Aquestive Therapeutics, Inc. formerly Monosol RX, LLC v. Neurelis, Inc.

1. Case Identification

• Case #: IPR2019-00449
• Patent #: 9,763,876
• Filed: January 28, 2019
• Petitioner(s): Aquestive Therapeutics, Inc.
• Patent Owner(s): Hale Biopharma Ventures, LLC
• Challenged Claims: 8-10, 15, 30-36

2. Patent Overview

• Title: Administration of Benzodiazepine Compositions
• Brief Description: The ’876 patent relates to methods for intranasally administering a pharmaceutical solution for treating disorders with a benzodiazepine drug. The solution consists of the drug, a tocopherol (like vitamin E), a combination of ethanol and benzyl alcohol as solubilizers, and an alkyl glycoside as a penetration enhancer.

3. Grounds for Unpatentability

Ground 1: Anticipation of Claims 8-10, 15, and 30-33 under §102(b) over Cartt’865

• Prior Art Relied Upon: Cartt (Application # US 2009/0258865), referred to as Cartt’865.
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Cartt’865, a parent application to the ’876 patent, qualifies as prior art under 35 U.S.C. §102(b) because the challenged claims are not entitled to its earlier priority date. This is based on the assertion that key limitations—including specific concentration ranges for ethanol, benzyl alcohol, diazepam, vitamin E, and all bioavailability data—were not supported or enabled until a later-filed provisional application. Petitioner contended that Cartt’865 anticipates the challenged claims by disclosing all their limitations. Specifically, Cartt’865’s Example 6 describes Solutions 6-00 and 6-02, which contain diazepam (7%), vitamin E (65% or 80%), ethanol (12-13% or 27-28%), and an alkyl glycoside. Petitioner asserted these examples, combined with general disclosures for component ranges in Cartt’s specification and claims, meet all limitations of the challenged claims.
  • Key Aspects: The central thesis of this ground is that the Patent Owner’s own parent application lacks written description support for the challenged claims, thereby invalidating its priority claim and turning the parent application into anticipating prior art.

Ground 2: Obviousness of Claims 8-10, 15, and 30-33 over Cartt’865 alone or in view of Ueda

• Prior Art Relied Upon: Cartt (Application # US 2009/0258865) and Ueda (Patent 4,657,901).
• Core Argument for this Ground:
  • Prior Art Mapping: As an alternative to anticipation, Petitioner argued the claims are obvious over Cartt’865 alone, as it discloses all elements either exactly or sufficiently, and a person of ordinary skill in the art (POSITA) could make minor modifications to arrive at the claimed invention. In combination with Ueda, Petitioner asserted that Ueda teaches using a combination of ethanol and benzyl alcohol to increase the absorption and penetration of low-solubility drugs. Ueda’s examples disclose compositions with 20% ethanol and 5% benzyl alcohol, and 25% ethanol and 10% benzyl alcohol, falling within the ranges of the challenged claims.
  • Motivation to Combine (for §103 grounds): A POSITA reviewing Cartt’865, which discloses using "one or more lower alcohols" including ethanol and benzyl alcohol, would be motivated to combine these specific alcohols as taught by Ueda. The motivation would be to optimize the formulation to enhance drug absorption and solubility, which Ueda explicitly states is a function of this alcohol combination.
  • Expectation of Success (for §103 grounds): A POSITA would have an expectation of success because both references relate to pharmaceutical formulations, and Ueda provides specific, successful examples of combining ethanol and benzyl alcohol to improve drug delivery.

Ground 3: Obviousness of Claims 34-36 over Cartt’865 in view of Meezan’962 and Jamieson

• Prior Art Relied Upon: Cartt (Application # US 2009/0258865), Meezan (Application # US 2006/0046962), and Jamieson (Application # US 2008/0070904).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground targets claims 34-36, which add limitations requiring specific bioavailability ranges (e.g., 80-125% of an intravenous dose). Petitioner argued that Cartt’865 provides the base formulation and a protocol for testing bioavailability (Example 9) but discloses no actual bioavailability data. Meezan’962 teaches that alkyl glycosides (a component in Cartt’865) significantly increase the bioavailability of intranasally administered drugs to levels of approximately 90-98%. Jamieson discloses that routine experimentation with intranasal benzodiazepine formulations containing similar components (surfactants, solvents) readily achieves bioavailabilities between 20% and 125%, with many examples falling within the 80-125% range of claim 34.
  • Motivation to Combine (for §103 grounds): A POSITA starting with the Cartt’865 formulation would be motivated to optimize it to achieve bioavailability levels required for FDA approval (generally 80-125%). Meezan’962 and Jamieson both teach that achieving such high bioavailability is possible with similar formulations and provide a clear path for doing so through routine optimization of components like alkyl glycosides and solvents.
  • Expectation of Success (for §103 grounds): The successful results disclosed in both Meezan’962 and Jamieson, which demonstrate achieving bioavailabilities near 100% with similar drug delivery systems, would provide a POSITA with a strong expectation of success in achieving the specific ranges recited in claims 34-36.

4. Key Claim Construction Positions

• "vitamin E": Petitioner argued this term should be construed broadly as "any of the natural or synthetic tocopherols, tocotrienols, any isomers thereof, any esters thereof, any analogs or derivatives thereof, or any combinations thereof," based on the patent’s express definition.
• "bioavailability": Should be construed according to the formula provided by both the ’876 patent and the Ritschel pharmacology handbook: the ratio of Area Under the Curve (AUC) for intranasal administration versus intravenous administration, adjusted for dose.
• "% (w/w)" and "% (w/v)": Petitioner asserted these terms are used interchangeably in the ’876 patent, as independent claim 1 uses (w/w) and dependent claims use (w/v) for the same alcohol element. Therefore, they should be interpreted as interchangeable.

5. Key Technical Contentions (Beyond Claim Construction)

• Priority Date Entitlement: The cornerstone of Petitioner’s case is the argument that the challenged claims are not entitled to the priority date of the parent Cartt’865 application. Petitioner contended that the specific concentration ranges of several key components (diazepam >10%, specific alcohol combinations and ranges) and the functional bioavailability limitations were not disclosed or enabled in the parent applications. This alleged lack of support under §112 pushes the effective filing date of the challenged claims to June 14, 2011, making the 2009 Cartt’865 publication prior art against them.

6. Relief Requested

• Petitioner requests the institution of an inter partes review and the cancellation of claims 8-10, 15, and 30-36 of Patent 9,763,876 as unpatentable.