Padagis US LLC v. Neurelis Inc

Prosecution History analysis

Examiner Search analysis

Invalidity Framework analysis

Petition

Petition Analysis

## 1. Case Identification
- Case Number: [IPR2025-00464](https://ai-lab.exparte.com/case/ptab/IPR2025-00464)
- Patent #: [8,895,546](https://ai-lab.exparte.com/patent/8895546)
- Filed: January 17, 2025
- Petitioner(s): [Padagis US LLC](https://ai-lab.exparte.com/party/padagis-israel-pharmaceuticals-ltd)
- Patent Owner(s): [Neurelis, Inc.](https://ai-lab.exparte.com/party/neurelis-inc)
- Challenged Claims: 1-22

## 2. Patent Overview
- Title: Administration Of Benzodiazepine Compositions
- Brief Description: The [’546 patent](https://ai-lab.exparte.com/case/ptab/IPR2025-00464/doc/1001) describes pharmaceutical solutions for the intranasal administration of benzodiazepine drugs. The solutions consist of a benzodiazepine, a tocopherol (e.g., vitamin E), specific alcohols, and an alkyl glycoside to improve solubility and delivery.

## 3. Grounds for Unpatentability

#### Ground 1: Obviousness over Gwozdz and Meezan - Claims 1-22 are obvious over Gwozdz in view of Meezan.
- **Prior Art Relied Upon:** [Gwozdz](https://ai-lab.exparte.com/case/ptab/IPR2025-00464/doc/1009) (WO 2009/120933), [Meezan](https://ai-lab.exparte.com/case/ptab/IPR2025-00464/doc/1010) (Application # 2006/0046962).
- **Core Argument for this Ground:**
  - **Prior Art Mapping:** Petitioner argued that the combination of [Gwozdz](https://ai-lab.exparte.com/case/ptab/IPR2025-00464/doc/1009) and [Meezan](https://ai-lab.exparte.com/case/ptab/IPR2025-00464/doc/1010) teaches or suggests every element of the challenged claims.
    - **Independent Claim 1:** [Gwozdz](https://ai-lab.exparte.com/case/ptab/IPR2025-00464/doc/1009) was asserted to teach a pharmaceutical solution for nasal administration (limitation 1) comprising a benzodiazepine drug like diazepam (limitation 1a), one or more tocopherols in an overlapping range of 30-99% w/w (limitation 1b), and a combination of ethanol and benzyl alcohol in an overlapping range of 1-70% w/w (limitation 1c). Petitioner contended [Meezan](https://ai-lab.exparte.com/case/ptab/IPR2025-00464/doc/1010) remedies the final element by teaching the use of alkyl glycosides as penetration enhancers to improve bioavailability (limitation 1d), particularly in amounts (e.g., 0.25%) that fall within the claimed ranges.
    - **Dependent Claims:** Petitioner argued that dependent claims reciting specific benzodiazepines (e.g., diazepam, claim 3), concentration ranges for the active drug and excipients (e.g., claims 4, 7-13), specific tocopherols (e.g., alpha-tocopherol, claim 6), and specific alkyl glycosides (dodecyl maltoside, claim 22) were either directly taught by [Gwozdz](https://ai-lab.exparte.com/case/ptab/IPR2025-00464/doc/1009) or [Meezan](https://ai-lab.exparte.com/case/ptab/IPR2025-00464/doc/1010), or would have been obvious modifications achieved through routine optimization by a person of ordinary skill in the art (POSA). For example, [Gwozdz](https://ai-lab.exparte.com/case/ptab/IPR2025-00464/doc/1009) was cited for disclosing diazepam concentrations of ~8-10% w/v, which overlaps with the ranges in claims 4 and 5.
  - **Motivation to Combine (for §103 grounds):** Petitioner asserted a POSA would combine [Gwozdz](https://ai-lab.exparte.com/case/ptab/IPR2025-00464/doc/1009) and [Meezan](https://ai-lab.exparte.com/case/ptab/IPR2025-00464/doc/1010) to solve the known problem of poor benzodiazepine solubility for non-oral dosage forms. [Gwozdz](https://ai-lab.exparte.com/case/ptab/IPR2025-00464/doc/1009) provided a base non-aqueous solvent system (tocopherol and alcohols) to solubilize drugs like diazepam for nasal delivery, and [Meezan](https://ai-lab.exparte.com/case/ptab/IPR2025-00464/doc/1010) provided a known method for further improving absorption and bioavailability by adding a penetration enhancer, such as an alkyl glycoside.
  - **Expectation of Success (for §103 grounds):** A POSA would have a reasonable expectation of success because [Gwozdz](https://ai-lab.exparte.com/case/ptab/IPR2025-00464/doc/1009) demonstrated improved solubility of diazepam in its solvent system, and [Meezan](https://ai-lab.exparte.com/case/ptab/IPR2025-00464/doc/1010) showed that alkyl glycosides were effective penetration enhancers compatible with alcohol-based, non-aqueous systems and effective for small molecules like diazepam.
  - **Key Aspects:** A central pillar of the petition is the argument that the Patent Owner is collaterally estopped from contesting the obviousness of this combination. Petitioner cited a Final Written Decision (FWD) in a prior inter partes review (IPR), IPR2019-00451, which found claims of a related patent ([’876 Patent](https://ai-lab.exparte.com/case/ptab/IPR2025-00464/doc/1003)) unpatentable over the same [Gwozdz](https://ai-lab.exparte.com/case/ptab/IPR2025-00464/doc/1009) and [Meezan](https://ai-lab.exparte.com/case/ptab/IPR2025-00464/doc/1010) combination. The petition argued the claims of the [’546 patent](https://ai-lab.exparte.com/case/ptab/IPR2025-00464/doc/1001) are materially identical to those already adjudicated, differing only in form (pharmaceutical solution vs. method of treatment).

## 4. Key Claim Construction Positions
- **"vitamin E"**: Petitioner argued the Board should construe "vitamin E" according to its express definition in the [’546 patent](https://ai-lab.exparte.com/case/ptab/IPR2025-00464/doc/1001) specification. This definition is broad, encompassing "any of the natural or synthetic tocopherols, tocotrienols, any isomers thereof, any esters thereof, any analogs or derivatives thereof, or any combinations thereof." This construction is relevant to claims 14 and 17-21.

## 5. Key Technical Contentions (Beyond Claim Construction)
- **Priority Date Entitlement**: Petitioner dedicated significant argument to establishing that the [’546 patent](https://ai-lab.exparte.com/case/ptab/IPR2025-00464/doc/1001) is not entitled to the priority date of the [’558 provisional](https://ai-lab.exparte.com/case/ptab/IPR2025-00464/doc/1008) application (March 28, 2008). The contention was that the provisional failed to provide written description support for the "alkyl glycoside" limitation, which is present in every challenged claim. The term first appeared in the later-filed [’439 Application](https://ai-lab.exparte.com/case/ptab/IPR2025-00464/doc/1039) (March 27, 2009), which Petitioner asserted is the correct priority date. This argument is critical because it establishes [Gwozdz](https://ai-lab.exparte.com/case/ptab/IPR2025-00464/doc/1009) (with a priority date of March 28, 2008) as valid prior art under pre-AIA 35 U.S.C. §102(e). Petitioner noted the Board reached the same conclusion on this issue in the related IPR2019-00451.

## 6. Arguments Regarding Discretionary Denial
- **§325(d) (Same or Substantially Same Prior Art)**: Petitioner argued against discretionary denial under §325(d), stating that while [Gwozdz](https://ai-lab.exparte.com/case/ptab/IPR2025-00464/doc/1009) and [Meezan](https://ai-lab.exparte.com/case/ptab/IPR2025-00464/doc/1010) were before the examiner in an IDS, they were never applied in a rejection or substantively analyzed in combination. Petitioner asserted the examiner materially erred in allowing the claims, a point underscored by the Board’s FWD in the related IPR2019-00451 which invalidated nearly identical claims on the same art.
- **Fintiv Factors**: To preempt discretionary denial under *Fintiv*, Petitioner stipulated that if the IPR is instituted, it will not pursue in a parallel district court proceeding the same grounds or any grounds that could have reasonably been raised in the petition.

## 7. Relief Requested
- Petitioner requested institution of an inter partes review and cancellation of claims 1-22 of Patent [8,895,546](https://ai-lab.exparte.com/patent/8895546) as unpatentable.

Benzodiazepine nasal spray patent challenged as obvious over Gwozdz & Meezan art, citing a prior IPR that found all 22 related claims unpatentable.