PTAB

IPR2016-00544

Argentum Pharmaceuticals LLC v. Alcon Research Ltd

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Petition
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1. Case Identification

2. Patent Overview

  • Title: High Concentration Olopatadine Ophthalmic Composition
  • Brief Description: The ’154 patent relates to aqueous ophthalmic solutions containing a high concentration of the antihistamine olopatadine (at least 0.67 w/v %) for treating ocular allergic conjunctivitis. The invention purports to use a specific combination of excipients—including a cyclodextrin derivative, polyvinylpyrrolidone (PVP), and polyethylene glycol (PEG)—to achieve solubility and stability at these high concentrations.

3. Grounds for Unpatentability

Ground 1: Claims 1-4, 8, 12-13, and 21-22 are obvious over Bhowmick, Yanni, and Castillo.

  • Prior Art Relied Upon: Bhowmick (WO 2008/015695), Yanni (a 1996 journal article), and Castillo (Patent 6,995,186).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued the combination of references taught every element of the challenged claims. Yanni disclosed that higher concentrations of olopatadine (1 w/v%) exhibited superior efficacy and longer duration of action compared to lower concentrations (0.1 w/v%) in treating allergic conjunctivitis. Bhowmick taught stable aqueous olopatadine solutions using cyclodextrins (including the claimed hydroxypropyl-γ-cyclodextrin, or HP-γ-CD) and hydroxypropyl methylcellulose (HPMC) to prevent precipitation. Castillo taught topical olopatadine solutions (up to approximately 0.6% w/v) containing PVP and PEG 400 to enhance stability. Collectively, the references disclosed all claimed components, including borates, polyols, and benzalkonium chloride, within or overlapping the claimed concentration ranges.
    • Motivation to Combine: A Person of Ordinary Skill in the Art (POSITA) would be motivated by Yanni’s teachings of superior efficacy to formulate an olopatadine solution with a higher concentration than was commercially available. To solve the known solubility and stability challenges associated with higher drug concentrations, a POSITA would logically turn to well-known ophthalmic formulation art. A POSITA would combine the cyclodextrin and HPMC stabilizing agents from Bhowmick with the PVP and PEG stabilizers from Castillo to create a stable, effective, high-concentration product based on the benefits shown in Yanni.
    • Expectation of Success: A POSITA would have a reasonable expectation of success. Castillo already provided an enabling disclosure for stable olopatadine solutions up to ~0.62% w/v. Formulating a solution at the slightly higher claimed concentration of 0.67% w/v using a known toolkit of solubilizers (cyclodextrins, PEG, PVP) would have been a matter of routine optimization, not invention. Bhowmick and other art taught that these excipients had a beneficial effect on olopatadine solubility without suggesting an upper concentration limit.

Ground 2: Claims 1-4, 8, 12-13, and 21-22 are obvious over Schneider in view of Hayakawa, Bhowmick, and Castillo.

  • Prior Art Relied Upon: Schneider (Application # 2011/0082145), Hayakawa (Patent 5,641,805), Bhowmick (WO 2008/015695), and Castillo (Patent 6,995,186).
  • Core Argument for this Ground:
    • Prior Art Mapping: Schneider explicitly taught ophthalmic solutions for allergic conjunctivitis containing olopatadine at concentrations of "0.60% w/v, or higher," directly suggesting the claimed concentration range. Schneider also expressly disclosed using polymers like HPMC, PEG, and PVP as lubricants or viscosity agents in its formulations. Hayakawa reinforced the feasibility of high-concentration formulas by disclosing olopatadine eye drops with concentrations up to 5 w/v%. The secondary references, Bhowmick and Castillo, provided the same specific teachings on using cyclodextrins, PEG, PVP, and other excipients to ensure the stability of olopatadine solutions, as detailed in Ground 1.
    • Motivation to Combine: A POSITA, starting with Schneider's clear disclosure of a high-concentration (≥0.60% w/v) olopatadine solution containing PEG and PVP, would be motivated to consult formulation-focused art like Bhowmick and Castillo. These references provided specific, proven methods for enhancing the stability and solubility of olopatadine solutions using cyclodextrins and specific concentrations of other excipients, which would be necessary to develop a commercially viable product. The motivation was to apply known stability-enhancing techniques to an already suggested high-concentration formulation.
    • Expectation of Success: The expectation of success was high because the prior art, particularly the combination of Schneider, Bhowmick, and Castillo, disclosed all the claimed components and overlapping concentration ranges. Creating the claimed composition would involve routine optimization of known ingredients for their established functions. Petitioner noted that the Federal Circuit had previously confirmed in a case involving Hayakawa that claims to olopatadine concentrations up to 5% w/v were enabled, reinforcing that a POSITA could reasonably expect to create such formulations.

4. Key Claim Construction Positions

  • Preamble (Claims 1, 4, 8, 21): Petitioner argued the preambles reciting the intended use ("for treatment of ocular allergic conjunctivitis") are non-limiting. It asserted the body of the claims defines a structurally complete invention, and the preamble merely states a purpose without imparting any structural limitations to the claimed composition.
  • "solution comprising ... at least 0.67 w/v % olopatadine dissolved in the solution": Petitioner contended this language, particularly the term "comprising," means the claims encompass solutions that contain the required amount of dissolved olopatadine but may also include additional, undissolved olopatadine in suspension.

5. Key Technical Contentions

  • Priority Date Entitlement: Petitioner argued the ’154 patent was not entitled to the filing date of its provisional application. It contended the provisional application failed the written description requirement of 35 U.S.C. § 112 because it exclusively disclosed and exemplified β-cyclodextrin derivatives for solubilizing olopatadine. In contrast, the challenged independent claims all require a hydroxypropyl-γ-cyclodextrin, which Petitioner argued was not described in the provisional, thereby making certain prior art available against the patent.

6. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 1-4, 8, 12-13, and 21-22 of Patent 8,791,154 as unpatentable.