PTAB

IPR2018-01369

Thermo Fisher Scientific Inc v. Regents Of University Of California

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Aggregation Sensor and Solutions and Kits Comprising The Same
  • Brief Description: The ’673 patent discloses an aggregation sensor for detecting and analyzing biomolecules. The technology is based on a water-soluble conjugated polymer containing first (light-harvesting) and second (energy-accepting) optically active units, where aggregation of the polymer enhances energy transfer between the units, resulting in a detectable change in the sensor's emission color.

3. Grounds for Unpatentability

Ground 1: 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 describing fluorene-based copolymers) and Inganas (WO 03/096016).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Hou disclosed the core of the claimed invention: a non-water-soluble conjugated copolymer (PFO-DBT) with first (fluorene) and second (DBT) optically active units. Hou’s copolymer demonstrated increased intermolecular energy transfer and a corresponding color change upon aggregation (i.e., increased concentration), meeting the primary structural and functional limitations of claim 1. Inganas taught the use of conjugated polymers in biosensors where aggregation in response to analyte binding causes a detectable spectral change. Crucially, Inganas taught that making such polymers water-soluble by adding zwitterionic side-chain functionalities was a necessary step for use in aqueous biological environments.
    • Motivation to Combine: A POSITA would combine the references to adapt Hou's high-performance copolymer, originally developed for LEDs, into a superior biosensor. Hou's polymer offered a more predictable and quantifiable color change based on concentration compared to Inganas’s own polymer system. A POSITA would have been motivated to incorporate the zwitterionic solubilizing functionalities taught by Inganas into Hou's polymer to make it compatible with the aqueous environments required for biosensing, a well-understood and necessary modification in the field.
    • Expectation of Success: Petitioner contended that the chemistry for adding zwitterionic side chains to Hou’s fluorene-based polymer was routine and well-known. A POSITA would have reasonably expected that this modification would successfully render the polymer water-soluble without unduly impairing the known and desirable energy-transfer properties of Hou’s copolymer, thereby creating the claimed aggregation sensor with predictable results.

Ground 2: Claims 1, 2, and 6 are obvious over Hou, Bazan, and the Handbook

  • Prior Art Relied Upon: Hou (a 2002 journal article), Bazan (WO 2004/001379), and the Molecular Probes Handbook (a 2002 product handbook).
  • Core Argument for this Ground:
    • Prior Art Mapping: Hou provided the fundamental conjugated copolymer with the required ratio of first and second optically active units that changes color upon aggregation. Bazan taught using similar polyfluorene copolymers as Fluorescence Resonance Energy Transfer (FRET) donors in a DNA detection assay, explicitly teaching how to make them water-soluble with cationic side-chains for this purpose. Bazan also taught that such systems could amplify a fluorophore’s emission by "more than 25 times," meeting the two-fold increase limitation of claim 2. The Handbook, a standard reference, taught the routine selection of FRET acceptor fluorophores (e.g., Alexa Fluor 750) with appropriate spectral properties to pair with a given donor polymer.
    • Motivation to Combine: A POSITA would combine these references to improve upon Bazan's FRET-based biosensor. Incorporating Hou's copolymer would introduce a different emission color useful for multiplex assays and add a secondary, quantitative detection mechanism based on the polymer's intrinsic aggregation response. To do this, a POSITA would add Bazan's taught cationic functionalities to Hou's polymer to enable water solubility and DNA binding. The Handbook would then be the natural tool to consult for selecting and attaching a commercially available FRET acceptor that is spectrally compatible with Hou's polymer, as required for the system to function.
    • Expectation of Success: The synthetic methods for modifying Hou's polymer with Bazan's solubilizing groups were well-established. A POSITA would have had a high expectation of success in creating a water-soluble version of Hou's polymer that would function effectively as a FRET donor. Selecting a compatible acceptor fluorophore from the Handbook was a routine and predictable task for a POSITA designing a FRET assay.

4. Key Claim Construction Positions

  • Petitioner adopted claim constructions from a related district court litigation that were critical to its obviousness arguments.
  • "grafted to": The district court construed this term as "attached to," which encompasses embodiments where the first and second optically active units are part of the same polymer backbone. Petitioner argued this construction was essential, as it allows the copolymer structure disclosed in the Hou reference, which features both units in the main chain, to directly read on the claim limitation that was added during prosecution to overcome a rejection.

5. Arguments Regarding Non-Merits Termination

  • Petitioner argued that the Patent Owner, The Regents of the University of California, has waived any right to sovereign immunity against this IPR proceeding.
  • The waiver allegedly occurred when the Patent Owner affirmatively filed a patent infringement lawsuit in U.S. district court asserting the ’673 patent. By availing itself of the federal courts to enforce its patent rights, the Patent Owner subjected itself to all related statutory challenges to the patent’s validity, including IPR.

6. Relief Requested

  • Petitioner requests 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.