DCT

1:25-cv-00478

Exelixis Inc v. Azurity Pharma Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:25-cv-00478, D. Del., 04/24/2025
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendants Azurity Pharmaceuticals, Inc. and Slayback Pharma LLC are incorporated in Delaware and therefore reside in the district. Venue is alleged to be proper for the foreign-based defendants, Azurity Pharmaceuticals India LLP and Slayback Pharma India LLP, under federal statutes permitting suit in any judicial district.
  • Core Dispute: Plaintiff alleges that Defendants' filing of a 505(b)(2) New Drug Application for generic Cabozantinib (S)-Malate tablets constitutes an act of infringement against six patents related to the drug's specific malate salt form, crystalline polymorphs, and manufacturing processes.
  • Technical Context: The technology involves specific salt forms and crystalline structures of the cancer drug cabozantinib, a tyrosine kinase inhibitor, which are important for drug stability, manufacturability, and bioavailability.
  • Key Procedural History: This action was initiated under the Hatch-Waxman Act following Defendants' submission of New Drug Application No. 220258 to the FDA. The application included a Paragraph IV certification asserting that Plaintiff's patents are invalid, unenforceable, or will not be infringed by the proposed generic product. The complaint was filed within the 45-day statutory window following receipt of Defendants' notification letter.

Case Timeline

Date Event
2009-01-16 Earliest Patent Priority Date ('776, '439, '440, '015, '349, '039 Patents)
2014-11-04 U.S. Patent No. 8,877,776 Issued
2016-01-01 Plaintiff's CABOMETYX® Product Approved by FDA
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
2022-04-12 U.S. Patent No. 11,298,349 Issued
2024-10-29 U.S. Patent No. 12,128,039 Issued
2025-03-05 Defendants' Notice Letter Sent
2025-04-24 Complaint Filing Date

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,”

  • Patent Identification: U.S. Patent No. 8,877,776, titled “(L)-malate salt of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide,” issued November 4, 2014 (Compl. ¶23).

The Invention Explained

  • Problem Addressed: The patent describes the need to find a suitable form of the active pharmaceutical ingredient (API) that has properties amenable to drug development, such as adequate stability, processability, and manufacturability (’776 Patent, col. 3:15-23). The background notes that other salt forms of the API exhibited undesirable properties, such as the hydrochloride salt's moisture sensitivity and the low crystallinity of the tartrate salt (’776 Patent, col. 7:35-47).
  • The Patented Solution: The invention is the specific (L)-malate salt of the API. This particular salt form is described as crystalline, non-hygroscopic, and possessing a combination of solubility and stability that make it suitable for pharmaceutical development, overcoming the deficiencies of other salt forms (’776 Patent, col. 7:20-24; Table 1).
  • Technical Importance: Identifying a stable and manufacturable salt form with appropriate physical properties is a critical step in converting a promising chemical compound into a viable and consistent drug product (’776 Patent, col. 3:15-23).

Key Claims at a Glance

  • The complaint asserts infringement of at least independent claim 1 and dependent claim 2 (Compl. ¶38).
  • Essential elements of independent claim 1:
    • N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (L)-malate salt.

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 ther[e]of for the treatment of cancer,”

  • Patent Identification: U.S. Patent No. 11,091,439, titled “Malate salt of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide, and crystalline forms ther[e]of for the treatment of cancer,” issued August 17, 2021 (Compl. ¶24).

The Invention Explained

  • Problem Addressed: Beyond selecting a suitable salt, drug development requires the identification and control of specific solid-state crystalline forms, or polymorphs, of that salt. Different polymorphs of the same compound can have different physical properties, including stability and dissolution rate, which can affect manufacturing consistency and drug performance (’015 Patent, col. 3:15-23).
  • The Patented Solution: The invention claims specific crystalline forms of the (L)-malate salt of cabozantinib, including a form designated N-2. This form is identified and defined by unique physical characteristics, particularly its X-ray powder diffraction (XRPD) pattern, which provides a structural fingerprint distinguishing it from other potential solid forms (’015 Patent, col. 9:4-14; Fig. 8).
  • Technical Importance: Controlling the crystalline form of an active pharmaceutical ingredient is crucial for ensuring product quality, consistency, and performance, which is a key manufacturing challenge and a focus of regulatory oversight (’015 Patent, col. 3:15-23).

Key Claims at a Glance

  • The complaint asserts infringement of at least claims 1, 3, and 4 (Compl. ¶47). Based on publicly available patent data, Claim 1 is independent.
  • Essential elements of independent claim 1:
    • A crystalline Form N-2
    • of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (L)-malate salt
    • characterized by an X-ray powder diffraction pattern comprising specific peaks.

U.S. Patent No. 11,091,440

  • Patent Identification: U.S. Patent No. 11,091,440, issued August 17, 2021 (Compl. ¶25).
  • Technology Synopsis: This patent is directed to a crystalline form of the (DL)-malate salt of cabozantinib, which is a racemic mixture of the (D)-malate and (L)-malate salts. It addresses the same technical challenge of identifying stable, characterizable solid forms of the drug suitable for pharmaceutical use.
  • Asserted Claims: At least claims 1 and 3 (Compl. ¶56).
  • Accused Features: The complaint alleges that "crystalline Cabozantinib (S)-Malate may be present" in the accused product, which forms the basis for infringement allegations (Compl. ¶59).

U.S. Patent No. 11,098,015

  • Patent Identification: U.S. Patent No. 11,098,015, issued August 24, 2021 (Compl. ¶26).
  • Technology Synopsis: This patent claims methods of treating cancer (such as kidney or liver cancer) by administering a crystalline form of the (L)-malate or (D)-malate salt of cabozantinib. The invention protects the specific use of these stable crystalline forms to achieve a therapeutic effect.
  • Asserted Claims: At least claims 1, 2, and 3 (Compl. ¶65).
  • Accused Features: The accused product is a generic version of a drug approved for treating cancer, and the complaint alleges it contains the crystalline malate salt, thereby forming the basis for infringing the claimed methods of use (Compl. ¶29, ¶68).

U.S. Patent No. 11,298,349 - “Processes for preparing quinoline compounds and pharmaceutical compositions containing such compounds,”

  • Patent Identification: U.S. Patent No. 11,298,349, titled “Processes for preparing quinoline compounds and pharmaceutical compositions containing such compounds,” issued April 12, 2022 (Compl. ¶27).
  • Technology Synopsis: This patent claims processes for manufacturing quinoline compounds, such as cabozantinib. The invention is directed to specific chemical synthesis steps and conditions used to produce the API.
  • Asserted Claims: At least claim 3 (Compl. ¶74).
  • Accused Features: The act of infringement is the filing of the NDA, which seeks approval to manufacture the drug. The complaint notes that Defendants have not contested infringement of the asserted claims in their notice letter (Compl. ¶74).

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

  • Patent Identification: U.S. Patent No. 12,128,039, titled “Processes for preparing quinoline compounds and pharmaceutical compositions containing such compounds,” issued October 29, 2024 (Compl. ¶28).
  • Technology Synopsis: Similar to the ’349 Patent, this patent is directed to processes for manufacturing quinoline compounds like cabozantinib, protecting specific methods of synthesis.
  • Asserted Claims: At least claim 1 (Compl. ¶82).
  • Accused Features: The filing of the NDA to manufacture the drug constitutes the alleged act of infringement. The complaint notes Defendants have not contested infringement of non-method-of-treatment claims in their notice letter (Compl. ¶82).

III. The Accused Instrumentality

Product Identification

  • The accused instrumentality is the "Azurity 505(b)(2) NDA Product," identified as Cabozantinib (S)-Malate Tablets in 13 mg, 26 mg, and 39 mg dosage strengths (Compl. ¶1, ¶31).

Functionality and Market Context

  • The accused product is a proposed generic version of Plaintiff's CABOMETYX® product (Compl. ¶32). According to the complaint, Defendants have represented to the FDA that their product contains the same active ingredient (cabozantinib (S)-malate), has the same dosage form, and is bioequivalent to CABOMETYX® (Compl. ¶32). The product is a tyrosine kinase inhibitor intended for the treatment of certain cancers (Compl. ¶29). Defendants are seeking FDA approval to commercially manufacture and sell this product in the United States before the expiration of the patents-in-suit (Compl. ¶33).

IV. Analysis of Infringement Allegations

No probative visual evidence provided in complaint.

’776 Patent Infringement Allegations

Claim Element (from Independent Claim 1 and Dependent Claim 2) Alleged Infringing Functionality Complaint Citation Patent Citation
N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (L)-malate salt The accused product is identified as "Cabozantinib (S)-Malate Tablets," where (S)-malate is chemically equivalent to (L)-malate. The product is alleged to have the same active ingredient as Plaintiff's CABOMETYX® (Compl. ¶32). ¶31, ¶32, ¶38 col. 10:46-51
[From Dep. Claim 2] wherein said salt is in crystalline Form N-2 The complaint alleges, based on a review of confidential NDA materials, that "Cabozantinib (S)-Malate Form N-2 may be present in the Azurity 505(b)(2) NDA Product." ¶41 col. 10:52-53

’439 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A crystalline Form N-2... Based on a review of confidential NDA materials, the complaint alleges that "crystalline Cabozantinib (S)-Malate may be present" and that the materials are insufficient to demonstrate its absence. ¶50 col. 8:40-42
...of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (L)-malate salt The accused product is identified as "Cabozantinib (S)-Malate Tablets," containing the same active ingredient as Plaintiff's product. ¶31, ¶32, ¶50 col. 5:27-38

Identified Points of Contention

  • Evidentiary Question: A central issue appears to be evidentiary. The complaint alleges that the claimed crystalline forms "may be present" and that Defendants' NDA materials are "insufficient to demonstrate" their absence (Compl. ¶41, ¶50). This suggests the dispute will focus on the physical characterization of the accused product and what analytical data (e.g., XRPD) reveals about its solid-state form.
  • Technical Question: What is the actual solid-state composition of the Defendants' product? The infringement analysis will likely depend on whether laboratory analysis of the Azurity tablets confirms the presence of the specific (L)-malate salt and, critically, whether it exists in the claimed crystalline forms (e.g., Form N-2) as defined by the patents.

V. Key Claim Terms for Construction

  • The Term: "crystalline"
  • Context and Importance: The infringement allegations against the '439, '440, and '015 patents depend on the accused product containing a "crystalline" form of the cabozantinib malate salt (Compl. ¶50, ¶59, ¶68). The definition of this term will be critical for determining whether the solid form of the API in Defendants' product falls within the scope of the claims, particularly if it exists as a mixture or has a low degree of crystallinity.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The patents do not appear to provide a special definition of "crystalline," which may support an argument that the term should be given its plain and ordinary meaning in the fields of chemistry and pharmaceutical sciences, referring generally to a solid possessing a long-range, ordered, three-dimensional atomic structure.
    • Evidence for a Narrower Interpretation: A party could argue that, in the context of the patents, "crystalline" should be understood to mean a form that is substantially pure and exhibits the specific, enumerated analytical characteristics (such as the XRPD peaks listed for Form N-1 and Form N-2) that distinguish it from amorphous material or other polymorphs (’015 Patent, col. 8:40-42).

VI. Other Allegations

  • Indirect Infringement: The complaint includes allegations of induced and contributory infringement for all asserted patents (Compl. ¶39, ¶48, ¶57, ¶66, ¶75, ¶83). With respect to the method-of-use claims in the '015 Patent, inducement would likely be based on the proposed product labeling instructing physicians and patients to use the drug for the patented methods of treating cancer.
  • Willful Infringement: The complaint alleges that Defendants acted without a reasonable basis for believing they would not be liable for infringement (Compl. ¶44, ¶53, ¶62, ¶71, ¶79, ¶87). This allegation is predicated on Defendants' knowledge of the Asserted Patents, evidenced by their submission of a Paragraph IV certification as part of their NDA (Compl. ¶34).

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

  • A core issue will be one of physical characterization: What does the analytical evidence show about the solid-state form of the active ingredient in the Azurity product? The case will likely depend heavily on competing laboratory data (e.g., XRPD, solid-state NMR) to determine if the specific crystalline structures claimed in patents like the ’439 Patent are present in the accused tablets.
  • A key legal question will be one of evidentiary burden: The complaint's framing that Defendants' data is "insufficient to demonstrate" the absence of the claimed forms raises the question of how the burden of proof will be allocated and met concerning the physical nature of a product that is not yet on the market.
  • For the process patents ('349 and '039), a central question will be one of discovery: Since the infringement allegation is based on the statutory act of filing an NDA to manufacture a product, the dispute may turn on whether discovery into Defendants' intended manufacturing process reveals the use of the claimed synthesis steps.