PTAB

IPR2025-00945

Azurity Pharmaceuticals Inc v. Helsinn Healthcare SA

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Compositions and methods for treating centrally mediated nausea and vomiting
  • Brief Description: The ’826 patent discloses methods for treating chemotherapy-induced nausea and vomiting (CINV) by co-administering three active agents: netupitant (a neurokinin-1 (NK1) receptor antagonist), palonosetron (a 5-HT3 receptor antagonist), and dexamethasone (a corticosteroid).

3. Grounds for Unpatentability

Ground 1: Claims 19, 22-23, and 25 are obvious over MASCC in view of Hoffmann

  • Prior Art Relied Upon: MASCC (a 2006 journal article) and Hoffmann (a 2006 journal article).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that MASCC taught the then-standard-of-care, three-drug regimen for treating acute and delayed CINV: an NK1 antagonist (aprepitant), a 5-HT3 antagonist (palonosetron), and dexamethasone. Hoffmann disclosed a class of potent, orally-active NK1 antagonists that included netupitant, describing it as having favorable characteristics such as high affinity and excellent penetration into the central nervous system. Petitioner asserted that the combination of these references taught all limitations of independent claim 19. The dependent claims’ limitations regarding specific dexamethasone dosing regimens (claims 22-23) were also taught by MASCC’s disclosure of using sub-therapeutic doses of dexamethasone with aprepitant.
    • Motivation to Combine: A Person of Ordinary Skill in the Art (POSA) would have been motivated to substitute the improved NK1 antagonist, netupitant (disclosed in Hoffmann), for the older aprepitant in the established three-drug regimen taught by MASCC. This substitution represented a simple replacement of one known element with another from the same class to achieve a predictable improvement in efficacy.
    • Expectation of Success: A POSA would have had a reasonable expectation of success because netupitant and aprepitant are both NK1 antagonists that work via the same mechanism. Hoffmann’s disclosure of netupitant’s “excellent” characteristics would have further supported this expectation.

Ground 2: Claims 19-20, 22-23, and 25 are obvious over MASCC in view of Bös

  • Prior Art Relied Upon: MASCC (a 2006 journal article) and Bös (Patent 6,297,375).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground presented a similar argument to Ground 1, with Bös serving as the source for netupitant. Petitioner contended that MASCC established the three-drug combination therapy baseline. Bös disclosed netupitant as a potent and selective NK1 antagonist useful for treating emesis and taught a broad oral dosage range of 10-1000 mg/day. This combination allegedly rendered claim 19 obvious. For dependent claim 20, Petitioner argued that optimizing within the broad range taught by Bös to arrive at the claimed 200-400 mg of netupitant would have been a matter of routine experimentation for a POSA.
    • Motivation to Combine: The motivation was again based on improving the standard therapy taught by MASCC. Bös provided a new, improved NK1 antagonist (netupitant) that was an attractive oral replacement for aprepitant, particularly given its demonstrated ability to completely block emesis in pre-clinical models.
    • Expectation of Success: A POSA would have expected success in substituting Bös’s netupitant into MASCC’s regimen. Bös provided clear guidance on therapeutically effective dose ranges, and MASCC taught that new drugs in the same class as aprepitant were anticipated, reinforcing the predictability of the combination.

Ground 3: Claims 1-3, 8-10, 15-18, and 24 are obvious over Herrstedt in view of Hoffmann and Hargreaves

  • Prior Art Relied Upon: Herrstedt (a 2007 journal article), Hoffmann (a 2006 journal article), and Hargreaves (a 2002 journal article).

  • Core Argument for this Ground:

    • Prior Art Mapping: This ground challenged the ’826 patent’s other independent claim, claim 1. Petitioner argued that Herrstedt taught treating CINV over a five-day period with a triple-drug combination of an NK1 antagonist (aprepitant), a 5-HT3 antagonist (palonosetron), and a sub-therapeutic dose of dexamethasone. Hoffmann provided the rationale for substituting netupitant for aprepitant. Critically, Hargreaves taught the limitation of claim 1 requiring at least 70% NK1 receptor occupancy in the striatum 72 hours post-administration. Hargreaves associated NK1 receptor occupancy of 75% or greater with therapeutic efficacy, making the claimed level an inherent and expected property of an effective dose.
    • Motivation to Combine: A POSA would combine these references to create an optimized antiemetic therapy. A POSA would have been motivated to replace aprepitant in Herrstedt’s regimen with the improved netupitant from Hoffmann and would have used the known receptor occupancy evaluation methods taught by Hargreaves to confirm a therapeutically effective dose, a standard practice in drug development.
    • Expectation of Success: Success was reasonably expected because the combination involved substituting known, improved components into an established therapeutic framework and applying standard measurement techniques (receptor occupancy) to verify dosage and efficacy.

  • Additional Grounds: Petitioner asserted additional obviousness grounds based on further combinations, including adding Bös to the Herrstedt combination (Ground 5) and adding ALOXI (a 2008 FDA label) to teach specific palonosetron formulations and dosages (Grounds 3 and 7).

4. Key Claim Construction Positions

  • "synergistically effective to antagonize NK1 activity": Petitioner argued that the ’826 patent failed to define this term or disclose any synergism. Therefore, "synergy" should be construed to mean an effect merely greater than what the prior art would have suggested for the combination. Petitioner contended this alleged synergy is an inherent property of combining palonosetron with any NK1 antagonist, not an unexpected result unique to netupitant, and thus cannot confer patentability on an otherwise obvious combination.

5. Key Technical Contentions (Beyond Claim Construction)

  • No Unexpected Results: A central contention was that the Patent Owner misled the patent examiner by arguing for unexpected results (synergy and superior nausea treatment) that were not supported by the data. Petitioner argued that during prosecution, the Patent Owner presented altered data tables that removed unsupportive results and failed to disclose that aprepitant, the prior art comparator, was also effective against nausea. Petitioner asserted that any benefits of the claimed combination were predictable and expected, not surprising.

6. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 1-25 of Patent 8,623,826 as unpatentable.