PTAB

IPR2013-00428

Apotex Corp v. Alcon Research Ltd

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Petition
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1. Case Identification

2. Patent Overview

  • Title: Self Preserved Aqueous Pharmaceutical Compositions
  • Brief Description: The ’299 patent relates to self-preserved ophthalmic compositions that achieve antimicrobial efficacy without traditional preservatives. The compositions use a system of zinc ions combined with a borate-polyol complex and maintain low concentrations of other anionic species that could interfere with the antimicrobial activity of zinc.

3. Grounds for Unpatentability

Ground 1: Obviousness over Xia and Chowhan - Claims 1, 2, 4, 8, 16, 17, and 20 are obvious over Xia in view of Chowhan.

  • Prior Art Relied Upon: Xia (WO 2005/097067) and Chowhan (Patent 6,143,799).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Xia taught self-preserved ophthalmic compositions using a soluble zinc compound as the antimicrobial agent. Chowhan taught ophthalmic compositions using borate-polyol complexes to enhance the efficacy of other antimicrobial agents. Petitioner asserted that the concentration ranges for zinc ions, borate, and polyols (including propylene glycol and sorbitol) recited in independent claim 1 were disclosed by or overlapped with the ranges taught in Xia and Chowhan. The limitation requiring low concentrations of anionic species was allegedly met because Chowhan taught that anions like phosphate can reduce antimicrobial activity, providing a reason to keep their concentration low. Finally, Petitioner contended that satisfying USP 27 preservative efficacy requirements was an inherent property of the combined formulation.
    • Motivation to Combine: A Person of Ordinary Skill in the Art (POSA) would combine the teachings because both references aimed to create effective, non-irritating ophthalmic preservatives. A POSA would have been motivated to combine Xia’s zinc-based preservative with Chowhan’s borate-polyol system, which was known to enhance antimicrobial agents, to achieve improved preservative efficacy without using traditional, potentially toxic agents.
    • Expectation of Success: Petitioner argued a POSA would have a reasonable expectation of success because the components were known to be compatible in ophthalmic solutions. Optimizing the concentration ranges of these known, result-effective variables would have been a matter of routine experimentation.

Ground 2: Obviousness over Xia, Chowhan, and Gadd - Claims 1-4, 8, 9, and 13-21 are obvious over Xia and Chowhan in view of Gadd.

  • Prior Art Relied Upon: Xia (WO 2005/097067), Chowhan (Patent 6,143,799), and Gadd (a 1978 journal article titled "Microorganisms and Heavy Metal Toxicity").
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground incorporated the arguments from Ground 1 regarding Xia and Chowhan. The additional reference, Gadd, was cited for its fundamental teaching that various anions (e.g., phosphate, carbonate) and multivalent metal cations (e.g., magnesium) can interfere with and reduce the antimicrobial activity of heavy metals like zinc. Petitioner argued this provided a strong, explicit rationale for the claimed limitations requiring low concentrations of multivalent buffering anions and metal cations other than zinc (as recited in claims 2, 3, and 9), reinforcing the teachings of Chowhan.
    • Motivation to Combine: A POSA developing a zinc-based antimicrobial composition as taught by Xia would consult fundamental literature like Gadd to understand factors that could affect zinc’s efficacy. Gadd’s disclosure on ionic interference would directly motivate a POSA to minimize such ions in the formulation taught by Xia and Chowhan to ensure the preservative system remained effective.
    • Expectation of Success: The expectation of success was argued to be high, as Gadd explained the scientific principle behind why minimizing interfering ions would preserve the antimicrobial activity of zinc, confirming the benefits suggested by Chowhan.

Ground 3: Obviousness over Xia, Chowhan, and the Travatan Label - Claims 5-7 and 28 are obvious over Xia and Chowhan in view of the Travatan Label.

  • Prior Art Relied Upon: Xia (WO 2005/097067), Chowhan (Patent 6,143,799), and the FDA Approved Drug Label for TRAVATAN® ("TL").

  • Core Argument for this Ground:

    • Prior Art Mapping: This ground built on the base combination of Xia and Chowhan to address claims reciting specific therapeutic agents and excipients. Xia was cited for teaching the inclusion of therapeutic agents like prostaglandins in its preserved compositions. The TL, the label for a commercial ophthalmic product, was cited for disclosing a specific formulation containing the prostaglandin travoprost, along with excipients like polyoxyl 40 hydrogenated castor oil and a pH of approximately 6.0. These elements directly mapped to the limitations of dependent claims 5, 6, 7, and independent claim 28.
    • Motivation to Combine: A POSA, guided by Xia to include a prostaglandin in a preserved ophthalmic solution, would look to existing successful commercial products like Travatan® for a suitable agent and formulation. The TL provided a clear example of a compatible and effective formulation. A POSA would therefore combine the preservative system of Xia/Chowhan with the specific active agent and excipients disclosed in the TL.
    • Expectation of Success: Success would be reasonably expected, as the combination involved adding a known preservative system to a well-established, commercially available drug formulation, a common practice in pharmaceutical development.

  • Additional Grounds: Petitioner asserted additional obviousness challenges based on combinations of the above references with Kiyobayashi (Japanese Application Publication 2003-104870), which provided further teachings on using low concentrations of zinc in borate-polyol ophthalmic compositions.

4. Key Claim Construction Positions

  • "self-preserved": Petitioner proposed this term refers to a solution not susceptible to significant microbial growth due to its inherent antimicrobial properties, allowing it to be used in a multi-dose container without needing to be maintained aseptically.
  • "zinc ions at a concentration of": Petitioner argued this term encompasses the concentration of zinc salt (e.g., zinc chloride) added to the composition, as the salt is presumed to completely dissociate into zinc ions in the aqueous solution.
  • "zinc chloride ionized" / "ionized zinc chloride": As these terms are not defined in the specification, Petitioner contended they should be interpreted as the concentration of zinc chloride added to the composition.

5. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 1-28 of Patent 8,268,299 as unpatentable.