-step methods recited in the asserted claims, or does it merely provide cautionary information about potential drug interactions?
- A second core issue will be one of claim construction: can the subjective-sounding limitation "as soon as it is safe to do so" in the ’998 Patent be construed with sufficient objective boundaries to be definite and enforceable, particularly in light of the detailed pharmacokinetic data provided in the specification?
- A key underlying question, likely to be raised by the defense, will be one of patent eligibility and obviousness: are methods of treatment that are defined by specific dosage regimens and waiting periods—discovered through clinical analysis of known drugs—patent-eligible under 35 U.S.C. § 101, and were these specific regimens non-obvious to a person of ordinary skill in the art of pharmacology?