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IPR2018-01369

Thermo Fisher Scientific, Inc. v. The Regents of the University of California

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1. Case Identification

2. Patent Overview

  • Title: Aggregation Sensor and Solutions and Kits Comprising The Same
  • Brief Description: The ’673 patent is directed to an aggregation sensor for detecting aggregants (e.g., target biomolecules) in a sample. The sensor comprises a conjugated polymer with a plurality of first optically active units and at least one second optically active unit, where the second unit can receive energy from the excited state of the first unit.

3. Grounds for Unpatentability

Ground 1: Obviousness over Hou and Inganas - Claims 1, 3, 7-12, 14-17, and 19 are obvious over Hou in view of Inganas.

  • Prior Art Relied Upon: Hou (a 2002 journal article, J. Mater. Chem.) and Inganas (WO 03/096016).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the claimed invention is an obvious repurposing of known conjugated copolymers from light-emitting diode (LED) applications to biosensors. Hou taught a non-water-soluble conjugated copolymer (PFO-DBT) comprising a first optically active unit (fluorene) and a second optically active unit (DBT). Hou disclosed that these copolymers exhibited increased intramolecular and intermolecular energy transfer upon an increase in concentration (i.e., aggregation), which maps to the core limitations of independent claim 1. Inganas taught that for biosensor applications, conjugated polymers must be made water-soluble, and disclosed doing so by appending a plurality of zwitterionic side-chain functionalities. Petitioner contended that combining Hou's polymer with Inganas's solubilizing method renders all limitations of claim 1 obvious.
    • Motivation to Combine: A POSITA would combine Hou's polymer with Inganas's solubilization teachings to create a superior biosensor. Hou's copolymers exhibited well-defined, predictable, and ratiometric color-changing emissions upon aggregation, offering significant advantages over the less distinct and unpredictable optical properties of Inganas's own polymers. Using Hou's polymer in Inganas's biosensor framework would result in an assay that was more sensitive, reliable, and suitable for quantitative analysis, particularly for aggregation-based detection like antigen-antibody binding.
    • Expectation of Success: A POSITA would have had a reasonable expectation of success in modifying Hou's polymer. The chemistry for preparing the copolymer (Suzuki coupling) and for appending solubilizing side-chains was routine and well-understood. A POSITA would expect that adding zwitterionic functionalities as taught by Inganas would successfully render Hou's polymer water-soluble without unduly impairing its fundamental energy transfer properties, allowing it to function as an effective aggregation sensor in an aqueous environment.

Ground 2: Obviousness over Hou, Bazan, and the Handbook - Claims 1, 2, and 6 are obvious over Hou in view of Bazan and the Molecular Probes Handbook.

  • Prior Art Relied Upon: Hou (a 2002 journal article, J. Mater. Chem.), Bazan (WO 2004/001379), and the Molecular Probes Handbook (a 2002 publication).
  • Core Argument for this Ground:
    • Prior Art Mapping: Hou provided the core conjugated copolymer structure as described in Ground 1. Bazan taught using a similar polyfluorene copolymer, made water-soluble with cationic side-chains, as a Förster Resonance Energy Transfer (FRET) donor to detect a DNA target. This established the use of such polymers in an "aggregation sensor" context where binding to a target facilitates energy transfer. The Molecular Probes Handbook, a standard reference, taught the selection and chemical attachment of suitable FRET acceptor fluorophores. This combination allegedly renders claim 1 obvious, with the Handbook teaching the additional limitations of claims 2 and 6, which require energy transfer to a subsequent optically active species (e.g., a fluorophore) to increase its emission.
    • Motivation to Combine: A POSITA would have been motivated to use Hou's copolymer in Bazan's FRET-based assay to improve its performance. Hou's polymer offered a different emission color than Bazan's, which would be advantageous for developing multiplexed assays. Furthermore, Hou's polymer provided an independent, concentration-dependent signal change that could be used for more reliable quantification of the target, an improvement over relying solely on the FRET signal. The Handbook would be the natural resource to consult for selecting an appropriate FRET acceptor to pair with Hou's polymer.
    • Expectation of Success: A POSITA would have had a high expectation of success. Hou's polymer was chemically similar to Bazan's, ensuring general compatibility. The methods for rendering the polymer water-soluble with cationic side-chains were taught by Bazan and known in the art. The principles of FRET are well-established, and the Handbook provided detailed guidance on selecting and using FRET pairs, making the design of a functioning assay with Hou's polymer and a suitable fluorophore (e.g., Alexa Fluor 750) a routine optimization task.

4. Key Claim Construction Positions

  • Petitioner adopted several claim constructions from a co-pending district court litigation. The construction of "grafted to" as simply "attached to" was critical to the obviousness argument. This construction allows copolymers where the second optically active unit is part of the main polymer backbone (as in Hou's copolymer) to meet the claim limitation, countering a potential argument that "grafted" requires a side-chain structure.
  • The term "aggregation" was construed broadly to include any relative increase in concentration of the optically active subunits that increases energy transfer. This construction allowed Petitioner to argue that the concentration-dependent effects observed in Hou's non-biological system constituted "aggregation" as claimed.

5. Arguments Regarding Discretionary Denial

  • Petitioner argued that the Patent Owner, The Regents of the University of California, has waived any right to sovereign immunity. The basis for this argument is that the Patent Owner affirmatively asserted the ’673 patent against the Petitioner in federal district court. By availing itself of the federal courts to enforce its patent rights, the Patent Owner cannot then selectively invoke sovereign immunity to shield the patent from a statutory challenge like an IPR proceeding that is directly related to that enforcement action.

6. Relief Requested

  • Petitioner requested institution of an inter partes review and cancellation of claims 1-3, 6-12, 14-17, and 19 of Patent 8,110,673 as unpatentable under 35 U.S.C. §103.