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 relates to methods and pharmaceutical formulations for treating opioid overdose. The invention describes administering an aqueous naloxone composition to a patient using a single-use, pre-primed nasal spray device that delivers the dose in a single actuation.

3. Grounds for Unpatentability

Ground 1: Obviousness over Wang et al. - Claims 1-7, 16, and 30-33 are obvious over Wang in view of Djupesland, HPE, Bahal, and Kushwaha.

• Prior Art Relied Upon: Wang (Chinese Patent No. 1,575,795), Djupesland (a 2013 journal article), HPE (Handbook of Pharmaceutical Excipients, 6th Ed.), Bahal (Patent 5,866,154), and Kushwaha (a 2011 journal article).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Wang discloses the foundational elements: a nasal spray for treating "morphine drug poisoning" (opioid overdose) containing naloxone hydrochloride and categories of excipients including osmotic pressure regulators (isotonicity agents), preservatives, and stabilizers, delivered in a single-dose form. Djupesland was cited for its disclosure of commercially available single-use, pre-primed nasal spray devices (e.g., the Aptar device) designed to deliver a precise volume like 100 µL in one actuation. The remaining references were used to fill in the specific, conventional details of the formulation. Bahal taught using a chelating agent like sodium edetate to prevent naloxone degradation. HPE provided standard concentrations for preservatives like benzalkonium chloride (BAC) in nasal sprays. Kushwaha identified edetates as permeation enhancers.
  • Motivation to Combine: A Person of Ordinary Skill in the Art (POSA) would combine Wang's general formulation with Djupesland's ready-to-use device because an acute, emergency condition like opioid overdose demands a simple, reliable, single-use product. A POSA would have been further motivated to consult standard pharmaceutical compendia like HPE and related patents like Bahal to select specific, well-characterized excipients to optimize Wang’s formulation for stability, preservation, and performance, arriving at the claimed composition.
  • Expectation of Success: Petitioner asserted a POSA would have had a high expectation of success, as the combination merely involved applying known excipients for their predictable functions (e.g., stabilization, preservation) to a known active ingredient (naloxone) in a standard delivery device (single-use sprayer).

Ground 2: Obviousness over Wang et al. and Wyse - Claims 10-15, 17-29, and 34-39 are obvious over Wang in view of Djupesland, HPE, Bahal, Kushwaha, and Wyse.

• Prior Art Relied Upon: All references from Ground 1, plus Wyse (Patent 9,192,570).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground incorporated the teachings of Wyse to address limitations concerning clinical outcomes and performance. Wyse was cited for its disclosure of "ready-to-use" devices that minimize "delivery time," teaching the limitations of claims 10 and 11. Furthermore, Wyse provided specific pharmacokinetic data for intranasal naloxone, including plasma concentrations achieved within minutes of administration, which Petitioner mapped to the limitations of claims 25-29 and 34-39. Wyse also explicitly taught using intranasal naloxone to treat "respiratory depression," a key symptom recited in claims 17 and 18.
  • Motivation to Combine: A POSA developing the product taught by Wang would have naturally looked to other art in the field, like Wyse, that addressed the same clinical problem. Wyse provided the very pharmacokinetic and clinical effect data (e.g., rapid onset, reversal of respiratory depression) that a formulator would seek to achieve, motivating the combination.

Ground 3: Obviousness over Wang et al. and the ’291 Patent - Claims 8-9 are obvious over Wang in view of Djupesland, HPE, Bahal, Kushwaha, and the ’291 patent.

• Prior Art Relied Upon: All references from Ground 1, plus the ’291 patent (Patent 8,198,291).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground focused on the dose delivery consistency limitations of claims 8 and 9 (±2.0% at 90% confidence and ±2.5% at 95% confidence). Petitioner argued that the ’291 patent teaches these limitations by disclosing performance data for a similar single-use, pre-primed device (the Pfeiffer Unitdose spray device). The ’291 patent reported that its device achieved a dose delivery with a 90% confidence interval of ±0.9% and a 95% confidence interval of ±1.5%, which falls within the claimed ranges.
  • Motivation to Combine: A POSA, having selected a formulation based on Wang and a device type based on Djupesland, would be rigorously motivated to ensure dose consistency to meet safety and regulatory standards. The POSA would therefore look to art like the ’291 patent to select a specific, commercially available device known to provide the required level of dose reproducibility.
• Additional Grounds: Petitioner asserted an additional obviousness challenge based on the core combination of references, further adding Wermeling 2013 or general POSA knowledge to teach the Tmax (time to maximum plasma concentration) limitations of claims 40-45.

4. Key Claim Construction Positions

• "pre-primed": Petitioner argued this term should be construed as defined in the ’747 patent’s specification: a device capable of delivering the composition on the first actuation, without needing prior priming actuations.
• "patient": Based on the specification, Petitioner asserted this term covers a single subject. This construction is relevant to interpreting pharmacokinetic claims, where data from a single subject meeting the criteria would satisfy the limitation.
• "delivery time": This term was construed according to its specification definition: the time from determining a need for treatment to the completion of delivery.
• Confidence Interval Terms ("±about 2.0%", "±about 2.5%"): Petitioner argued these should be interpreted as ranges, not exact values, based on the specification’s definition of "confidence interval," covering devices that perform within the claimed range.

5. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial under §325(d) would be inappropriate. Although the primary reference, Wang, was listed in an Information Disclosure Statement (IDS) during prosecution, it was presented only as a machine translation. Petitioner asserted that the Examiner never substantively considered or relied upon Wang for any rejection, meaning the invalidity grounds presented in the petition were not previously considered by the USPTO.

6. Relief Requested

• Petitioner requests institution of an inter partes review and cancellation of claims 1-45 of Patent 9,468,747 as unpatentable under 35 U.S.C. §103.