Azurity Pharmaceuticals Inc v. Exelixis Inc

1. Case Identification

• Case #: IPR2025-00210
• Patent #: 11,298,349
• Filed: November 18, 2024
• Petitioner(s): Azurity Pharmaceuticals, Inc.
• Patent Owner(s): Exelixis, Inc.
• Challenged Claims: 1-3

2. Patent Overview

• Title: Pharmaceutical Compositions of Cabozantinib
• Brief Description: The ’349 patent claims oral pharmaceutical compositions (tablets or capsules) containing cabozantinib (L)-malate combined with broad categories of excipients (fillers, disintegrants, glidants, and lubricants). The compositions are defined as being “essentially free” of process byproducts or a specific impurity, 6,7-dimethoxy-quinoline-4-ol.

3. Grounds for Unpatentability

Ground 1: Anticipation of Claims 1-3 under 35 U.S.C. §102 by Wilson

• Prior Art Relied Upon: Wilson (Patent 9,717,720).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that the ’349 patent’s challenged claims are not entitled to their asserted priority date. The claims were significantly broadened in a February 8, 2021 amendment to recite generic categories of excipients (e.g., "one or more fillers") for the first time, whereas prior applications in the family only disclosed narrow formulations with specific excipients. Petitioner contended this added new matter, making the effective filing date February 8, 2021. Consequently, Wilson, a patent from the same family that issued in 2017, constitutes prior art. Wilson allegedly discloses a specific capsule formulation (a species) that meets every limitation of the broad genus claims of the ’349 patent. Specifically, Wilson disclosed a pharmaceutical capsule for oral administration comprising cabozantinib (L)-malate, a filler (microcrystalline cellulose), a disintegrant (croscarmellose sodium), a glidant (fumed silica), and a lubricant (stearic acid). Wilson further taught that the formation of the 6,7-dimethoxy-quinoline-4-ol impurity was minimized to 50 ppm or less, satisfying the "essentially free" limitation.

Ground 2: Obviousness of Claims 1-3 under 35 U.S.C. §103 over Brown in view of Kubo and Remington

• Prior Art Relied Upon: Brown (WO 2010/083414), Kubo (Patent 7,169,789), and Remington: The Science and Practice of Pharmacy (“Remington”).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Brown disclosed the active ingredient, cabozantinib (L)-malate ("Compound IB"), and taught preparing it in oral dosage forms like tablets and capsules using standard excipients such as fillers, disintegrants, and lubricants. Brown's synthesis produced the compound with "de minimis" levels of the 6,7-dimethoxy-quinoline-4-ol impurity. Kubo taught an alternative, one-step synthesis for a key intermediate that was superior to Brown's two-step process. Remington, a standard pharmaceutical treatise referenced by Brown, provided a roadmap for routine formulation, identifying common and preferred excipients for each claimed category (e.g., microcrystalline cellulose as a filler, croscarmellose sodium as a disintegrant), rendering the claimed composition obvious.
  • Motivation to Combine: A Person of Ordinary Skill in the Art (POSA) would combine Brown's disclosure of Compound IB with Kubo’s improved synthesis to increase efficiency, reduce costs, and potentially improve purity. The one-step reaction taught by Kubo was described as an "alternative" for preparing the same class of compounds and was more efficient. A POSA, following Brown's explicit instruction to use "methods know[n] in the pharmaceutical formulation art," would have naturally consulted a standard reference like Remington to select common, well-characterized excipients to formulate the active ingredient into a tablet or capsule. Furthermore, a POSA would be motivated to limit the potentially genotoxic 6,7-dimethoxy-quinoline-4-ol impurity to below 200 ppm in accordance with known regulatory guidance.
  • Expectation of Success: A POSA would have had a high expectation of success. The synthesis modification suggested by Kubo was for the same class of compounds and offered clear advantages, and the ’349 patent itself demonstrates its success. Formulating a known active pharmaceutical ingredient using standard, widely-used excipients as taught by Remington was a routine and predictable process in the art.

4. Key Claim Construction Positions

• "essentially free of process byproducts or contaminants" (Claim 1): Petitioner asserted this phrase is expressly defined in the ’349 patent’s specification to mean the composition is “admixed with 200 parts per million (ppm) or less of such byproducts or contaminants.”
• "essentially free of 6,7-dimethoxy-quinoline-4-ol" (Claim 3): While not expressly defined, Petitioner adopted the construction from a prior district court litigation, which applied a numerical limit of 200 ppm or less for this specific impurity.

5. Arguments Regarding Discretionary Denial

• Fintiv Factors (§314(a)): Petitioner argued against discretionary denial, asserting that no parallel litigation exists between Azurity and Exelixis. While a litigation against a different party (MSN) occurred, Petitioner argued it involved different issues: it only concerned claim 3, did not raise an anticipation challenge, relied on different obviousness combinations, and crucially, never addressed the effective filing date of the challenged claims. Thus, the core arguments in this IPR are distinct.
• Advanced Bionics Test (§325(d)): Petitioner contended that denial under §325(d) is improper. The Ground 1 anticipation argument is entirely new, as the Examiner never considered the effective filing date issue that makes Wilson prior art. The Ground 2 obviousness argument relies on a new combination of references (adding Kubo and Remington to Brown) and arguments not previously presented to or considered by the Office.

6. Relief Requested

• Petitioner requests institution of an inter partes review and cancellation of claims 1-3 of Patent 11,298,349 as unpatentable.