Nalox 1 Pharmaceuticals LLC v. Opiant Pharmaceuticals Inc

1. Case Identification

• Case #: IPR2019-00697
• Patent #: 9,775,838
• Filed: February 19, 2019
• Petitioner(s): Nalox-1 Pharmaceuticals, LLC
• Patent Owner(s): Adapt Pharma Ltd, Opiant Pharmaceuticals, Inc.
• Challenged Claims: 1-46

2. Patent Overview

• Title: Nasal Drug Products and Methods of Their Use
• Brief Description: The ’838 patent relates to pharmaceutical compositions and methods for treating opioid overdose. The invention involves administering an intranasal spray of a naloxone solution from a pre-primed, single-use device to a patient.

3. Grounds for Unpatentability

Ground 1: Obviousness over Wyse and HPE - 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 (excerpts from the Handbook of Pharmaceutical Excipients, 6th Ed., 2009).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Wyse disclosed the core elements of independent claim 1: a method of treating opioid overdose by intranasally delivering a 100 µL spray of a naloxone solution from a single-use, ready-to-use (i.e., pre-primed) device. Wyse disclosed a naloxone concentration range (5-50 mg/mL) that results in a dose (0.5-5 mg) overlapping the claimed range (4-10 mg). Wyse also taught using an isotonicity agent like sodium chloride. The only element not explicitly in Wyse was the specific preservative, benzalkonium chloride (BAC), at the claimed concentration. Petitioner asserted that HPE, a standard pharmaceutical reference, disclosed that BAC is a common and effective antimicrobial preservative for nasal sprays, typically used in a concentration range (0.002-0.02% w/v) that squarely contains the claimed range of 0.005-0.015%.
  • Motivation to Combine: Petitioner contended that a person of ordinary skill in the art (POSITA), when developing the formulation taught in Wyse, would have been motivated to include a preservative for microbiological stability. A POSITA would naturally consult a standard reference like HPE to select a suitable preservative. HPE’s disclosure of BAC as a safe, effective, and commonly used preservative for nasal sprays would have provided a clear motivation to include it in Wyse’s formulation.
  • Expectation of Success: Petitioner argued there was a high expectation of success because combining a known active ingredient formulation (Wyse) with a standard, well-characterized excipient (BAC from HPE) for its established purpose is a routine and predictable step in pharmaceutical formulation.

Ground 2: Obviousness over Wyse, HPE, and the '291 patent - 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 (a 2009 handbook), 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 argue the claims related to spray plume characteristics. The ’291 patent taught delivering an intranasal butorphanol formulation using a Pfeiffer Unitdose device, similar to the Aptar device in Wyse. The ’291 patent disclosed that this delivery resulted in a round spray plume with an average ovality ratio of about 1.1, which is less than the claimed ratio of about 2.0.
  • Motivation to Combine: Petitioner argued a POSITA would combine these references because both Wyse and the ’291 patent described intranasal opioid compositions delivered from similar single-use devices. To optimize the formulation in Wyse, a POSITA would have looked to the known performance of the same or similar delivery devices, as detailed in the ’291 patent.
  • Expectation of Success: A POSITA would have reasonably expected that two formulations with similar viscosity, when delivered from the same type of device, would produce spray plumes with similar ovality. Since neither the Wyse nor the claimed formulation contained viscosity-altering agents, there was a high expectation of success in achieving the claimed spray characteristics.

Ground 3: Obviousness over Wyse, HPE, and Djupesland - Claims 24, 35, and 37 are obvious over Wyse in view of HPE and Djupesland.

• Prior Art Relied Upon: Wyse (Patent 9,192,570), HPE (a 2009 handbook), and Djupesland (a 2013 journal article).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground added Djupesland to the Wyse/HPE combination to address claims reciting specific device features. Wyse suggested using the Aptar device. Djupesland provided specific details for that same commercial Aptar device, disclosing a reservoir fill volume of 125 µL to deliver a 100 µL spray. This satisfied claim limitations requiring a reservoir volume of "not more than about 140 µL" (claim 24) and "approximately 125 µL" (claim 35). Djupesland also disclosed that the device consists of a vial (reservoir), a piston, and a swirl chamber, meeting the limitations of claim 37.
  • Motivation to Combine: A POSITA would be motivated to combine these teachings because Wyse and Djupesland refer to the exact same commercial nasal spray device. Djupesland simply provided further, publicly available technical details for the device suggested for use in Wyse.
  • Expectation of Success: The combination was merely the application of known technical specifications of a specific commercial device to the formulation of the primary reference, carrying a high expectation of success.
• Additional Grounds: Petitioner asserted additional obviousness challenges based on combinations including Wang (for specific naloxone dosage ranges) and Zomig Review (for further specific device features), relying on similar design choice and optimization rationales.

4. Key Technical Contentions (Beyond Claim Construction)

• Priority Date Challenge: Petitioner dedicated significant argument to establishing that the '838 patent was not entitled to its claimed priority date of March 14, 2014, from the '379 provisional application. Petitioner contended the '379 provisional failed to provide adequate written description support for the claimed concentration range of benzalkonium chloride (0.005% to 0.015% w/v). Therefore, Petitioner argued the patent's effective priority date was no earlier than March 16, 2015, which rendered several key references, including Wyse, available as prior art under 35 U.S.C. §102.

5. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial under §325(d) would be inappropriate. It contended that the core prior art combination of Wyse and HPE was never before the U.S. Patent and Trademark Office during prosecution of the '838 patent. Although Wyse was cited during prosecution of a related patent, it was not combined with HPE. Petitioner asserted that HPE was not cumulative of any cited reference and that its arguments based on this new combination presented a reasonable likelihood of prevailing, thus warranting institution per the Becton Dickinson factors.

6. Relief Requested

• Petitioner requested institution of an inter partes review (IPR) and cancellation of claims 1-46 of the '838 patent as unpatentable under 35 U.S.C. §103.