Thermo Fisher Scientific Inc v. Regents Of University Of California

1. Case Identification

• Case #: IPR2018-01367
• Patent #: 8,835,113
• Filed: July 10, 2018
• Petitioner(s): Thermo Fisher Scientific Inc., Life Technologies Corp., and Affymetrix, Inc.
• Patent Owner(s): The Regents of the University of California
• Challenged Claims: 1, 3-5, 7, 20, 22, and 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 ("aggregant"), such as a polynucleotide or polypeptide, in a sample. The method uses an "aggregation sensor" comprising a conjugated polymer with a plurality of "first optically active units" and one or more "second optically active units." The binding of an aggregant causes the polymer chains to aggregate, which increases energy transfer from the first to the second units, producing a detectable change in the polymer's optical properties.

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 (J. Mater. Chem., 2002) and Inganas (International Publication No. WO 03/096016).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Hou taught a conjugated copolymer (PFO-DBT) that meets the structural limitations of the claimed aggregation sensor. Hou’s copolymer comprised first optically active units (fluorene) and second optically active units (DBT) and exhibited a predictable, concentration-dependent change in its optical properties due to increased intermolecular energy transfer as polymer concentration increased—a phenomenon Petitioner asserted meets the district court’s construction of "aggregation." Inganas taught a method of using water-soluble conjugated polymers as biosensors to detect analytes ("aggregants"), such as proteins and DNA. Inganas’s method involved detecting an optical change in the polymer upon aggregation caused by the analyte binding to a receptor associated with the polymer.
  • Motivation to Combine: A Person of Ordinary Skill in the Art (POSITA) would have sought to improve upon Inganas’s biosensor, which exhibited less distinct and unpredictable optical changes. Petitioner contended that Hou’s copolymer, with its well-resolved emission peaks and clear correlation between concentration and color change, offered a more reliable and sensitive alternative. A POSITA would combine Hou's superior polymer with Inganas's method of use, including rendering the polymer water-soluble with zwitterionic side chains as taught by Inganas, to create an improved biosensor.
  • Expectation of Success: A POSITA would have had a reasonable expectation of success. The chemistry for attaching zwitterionic functionalities to fluorene-based polymers to confer water solubility was known and routine. It was also known that such modifications would not unduly impair the photoluminescent properties of the polymer, thus preserving the color-changing behavior described by Hou that was desirable for the biosensing application taught by Inganas.

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

• Prior Art Relied Upon: Hou (J. Mater. Chem., 2002), Bazan (International Publication No. WO 2004/001379), and the Molecular Probes Handbook (9th Ed., 2002).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner asserted this combination teaches using Hou's PFO-DBT copolymer in a biosensing method to detect a polynucleotide. Bazan taught using polyfluorene copolymers (similar to Hou’s) as FRET donors in assays to detect DNA. In Bazan’s system, the target DNA acts as an aggregant by bringing the cationic polymer and a FRET acceptor-labeled probe together, permitting energy transfer. The Molecular Probes Handbook provided a guide for a POSITA to select a suitable FRET acceptor dye (e.g., Alexa Fluor 750) to pair with the emission wavelength of Hou’s polymer. For dependent claims 3-5, Bazan taught that such systems could increase a fluorophore's emission by "more than 25 times," meeting the claimed two- to four-fold increase.
  • Motivation to Combine: A POSITA would have been motivated to incorporate Hou's polymer into Bazan's FRET-based DNA detection assay to improve its quantitative capabilities and enable multiplexing. Hou's polymer offered a secondary, concentration-dependent signal that could be used to confirm FRET results and quantify the DNA-polymer complex. To implement this, a POSITA would have been motivated to add the cationic side-chains taught by Bazan to Hou's polymer, enabling both water solubility and the electrostatic binding to DNA necessary for the assay.
  • Expectation of Success: A POSITA would have reasonably expected success in preparing and using the combined system. The synthetic routes, including Suzuki coupling methods used by Hou and referenced by Bazan, were well-established for creating such copolymers. A POSITA would expect that the resulting water-soluble polymer would bind to DNA, aggregate, and efficiently transfer energy to a properly selected FRET acceptor from the Handbook, thereby creating a functional and improved biosensor.

4. Key Claim Construction Positions

• Petitioner adopted claim constructions from the concurrent district court litigation for the purposes of the IPR. Two key constructions were central to its arguments:
  • "aggregation sensor": Construed as "a sensor for the detection and analysis of an aggregant," where "aggregation" is "a relative increase in the concentration of the second optically active subunit(s)...that increases the ability to transfer energy." This construction allowed Petitioner to map Hou’s teachings on concentration-dependent optical effects to the "aggregation" limitation.
  • "grafted to": Construed as "attached to." This construction was critical for asserting that Hou's copolymer, where both the first and second units are part of the main polymer backbone, met the claim limitation.

5. Arguments Regarding Discretionary Denial

• Petitioner argued that the Patent Owner, The Regents of the University of California, had waived any right to sovereign immunity. This argument was based on the Patent Owner having affirmatively availed itself of the U.S. court system by asserting the ’113 patent against the Petitioner in federal district court, thereby waiving immunity for related statutory proceedings like an IPR.

6. Relief Requested

• Petitioner requests institution of 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.