PTAB

IPR2019-00686

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 ’253 patent relates to a single-use, pre-primed device for the intranasal delivery of a pharmaceutical composition containing naloxone. The composition is intended for the emergency treatment of known or suspected opioid overdose.

3. Grounds for Unpatentability

Ground 1: Claims 1-7, 12-14, and 16 are obvious over Wang, 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, 2009), Bahal (Patent 5,866,154), and Kushwaha (a 2011 journal article).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the combination of references taught all limitations of the independent claim. Wang taught the core concept of an intranasal naloxone formulation for opioid overdose, disclosing a dose range (0.1-10 mg), spray volume (20-200 µL), and the use of key excipients like an isotonicity agent, preservative, stabilizer, and pH adjuster. Djupesland taught the use of single-use, pre-primed nasal spray devices (e.g., the Aptar device) capable of delivering a 100 µL volume in a single actuation. The remaining references—HPE, Bahal, and Kushwaha—were presented as providing standard, well-known information that a POSA would have used to optimize the formulation. Specifically, HPE taught typical concentrations for preservatives like benzalkonium chloride (BAC); Bahal taught using a chelating agent like disodium edetate to stabilize naloxone against oxidation; and Kushwaha taught that edetate also functions as a permeation enhancer to improve absorption.
    • Motivation to Combine: A person of ordinary skill in the art (POSA) would combine Wang's formulation with Djupesland's device to create a simple, ready-to-use product for the urgent treatment of opioid overdose, where speed and ease of use are critical. A POSA would have been further motivated to consult standard references like HPE, Bahal, and Kushwaha as a matter of routine pharmaceutical development to select appropriate excipients and concentrations to ensure the final product was stable, safe, and effective.
    • Expectation of Success: Petitioner asserted a POSA would have had a reasonable expectation of success because combining these known elements for their known purposes would produce a predictable and effective naloxone nasal spray.

Ground 2: Claims 10-11 and 17-29 are obvious over the combination of Ground 1 in view of Wyse

  • Prior Art Relied Upon: The references from Ground 1, plus Wyse (Patent 9,192,570).
  • Core Argument for this Ground: This ground built upon the base combination in Ground 1 by adding Wyse to address claims reciting specific delivery times and pharmacokinetic profiles (e.g., plasma concentration levels over time). Petitioner argued Wyse taught the need for "ready-to-use" naloxone formulations that minimize delivery time and provided pharmacokinetic data showing that specific plasma concentrations could be achieved rapidly (e.g., within 2.5 to 10 minutes). A POSA, motivated by the fundamental goal of rapidly reversing a life-threatening overdose, would have sought to achieve the fast delivery times and quick onset of action taught by Wyse, rendering the dependent claims obvious.

Ground 3: Claim 15 is obvious over the combination of Ground 1 in view of Wyse or Wermeling 2013

  • Prior Art Relied Upon: The references from Ground 1, plus Wyse (Patent 9,192,570) or Wermeling 2013 (a 2013 journal article).

  • Core Argument for this Ground: This ground targeted claim 15, which recited a Tmax (time to maximum plasma concentration) of between 20 and 30 minutes. Petitioner pointed to disclosures in both Wyse and Wermeling of Tmax values for intranasal naloxone that either overlapped with or strongly suggested the claimed range. For example, Wermeling disclosed an expected Tmax of approximately 20 minutes. A POSA seeking rapid absorption and onset would have been motivated to develop a formulation exhibiting such a Tmax and would have reasonably expected to achieve it, making the claimed range obvious.

  • Additional Grounds: Petitioner asserted an additional obviousness challenge against claims 8 and 9 based on the Ground 1 combination in view of the '291 patent (Patent 8,198,291). This ground argued that a POSA seeking a device with high dose consistency would have looked to the '291 patent, which disclosed a similar single-use spray device and reported dose delivery confidence intervals that met the limitations of claims 8 and 9.

4. Key Claim Construction Positions

  • Petitioner argued that claim terms should be given their ordinary and customary meaning, which in several key instances was explicitly defined in the '253 patent’s specification.
  • "pre-primed": A device capable of delivering the composition on the first actuation without needing to be primed by the user.
  • "patient": A single subject afflicted with a condition likely to benefit from the treatment.
  • "delivery time": The time elapsed from determining a need for treatment to the completion of the delivery.
  • Confidence Interval terms (claims 8-9): The terms reciting a "90% confidence interval...is ±about 2.0%" and a "95% confidence interval...is ±about 2.5%" should be interpreted as ranges, covering devices with confidence intervals within the recited percentages, not exactly at them.

5. Key Technical Contentions (Beyond Claim Construction)

  • Petitioner dedicated a substantial portion of its argument to asserting that the ’253 patent was not entitled to the March 14, 2014 priority date of its provisional application (the '379 provisional).
  • The core contention was that the '379 provisional failed to provide adequate written description support under §112 for the claimed invention. Specifically, the provisional provided only general disclosures and did not recite the specific quantitative ranges for the excipients or the specific pH range that are express limitations in the challenged claims.
  • This argument was critical because it sought to establish a later priority date for the ’253 patent (March 16, 2015), thereby making several key references, including Wyse and Wermeling, available as prior art.

6. Arguments Regarding Discretionary Denial

  • Petitioner argued that the Board should not exercise its discretion to deny institution under §325(d), which allows denial if the same or substantially the same prior art or arguments were previously presented to the Office.
  • Petitioner acknowledged that the primary prior art reference, Wang, was cited in an Information Disclosure Statement (IDS) during prosecution. However, it contended that Wang was never substantively considered by the Examiner because only a machine-translated version was provided, and it was never used as the basis for any rejection.

7. Relief Requested

  • Petitioner requested that the Board institute an inter partes review and cancel claims 1-29 of Patent 9,211,253 as unpatentable under 35 U.S.C. §103.