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 in a Container
  • Brief Description: The ’010 patent relates to stable, sterile pharmaceutical formulations of the anesthetic propofol. The invention is specifically directed to storing these formulations in containers sealed with inert closures, such as siliconized bromobutyl or chlorobutyl rubber stoppers, to prevent the chemical degradation of propofol, particularly in formulations with low concentrations of soybean oil solvent.

3. Grounds for Unpatentability

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

  • Prior Art Relied Upon: Diprivan PDR (a 1997 Physician's Desk Reference entry), Farinotti (a 1994 journal article), and Patent 5,383,864 (the '864 Patent).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the combination of Diprivan PDR and Farinotti disclosed all elements of independent claim 1 except for the "siliconized" nature of the closure. Together, these references described the commercially available Diprivan product: a sterile 1% propofol and 10% soybean oil emulsion in a vial with a bromobutyl rubber stopper. Petitioner contended this prior art product inherently met the claimed stability requirements. The '864 patent was then introduced to teach the missing element, as it disclosed using "siliconized bromobutyl rubber" stoppers for sterile pharmaceutical compositions (specifically diazepam) to ensure stability during prolonged contact.
    • Motivation to Combine: A person of ordinary skill in the art (POSA) would combine the references to gain the well-known manufacturing and handling advantages of siliconized stoppers, such as improved machinability, reduced clumping, and lubricity for easier insertion into vials. These known process improvements would have provided ample motivation to substitute the known unsiliconized stopper of the Diprivan product with the known siliconized version taught by the '864 patent.
    • Expectation of Success: A POSA would have had a high expectation of success. The substitution was a routine modification of a known component to achieve a predictable improvement in manufacturing efficiency. Furthermore, because silicone was widely known to be a non-reactive and inert material, a POSA would expect that its use would not negatively impact the stability of the already-stable Diprivan formulation.

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

  • Prior Art Relied Upon: Diprivan PDR (a 1997 Physician's Desk Reference entry), Farinotti (a 1994 journal article), and Lundgren (International Publication No. WO 2000/012043) (the WO’043 Patent).
  • Core Argument for this Ground:
    • Prior Art Mapping: This argument was structurally identical to Ground 1, relying on Diprivan PDR and Farinotti for the base propofol formulation and its packaging. It substituted the '864 patent with the 'WO'043 patent to teach the "siliconized" limitation. The 'WO'043 patent taught a pharmaceutical composition for a thrombin inhibitor in vials sealed with a siliconized bromobutyl rubber stopper. Critically, 'WO'043 explicitly stated that this siliconized closure imparted greater stability to the composition than unsiliconized closures.
    • Motivation to Combine: The motivation was substantially the same as in Ground 1, focusing on known benefits. The 'WO'043 patent provided an explicit rationale for using siliconized bromobutyl stoppers to improve the stability of parenteral drug solutions. Petitioner argued a POSA would be motivated to apply this known, successful solution to another parenteral drug like Diprivan to achieve similar stability and handling benefits.
    • Expectation of Success: The expectation of success was high, as the combination involved applying a known technology (siliconized stoppers) to a known product (Diprivan) to achieve a predictable and desired result (maintaining or improving stability and processability). The 'WO'043 patent's success in a similar context further supported this expectation.

4. Key Claim Construction Positions

  • Petitioner noted it accepted the Patent Owner's constructions from a related litigation for the purposes of the inter partes review (IPR) to adopt the broadest reasonable interpretation.
  • "from about zero to about 10% by weight solvent for propofol": This phrase was construed to mean from approximately 0% to approximately 10% solvent by weight. This interpretation, accepted by Petitioner, explicitly includes compositions containing exactly 10% solvent, which is the concentration in the prior art Diprivan product.
  • "siliconized": This term was construed to mean surface-treated, coated, or manufactured with silicone or one or more siloxane polymers. This definition was based on technical dictionaries and publications in the field of parenteral drug packaging.
  • "inert to propofol": This phrase was construed to mean having no significant reactivity to propofol. This was based on the '010 patent's specification, which used the terms "inert" and "non-reactive" interchangeably and explained that an "inert" closure does not cause "significant" degradation.

5. Relief Requested

  • Petitioner requested the institution of an IPR and the cancellation of claims 1, 13-15, 17, 18, 20, and 24-28 of Patent 8,476,010 as unpatentable under 35 U.S.C. §103.