PTAB

IPR2025-00949

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 ’297 patent discloses methods for treating or preventing chemotherapy-induced nausea and vomiting (CINV) by co-administering a 5-HT3 antagonist (palonosetron), an NK1 antagonist (netupitant), and often a corticosteroid (dexamethasone).

3. Grounds for Unpatentability

Ground 1: Obviousness over Herrstedt and Bös - Claims 1-4, 8-13, 17-19, and 23 are obvious over Herrstedt in view of Bös.

  • Prior Art Relied Upon: Herrstedt (a 2007 journal article on anti-emetic therapy) and Bös (Patent 6,297,375).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Herrstedt taught the standard of care for preventing CINV was a three-drug combination therapy effective against both acute and delayed emesis: a 5-HT3 antagonist (identifying palonosetron as a favorable option), a corticosteroid (dexamethasone), and an NK1 antagonist (aprepitant). Bös disclosed netupitant as a new, potent, and highly selective NK1 antagonist, providing data from animal models showing it "completely blocked" emesis. Petitioner asserted that combining these references teaches all limitations of the independent claims, as the base regimen is explicitly taught by Herrstedt and a suitable, equivalent NK1 antagonist is taught by Bös.
    • Motivation to Combine: A person of ordinary skill in the art (POSITA) would have been motivated to substitute the first-generation NK1 antagonist (aprepitant) in Herrstedt’s established regimen with the newer NK1 antagonist (netupitant) disclosed by Bös. This represents a simple and predictable substitution of one known, functionally equivalent component for another to improve or update a known therapy.
    • Expectation of Success: Since both aprepitant and netupitant are NK1 antagonists that treat emesis through the same mechanism (NK1 receptor antagonism), a POSITA would have had a high and reasonable expectation of success in making the substitution.

Ground 2: Obviousness over Herrstedt, Bös, and ALOXI - Claims 5-6, 14-15, and 20-21 are obvious over Herrstedt and Bös in view of ALOXI.

  • Prior Art Relied Upon: Herrstedt (a 2007 journal article), Bös (Patent 6,297,375), and ALOXI (an Aug. 2008 FDA-approved drug label for palonosetron).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground built on the combination of Herrstedt and Bös to address claims reciting specific dosage amounts. The claims require blood levels induced by an intravenous regimen to be equivalent to specific oral doses. Bös taught a broad effective oral dose range for netupitant (10-1000 mg) that encompasses the claimed 300 mg, a midpoint value a POSITA would arrive at through routine optimization. The ALOXI label, for an FDA-approved oral palonosetron product, explicitly taught the claimed oral dose of 0.56 mg palonosetron hydrochloride. Petitioner asserted that formulating an intravenous administration to achieve blood levels equivalent to these known oral doses was a matter of routine skill, as both intravenous and oral formulations were standard options.
    • Motivation to Combine: A POSITA implementing the therapy from Ground 1 would be motivated to use known, effective, and FDA-approved dosages to ensure safety and efficacy. ALOXI provided a precise, clinically validated oral dose for palonosetron, and Bös provided a standard starting range for netupitant that a POSITA would optimize through routine experimentation.
    • Expectation of Success: A POSITA would have a high expectation of success using dosage information from an FDA-approved product label (ALOXI) and a known effective range from the prior art (Bös), as dose optimization and formulation development to achieve bioequivalence are routine and predictable aspects of pharmaceutical science.

Ground 3: Obviousness over Herrstedt, Bös, and Hargreaves - Claims 7, 16, and 22 are obvious over Herrstedt and Bös in view of 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 claims requiring that netupitant occupies at least 70% of the patient’s striatum NK1 receptors for 72 hours post-administration. Petitioner asserted that Hargreaves taught that high NK1 receptor occupancy (>75%) in the brain is directly associated with the therapeutic anti-emetic effect of NK1 antagonists. The petition argued that achieving this level of occupancy is an inherent property of administering a therapeutically effective dose (e.g., 300 mg) of a potent NK1 antagonist like netupitant. Furthermore, due to netupitant's known long half-life, a POSITA would expect this high occupancy to be sustained for at least 72 hours.
    • Motivation to Combine: To ensure the efficacy of the chosen NK1 antagonist, a POSITA would be motivated to achieve a dose that results in sufficient target engagement, a principle explained by Hargreaves. Hargreaves provided the scientific basis for understanding that effective doses correlate with high receptor occupancy, guiding a POSITA in dose selection.
    • Expectation of Success: A POSITA would reasonably expect that a therapeutically effective dose of netupitant, as disclosed by Bös, would inherently achieve the high and sustained receptor occupancy taught by Hargreaves to be necessary for the desired anti-emetic effect.

4. Key Claim Construction Positions

  • The petition argued that the claim term "inducing in said subject therapeutically effective blood levels" does not require achieving a specific, critical blood concentration that is distinct from simply administering an effective dose.
  • Petitioner contended this phrase is equivalent to administering a "therapeutically effective amount" of the drugs. This position was supported by the prosecution history, where the examiner adopted this interpretation without rebuttal from the Patent Owner, thereby allowing prior art that disclosed effective amounts to satisfy the "blood levels" limitation.

5. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 1-23 of Patent 10,828,297 as unpatentable under 35 U.S.C. §103.