PTAB

IPR2019-00692

Nalox 1 Pharmaceuticals LLC v. Opiant Pharmaceuticals Inc

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Nasal Drug Products and Methods of Their Use
  • Brief Description: The ’177 patent discloses pharmaceutical compositions containing the opioid antagonist naloxone for intranasal delivery to treat opioid overdose. The invention covers specific formulations, typically comprising about 4 mg of naloxone, a preservative such as benzalkonium chloride (BAC), an isotonicity agent, and other excipients, delivered as a small-volume spray from a pre-primed device.

3. Grounds for Unpatentability

Ground 1: Claims 1-2 are obvious over Wang in view of HPE and Djupesland

  • Prior Art Relied Upon: Wang (Chinese Patent No. 1,575,795), HPE (Handbook of Pharmaceutical Excipients, 6th ed. 2009), and Djupesland (a 2013 journal article).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Wang taught all key elements of the claimed formulation for treating opioid overdose, including a naloxone dose range of 0.1–10 mg (encompassing the claimed 4 mg), the use of preservatives like BAC, and an isotonicity agent. Djupesland was cited for its disclosure of pre-primed, single-use nasal spray devices (e.g., the Aptar device) suitable for delivering a 100 µL spray volume. HPE, a standard pharmaceutical compendium, was used to demonstrate that the claimed concentration of BAC was a well-known and obvious choice for a nasal spray preservative.
    • Motivation to Combine: A POSITA would combine Wang's formulation with Djupesland's device because an acute condition like opioid overdose necessitates a ready-to-use, single-dose delivery system. A formulator would naturally consult a standard reference like HPE to select appropriate excipients and their concentrations.
    • Expectation of Success: The combination involved applying a known drug formulation to a standard delivery device using conventional excipients, leading to a high expectation of achieving a predictable and effective product.

Ground 4: Claims 10-11 are obvious over Wang, HPE, and Djupesland in view of Wyse

  • Prior Art Relied Upon: Wang (Chinese Patent No. 1,575,795), HPE (Handbook of Pharmaceutical Excipients, 6th ed. 2009), Djupesland (a 2013 journal article), and Wyse (Patent 9,192,570).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground challenged claims reciting specific pharmacokinetic (PK) outcomes. Petitioner asserted that Wyse disclosed a 2 mg intranasal naloxone composition that resulted in a Cmax of about 1-3 ng/mL and an AUC of about 2.5-4.5 ng-hr/mL. These values are approximately half of the claimed Cmax (≥ 3 ng/mL) and AUC (≥ 8 hr*ng/mL).
    • Motivation to Combine: A POSITA would combine the teachings of Wang and Wyse as both relate to intranasal naloxone sprays. To create a more effective treatment, a POSITA would be motivated to increase the dose from Wyse's 2 mg to the 4 mg dose suggested by Wang. Petitioner argued that due to naloxone's known linear PK properties, doubling the dose would predictably double the Cmax and AUC, thereby meeting the claimed PK limitations.
    • Expectation of Success: The well-understood linear pharmacokinetics of naloxone provided a strong basis for a POSITA to expect that increasing the dose would predictably achieve the higher plasma concentrations recited in the claims.

Ground 5: Claims 12, 13-15, and 21 are obvious over Wang, HPE, and Djupesland in view of the '291 patent

  • Prior Art Relied Upon: Wang (Chinese Patent No. 1,575,795), HPE (Handbook of Pharmaceutical Excipients, 6th ed. 2009), Djupesland (a 2013 journal article), and the '291 patent (Patent 8,198,291).

  • Core Argument for this Ground:

    • Prior Art Mapping: This ground added the ’291 patent to address limitations related to the physical spray characteristics, such as droplet size distribution and plume shape. The ’291 patent described these characteristics for a different drug delivered from a similar device (Pfeiffer Unitdose), disclosing that less than 10% of droplets were smaller than 10 µm and the plume had a round shape with a low ovality ratio (~1.1), meeting the claim limitations.
    • Motivation to Combine: A POSITA developing the formulation taught by Wang for use in a device from Djupesland would look to a reference like the ’291 patent to understand and optimize the spray characteristics for effective nasal delivery while minimizing inhalation risk.
    • Expectation of Success: Petitioner argued that since the formulations in Wang, the ’291 patent, and the challenged patent are all low-viscosity aqueous solutions, a POSITA would reasonably expect them to produce nearly identical spray characteristics when delivered from the same or similar devices.

  • Additional Grounds: Petitioner asserted additional obviousness challenges against the remaining claims based on various combinations of the core prior art (Wang, HPE, Djupesland, Wyse, '291 patent) with further references such as Bahal, Kushwaha, and Zomig Review to address specific dependent claim limitations.

4. Key Claim Construction Positions

  • Pharmacokinetic Terms ("geometric mean Cmax"): Petitioner argued that terms reciting pharmacokinetic parameters like "geometric mean naloxone Cmax" were ambiguous. The use of the singular "the patient" in the claims suggested a single-subject measurement, while the term "geometric mean" implies a calculation across a population. Petitioner stated its analysis rendered the claims obvious under either interpretation.
  • Droplet Size Terms: Petitioner proposed that claim terms related to droplet size distribution (e.g., "no more than about [x]% of the droplets have a diameter less than 10 µm") should be construed as referring to volume-weighted distributions (e.g., Dv10). This was based on the consistent use of volume-weighted measurements throughout the ’177 patent's specification.

5. Key Technical Contentions (Beyond Claim Construction)

  • Priority Date Challenge: Petitioner contended that the ’177 patent was not entitled to its March 14, 2014 priority date. It was argued that the priority provisional application ('379 provisional) failed to provide adequate written description support for the specific claimed concentration range of the preservative BAC (0.005% to 0.015% w/v). As a result, Petitioner asserted the patent’s effective priority date was no earlier than March 16, 2015, making Wyse (filed December 19, 2014) available as prior art under 35 U.S.C. §102(a)(2).

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, it was provided with only a machine translation and was never substantively considered or used in any rejection by the Examiner.

7. Relief Requested

  • Petitioner requested the institution of an inter partes review and the cancellation of claims 1-30 of Patent 9,561,177 as unpatentable under 35 U.S.C. §103.