Aquestive Therapeutics Inc v. Neurelis Inc

1. Case Identification

• Case #: IPR2019-00451
• Patent #: 9,763,876
• Filed: January 29, 2019
• Petitioner(s): Aquestive Therapeutics, Inc.
• Patent Owner(s): Hale Biopharma Ventures, LLC
• Challenged Claims: 1-36

2. Patent Overview

• Title: Administration of Benzodiazepine Compositions
• Brief Description: The ’876 patent discloses methods for treating disorders with benzodiazepine drugs. The method involves intranasally administering a pharmaceutical solution consisting of a benzodiazepine, a tocopherol (vitamin E), specific alcohols (ethanol and benzyl alcohol), and an alkyl glycoside.

3. Grounds for Unpatentability

Ground 1: Obviousness over Gwozdz in view of Meezan’962

• Claims: 1-16 and 24-36 are obvious over Gwozdz in view of Meezan’962.
• Prior Art Relied Upon: Gwozdz (WO 2009/120933) and Meezan’962 (Application # 2006/0046962).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Gwozdz taught the core elements of independent claim 1: a pharmaceutical solution for intranasal administration containing a benzodiazepine (e.g., diazepam) dissolved in a combination of a tocopherol (e.g., vitamin E) and alcohols (e.g., ethanol and benzyl alcohol). Gwozdz disclosed concentration ranges for the tocopherols (about 30-99%) and combined alcohols (about 1-70%) that overlap with or render obvious the ranges recited in the challenged claims. Petitioner contended the only key element missing from Gwozdz was an alkyl glycoside. This missing element, Petitioner asserted, was supplied by Meezan’962, which explicitly taught adding alkyl glycosides (such as the claimed dodecyl maltoside) to intranasal drug formulations to enhance bioavailability and absorption.
  • Motivation to Combine: Petitioner asserted a person of ordinary skill in the art (POSITA), seeking to optimize the intranasal benzodiazepine formulation taught by Gwozdz, would be motivated to consult Meezan’962. Both references addressed the known problem of improving the delivery of drugs across mucosal membranes. A POSITA would have recognized that incorporating Meezan’962’s teaching of using an alkyl glycoside as a bioavailability enhancer was a known and logical step to improve the performance of Gwozdz’s base formulation.
  • Expectation of Success: Petitioner argued a POSITA would have a reasonable expectation of success. Meezan’962 demonstrated that adding an alkyl glycoside could dramatically increase the bioavailability of nasally administered drugs (from 3% to as high as 98%). Therefore, a POSITA would expect that adding this component to the Gwozdz formulation would successfully increase the bioavailability of the benzodiazepine, particularly to meet standard FDA bioequivalence targets (e.g., 80-125%) as claimed.

Ground 2: Obviousness over Gwozdz, Meezan’962, and Cartt’784

• Claims: 17-23 are obvious over Gwozdz and Meezan’962, further in view of Cartt’784.
• Prior Art Relied Upon: Gwozdz (WO 2009/120933), Meezan’962 (Application # 2006/0046962), and Cartt’784 (Application # 2008/0279784).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground built upon the Gwozdz/Meezan’962 combination from Ground 1 to address dependent claims 17-23, which added limitations related to specific administration parameters. These claims recited a therapeutically effective amount (e.g., 1-20 mg), a spray volume (e.g., 10-200 µL), and a spray protocol (e.g., administering to one or both nostrils, optionally with subsequent sprays). Petitioner argued that while Gwozdz/Meezan’962 provided the formulation, Cartt’784 expressly taught these missing administration details. Cartt’784 was directed specifically to the nasal administration of benzodiazepines and disclosed dosage amounts, spray volumes, and multi-spray protocols that directly corresponded to the limitations of claims 17-23.
  • Motivation to Combine: Petitioner contended that because Gwozdz and Meezan’962 did not provide specific dosing regimens, a POSITA would naturally look to other references in the same field for such guidance. Cartt’784 provided a detailed roadmap for administering intranasal benzodiazepines. A POSITA would be motivated to apply the established and detailed dosing protocols from Cartt’784 to the Gwozdz/Meezan’962 formulation to create a complete, clinically practical treatment method.
  • Expectation of Success: Success would have been expected because Cartt’784 provided standard, well-defined parameters for the nasal delivery of the very class of drug used in the primary combination. Applying these conventional dosing regimens to the formulation would have been a routine adaptation for a POSITA.

4. Key Claim Construction Positions

• "about 56.47% (w/v) vitamin E": Petitioner argued that based on the patent’s definition of "about" (allowing for ±1% to ±20%), a POSITA would understand this term to mean a range of ±5%, or "53.65% to 59.29% (w/v) vitamin E". This construction was important for mapping the broad ranges for tocopherols disclosed in Gwozdz.
• "% (w/w)" and "% (w/v)": Petitioner asserted that the ’876 patent used these terms interchangeably, pointing to how independent claim 1 recited "% (w/w)" for the alcohol element while dependent claim 5 switched to "% (w/v)" for the same element. Petitioner argued the terms should be treated as interchangeable for purposes of the obviousness analysis.

5. Arguments Regarding Discretionary Denial

• Petitioner argued against discretionary denial under §325(d). Although the Examiner considered Meezan’962 during prosecution of a parent application, Petitioner asserted it was applied in a new light in the petition. Specifically, it was combined with a different primary reference (Gwozdz) that was not before the Examiner, and the invalidity arguments were supported by new expert testimony. Therefore, the petition raised new issues that warranted review.

6. Relief Requested

• Petitioner requests institution of an inter partes review and cancellation of claims 1-36 of the ’876 patent as unpatentable.