PTAB

IPR2019-00697

Nalox-1 Pharmaceuticals, LLC v. Opiant Pharmaceuticals, Inc.

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1. Case Identification

2. Patent Overview

  • Title: Nasal Drug Products and Methods of Their Use
  • Brief Description: The ’838 patent relates to methods and pharmaceutical compositions for the emergency treatment of opioid overdose. The invention describes delivering a specific dose of the opioid antagonist naloxone using an intranasal spray from a single-use, pre-primed device.

3. Grounds for Unpatentability

Ground 1: Claims 1–4, 18–23, 25–29, 30–34, 36, and 39–40 are obvious over Wyse in view of HPE.

  • Prior Art Relied Upon: Wyse (Patent 9,192,570) and HPE (Handbook of Pharmaceutical Excipients, 6th ed. 2009).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Wyse taught the core elements of independent claim 1. Wyse disclosed methods of treating opioid overdose with intranasal naloxone, delivered in a 100 µL spray (within the claimed 25-200 µL) from a pre-primed, single-use device (the Aptar device). Petitioner asserted that Wyse’s disclosed concentration range of 5-50 mg/mL for a 100 µL spray delivers a 0.5-5 mg dose, which overlaps with the claimed range of "about 4 mg and about 10 mg naloxone." Wyse also taught including an isotonicity agent (sodium chloride) and a preservative.
    • Motivation to Combine (for §103 grounds): Petitioner contended that while Wyse disclosed using a preservative, it also stated that other suitable agents would be readily understood by a person of ordinary skill in the art (POSITA). A POSITA would have been motivated to consult a standard pharmaceutical compendium like HPE to select a well-known, FDA-approved preservative for nasal sprays. HPE taught that benzalkonium chloride (BAC) is a common and effective preservative for such applications and is typically used in a concentration range of 0.002–0.02% w/v, which squarely encompasses the claimed range of 0.005–0.015% w/v.
    • Expectation of Success (for §103 grounds): A POSITA would have had a high expectation of success in substituting a standard, compatible preservative like BAC into the naloxone formulation of Wyse to arrive at the claimed invention without undue experimentation.

Ground 3: Claims 13-17 and 41-46 are obvious over Wyse in view of HPE and the '291 patent.

  • Prior Art Relied Upon: Wyse (Patent 9,192,570), HPE (Handbook of Pharmaceutical Excipients, 6th ed. 2009), and the ’291 patent (Patent 8,198,291).

  • Core Argument for this Ground:

    • Prior Art Mapping: This ground built upon the combination of Wyse and HPE to address limitations related to the spray plume characteristics (ovality ratio) required by claims 13-17 and independent claim 41. The ’291 patent was introduced to teach that an intranasal opioid (butorphanol) delivered from a similar Pfeiffer Unitdose device produced a round spray plume with an average ovality ratio of about 1.1, which is less than the claimed ratio of 2.0.
    • Motivation to Combine (for §103 grounds): A POSITA would combine these references because Wyse recommended using the same type of device (Aptar/Pfeiffer) that was analyzed in the ’291 patent. Petitioner argued that spray plume characteristics like ovality are primarily functions of the spray device, not the formulation, especially when the formulations (like those in Wyse and the '291 patent) lack significant viscosity-altering ingredients.
    • Expectation of Success (for §103 grounds): A POSITA would reasonably expect that the naloxone formulation from Wyse/HPE, when administered through the device recommended by Wyse, would produce a spray plume with the same favorable ovality characteristics taught by the ’291 patent for a similar formulation in a nearly identical device.

  • Additional Grounds: Petitioner asserted additional obviousness challenges based on similar combinations. These included adding Wang (Chinese Patent No. 1,575,795) to the Wyse/HPE combination to explicitly teach naloxone doses up to 10 mg, and adding Djupesland (a 2012 journal article) and Zomig Review (a 2002 FDA review) to further detail the inherent physical characteristics of the pre-primed Aptar delivery device.

4. Key Claim Construction Positions

  • "pre-primed": Petitioner adopted the patent’s explicit definition: a device capable of delivering a pharmaceutical composition with the first actuation of the spray pump, without needing prior actuations to prime the device.
  • "patient": Petitioner argued this term, as defined in the patent, refers to a single subject. This construction was relevant to pharmacokinetic claims reciting specific plasma concentrations achieved in "the patient."
  • "geometric mean naloxone Cmax" and "geometric mean ... AUC": Petitioner contended these terms created ambiguity in claims 41-46. While "the patient" implied a single subject, the term "geometric mean" inherently requires a population of subjects. Petitioner asserted the claims were obvious under either interpretation but highlighted this ambiguity as a flaw in the claims.

5. Arguments Regarding Discretionary Denial

  • Petitioner argued that discretionary denial under 35 U.S.C. §325(d) would be inappropriate because its grounds were not the same or substantially the same as those considered during the prosecution of the related ’177 patent.
  • Petitioner’s central argument was that while the primary reference, Wyse, was cited during prosecution of the related patent, the key secondary reference, HPE, was never considered by the examiner. Therefore, the combination of Wyse and HPE constituted a new ground of unpatentability.
  • Furthermore, Petitioner argued that the examiner in the related case had erred by concluding that Wyse "taught away" from using benzalkonium chloride (BAC). The petition presented new arguments and expert testimony to demonstrate that a POSITA would not have understood Wyse to teach away from BAC, and that denial would prevent this alleged error from being corrected.

6. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 1-46 of Patent 9,775,838 as unpatentable.