DCT

1:25-cv-00560

AVEO Pharma Inc v. Somerset Therap LLC

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:25-cv-00560, D. Del., 05/07/2025
  • Venue Allegations: Venue is asserted based on the domestic defendants being incorporated in Delaware and the foreign defendant being subject to personal jurisdiction in the district.
  • Core Dispute: Plaintiff alleges that Defendants' proposed generic version of the cancer drug FOTIVDA® (tivozanib), for which they have filed an Abbreviated New Drug Application (ANDA), will infringe a patent covering methods of treatment for refractory renal cell carcinoma.
  • Technical Context: The technology concerns specific dosing regimens for tivozanib, a tyrosine kinase inhibitor, for treating advanced kidney cancer in patients who have not responded to prior therapies.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants' submission of ANDA No. 220384 and a subsequent Paragraph IV Notice Letter to Plaintiff, asserting that the patent-in-suit is invalid or not infringed. The complaint was filed within the 45-day statutory window, triggering an automatic 30-month stay of FDA approval for the Defendants' generic product. Plaintiff's branded product, FOTIVDA®, has New Chemical Entity (NCE) exclusivity expiring on March 10, 2026.

Case Timeline

Date Event
2018-11-05 '365 Patent Priority Date
2020-03-31 Plaintiff's FOTIVDA® New Drug Application (NDA) Submitted
2021-03-10 Plaintiff's FOTIVDA® NDA Approved by FDA
2022-11-22 U.S. Patent No. 11,504,365 Issued
2025-03-26 Defendant's ANDA Submitted to FDA (on or before this date)
2025-03-26 Defendant Sent Paragraph IV Notice Letter
2025-03-27 Plaintiff Received Paragraph IV Notice Letter
2025-05-07 Complaint Filed
2026-03-10 FOTIVDA® New Chemical Entity (NCE) Exclusivity Expires

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

U.S. Patent No. 11,504,365 - “Use of Tivozanib to Treat Subjects with Refractory Cancer”

  • Issued: November 22, 2022.

The Invention Explained

  • Problem Addressed: The patent addresses the need for effective treatments for patients with advanced renal cell carcinoma (RCC) whose cancer has become "refractory," meaning it has failed to respond to or has progressed after standard first- and second-line therapies (’365 Patent, col. 2:6-11).
  • The Patented Solution: The invention provides specific methods of using tivozanib, a small-molecule inhibitor of vascular endothelial growth factor (VEGF) receptors, to treat this refractory patient population. The patented methods claim specific treatment cycles, such as administering 1.5 mg of tivozanib for 21 days followed by a 7-day rest period, and include a defined dose-reduction step (e.g., from 1.5 mg to 1.0 mg) if a patient experiences moderate hepatic impairment (’365 Patent, Abstract; col. 2:35-40; col. 18:1-6).
  • Technical Importance: Tivozanib is described as a highly potent and selective VEGF receptor inhibitor, which interferes with tumor angiogenesis (the growth of new blood vessels that feed a tumor) while potentially causing fewer off-target toxicities than other, less selective kinase inhibitors (’365 Patent, col. 1:21-49).

Key Claims at a Glance

  • The complaint asserts independent claims 1 and 7 (Compl. ¶54).
  • Independent Claim 1 recites a method with the following essential elements:
    • Treating a human subject with refractory advanced RCC who has previously received at least two anti-cancer therapies, one of which included a tyrosine kinase inhibitor (TKI).
    • The method involves administering treatment cycles "consisting essentially of" orally administering 1.5 mg of tivozanib hydrochloride daily for 21 days, followed by 7 days off.
    • This cycle continues until the subject experiences moderate hepatic impairment, at which point the dose is reduced from 1.5 mg to 1.0 mg.
    • The method is performed "thereby to achieve a progression free survival in the subject of at least 5 months."
  • Independent Claim 7 recites a method with the following essential elements:
    • Treating a human subject with refractory advanced RCC who has received at least two prior anti-cancer therapies (including a TKI) and is "experiencing moderate hepatic impairment."
    • The method involves administering treatment cycles "consisting essentially of" orally administering 1.0 mg of tivozanib hydrochloride daily for 21 days, followed by 7 days off.
    • The administration is performed "thereby to treat RCC."

III. The Accused Instrumentality

Product Identification

  • Defendants' proposed generic tivozanib hydrochloride capsules, which are the subject of Abbreviated New Drug Application (ANDA) No. 220384 (the "Proposed ANDA Product") (Compl. ¶¶1, 44).

Functionality and Market Context

  • The Proposed ANDA Product is a generic equivalent of Plaintiff's FOTIVDA® product and seeks approval for the same strengths (equivalent to 1.34 mg and 0.89 mg of tivozanib base) (Compl. ¶44). The complaint alleges that, as required by FDA regulations, the proposed labeling for the generic product will be substantially a copy of the FDA-approved label for FOTIVDA® (Compl. ¶55). This label allegedly instructs physicians to use the product for "the treatment of adult patients with relapsed or refractory advanced renal cell carcinoma (RCC) following two or more prior systemic therapies" and to reduce the dose for patients with moderate hepatic impairment (Compl. ¶¶36, 56, 62). The product is intended to be a direct market competitor and substitute for FOTIVDA® (Compl. ¶68).
  • No probative visual evidence provided in complaint.

IV. Analysis of Infringement Allegations

The complaint alleges that Defendants will induce infringement by physicians and patients who follow the instructions on the Proposed ANDA Product's label (Compl. ¶55).

'365 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A method of treating a human subject with refractory advanced renal cell carcinoma (RCC) having previously received at least two anti-cancer therapies, at least one of which included a tyrosine kinase inhibitor (TKI)... The proposed label will allegedly indicate the product for treating patients with relapsed or refractory advanced RCC who have received two or more prior therapies, and will reference a clinical study where all patients had received a prior TKI, thereby instructing use in the claimed patient population. ¶56, ¶58, ¶59 col. 2:6-11
...administering to the subject treatment cycles consisting essentially of: orally administering a pharmaceutical composition comprising an active agent consisting essentially of 1.5 mg tivozanib hydrochloride daily for 21 days followed by 7 days without administration of tivozanib hydrochloride... The proposed label will allegedly recommend a dosage equivalent to 1.5 mg of tivozanib hydrochloride, taken daily for 21 days on treatment followed by 7 days off treatment. ¶60 col. 2:35-40
...until the subject experiences moderate hepatic impairment, upon which the amount of tivozanib hydrochloride in each treatment cycle is reduced from 1.5 mg to 1.0 mg, The proposed label will allegedly contain instructions for physicians to assess for hepatic impairment and to reduce the dose for patients with moderate hepatic impairment to an amount equivalent to 1.0 mg of tivozanib hydrochloride. ¶62, ¶63 col. 18:26-30
...thereby to achieve a progression free survival in the subject of at least 5 months. The proposed label will allegedly report clinical trial efficacy results showing a median progression-free survival of 5.6 months, which allegedly encourages physicians to administer the drug to achieve this outcome. ¶65 col. 23:41-43
  • Identified Points of Contention:
    • Scope Questions: A central dispute may concern the "thereby to achieve" limitation. A court will have to determine if this phrase requires that a patient actually achieve at least five months of progression-free survival for direct infringement to occur, or if it merely describes the intended purpose and benefit of performing the preceding administration steps as instructed by the label.
    • Technical Questions: The infringement theory is based entirely on inducement via the product label. A key question is whether the label's instructions are sufficiently directive to establish that Defendants specifically intended for physicians to perform every element of the claimed method. For Claim 1, this includes not just the initial dosing but also the specific dose reduction upon the occurrence of moderate hepatic impairment.

V. Key Claim Terms for Construction

  • The Term: "thereby to achieve a progression free survival in the subject of at least 5 months" (Claim 1)

  • Context and Importance: The construction of this "thereby" clause is critical. It determines whether the claim requires a specific clinical outcome to be met for infringement or if it describes the purpose of the preceding method steps. This will significantly impact the ability to prove both direct and induced infringement.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation (Purpose): The specification presents the method and then separately discusses the clinical trial results, including the progression-free survival data, as evidence of the method's efficacy (’365 Patent, Fig. 1; col. 23:41-54). This may support an interpretation that the clause states the intended result of practicing the method, rather than a required step of it.
    • Evidence for a Narrower Interpretation (Required Outcome): The use of the active phrase "to achieve" could be argued to impose a functional requirement that must be met for the method to be complete. The claim is not phrased as a "method for achieving" but a "method... thereby to achieve," which a party could argue links the method steps to a necessary result.

  • The Term: "consisting essentially of" (Claims 1 and 7)

  • Context and Importance: This transitional phrase limits the scope of the claimed "treatment cycles." Its construction will determine whether the administration of other drugs or supportive care alongside the claimed tivozanib regimen would fall outside the claim scope and thus avoid infringement.

  • Intrinsic Evidence for Interpretation:

    • Evidence for a Broader Interpretation: The patent does not define the term, so it would likely be given its standard legal meaning, which permits additional, unrecited steps as long as they do not materially affect the basic and novel properties of the claimed invention. Plaintiff may argue that the basic and novel property is the specific tivozanib dosing and dose-reduction schedule, which is unaffected by standard supportive care.
    • Evidence for a Narrower Interpretation: A defendant could argue that a key property of the invention is tivozanib's efficacy as a monotherapy, as noted in the complaint (Compl. ¶64). Therefore, the administration of any other active anti-cancer agent could be argued to materially affect the invention's properties, placing such a combined treatment outside the claim's scope.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges active inducement of infringement, stating that Defendants' proposed product label will instruct and encourage physicians to perform the patented methods (Compl. ¶¶53, 57, 69). It also pleads contributory infringement, alleging the Proposed ANDA Product is not a staple article of commerce and is especially adapted for an infringing use (Compl. ¶71).
  • Willful Infringement: Willfulness is alleged based on Defendants' knowledge of the '365 Patent, as demonstrated by the act of sending the Paragraph IV Notice Letter, and their continued intent to market the product for infringing uses upon FDA approval (Compl. ¶¶68, 74).

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

  • A central issue will be one of claim scope: can the "thereby to achieve" limitation in Claim 1 be met by a physician administering the drug with the intent to achieve the stated clinical outcome as encouraged by the product label, or must the patient actually achieve five months of progression-free survival for direct infringement to have occurred?
  • A key evidentiary question will be one of induced infringement: does the act of providing a product label that mirrors the branded drug's label, including descriptions of clinical trial results and instructions for specific patient populations and dose adjustments, suffice to prove Defendants' specific intent to encourage physicians to perform the complete, multi-step methods of the asserted claims?
  • A final question will be one of definitional scope: how will the court construe the patient population defined as "refractory," particularly regarding the nature and timing of the "at least two anti-cancer therapies," and will this definition be influenced by the specific enrollment criteria of the TIVO-3 clinical trial described in the patent?