PTAB

IPR2013-00429

Apotex Corp v. Alcon Research Ltd

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1. Case Identification

2. Patent Overview

  • Title: Self Preserved Aqueous Pharmaceutical Compositions
  • Brief Description: The ’630 patent discloses multi-dose, self-preserved ophthalmic solutions. The compositions use zinc ions in combination with a borate-polyol system to achieve antimicrobial efficacy, allegedly avoiding the need for traditional preservatives while controlling for ions that could interfere with zinc's activity.

3. Grounds for Unpatentability

Ground 1: Claims 1-5 are obvious over Xia in view of Chowhan and Gadd.

  • Prior Art Relied Upon: Xia (International Publication No. WO 2005/097067), Chowhan (Patent 6,143,799), and Gadd (a 1978 article in Microbial Ecology).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the combination of Xia and Chowhan teaches all components of the claimed ophthalmic solution within the recited concentration ranges. Xia discloses self-preserved ophthalmic solutions using a preservative-effective amount of a soluble zinc compound. Chowhan teaches using borate-polyol complexes (including boric acid, propylene glycol, and sorbitol) as antimicrobial agents in ophthalmic compositions, disclosing concentration ranges that overlap with those in claim 1. Gadd, an early article on heavy metal toxicity to microbes, teaches that multivalent anions (like phosphate) and multivalent cations (like magnesium and calcium) can interfere with and reduce the antimicrobial activity of metals like zinc. This provides the rationale for the claimed limitations requiring low concentrations (<5 mM) of such interfering species.
    • Motivation to Combine: A person of ordinary skill in the art (POSITA) would combine the zinc-based preservative system of Xia with the borate-polyol system of Chowhan to achieve robust antimicrobial activity while avoiding the known toxicity and irritation of traditional preservatives, a benefit taught by both references. A POSITA would have been further motivated to consult Gadd to understand the known principles of heavy metal antimicrobial activity, specifically how to avoid the inhibitory effects of certain ions—a concern also noted by Chowhan regarding phosphate buffers.
    • Expectation of Success: A POSITA would have had a reasonable expectation of success because the references teach combining known antimicrobial agents (zinc and borate-polyol) in well-understood ophthalmic formulations. Petitioner contended that optimizing the concentrations to fall within the claimed ranges and achieve the desired preservative effect (satisfying USP 27 standards) would have been a matter of routine experimentation, as the components were known result-effective variables.

Ground 2: Claims 6-11 are obvious over Xia, the Travatan Label, Chowhan, and Gadd.

  • Prior Art Relied Upon: Xia (WO 2005/097067), the Travatan Label ("TL"), Chowhan (Patent 6,143,799), and Gadd (1978 article).

  • Core Argument for this Ground:

    • Prior Art Mapping: This ground builds on the combination in Ground 1 by adding the FDA-approved drug label for Travatan®, an ophthalmic solution containing the prostaglandin travoprost. Claims 6-11 are directed to compositions containing a prostaglandin analog, specifically travoprost (claim 7), and a non-ionic surfactant. Xia explicitly teaches that its zinc preservative system can be used with therapeutic agents including prostaglandins. The TL discloses a commercially successful ophthalmic formulation containing a therapeutic amount of travoprost, along with a non-ionic surfactant (polyoxyl 40 hydrogenated castor oil) and a borate-polyol system, thereby teaching the specific components recited in claims 8 and 10.
    • Motivation to Combine: A POSITA seeking to apply Xia’s zinc preservation system to a prostaglandin-based therapy would be motivated to look to a known, FDA-approved product like Travatan® for a specific, proven prostaglandin agent (travoprost) and a compatible formulation. The TL provides an exemplary and successful formulation, including the specific non-ionic surfactant recited in the claims. The motivation to combine this with Gadd's teachings on avoiding ionic interference remains the same as in Ground 1.
    • Expectation of Success: Combining the zinc system from Xia with the established travoprost formulation from the TL would have been predictable. A POSITA would expect success in adding a known preservative enhancer (zinc) to a stable, well-characterized commercial formulation, especially since the base components (borate-polyol systems) are present in both Chowhan and the TL.

  • Additional Grounds: Petitioner asserted additional obviousness challenges for claims 1-2 and 8-10 based on combinations that substitute Kiyobayashi (Japanese Patent Application 2001-302613) into the grounds above. Kiyobayashi was argued to provide a further reason for using low concentrations of zinc, as it teaches effective antimicrobial activity for zinc salts within the claimed ranges.

4. Key Claim Construction Positions

  • "zinc ions at a concentration of": Petitioner argued this term's broadest reasonable interpretation encompasses the concentration of zinc salt added to the solution, assuming complete dissociation into zinc ions in an aqueous composition, as supported by the patent's specification.
  • "self-preserved": This term was construed to mean a solution that is not susceptible to significant microbial growth and is suitable for use in a multi-dose container, based on its antimicrobial properties.
  • "substantially free of multivalent buffering anions": Petitioner asserted this means the solution contains an amount of such anions that does not inhibit its ability to satisfy specified preservative efficacy standards (e.g., USP). This construction is critical because it allows for the presence of some interfering ions as long as efficacy is maintained, aligning with the teachings of the prior art.

5. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 1-11 of Patent 8,323,630 as unpatentable under 35 U.S.C. §103.