PTAB

IPR2016-01640

Apotex Inc v. Alcon Research Ltd

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1. Case Identification

2. Patent Overview

  • Title: High Concentration Olopatadine Ophthalmic Composition
  • Brief Description: The ’154 patent discloses aqueous ophthalmic solutions containing a "relatively high" concentration of olopatadine (at least 0.67 w/v%) for treating allergic conjunctivitis. The compositions purportedly use a unique set of excipients—including a cyclodextrin derivative, polyvinylpyrrolidone (PVP), and polyethylene glycol (PEG)—to solubilize the olopatadine and maintain stability.

3. Grounds for Unpatentability

Ground 1: Obviousness over Bhowmick, Yanni, and Castillo - Claims 1-4, 8, 12, 13, 21, and 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 that the combination of these references teaches every limitation of the challenged claims. Yanni disclosed that higher concentrations of olopatadine (up to 1 w/v%) provided superior and longer-lasting anti-allergic effects compared to lower concentrations. Bhowmick taught using cyclodextrins, including the claimed hydroxypropyl-γ-cyclodextrin (HP-γ-CD), to create stable aqueous solutions of olopatadine and prevent precipitation. Castillo taught enhancing the stability of olopatadine solutions (up to 0.6% w/v%) with PVP and PEG 400. Together, these references disclose all claimed components (olopatadine >0.67%, HP-γ-CD, PVP, PEG, benzalkonium chloride, water) and their use in ophthalmic solutions. Dependent claims adding common buffering agents (borates) and tonicity agents (polyols) were also rendered obvious as these are well-known additives disclosed in Bhowmick and Castillo.
    • Motivation to Combine: A person of ordinary skill in the art (POSA), motivated by Yanni’s teaching of enhanced efficacy at higher concentrations, would seek to formulate an olopatadine solution greater than the ~0.62% taught in Bhowmick and Castillo. To achieve the required solubility and stability for such a high-concentration formula, a POSA would have naturally looked to the teachings of Bhowmick and Castillo, which are directed specifically to stabilizing olopatadine solutions. A POSA would combine Bhowmick’s cyclodextrins with Castillo’s PVP and PEG 400, as all were known and effective solubilizers and stabilizers for olopatadine.
    • Expectation of Success: A POSA would have had a reasonable expectation of success. The claimed olopatadine concentration (at least 0.67 w/v%) is only slightly higher than the concentrations shown to be stable in Bhowmick and Castillo (~0.62 w/v%). Formulating this slightly higher concentration using a known combination of effective excipients would have been a matter of routine optimization. The prior art taught no incompatibilities between the components and demonstrated their collective benefit for olopatadine solubility.

Ground 2: Obviousness over Schneider, Hayakawa, Bhowmick, and Castillo - Claims 1-4, 8, 12, 13, 21, and 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: This ground asserted that Schneider, as a primary reference, provided a strong starting point for the claimed invention. Schneider explicitly taught aqueous ophthalmic solutions containing olopatadine at concentrations of "0.60% w/v, or higher" for treating allergic conjunctivitis. Schneider also disclosed the optional inclusion of polymers like HPMC, PEG, and PVP as lubricants or viscosity agents. Hayakawa further supported the feasibility of high concentrations by disclosing stable olopatadine solutions up to 5 w/v%. The teachings of Bhowmick (cyclodextrins for stability) and Castillo (PVP and PEG for stability) were incorporated to provide the specific combination of excipients required by the claims, filling any gaps in Schneider’s disclosure.
    • Motivation to Combine: A POSA starting with Schneider’s disclosure of a high-concentration olopatadine solution would be motivated to ensure its long-term stability for a viable pharmaceutical product. While Schneider mentioned some excipients, a POSA would have been motivated by Hayakawa's teachings on the superior antihistamine effects of higher concentrations to ensure such a formulation was stable. The POSA would have consulted art specifically directed to olopatadine stability, such as Bhowmick and Castillo, and would have been motivated to incorporate their proven excipients (cyclodextrins, PVP, PEG) into Schneider’s base formulation.
    • Expectation of Success: Success was reasonably expected because the combination involved using known excipients for their predictable and established functions—stabilizing olopatadine. The prior art confirmed that high concentrations of olopatadine were stable and effective, and the proposed excipients were well-known to be compatible and effective for this purpose. Arriving at the specific claimed concentration ranges for the excipients would have been the result of routine optimization to maximize the known benefits.

4. Key Claim Construction Positions

  • Preamble (Claims 1, 4, 8, 21): Petitioner argued the preamble reciting "An aqueous ophthalmic solution for treatment of ocular allergic conjunctivitis" is non-limiting. It merely stated an intended use, and the claim body fully set forth a structurally complete composition.
  • "solution comprising ... at least 0.67 w/v % olopatadine ... dissolved in the solution": Petitioner asserted this language, consistent with the specification, means the solution must contain at least the recited amount of dissolved olopatadine but could also contain additional undissolved olopatadine in suspension.
  • "w/v %": Petitioner proposed this term be construed according to the industry standard as the mass of the component in grams per 100 milliliters of solution, multiplied by 100.

5. Key Technical Contentions (Beyond Claim Construction)

  • No Entitlement to Priority Date: Petitioner argued the ’154 patent was not entitled to the filing date of its provisional application. The provisional application focused exclusively on using β-cyclodextrin derivatives to aid olopatadine solubility. In contrast, every independent claim of the ’154 patent recites hydroxypropyl-γ-cyclodextrin. Because the provisional failed to mention or provide examples utilizing γ-cyclodextrin derivatives, it did not provide adequate written description support for the issued claims.

6. Relief Requested

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