PTAB

IPR2022-00966

Eyenovia Inc v. Sydnexis Inc

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Ophthalmic Atropine Solutions for Myopia
  • Brief Description: The ’534 patent describes ophthalmic solutions for treating myopia using low-concentration atropine. The technology addresses the known chemical instability of atropine at higher pH levels (which are more comfortable for the eye) by substituting deuterium oxide (D₂O) for water as the solvent to reduce degradation via base-catalyzed hydrolysis.

3. Grounds for Unpatentability

Ground 1: Obviousness over Chia, Siegel, and Remington - Claims 1, 8-13, and 15-17 are obvious over Chia, Siegel, and Remington.

  • Prior Art Relied Upon: Chia (a 2012 ophthalmology journal article), Siegel (a 1964 pharmaceutical sciences journal article), and Remington (a 1995 pharmaceutical sciences textbook).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the prior art taught all elements of the challenged claims. Chia disclosed clinically effective low-concentration (0.01%) atropine eye drops for treating myopia, providing the base formulation. Siegel taught substituting deuterium oxide (D₂O) for water to increase the stability of ophthalmic solutions containing carboxylic esters (like procaine) that degrade via base-catalyzed hydrolysis. Remington taught the use of standard ophthalmic formulation components, such as buffer agents, osmolarity adjusting agents, and preservatives, which are recited in the claims.
    • Motivation to Combine: A Person of Ordinary Skill in the Art (POSA) would combine these references to create a commercially viable, stable version of Chia's successful low-concentration atropine formulation. The primary motivation argued was to improve the formulation's long-term stability, particularly at a higher, more comfortable pH (closer to the eye's natural pH of 7.4) where atropine was known to be unstable. This would improve patient comfort and compliance for a long-term treatment regimen.
    • Expectation of Success: A POSA would have a reasonable expectation of success. Petitioner asserted that atropine and procaine (from Siegel) are both carboxylic esters that degrade by the same base-catalyzed hydrolysis mechanism. Therefore, the known solvent isotope effect of D₂O, which stabilized procaine, would predictably increase atropine's stability without negatively affecting its established clinical efficacy.

Ground 2: Obviousness over Chia, Siegel, Remington, and Kondritzer - Claims 1-13, 15-27, and 29-30 are obvious over Chia, Siegel, Remington, and Kondritzer.

  • Prior Art Relied Upon: Chia (2012 article), Siegel (1964 article), Remington (1995 textbook), and Kondritzer (a 1957 pharmaceutical journal article).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground incorporated the teachings of Ground 1 and added Kondritzer, a seminal study on atropine stability. Kondritzer provided specific data confirming that atropine's degradation is governed by pH, with optimal stability in an acidic range (pH 3-5) and rapid degradation via base-catalyzed hydrolysis above pH 5. Petitioner argued this reference explicitly defined the known stability problem that a POSA would be motivated to solve using Siegel's D₂O solution for Chia's atropine formulation.
    • Motivation to Combine (for §103 grounds): Kondritzer reinforced the motivation to combine by providing the specific technical rationale and data for why a POSA would seek to stabilize atropine at higher pH levels. The data in Kondritzer, when combined with the other references, would make it obvious to a POSA to formulate a D₂O-based atropine solution within the specific pD ranges and stability profiles recited in the dependent claims.
    • Expectation of Success (for §103 grounds): Kondritzer’s detailed data on atropine's long half-life at various pH levels (e.g., 266 years at pH 5 and 20°C) provided a concrete basis for a POSA to expect that a D₂O-stabilized formulation could easily meet the patent's claimed stability requirements (e.g., retaining at least 80% potency after an extended period).

4. Key Claim Construction Positions

  • Petitioner argued that the claim term "extended period of time" (recited in claims such as 3-6 and 20-23) should be construed to mean "at least about 1 week."
  • This proposed construction was based on the specification's repeated references to "about 1 week" as an example of an "extended period." This construction was central to Petitioner's arguments that the claimed stability metrics were obvious properties of an otherwise obvious formulation.

5. Arguments Regarding Discretionary Denial

  • Petitioner argued that discretionary denial under 35 U.S.C. § 325 would be improper.
  • The petition contended that the asserted prior art combinations are materially different from, and not cumulative of, the art considered by the USPTO during prosecution of the ’534 patent and its parent applications. Petitioner argued the Examiner previously relied on less pertinent references for D₂O (Herekar and Teva), never substantively analyzed Siegel (which was only listed in an IDS), and did not consider a reference analogous to Kondritzer's foundational stability data for atropine.

6. Relief Requested

  • Petitioner requested the institution of an inter partes review and the cancellation of claims 1-13, 15-27, and 29-30 of the ’534 patent as unpatentable under 35 U.S.C. §103.