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IPR2018-01156

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

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1. Case Identification

2. Patent Overview

  • Title: Methods and Compositions for Detection and Analysis of Polynucleotides Using Light Harvesting Multichromophores
  • Brief Description: The ’817 patent describes a light-harvesting system for detecting biological analytes based on Förster Resonance Energy Transfer (FRET). The system uses a water-soluble, multichromophore conjugated polymer as an energy donor that, upon excitation, transfers energy to a nearby signaling chromophore, resulting in a significantly amplified fluorescence signal.

3. Grounds for Unpatentability

Ground 1: Claims 1 and 3 are obvious over Cardullo, McQuade, and LeClerc.

  • Prior Art Relied Upon: Cardullo (PNAS 85: 8790-8794 (1988)), McQuade (J. Am. Chem. Soc. 122: 12389-12390 (2000)), and LeClerc (WO 02/081735).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Cardullo teaches a FRET-based system for detecting nucleic acid hybridization in solution, using multiple small-molecule donor dyes (acridine orange) to create a modest "antenna effect" that increases energy transfer to an acceptor dye by a factor of ~2. McQuade teaches a light-harvesting sensor using a water-soluble, polycationic conjugated polymer that functions as a highly efficient multichromophore donor, achieving an approximate 10-fold increase in fluorescence from a signaling chromophore compared to direct excitation. LeClerc teaches that such water-soluble, cationic conjugated polymers bind to DNA in solution, making them suitable for use in aqueous assays like Cardullo's.
    • Motivation to Combine: A POSITA would combine these references to improve the sensitivity of Cardullo’s DNA detection system. Petitioner asserted a POSITA would replace Cardullo’s less efficient acridine orange donors with McQuade's highly efficient conjugated polymer to harness its superior "antenna effect" and amplification power. LeClerc provided the teaching that such polymers are compatible with and can bind to DNA in the solution-based environment of Cardullo's assay.
    • Expectation of Success: A POSITA would have had a high expectation of success because the combination involved substituting a known type of donor (small molecule) with another known, functionally similar, and superior type of donor (conjugated polymer) in an established FRET system. McQuade’s demonstration of a 10-fold signal increase provided a strong expectation of achieving the claimed >4-fold amplification, and LeClerc confirmed the operational compatibility of the components in a solution.

Ground 2: Claims 1 and 3 are obvious over Cardullo, LeClerc, and Harrison.

  • Prior Art Relied Upon: Cardullo (PNAS 85: 8790-8794 (1988)), LeClerc (WO 02/081735), and Harrison (J. Am. Chem. Soc. 122: 8561-8562 (2000)).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground relied on Cardullo and LeClerc for the same teachings as in Ground 1. In place of McQuade, Petitioner cited Harrison, which teaches a FRET system for "amplified sensing" using a water-soluble, polycationic conjugated polymer as a donor in an aqueous solution. Harrison demonstrated that the polymer's "antenna effect" resulted in an approximate 2.5-fold increase in fluorescence from an acceptor dye.
    • Motivation to Combine: The motivation was similar to Ground 1: to improve the sensitivity of Cardullo's FRET assay. A POSITA would be motivated by the general principle of amplified sensing using conjugated polymers, as taught by Harrison, to replace Cardullo’s donors with a conjugated polymer donor from LeClerc, which was known to be suitable for DNA detection.
    • Expectation of Success: Petitioner argued a POSA would expect success because the combination involved known and compatible components. Although Harrison only showed a 2.5-fold increase, Petitioner contended that achieving the claimed >4-fold amplification would have been a matter of routine optimization for a POSA (e.g., adjusting polymer length or selecting an optimal donor-acceptor pair), given the well-known principles of FRET and the "antenna effect" of conjugated polymers.

4. Key Claim Construction Positions

  • "direct excitation": Petitioner argued this term, as used in the claims, is indefinite based on an Office Action in a related patent's prosecution. There, the examiner found the phrase "vague and indefinite because it is unclear what the phrase 'direct excitation' means." For the purposes of the petition, Petitioner proposed construing the term to mean "direct excitation of the signaling chromophore," consistent with an amendment made by the Patent Owner to overcome the indefiniteness rejection in the related case.
  • "multichromophore system": Petitioner contended this term should be construed to mean "a polycationic multichromophore." This position was based on a District Court's construction in related litigation and language in the ’817 patent specification, which Petitioner argued constituted a clear disavowal of non-polycationic embodiments by repeatedly describing "the present invention" as using polycationic multichromophores.

5. Arguments Regarding Discretionary Denial

  • Petitioner argued that the Patent Owner, The Regents of the University of California, waived its right to sovereign immunity. The basis for this argument was that the Patent Owner had affirmatively availed itself of the U.S. district courts by filing a patent infringement lawsuit on a related patent (’799 patent) against the Petitioner. Petitioner asserted that this waiver extends to this IPR, which is a statutory right available to an accused infringer, and that allowing the Patent Owner to invoke immunity would be unfair.

6. Relief Requested

  • Petitioner requested the institution of an inter partes review and cancellation of claims 1 and 3 of Patent RE46,817 as unpatentable under 35 U.S.C. §103.