Nalox 1 Pharmaceuticals LLC v. Opiant Pharmaceuticals Inc

1. Case Identification

• Case #: IPR2019-00686
• Patent #: 9,211,253
• Filed: February 19, 2019
• Petitioner(s): Nalox-1 Pharmaceuticals, LLC
• Patent Owner(s): Opiant Pharmaceuticals, Inc.
• Challenged Claims: 1-29

2. Patent Overview

• Title: Nasal Drug Products and Methods of Their Use
• Brief Description: The ’253 patent discloses pharmaceutical compositions and single-use, pre-primed nasal spray devices for administering naloxone to treat opioid overdose. The claims are directed to specific aqueous formulations of naloxone hydrochloride and their delivery via such devices.

3. Grounds for Unpatentability

Ground 1: Obviousness over Wang, Djupesland, HPE, Bahal, and Kushwaha - Claims 1-7, 12-14, and 16

• 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 the combination of references taught all limitations of independent claim 1. Wang, the primary reference, disclosed intranasal naloxone compositions for treating opioid overdose, including the active ingredient, an isotonicity agent, a preservative (benzalkonium chloride or BAC), a stabilizing agent (sodium edetate), and a pH adjuster, all within the claimed ranges for a dose of about 4 mg. Djupesland disclosed single-use, pre-primed nasal spray devices (e.g., the Aptar device) suitable for delivering a 100 µL volume per actuation. The remaining references, HPE, Bahal, and Kushwaha, were cited to provide further detail on the conventional properties, concentrations, and functions of the specific excipients disclosed by Wang, confirming their suitability and known benefits in nasal formulations.
  • Motivation to Combine: A Person of Ordinary Skill in the Art (POSA) would combine Wang's formulation with Djupesland's device because opioid overdose is an acute condition requiring rapid, reliable administration. Djupesland's single-use, pre-primed device was known to be ideal for such emergency situations, offering immediate, ready-to-use application without drug loss from priming. A POSA would have been motivated to consult references like HPE, Bahal, and Kushwaha to optimize Wang’s formulation using well-known excipients for stability and permeation enhancement.
  • Expectation of Success: A POSA would have had a high expectation of success because the combination involved placing a known formulation (Wang) into a standard, commercially available delivery device (Djupesland) and optimizing it with commonplace excipients (HPE, Bahal, Kushwaha) for their known purposes. The result would have been a predictable improvement in usability and delivery consistency.

Ground 2: Obviousness over Wang, Djupesland, HPE, Bahal, Kushwaha, and Wyse - Claims 10-11 and 17-29

• Prior Art Relied Upon: The combination 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, adding Wyse to teach limitations in dependent claims related to rapid delivery times, symptoms of overdose, and specific pharmacokinetic (pK) profiles. Wyse taught ready-to-use naloxone formulations designed to minimize delivery time for reversing overdose, which is manifested by respiratory depression. Wyse also provided pK data for an intranasal naloxone formulation that achieved plasma concentrations meeting the limitations of claims 25-29 (e.g., ≥0.2 ng/mL within 2.5 minutes).
  • Motivation to Combine: A POSA would combine Wyse with the primary combination because Wyse addressed the same fundamental problem: the need for a rapid-acting, easy-to-use intranasal naloxone product. Wyse’s teachings on the importance of ready-to-use devices to minimize delivery time and its disclosure of treating respiratory depression would have been directly relevant to a POSA developing the formulation taught by Wang for use in the device taught by Djupesland.
  • Expectation of Success: A POSA would expect that increasing the naloxone concentration from the 2 mg dose in Wyse to the 4 mg dose taught by Wang would predictably result in achieving the claimed plasma concentration thresholds even faster, providing a strong expectation of success.

Ground 3: Obviousness over Wang, Djupesland, HPE, Bahal, Kushwaha, and the ’291 Patent - Claims 8 and 9

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

• Core Argument for this Ground:

  • Prior Art Mapping: This ground added the ’291 patent to teach the dose delivery precision limitations of claims 8 and 9, which required a 90% confidence interval of about ±2% and a 95% confidence interval of about ±2.5%, respectively. The ’291 patent disclosed a study of a single-use, pre-primed nasal spray device (the Pfeiffer Unitdose device), similar to the Aptar device in Djupesland, demonstrating that it could achieve these exact levels of dose consistency.
  • Motivation to Combine: A POSA seeking to ensure the formulation of Wang was delivered with high reliability and repeatability from a device like that in Djupesland would have been motivated to look to references like the ’291 patent. The ’291 patent provided evidence that such devices were known in the art to provide the precise dose consistency required by the claims.
  • Expectation of Success: Because the ’291 patent demonstrated that commercially available single-use devices already achieved the claimed levels of precision, a POSA would have reasonably expected that loading Wang's formulation into a similar device would yield the same predictable and reliable dose delivery performance.

• Additional Grounds: Petitioner asserted an additional obviousness challenge for claim 15 based on the primary combination in view of Wyse, Wermeling 2013, or general POSA knowledge regarding the target Tmax for rapid drug absorption.

4. Key Claim Construction Positions

• “pre-primed”: Petitioner argued this term should be construed as defined in the ’253 patent’s specification: a device capable of delivering the composition on the first actuation without prior priming.
• “delivery time”: Petitioner argued this term should be construed as defined in the specification: the time from determining a need for treatment to the completion of delivery.
• “90% confidence interval...is ±about 2.0%” and “95% confidence interval...is ±about 2.5%”: Petitioner argued that since the patent did not explicitly define these terms, they should be interpreted as ranges of values that include the true average value of dose delivery, consistent with the patent's definition of "confidence interval."

5. Key Technical Contentions (Beyond Claim Construction)

• Lack of Priority: Petitioner argued that the ’253 patent was not entitled to the filing date of its provisional application (the ’379 provisional) because the provisional failed to provide adequate written description support for the claimed ranges of specific excipients (e.g., isotonicity agent, preservative, stabilizing agent). Therefore, Petitioner contended the patent’s effective priority date was its actual filing date of March 16, 2015, making several key references available as prior art.

6. Arguments Regarding Discretionary Denial

• Petitioner argued that discretionary denial under 35 U.S.C. §325(d) would be inappropriate. Although the primary reference, Wang, was cited in an Information Disclosure Statement during prosecution, it was submitted with only a machine translation and was never substantively considered or relied upon by the Examiner in any rejection.

7. Relief Requested

• Petitioner requested institution of an inter partes review (IPR) and cancellation of claims 1-29 of the ’253 patent as unpatentable under 35 U.S.C. §103.