DCT

1:25-cv-00452

Exelixis Inc v. Biocon Pharma Ltd

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:25-cv-00452, D. Del., 04/11/2025
  • Venue Allegations: Plaintiff alleges venue is proper in the District of Delaware because Defendant Biocon Pharma, Inc. is a Delaware corporation, the other two Biocon defendants are foreign corporations that may be sued in any district, and all defendants have previously availed themselves of the forum and maintain systematic contacts with the state.
  • Core Dispute: Plaintiff alleges that Defendants' submission of an Abbreviated New Drug Application (ANDA) to market a generic version of the cancer drug CABOMETYX® constitutes an act of infringement of five U.S. patents covering the drug's active ingredient, its crystalline forms, and manufacturing processes.
  • Technical Context: The technology concerns specific malate salt forms and crystalline structures (polymorphs) of cabozantinib, a tyrosine kinase inhibitor, which are critical for ensuring the drug's stability, manufacturability, and bioavailability in a solid dosage form.
  • Key Procedural History: The litigation was triggered by Defendants' submission of ANDA No. 220121 and a corresponding Paragraph IV certification notice letter, received by Plaintiff on March 4, 2025, asserting that the patents-in-suit are invalid, unenforceable, or will not be infringed. This complaint was filed within the 45-day statutory window, potentially triggering a 30-month stay on the FDA’s approval of Defendants’ generic product.

Case Timeline

Date Event
2009-01-16 Earliest Priority Date for ’776, ’439, ’440, and ’015 Patents
2011-02-10 Earliest Priority Date for ’039 Patent
2014-11-04 U.S. Patent No. 8,877,776 Issued
2016-01-01 CABOMETYX® Approved by the FDA (approximate date)
2021-08-17 U.S. Patent No. 11,091,439 Issued
2021-08-17 U.S. Patent No. 11,091,440 Issued
2021-08-24 U.S. Patent No. 11,098,015 Issued
2024-10-29 U.S. Patent No. 12,128,039 Issued
2025-03-03 Defendants' Paragraph IV Notice Letter Dated
2025-03-04 Plaintiff Receives Notice Letter
2025-04-11 Complaint for Patent Infringement Filed

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

U.S. Patent No. 8,877,776 - “(L)-malate salt of N-(4-{[6,7-bis(methyloxy) quinolin-4-yl]oxy}phenyl)-N’-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide”

The Invention Explained

  • Problem Addressed: The patent family background describes the deregulation of protein kinase activity as a cause of uncontrolled cell growth associated with cancer, creating a need for small-molecule kinase inhibitors (’439 Patent, col. 2:5-12). More broadly, the specification notes the general challenge in drug development of finding a form of a therapeutic agent with suitable properties for manufacturing, storage, and stability (’439 Patent, col. 3:20-29).
  • The Patented Solution: The invention is a specific salt form of the kinase inhibitor cabozantinib: the (L)-malate salt. Creating a salt is a common strategy to improve a drug compound's physicochemical properties. The patent discloses that this specific salt form has a combination of desirable pharmaceutical properties, including good solubility and stability, making it suitable for development into a commercial drug product (’439 Patent, col. 7:10-25).
  • Technical Importance: The selection of an optimal salt form with stable and consistent properties is a critical step in converting an active pharmaceutical ingredient into a safe, effective, and manufacturable drug product.

Key Claims at a Glance

  • The complaint asserts independent claim 1 and dependent claims 2, 3, and 5 (Compl. ¶35).
  • Independent Claim 1:
    • The (L)-malate salt of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide.

U.S. Patent No. 11,091,439 - “Malate salt of N-(4-{[6,7-bis(methyloxy) quinolin-4-yl]oxy}phenyl)-N’-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, and crystalline forms therof for the treatment of cancer”

The Invention Explained

  • Problem Addressed: As with the parent ’776 Patent, this patent addresses the need for a stable, manufacturable form of the cabozantinib molecule suitable for pharmaceutical use (’439 Patent, col. 3:20-29).
  • The Patented Solution: This invention identifies and characterizes specific crystalline polymorphs of the (L)-malate salt of cabozantinib. A single chemical compound can often solidify into multiple different crystal structures, or polymorphs, each with distinct physical properties. This patent claims a specific polymorph designated "Form N-2" and defines it by its unique analytical data, including its X-ray powder diffraction (XRPD) pattern (Figure 8) and solid-state nuclear magnetic resonance (ssNMR) spectra (Figures 9-11) (’439 Patent, col. 9:8-21).
  • Technical Importance: Identifying and controlling a specific, stable polymorph is essential for pharmaceutical manufacturing to ensure batch-to-batch consistency in a drug's dissolution rate, stability, and bioavailability.

Key Claims at a Glance

  • The complaint asserts independent claim 1 and dependent claims 3 and 4 (Compl. ¶44).
  • Independent Claim 1:
    • A crystalline form of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (L)-malate salt,
    • wherein said crystalline form is Form N-2.

U.S. Patent No. 11,091,440 - “Malate salt of N-(4-{[6,7-bis(methyloxy) quinolin-4-yl]oxy}phenyl)-N’-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, and crystalline forms thereof for the treatment of cancer”

  • Technology Synopsis: This patent claims a pharmaceutical composition comprising the specific crystalline "Form N-2" of cabozantinib (L)-malate. The invention addresses the need for a finished drug formulation containing a stable and well-characterized polymorphic form of the active ingredient (’440 Patent, col. 11:57-65).
  • Asserted Claims: Independent claim 1 and dependent claim 3 are asserted (Compl. ¶52).
  • Accused Features: The Biocon ANDA Product, as a pharmaceutical composition in tablet form, is accused of containing the claimed crystalline Form N-2 (Compl. ¶¶29, 38, 52).

U.S. Patent No. 11,098,015 - “Malate salt of N-(4-{[6,7-bis(methyloxy) quinolin-4-yl]oxy}phenyl)-N’-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, and crystalline forms thereof for the treatment of cancer”

  • Technology Synopsis: This patent is directed to a different crystalline polymorph of cabozantinib (L)-malate, designated "Form N-1." Similar to the patents covering Form N-2, this invention provides a distinct, stable solid form of the drug, characterized by its own unique XRPD and ssNMR data, to ensure manufacturing consistency and predictable performance (’015 Patent, col. 8:41-54).
  • Asserted Claims: Independent claim 1 and dependent claims 2 and 3 are asserted (Compl. ¶60).
  • Accused Features: The Biocon ANDA Product is accused of containing the claimed crystalline Form N-1 (Compl. ¶60).

U.S. Patent No. 12,128,039 - “Processes for preparing quinoline compounds and pharmaceutical compositions containing such compounds”

  • Technology Synopsis: This patent claims processes for preparing quinoline compounds, such as cabozantinib, and compositions containing them. The invention is directed at manufacturing methods that minimize the formation of process impurities, specifically claiming compositions containing the final drug product that are "essentially free" of certain process-related byproducts (’039 Patent, col. 3:39-43, col. 8:30-34).
  • Asserted Claims: Independent claim 1 is asserted (Compl. ¶68).
  • Accused Features: Defendants' process for manufacturing the Biocon ANDA Product and the resulting composition are accused of infringing the claimed methods and compositions (Compl. ¶¶68-69).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentality is Defendants' proposed generic drug product, identified as the "Biocon ANDA Product" (Compl. ¶1).
  • Functionality and Market Context: The product is described as "Cabozantinib (S)-Malate Tablets, 20 mg, 40 mg, and 60 mg," intended as a generic version of Plaintiff's CABOMETYX® (Compl. ¶28). The complaint alleges that by filing an ANDA, Defendants have represented to the FDA that their product has the same active ingredient, dosage forms, and strengths as CABOMETYX® and is bioequivalent to it (Compl. ¶29). CABOMETYX® is a tyrosine kinase inhibitor approved for treating several types of cancer, including renal cell carcinoma and hepatocellular carcinoma, indicating a significant commercial market (Compl. ¶26).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

U.S. Patent No. 8,877,776 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
The (L)-malate salt of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide. The Biocon ANDA Product is alleged to have the same active ingredient as CABOMETYX®, which is the (L)-malate salt of cabozantinib. ¶29 col. 29:5-9

U.S. Patent No. 11,091,439 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A crystalline form of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (L)-malate salt, The Biocon ANDA Product is a solid tablet formulation containing the (L)-malate salt of cabozantinib. ¶¶28-29 col. 8:26-34
wherein said crystalline form is Form N-2. Based on a review of confidential materials from Defendants' ANDA submission, Plaintiff alleges that the crystalline Form N-2 may be present in the Biocon ANDA Product. ¶38 col. 9:8-21

Identified Points of Contention

  • Factual Questions (Polymorphic Form): For the ’439, ’440, and ’015 Patents, a central dispute may be factual: what is the actual crystalline form (or forms) of cabozantinib (L)-malate in the Biocon ANDA Product? The complaint's allegation that Form N-2 "may be present" suggests this is a primary point for discovery and expert testimony, likely involving detailed analysis of Defendants' proposed commercial product using techniques like XRPD and ssNMR (Compl. ¶38).
  • Scope Questions (Process Patent): For the ’039 Patent, which claims processes and compositions with low impurity levels, a key question will be whether Defendants' manufacturing process falls within the scope of the claims and whether their final product meets the purity limitations defined in the patent.
  • Infringement vs. Validity: The complaint notes that for the ’439, ’440, ’015, and ’039 patents, Defendants' notice letter contested validity but not infringement (Compl. ¶¶44, 52, 60, 68). While Plaintiff must still prove infringement, this suggests the primary legal battleground for these patents, from Defendants' perspective, may be their validity rather than a dispute over whether the ANDA product meets the claim limitations.

V. Key Claim Terms for Construction

  • Patent: U.S. Patent No. 8877776

    • The composition claim for the (L)-malate salt is a precise chemical definition. It does not contain technical terms that are typically subject to significant construction disputes; the case is more likely to turn on questions of validity (e.g., obviousness) than claim scope.

  • Patent: U.S. Patent No. 11091439

    • The Term: "Form N-2"
    • Context and Importance: The term defines the specific crystal polymorph of the drug substance. The infringement analysis for the ’439 and ’440 patents will depend entirely on whether the Biocon ANDA Product is found to contain this specific form. Practitioners may focus on this term because the patent defines it by a set of analytical characteristics, and any dispute will involve comparing the accused product's characteristics to those recited in the claims and specification.
    • Intrinsic Evidence for Interpretation: The patent itself provides the definition for the term, tying it to specific analytical data.
      • Evidence for a Broader Interpretation: A party might argue that "Form N-2" does not require a perfect match to every characteristic peak listed in the specification, but rather substantial similarity to the overall XRPD pattern shown in Figure 8 or key identifying peaks (’439 Patent, Fig. 8).
      • Evidence for a Narrower Interpretation: A party could argue that the term is strictly defined by the specific peaks enumerated in the specification or the dependent claims. For example, claim 4 identifies a list of ten specific XRPD peaks, and a party could contend that a crystalline form must exhibit all or most of these peaks to be considered "Form N-2" (’439 Patent, col. 32:49-56).

VI. Other Allegations

  • Indirect Infringement: The complaint alleges that upon FDA approval, Defendants will indirectly infringe by inducing and contributing to infringement (Compl. ¶¶36-37, 45-46). The alleged basis for inducement is that Defendants’ product labeling will instruct physicians and patients to administer the drug, thereby causing direct infringement by the end-users.
  • Willful Infringement: Willfulness is alleged based on Defendants' knowledge of the Asserted Patents, evidenced at least by their submission of the Paragraph IV certification (Compl. ¶31). The complaint further pleads that Defendants acted "without a reasonable basis for believing that they would not be liable for... infringing," which frames the willfulness inquiry around the objective reasonableness of Defendants' non-infringement and invalidity positions (Compl. ¶41, ¶49, ¶57, ¶65, ¶73).

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

  • A primary evidentiary question will be one of polymorphic identity: What is the precise crystalline structure of the cabozantinib malate in Defendants' proposed generic product? The case for at least three of the five asserted patents may turn on whether sophisticated analytical testing demonstrates the presence of the specific "Form N-1" or "Form N-2" polymorphs as defined in the patents.
  • A central legal issue will be one of validity: As Defendants have challenged the validity of the patents in their Paragraph IV certification, the case will likely involve significant disputes over whether the claimed salt and its specific crystalline forms were obvious or anticipated by prior art, particularly in light of the pre-existing disclosure of the base cabozantinib compound.
  • A key question for the process patent will be one of scope and proof: Can Plaintiff demonstrate that Defendants' confidential manufacturing process falls within the scope of the ’039 patent's process claims, and that the resulting drug substance meets the claimed purity limitations, thereby infringing the patent's composition claims?