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

1. Case Identification

• Case #: IPR2018-01367
• Patent #: 8,835,113
• Filed: July 10, 2018
• Petitioner(s): Thermo Fisher Scientific Inc.
• Patent Owner(s): The Regents of the University of California
• Challenged Claims: 1, 3-5, 7, 20, 22, 25-27

2. Patent Overview

• Title: Methods and Compositions for Assaying a Sample for an Aggregant
• Brief Description: The ’113 patent discloses methods for detecting a target molecule (an "aggregant"), such as DNA or a polypeptide, using an "aggregation sensor." The sensor is a conjugated polymer with at least two types of optically active units, where energy transfer between the units changes upon aggregation, altering the sensor's fluorescent signal.

3. Grounds for Unpatentability

Ground 1: Obviousness over Hou and Inganas - Claims 1, 20, 22, 25, and 26 are obvious over Hou in view of Inganas.

• Prior Art Relied Upon: Hou (Q. Hou et al., J. Mater. Chem., 2002) and Inganas (WO 03/096016).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Hou taught the core of the claimed aggregation sensor. Hou disclosed a non-water-soluble conjugated copolymer (PFO-DBT) containing a first optically active unit (fluorene) and a second optically active unit (DBT). Critically, Hou showed that energy transfer from the first unit to the second unit increased as the polymer's concentration increased (i.e., upon aggregation), resulting in a predictable color change. Inganas taught the claimed method: using water-soluble conjugated polymers as biosensors to detect analytes (aggregants) through aggregation-induced changes in optical properties. Inganas specifically taught making polymers water-soluble by adding zwitterionic side chains for use in aqueous environments.
  • Motivation to Combine: A Person of Ordinary Skill in the Art (POSA) would combine Hou's copolymer with Inganas's biosensor method to create a more reliable and sensitive assay. Petitioner asserted that repurposing polymers from Light Emitting Diode (LED) applications (Hou's focus) for biosensors was a well-known practice. A POSA would have recognized that Hou's polymer, with its two well-resolved emission peaks and predictable, concentration-dependent color change, was superior to Inganas's polymer, which had a single broad peak and less predictable optical behavior. To use Hou’s polymer in Inganas’s aqueous biosensor system, a POSA would have been motivated to add the zwitterionic solubilizing functionalities taught by Inganas.
  • Expectation of Success: A POSA would have had a reasonable expectation of success. The synthesis of Hou's copolymer used standard, well-known Suzuki coupling methods. Modifying the fluorene units of Hou's polymer by adding zwitterionic side-chains, as taught by Inganas, was a routine chemical modification to achieve water solubility for biosensing applications. The resulting polymer would be expected to function as an aggregation sensor, as Hou already demonstrated the principle of concentration-dependent energy transfer.

Ground 2: Obviousness over Hou, Bazan, and the Handbook - Claims 1, 3-5, 7, and 27 are obvious over Hou, Bazan, and the Handbook.

• Prior Art Relied Upon: Hou (Q. Hou et al., J. Mater. Chem., 2002), Bazan (WO 2004/001379), and the Molecular Probes Handbook ("Handbook") (9th ed., 2002).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground builds upon Hou's disclosure of the core PFO-DBT conjugated copolymer. Bazan taught using similar polyfluorene copolymers as Fluorescence Resonance Energy Transfer (FRET) donors to detect target DNA. In Bazan's system, the polymer binds to the target DNA, bringing it into close proximity with a FRET acceptor dye (an "optically active species"), which causes a detectable signal. The Handbook, a standard reference for a POSA, provided detailed information on selecting and using FRET pairs, including specific dyes like Alexa Fluor that would be suitable acceptors for Hou's polymer.
  • Motivation to Combine: A POSA would combine these references to create an improved quantitative biosensor. A POSA would have been motivated to use Hou's superior polymer within Bazan's FRET-based assay framework, as Hou's polymer offered the advantage of a built-in, secondary confirmation mechanism (the aggregation-based color change) in addition to the FRET signal. This would allow for more robust and reliable quantification of the target aggregant (e.g., DNA). The Handbook was the natural and obvious resource a POSA would consult to select a suitable FRET acceptor dye (like Alexa Fluor 750) to pair with Hou's polymer's emission wavelength.
  • Expectation of Success: A POSA would have had a high expectation of success. The chemical modifications needed—adding cationic functionalities to Hou's polymer to make it water-soluble and enable DNA binding, as taught by Bazan—were routine. Selecting a FRET acceptor with an appropriate absorption spectrum from a standard resource like the Handbook to match the emission of Hou's polymer was a fundamental and well-understood task in the field. Bazan explicitly taught that its FRET system could increase a fluorophore's emission by "more than 25 times," providing a clear expectation of achieving the two- to four-fold increases required by dependent claims 3-5.

4. Key Claim Construction Positions

• Petitioner adopted the constructions from a concurrent district court litigation for key terms. These constructions were central to its obviousness arguments.
• "grafted to": Construed as "attached to." This construction allows Hou's copolymer, where the first and second units are part of the same main polymer chain, to meet the claim limitation.
• "aggregation": Construed broadly as "a relative increase in the concentration of the second optically active subunit(s) ... that increases the ability to transfer energy." This construction allowed the petitioner to argue that the concentration-dependent optical effects described in Hou constituted "aggregation" as claimed.

5. Arguments Regarding Discretionary Denial

• Petitioner argued that the Patent Owner, The Regents of the University of California, waived any right to sovereign immunity. The Patent Owner affirmatively availed itself of the U.S. district courts by filing a patent infringement lawsuit involving the ’113 patent against the Petitioner. Petitioner contended that having filed suit, the Patent Owner cannot selectively invoke immunity to bar the Petitioner from seeking IPR, which is a statutory right available to an accused infringer.

6. Relief Requested

• Petitioner requested institution of an inter partes review and cancellation of claims 1, 3-5, 7, 20, 22, and 25-27 of Patent 8,835,113 as unpatentable under 35 U.S.C. §103.