Nalox 1 Pharmaceuticals LLC v. Opiant Pharmaceuticals Inc

1. Case Identification

• Case #: IPR2019-00689
• Patent #: 9,468,747
• Filed: February 19, 2019
• Petitioner(s): Nalox-1 Pharmaceuticals, LLC
• Patent Owner(s): Opiant Pharmaceuticals, Inc.
• Challenged Claims: 1-45

2. Patent Overview

• Title: Nasal Drug Products and Methods of Their Use
• Brief Description: The ’747 patent discloses pharmaceutical compositions of naloxone for nasal delivery to treat opioid overdose. The invention is directed to methods and formulations delivered via a single-use, pre-primed nasal spray device for rapid administration by trained or untrained individuals.

3. Grounds for Unpatentability

Ground 1: Obviousness over Wang, Djupesland, HPE, Bahal, and Kushwaha - Claims 1–7, 16, and 30–33 are obvious over this combination.

• Prior Art Relied Upon: Wang (Chinese Patent No. 1,575,795), Djupesland (a 2013 journal article), HPE (Handbook of Pharmaceutical Excipients, 6th ed., 2009), Bahal (Patent 5,866,154), and Kushwaha (a 2011 journal article).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Wang taught the core of the claimed invention: an intranasal naloxone formulation for treating opioid overdose containing key excipients like an isotonicity agent (NaCl), a preservative (BAC), a stabilizer (sodium edetate), and a pH adjuster (hydrochloric acid). To deliver this formulation, a person of ordinary skill in the art (POSA) would have looked to known single-use, pre-primed nasal spray devices, such as the Aptar device described in Djupesland, which delivers a standard 100 µL spray volume. The specific concentrations of excipients were allegedly obvious from standard industry references like HPE, which provided typical ranges for preservatives like BAC in nasal sprays. Bahal was cited for its teaching that a chelating agent like sodium edetate stabilizes naloxone against oxidative degradation, and Kushwaha was cited for teaching that edetate also functions as a permeation enhancer.
  • Motivation to Combine: A POSA would combine these references to address the well-known and urgent public health need for a safe, stable, and easy-to-use naloxone product for emergency overdose situations. The combination represented the use of known components (a naloxone formulation and a standard delivery device) for their intended purposes to achieve a predictable and improved result over existing improvised methods.
  • Expectation of Success: A POSA would have had a high expectation of success, as the combination involved standard pharmaceutical formulation techniques and commercially available, well-characterized delivery devices.

Ground 2: Obviousness over Wang, Djupesland, HPE, Bahal, Kushwaha, and Wyse - Claims 10–15, 17–29, and 34–39 are obvious over this combination.

• Prior Art Relied Upon: The references from Ground 1, with the addition of Wyse (Patent 9,192,570).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground built upon the combination in Ground 1 by adding Wyse to address dependent claims related to specific pharmacokinetic (pK) profiles and clinical outcomes. Wyse disclosed methods for treating opioid overdose that emphasized the need for rapid reversal, teaching the use of ready-to-use devices to minimize delivery time. Critically, Wyse provided pK data for a 2 mg intranasal naloxone dose, demonstrating that specific plasma concentrations (e.g., ≥0.2 ng/mL within 2.5 minutes) could be achieved. Wyse also taught treating respiratory depression, the primary symptom of overdose, and ensuring the patient remains free from it for a period post-administration.
  • Motivation to Combine: The primary motivation was to optimize the formulation from Wang to achieve the rapid onset and sustained therapeutic effect disclosed as desirable in Wyse. A POSA would have been motivated to develop a formulation that met or exceeded the pK performance shown in Wyse to ensure the fastest possible reversal of life-threatening respiratory depression.
  • Expectation of Success: Petitioner argued a POSA would reasonably expect that administering a higher dose of naloxone (e.g., 4 mg as claimed) in a concentrated solution would predictably result in higher and faster plasma concentrations than those reported for the 2 mg dose in Wyse.

Ground 4: Obviousness over Wang, Djupesland, HPE, Bahal, Kushwaha, and the ’291 Patent - Claims 8-9 are obvious over this combination.

• Prior Art Relied Upon: The references from Ground 1, with the addition of the ’291 patent (Patent 8,198,291).

• Core Argument for this Ground:

  • Prior Art Mapping: This ground specifically targeted claims 8 and 9, which recite dose delivery consistency within specified confidence intervals (±2.0% at 90% C.I. and ±2.5% at 95% C.I.). The ’291 patent was introduced because it disclosed a single-use, pre-primed device (the Pfeiffer Unitdose device) capable of meeting these precise delivery standards, reporting a 95% confidence interval of about ±1.5%.
  • Motivation to Combine: A POSA developing an emergency-use drug product would be rigorously motivated to select a delivery device with high reliability and dose-to-dose consistency. The ’291 patent demonstrated that such devices were known and available.
  • Expectation of Success: A POSA would reasonably expect the device’s mechanical performance to be maintained when loaded with the formulation taught by Wang, as dose consistency is primarily a function of the device itself.

• Additional Grounds: Petitioner asserted an additional obviousness challenge (Ground 3) against claims 40-45 based on the primary combination in view of Wyse or Wermeling 2013 to address claimed Tmax limitations.

4. Key Claim Construction Positions

• “pre-primed”: Petitioner argued this term should be construed according to its definition in the ’747 patent’s specification as a device capable of delivering the composition on the first actuation, without prior priming strokes.
• “patient”: Petitioner adopted the patent’s definition of a patient as any subject afflicted with a condition likely to benefit from treatment, arguing this covers a single subject.
• “delivery time”: Petitioner adopted the patent’s definition as the time elapsed between determining a need for administration and the completion of delivery.

5. Key Technical Contentions (Beyond Claim Construction)

• Lack of Priority: Petitioner dedicated a significant portion of its argument to the assertion that the ’747 patent was not entitled to the March 14, 2014 filing date of its provisional application. Petitioner argued the provisional application failed to provide adequate written description support for the specific quantitative ranges of excipients recited in the independent claims. This would push the patent’s effective priority date to March 16, 2015, making more publications available as prior art.

6. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial under §325(d) would be inappropriate. Although the primary reference, Wang, was cited in an Information Disclosure Statement (IDS) during prosecution, Petitioner contended it was never substantively considered by the Examiner. The version provided was a machine translation, and the Examiner never relied on it to make any rejection, thus warranting a full review in an inter partes review (IPR).

7. Relief Requested

• Petitioner requested institution of IPR and cancellation of claims 1-45 of the ’747 patent as unpatentable under 35 U.S.C. §103.