PTAB

IPR2017-01100

Actavis LLC v. Abraxis Bioscience LLC

Log In
Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Formulations of Pharmacological Agents, Methods for the Preparation Thereof and Methods for the Use Thereof
  • Brief Description: The ’260 patent is directed to pharmaceutical formulations of nanoparticles comprising a solid core of paclitaxel (an anticancer drug) coated with albumin. The claims require the nanoparticles to be less than 400 nm in size, suspended at a paclitaxel concentration of at least 5 mg/ml, and stable for at least three days.

3. Grounds for Unpatentability

Ground 1: Obviousness over Desai, Shively, Liversidge, and Remington's - Claims 1-27 are obvious over Desai in view of Shively, Liversidge, and Remington's.

  • Prior Art Relied Upon: Desai (Patent 5,439,686), Shively (Patent 5,407,683), Liversidge (Patent 5,399,363), and Remington's (Remington's Pharmaceutical Sciences, 18th ed. 1990).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the prior art disclosed all structural elements of the claimed formulation, and the claimed stability was an inherent and expected result of combining them.
      • Desai, a prior patent from the same inventors, taught the core invention: stable aqueous suspensions of albumin-coated paclitaxel nanoparticles, including sizes as small as 200 nm. Desai disclosed that these formulations showed "good... stability under a variety of temperature conditions over almost four weeks," meeting every limitation of claim 1 except the specific paclitaxel concentration.
      • Shively addressed the problem of administering large volumes of the commercial paclitaxel formulation (Taxol®) and explicitly taught using a more concentrated, "pharmaceutically effective amount" of "5 mg/ml of taxol" to reduce infusion volume.
      • Liversidge and Remington's represented the general knowledge of a person of ordinary skill in the art (POSITA). They taught the benefits of smaller particle sizes (e.g., <400 nm) for improving stability, bioavailability, and enabling sterile filtration (through 0.22 µm filters). These references also identified albumin as a "preferred" stabilizer for parenteral suspensions, capable of maintaining nanoparticle stability even at high concentrations (Liversidge demonstrated stability at 10 mg/ml).
    • Motivation to Combine: A POSITA would combine Desai’s stable albumin-paclitaxel nanoparticles with Shively’s therapeutically effective 5 mg/ml concentration to achieve the well-understood goal of delivering a higher dose of paclitaxel in a smaller, more convenient volume. This combination addressed the known drawbacks of the toxic emulsifiers and large infusion volumes associated with Taxol®. The teachings of Liversidge and Remington’s provided further motivation to optimize the particle size to the sub-400 nm range to enhance stability and allow for required sterile filtration, both of which were routine formulation considerations.
    • Expectation of Success: A POSITA would have had a high expectation of success. Desai already established that albumin-paclitaxel nanoparticles were stable for weeks. Liversidge confirmed that albumin could stabilize similar nanoparticles at a concentration of 10 mg/ml, double the concentration taught by Shively. Therefore, applying a 5 mg/ml concentration to Desai's already-stable formulation was a predictable optimization, not an inventive leap. Petitioner contended that the claimed three-day stability was far less than the nearly four-week stability already demonstrated by Desai.
    • Key Aspects: Petitioner’s central argument was that the "unexpected results" that led to the patent's allowance were based on a flawed comparison. During prosecution, the patent owner compared the stability of its formulation to Taxol® (which contains no albumin stabilizer), rather than to the closest prior art, Desai (which does). Petitioner argued this created a false narrative of unexpectedness, when in fact the stability was entirely expected based on the teachings of Desai, Liversidge, and Remington's.

4. Key Claim Construction Positions

  • "stable for at least 3 days...": Petitioner argued this functional limitation is non-limiting and adds no patentable weight to the claims. It was contended to be an inherent property of the structurally obvious composition, which combines two known stabilizers: small particle size and an albumin coating. The stability is merely the natural result of the claimed structure.
  • "average diameter of the nanoparticles is no greater than about 200 nm": Petitioner proposed this term should be construed to include particle sizes up to 220 nm. This construction was based on the patent’s explicit purpose for this size limitation: to allow for sterile filtration, which is commonly performed using 0.22 micron (220 nm) filters.

5. Key Technical Contentions (Beyond Claim Construction)

  • Predictability of Stability via Calculation: Petitioner argued that a POSITA could have reasonably predicted the stability of the claimed formulation using well-established scientific principles. By applying Stokes' law (for sedimentation rate) and equations for Brownian motion (for particle displacement), a POSITA would have calculated that the randomizing effect of Brownian motion on 200 nm particles would overcome the tendency to sediment over a three-day period. This calculation demonstrated that the claimed stability was not only expected but scientifically confirmable.

6. Relief Requested

  • Petitioner requested the institution of an inter partes review and the cancellation of claims 1-27 of Patent 8,853,260 as unpatentable under 35 U.S.C. §103.