PTAB

IPR2025-00946

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 ’357 patent discloses methods for treating chemotherapy-induced nausea and vomiting (CINV). The methods involve the co-administration of netupitant (a neurokinin-1 (NK₁) receptor antagonist), palonosetron (a 5-HT₃ receptor antagonist), and dexamethasone (a corticosteroid).

3. Grounds for Unpatentability

Ground 1: Obviousness over Herrstedt and Bös - Claims 2-4, 11-16, 40, 52-54, and 56-62 are obvious over Herrstedt in view of Bös.

  • Prior Art Relied Upon: Herrstedt (a 2007 journal article summarizing CINV treatments) and Bös (Patent 6,297,375).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner asserted that Herrstedt established the standard of care for preventing CINV was a triple-drug combination: an NK₁ antagonist (specifically aprepitant), a 5-HT₃ antagonist (such as palonosetron), and a corticosteroid (dexamethasone). Herrstedt further taught that when combined with an NK₁ antagonist, the dexamethasone dose should be reduced to a sub-therapeutic level (e.g., by 50%) due to metabolic interactions. Bös disclosed netupitant as a new, potent, and highly selective NK₁ antagonist for treating emesis. Petitioner argued that substituting the older NK₁ antagonist (aprepitant) in Herrstedt’s regimen with the improved one (netupitant) from Bös renders the claimed methods obvious.
    • Motivation to Combine: A person of ordinary skill in the art (POSITA) would combine Herrstedt and Bös by making the simple substitution of one known NK₁ antagonist for another. The motivation was to improve the established standard-of-care regimen with a newer, more potent, and selective compound from the same therapeutic class, which Petitioner characterized as a routine and predictable path of drug development.
    • Expectation of Success: A POSITA would have had a reasonable expectation of success because netupitant and aprepitant are both NK₁ antagonists that act on the same receptor to achieve the same therapeutic goal (anti-emesis). Bös provided data showing netupitant’s high potency and selectivity, reinforcing the expectation that it would be at least as effective as aprepitant in Herrstedt's combination therapy.

Ground 2: Obviousness over Herrstedt, Bös, and Herrington - Claims 41-42 are obvious over Herrstedt, Bös, and Herrington.

  • Prior Art Relied Upon: Herrstedt (a 2007 journal article), Bös (Patent 6,297,375), and Herrington (a 2008 journal article).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground built upon the combination of Herrstedt and Bös. The challenged claims add limitations requiring a single administration of netupitant effective for at least five days. Petitioner argued that Herrington explicitly taught a single, day-one dose of aprepitant was as effective as a multi-day regimen for preventing both acute and delayed CINV. Bös taught that netupitant has a long functional half-life (approx. 30 hours), making it well-suited for a single-dose regimen.
    • Motivation to Combine: A POSITA would be motivated to modify the base regimen from Herrstedt and Bös to a single-dose administration based on Herrington's findings. The primary motivation was to increase patient compliance and simplify the treatment protocol, which are well-known goals in pharmacology. Herrington’s clinical data demonstrating the efficacy of single-dose aprepitant would have directly suggested applying the same simplified approach to a similar, long-acting NK₁ antagonist like netupitant.
    • Expectation of Success: Success was reasonably expected because Herrington had already demonstrated the single-dose concept worked for a similar drug (aprepitant). The long half-life of netupitant disclosed in Bös would have further assured a POSITA that a single dose would maintain therapeutic levels for the required five-day period.

Ground 3: Obviousness over Herrstedt, Bös, and Hargreaves - Claim 55 is obvious over Herrstedt, Bös, and Hargreaves.

  • Prior Art Relied Upon: Herrstedt (a 2007 journal article), Bös (Patent 6,297,375), and Hargreaves (a 2002 journal article).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground addressed dependent claim 55, which recites that netupitant occupies at least 70% of the patient's striatum NK₁ receptors ninety-six hours after administration. Petitioner contended that Hargreaves taught a direct correlation between NK₁ receptor occupancy and antiemetic effect, showing that therapeutically effective doses of aprepitant achieved high levels of receptor occupancy (≥75%).
    • Motivation to Combine: Petitioner argued that the claimed receptor occupancy is not a patentable feature but is instead an inherent property of administering a therapeutically effective dose of any potent NK₁ antagonist, including the netupitant regimen made obvious by Herrstedt and Bös. A POSITA would have been motivated to use the known techniques in Hargreaves (e.g., PET scans) to confirm the optimal dosage and mechanism of action for netupitant, a routine step in drug development.
    • Expectation of Success: There was a high expectation of success in observing this property. Because Hargreaves linked high receptor occupancy to efficacy for aprepitant, a POSITA would fully expect that another potent NK₁ antagonist like netupitant would function identically and exhibit similar high occupancy levels when administered at an effective dose.

4. Key Claim Construction Positions

  • inducing in a subject blood levels of ... netupitant effective to treat said CINV: Petitioner argued this phrase should be construed to mean simply administering a therapeutically effective amount of the drug. Petitioner contended that achieving a "blood level" is an inherent and necessary consequence of any oral or intravenous administration intended to reach the central nervous system and does not add a patentable limitation beyond requiring an effective dose.
  • sub-therapeutic dose of dexamethasone: Petitioner proposed this term means a dose less than the standard minimum effective dose when administered alone, which the patent specification and prior art defined as 20 mg on day one for highly emetic chemotherapy. This construction was central to mapping Herrstedt, which taught reducing the dexamethasone dose by about 50% when co-administered with an NK₁ antagonist.

5. Relief Requested

  • Petitioner requests the institution of an inter partes review and cancellation of claims 2-4, 11-16, 40-42, and 52-62 of the ’357 patent as unpatentable under 35 U.S.C. §103.