PTAB

IPR2016-00254

Bass J Kyle v. Fresenius Kabi USA LLC

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1. Case Identification

2. Patent Overview

  • Title: Sterile Pharmaceutical Composition of Propofol
  • Brief Description: The ’010 patent discloses sterile pharmaceutical compositions of the anesthetic agent propofol stored in a container. The invention is directed to ensuring the stability of propofol formulations, particularly those with reduced solvent content, by using specific non-reactive or inert container closures, such as siliconized bromobutyl or chlorobutyl rubber stoppers.

3. Grounds for Unpatentability

Ground 1: Claims 1, 13-15, 17, 18, 20, and 24-28 are obvious over Diprivan PDR, Farinotti, and the ’864 Patent.

  • Prior Art Relied Upon: Diprivan PDR (a 1997 Physician's Desk Reference entry), Farinotti (a 1994 journal article), and van den Heuvel (Patent 5,383,864).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the combination of the Diprivan PDR and Farinotti disclosed all elements of claim 1 except for the specific requirement of a siliconized closure. These references described the commercially available Diprivan product, a sterile propofol composition in a vial with a bromobutyl rubber stopper, with a composition (1% propofol, 10% soybean oil solvent) and stability profile that met the claim limitations. The only missing element, the siliconized bromobutyl rubber stopper, was explicitly taught by the ’864 patent for use with injectable pharmaceuticals to provide an inert sealing member that does not react with the formulation.
    • Motivation to Combine: A POSITA would combine these references not for the stability reasons argued by the patentee, but for well-known and unrelated design advantages. The art taught that siliconizing stoppers provided significant benefits in manufacturing, such as improved machinability, reduced friction for easier insertion into vials, and prevention of stoppers clumping together during production. These known processing efficiencies provided ample motivation to substitute the known siliconized stopper from the ’864 patent for the standard stopper used with the Diprivan product.
    • Expectation of Success: A POSITA would have had a high expectation of success. Silicone was widely known in the art as an inert, non-reactive material. Therefore, applying a silicone coating to the stopper of a known, stable product like Diprivan would not be expected to negatively impact its stability. The benefits of improved handling and manufacturing were predictable and achievable through a routine substitution.

Ground 2: Claims 1, 13-15, 17, 18, 20, and 24-28 are obvious over Diprivan PDR, Farinotti, and the WO’043 Patent.

  • Prior Art Relied Upon: Diprivan PDR, Farinotti, and Lundgren (WO 2000/012043).
  • Core Argument for this Ground:
    • Prior Art Mapping: The argument for Diprivan PDR and Farinotti is identical to Ground 1, establishing that these references teach a commercial propofol product meeting all claim limitations except for the siliconized stopper. The WO’043 patent was presented as an alternative to the ’864 patent, teaching a pharmaceutical composition in a container (vial, bottle, syringe) sealed with a siliconized bromobutyl rubber stopper. The WO’043 patent explicitly disclosed that siliconized stoppers imparted greater stability to the pharmaceutical composition compared to unsiliconized stoppers.
    • Motivation to Combine: The motivation was substantially similar to Ground 1, including the desire for improved manufacturing and handling characteristics. Additionally, the WO’043 patent provided an explicit motivation to use a siliconized bromobutyl rubber stopper to improve the stability of a packaged pharmaceutical formulation. A POSITA seeking to optimize the packaging for Diprivan would have been motivated by both the manufacturing advantages and the stability benefits taught in the art for siliconized closures.
    • Expectation of Success: A POSITA would have reasonably expected this combination to succeed. The WO’043 patent demonstrated that siliconized bromobutyl rubber stoppers were effective for packaging injectable drugs and could enhance stability. Combining this known closure technology with the known Diprivan formulation was a predictable and straightforward design choice with a high likelihood of success.

4. Key Claim Construction Positions

  • "from about 0 to about 10% by weight solvent for propofol": Petitioner accepted the Patent Owner's construction from a related litigation, interpreting the phrase to mean approximately 0% to 10% solvent, explicitly including compositions with exactly 10% solvent. This construction was critical because the primary prior art, commercial Diprivan, contained 10% soybean oil, bringing it squarely within the scope of the claims.
  • "siliconized": Petitioner argued this term has a well-known meaning: surface-treated or coated with a silicone polymer. This construction was necessary to connect the teachings of the ’864 and WO’043 patents, which disclose coating rubber stoppers with silicone, to the claim language.
  • "inert to propofol": Petitioner contended this phrase means having no significant reactivity with propofol, consistent with the patent's specification which uses "inert" and "non-reactive" interchangeably. This construction supported the argument that a POSITA would expect success, as silicone was known to be a chemically inert material.

5. Relief Requested

  • Petitioner requested the institution of an inter partes review and cancellation of claims 1, 13-15, 17, 18, 20, and 24-28 of the ’010 patent as unpatentable under 35 U.S.C. §103.