Bio Rad Laboratories Inc v. California Institute Of Technology

1. Case Identification

• Case #: IPR2025-01546
• Patent #: 12,168,797
• Filed: September 15, 2025
• Petitioner(s): Bio-Rad Laboratories, Inc.
• Patent Owner(s): California Institute of Technology
• Challenged Claims: 1-2, 5-11, 13-15, and 18

2. Patent Overview

• Title: Signal Encoding and Decoding in Multiplexed Biochemical Assays
• Brief Description: The ’797 patent describes a system for detecting multiple nucleic acid analytes in a single sample. The system uses a coding scheme that distinguishes analytes based on both the wavelength (color) and the cumulative intensity of fluorescent signals, governed by a specific mathematical formula relating the number of analytes, colors, and signal intensity.

3. Grounds for Unpatentability

Ground 1: Obviousness of Core System - Claims 1-2, 5-6, 10, and 18 are obvious over Jouvenot.

• Prior Art Relied Upon: Jouvenot (Patent 9,921,154), with supporting teachings from Larson (Application # 2011/0250597).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Jouvenot taught the core inventive concept: a multiplexed digital PCR system that distinguishes between two different targets within a single detection channel using different signal intensities. Jouvenot’s Example 1 and Figure 4 show a decoding scheme where intensity level 1 corresponds to a first target, intensity level 2 to a second target, and a cumulative intensity of 3 corresponds to both targets being present. Petitioner contended this is the same fundamental coding scheme claimed in the ’797 patent. The processor, detector, and sample chamber elements of claim 1 were also disclosed in Jouvenot’s system.
  • Motivation to Combine (Modify): Petitioner asserted that a person of ordinary skill in the art (POSITA) would have been motivated to expand Jouvenot’s single-channel, two-target system to the claimed four-channel system. Both Jouvenot and Larson explicitly stated that increasing the number of color channels was a known and desirable way to increase the degree of multiplexing. The ’797 patent itself acknowledged that instruments for detecting four colors were widely available and commonly used in the art.
  • Expectation of Success: A POSITA would have had a reasonable expectation of success in creating a four-channel system because it involved the simple replication of Jouvenot’s well-understood single-channel intensity-based detection method across multiple, independent color channels using standard, commercially available fluorophores and detectors.

Ground 2: Obviousness of Fluorophore Selection - Claims 6-9 are further obvious over Jouvenot in view of Larson, Brabetz, and/or Lakowicz.

• Prior Art Relied Upon: Jouvenot (Patent 9,921,154), Larson (Application # 2011/0250597), Brabetz (Patent 8,614,061), and Lakowicz (a 2006 publication).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground built upon the combination in Ground 1. To the extent Jouvenot did not explicitly disclose the specific fluorophore colors (blue, red) recited in claim 6, Petitioner argued that Larson, Brabetz, and Lakowicz all disclosed extensive lists of common, off-the-shelf fluorophores, including blue, green, yellow, and red dyes suitable for multiplex PCR. These references also disclosed fluorophores with the specific excitation and emission wavelengths recited in dependent claims 7, 8, and 9.
  • Motivation to Combine: A POSITA seeking to build the multi-channel system of Ground 1 would have been motivated to consult references like Larson, Brabetz, and Lakowicz to select spectrally distinct, well-known fluorophores. The motivation was to achieve higher degrees of multiplexing with minimal spectral overlap, a routine consideration in assay design.
  • Expectation of Success: Success was expected because the fluorophores disclosed in the secondary references were standard, commercially available reagents known to be effective and reliable for multiplex PCR applications like the one described in Jouvenot.

Ground 3: Obviousness of Geometric Progression - All challenged claims are obvious over Jouvenot in further view of Lehnen.

• Prior Art Relied Upon: Jouvenot (Patent 9,921,154) and Lehnen (European Patent Specification 0,594,763 B1).

• Core Argument for this Ground:

  • Prior Art Mapping: This ground was presented as an alternative to address the specific mathematical formula in claim 1, M=C*log2(F+1). Petitioner argued that to the extent Jouvenot’s intensity scheme (1, 2, 3) was not considered to teach the geometric (power-of-2) progression of intensities implied by the formula, Lehnen explicitly disclosed using binary, power-of-2 encoding (e.g., reagents in proportions of 1:2:4:8) for multiplexed assays.
  • Motivation to Combine: A POSITA implementing Jouvenot’s multiplexing system would have been motivated to adopt Lehnen’s power-of-2 intensity progression. Lehnen explicitly taught that this approach results in signals that are "uniquely interpretable," thereby ensuring the unambiguous identification of all possible analyte combinations, which is the stated goal of the ’797 patent.
  • Expectation of Success: A POSITA would have had a reasonable expectation of success in applying Lehnen’s intensity scheme to Jouvenot’s system, as Jouvenot itself taught methods for modulating signal intensity, such as by varying the number of fluorophores attached to a probe.

• Additional Grounds: Petitioner asserted numerous additional obviousness challenges for dependent claims 11, 13-15, and 18. These grounds relied on the same core arguments based on Jouvenot and Larson, but added further references (Maltezos, Dube, Wittwer, Neuzil, Oleksy, and Slepnev) to demonstrate the obviousness of incorporating standard, well-known optical components such as band-pass filters, photodetectors, and display monitors.

4. Key Claim Construction Positions

• Petitioner requested that claim terms be interpreted consistent with the Patent Owner's positions in parallel district court litigation to demonstrate invalidity even under the Patent Owner's purported constructions.
• Petitioner noted that the term “F” (maximum cumulative intensity) is likely indefinite due to internal inconsistencies in the claims. However, Petitioner argued this does not preclude an obviousness determination, as the prior art clearly teaches values of F (e.g., F=3) that fall within the scope of the claims as asserted by the Patent Owner.
• "Analyte-specific hybridization probes" was construed as "a reagent capable of generating a signal in the presence of a particular analyte and that hybridizes to the analyte," consistent with the patent's specification.

5. Relief Requested

• Petitioner requested the institution of an inter partes review and the cancellation of claims 1-2, 5-11, 13-15, and 18 of the ’797 patent as unpatentable.