Azurity Pharmaceuticals, Inc. v. EXELIXIS, INC.

Petition

Petition summary

## 1. Case Identification
- Case Number: [IPR2025-00210](https://ai-lab.exparte.com/case/ptab/IPR2025-00210)
- Patent #: 11,298,349
- Filed: November 18, 2024
- Petitioner(s): [AZURITY PHARMACEUTICALS, INC.](https://ai-lab.exparte.com/party/azurity-pharmaceuticals-inc)
- Patent Owner(s): [EXELIXIS, INC.](https://ai-lab.exparte.com/party/exelixis-inc)
- Challenged Claims: 1-3

## 2. Patent Overview
- Title: Pharmaceutical Formulations of Cabozantinib (L)-malate
- Brief Description: The [’349 patent](https://ai-lab.exparte.com/case/ptab/IPR2025-00210/doc/1001) relates to pharmaceutical capsule or tablet formulations of cabozantinib (L)-malate that are "essentially free" of certain process byproducts, specifically 6,7-dimethoxy-quinoline-4-ol.

## 3. Grounds for Unpatentability
#### Ground 1: Anticipation - Claims 1-3 are anticipated by Wilson
- **Prior Art Relied Upon:** Patent 9,717,720 ("[Wilson](https://ai-lab.exparte.com/case/ptab/IPR2025-00210/doc/1002)").
- **Core Argument for this Ground:**
  - **Prior Art Mapping:** Petitioner argued that the [’349 patent](https://ai-lab.exparte.com/case/ptab/IPR2025-00210/doc/1001) is not entitled to its claimed priority date because its priority applications fail to provide adequate written description support for the broad, functionally-defined claims. The claims require a composition with any combination of excipients from four broad categories (fillers, disintegrants, glidants, lubricants) that achieves a specific purity level (<200 ppm of contaminants). Petitioner asserted that the priority applications only disclose a few specific formulations and provide no guidance for a person of ordinary skill in the art (POSITA) to predict which of the countless other possible excipient combinations would achieve the claimed result, especially given the unpredictable nature of excipient interactions. Therefore, Petitioner contended the challenged claims are only entitled to their actual filing date of February 8, 2021. [Wilson](https://ai-lab.exparte.com/case/ptab/IPR2025-00210/doc/1002), a patent from the same family that issued in 2017, is thus prior art. [Wilson](https://ai-lab.exparte.com/case/ptab/IPR2025-00210/doc/1002) allegedly discloses a specific capsule formulation containing cabozantinib (L)-malate, a filler (microcrystalline cellulose), a disintegrant (croscarmellose sodium), a glidant (fumed silica), and a lubricant (stearic acid), which was shown to have less than 50 ppm of the 6,7-dimethoxy-quinoline-4-ol impurity. As this specific embodiment disclosed in [Wilson](https://ai-lab.exparte.com/case/ptab/IPR2025-00210/doc/1002) falls within the scope of the broad genus claims of the [’349 patent](https://ai-lab.exparte.com/case/ptab/IPR2025-00210/doc/1001), Petitioner argued it anticipates claims 1-3.

#### Ground 2: Obviousness - Claims 1-3 are obvious over Brown in view of Kubo and Remington
- **Prior Art Relied Upon:** WO 2010/083414 ("[Brown](https://ai-lab.exparte.com/case/ptab/IPR2025-00210/doc/1003)"), Patent 7,169,789 ("[Kubo](https://ai-lab.exparte.com/case/ptab/IPR2025-00210/doc/1028)"), and *[Remington](https://ai-lab.exparte.com/case/ptab/IPR2025-00210/doc/1004): The Science and Practice of Pharmacy* ("[Remington](https://ai-lab.exparte.com/case/ptab/IPR2025-00210/doc/1004)").
- **Core Argument for this Ground:**
  - **Prior Art Mapping:** Petitioner argued that [Brown](https://ai-lab.exparte.com/case/ptab/IPR2025-00210/doc/1003) disclosed cabozantinib (L)-malate ("Compound IB"), its formulation into tablets and capsules, and a list of suitable excipients including fillers, disintegrants, and lubricants. [Brown](https://ai-lab.exparte.com/case/ptab/IPR2025-00210/doc/1003) also disclosed a two-step synthesis for an intermediate that resulted in "de minimis" levels of the 6,7-dimethoxy-quinoline-4-ol impurity. [Kubo](https://ai-lab.exparte.com/case/ptab/IPR2025-00210/doc/1028), which is cited on the face of the [’349 patent](https://ai-lab.exparte.com/case/ptab/IPR2025-00210/doc/1001), taught an alternative, one-step synthesis for the same intermediate using the same class of starting materials as [Brown](https://ai-lab.exparte.com/case/ptab/IPR2025-00210/doc/1003). [Remington](https://ai-lab.exparte.com/case/ptab/IPR2025-00210/doc/1004), a standard pharmaceutical treatise, taught that it was conventional to formulate active ingredients into tablets using the four claimed categories of excipients (fillers, disintegrants, glidants, lubricants). Petitioner asserted that combining these references renders the claims obvious.
  - **Motivation to Combine:** A POSITA would combine [Brown](https://ai-lab.exparte.com/case/ptab/IPR2025-00210/doc/1003) and [Kubo](https://ai-lab.exparte.com/case/ptab/IPR2025-00210/doc/1028) because Kubo’s one-step synthesis was described as an "alternative" to the two-step process and was more efficient, saving steps, cost, and hazardous reagents while improving yield and purity. A POSITA would be motivated to use the formulation teachings of [Brown](https://ai-lab.exparte.com/case/ptab/IPR2025-00210/doc/1003) and [Remington](https://ai-lab.exparte.com/case/ptab/IPR2025-00210/doc/1004) because they represent standard, known techniques for preparing a solid oral dosage form of a compound like cabozantinib (L)-malate. Further, a POSITA would be motivated to limit the 6,7-dimethoxy-quinoline-4-ol impurity to below 200 ppm to comply with regulatory guidance for potentially genotoxic impurities, which this quinoline-based structure suggests.
  - **Expectation of Success:** A POSITA would have a reasonable expectation of success in modifying Brown’s synthesis with Kubo’s teaching because they involve analogous chemistry. The [’349 patent](https://ai-lab.exparte.com/case/ptab/IPR2025-00210/doc/1001) itself, which uses the one-step synthesis, confirms its success. Success in formulating the resulting high-purity compound using standard excipients from [Remington](https://ai-lab.exparte.com/case/ptab/IPR2025-00210/doc/1004) was also expected, as it involved routine and predictable formulation work.

## 4. Key Claim Construction Positions
- **"essentially free of process byproducts or contaminants" (Claim 1):** Petitioner applied the patent's express definition: "admixed with 200 parts per million (ppm) or less of such byproducts or contaminants." This numerical limit was central to both the anticipation and obviousness arguments.
- **"essentially free of 6,7-dimethoxy-quinoline-4-ol" (Claim 3):** Petitioner adopted a construction of "200 ppm or less" for this term, consistent with a prior district court ruling involving the [’349 patent](https://ai-lab.exparte.com/case/ptab/IPR2025-00210/doc/1001) and the definition provided for the similar term in claim 1.

## 5. Key Technical Contentions (Beyond Claim Construction)
- **Unpredictability of Excipient Interactions:** A central pillar of the priority date challenge (Ground 1) was the technical argument that achieving the claimed purity is highly unpredictable across the full scope of the claimed excipient categories. Petitioner cited testimony from the Patent Owner's own expert in separate litigation, who allegedly admitted that the interaction of cabozantinib (L)-malate with excipients is unpredictable and can lead to an increase in impurities. This unpredictability, Petitioner argued, means the limited examples in the priority applications cannot support the broad, result-defined claims.

## 6. Arguments Regarding Discretionary Denial
- Petitioner argued that discretionary denial under *Fintiv* is inappropriate.
  - **Factors 1-4:** There is no parallel litigation between Azurity and [Exelixis](https://ai-lab.exparte.com/party/exelixis-inc), so no stay is possible and no resources have been invested by the parties or a court. While a separate litigation against MSN exists, Petitioner argued the grounds are different, as this petition raises anticipation based on a priority date challenge (which was not litigated) and an obviousness combination (Brown/Kubo/Remington) that differs from the one tried.
  - **Factor 5:** Azurity was not a party to the MSN litigation, and the issues are sufficiently different to avoid duplication of effort.
  - **Factor 6 & *Advanced Bionics*:** Petitioner argued the merits are compelling. The anticipation ground relies on a failure of written description, and the obviousness ground is supported by strong evidence of motivation to combine and an alleged examiner error in failing to consider a combination of references. Petitioner also noted that [Remington](https://ai-lab.exparte.com/case/ptab/IPR2025-00210/doc/1004) was not before the examiner during prosecution.

## 7. Relief Requested
- Petitioner requested institution of an inter partes review and cancellation of claims 1-3 of Patent 11,298,349 as unpatentable.