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 volume. The core technology is a coding scheme that uses a combination of signal wavelength (color) and signal intensity to create a unique signature for each analyte, allowing for the unambiguous decoding of cumulative signals to determine the presence or absence of multiple targets.

3. Grounds for Unpatentability

Ground 1: Obviousness over Jouvenot and Larson - Claims 1-2, 5-11, 13-15, and 18 are obvious over Jouvenot in view of Larson.

• Prior Art Relied Upon: Jouvenot (Patent 9,921,154) and Larson (Application # 2011/0250597).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Jouvenot teaches the foundational concept of the ’797 patent: a digital PCR system that distinguishes multiple targets within a single color channel by using different signal intensities. Jouvenot's Example 1 demonstrates detecting two distinct targets and their combination based on three discrete intensity levels (e.g., intensity 1 for target A, intensity 2 for target B, and intensity 3 for A+B). This establishes the core principle of encoding analytes by signal intensity at a given wavelength. Larson was asserted to teach a virtually identical scheme, confirming this was a known technique.
  • Motivation to Combine: The primary inventive step alleged in the ’797 patent is extending this single-channel, intensity-based encoding to a multi-channel system (specifically, at least four channels). Petitioner contended a person of ordinary skill in the art (POSITA) would be motivated to make this extension to increase the degree of multiplexing, a well-understood goal in the field. This motivation was allegedly explicit in both references. Jouvenot states its assays "may be extended in various ways," including using multiple channels for different targets. Larson repeatedly teaches that "adding multiple colors increases the number of possible reactions geometrically" and contemplates systems with up to 20 color channels.
  • Expectation of Success: A POSITA would have had a high expectation of success because the combination amounted to duplicating a known single-channel detection scheme across multiple, independent color channels. Petitioner argued this was a predictable design choice, not an inventive leap, particularly because, as the ’797 patent itself admits, multi-channel PCR instruments capable of detecting four or more colors were widely used and commercially available at the time.

Ground 2: Obviousness over Jouvenot, Larson, and Lehnen - Claims 1-2, 5-11, 13-15, and 18 are obvious over Jouvenot and Larson in further view of Lehnen.

• Prior Art Relied Upon: Jouvenot (Patent 9,921,154), Larson (Application # 2011/0250597), and Lehnen (European Patent 0,594,763).

• Core Argument for this Ground:

  • Prior Art Mapping: This ground was presented as an alternative to address the specific mathematical formula recited in claim 1: M=C*log2(F+1). This formula describes a system where signal intensities for different analytes follow a geometric progression (e.g., 1, 2, 4, 8). Petitioner argued that if Jouvenot's linear intensity scheme (1, 2, 3) was deemed insufficient to teach this specific relationship, Lehnen explicitly discloses it. Lehnen teaches a multiplexing system using binary, power-of-2 encoding (proportions of 1:2:4:8) based on signal intensity to ensure that every possible combination of analytes produces a "uniquely interpretable" sum.
  • Motivation to Combine: A POSITA, seeking to build the higher-plex system suggested by Jouvenot and Larson, would have been motivated to incorporate Lehnen’s more robust encoding scheme. Lehnen’s power-of-2 progression directly addresses the challenge of creating an unambiguous decoding system, which is the stated purpose of the ’797 patent’s claimed formula. A POSITA would combine Lehnen's superior mathematical approach with the practical system of Jouvenot/Larson to create a predictable and reliable high-plex assay.
  • Expectation of Success: Success would be expected, as Lehnen provides the precise algorithm for signal assignment, and Jouvenot teaches methods for modulating signal intensity (e.g., by varying the number of fluorophores on a probe) to achieve the desired progression.

• Additional Grounds: Petitioner asserted numerous additional obviousness challenges for dependent claims. These grounds relied on the core combinations of Jouvenot and Larson (with or without Lehnen) and added various secondary references to show that other claimed elements were well-known, standard components. These included: Larson, Brabetz, and Lakowicz for specific blue, green, and red fluorophores; Brabetz, Maltezos, and Neuzil for band-pass filters; Maltezos, Dube, and Wittwer for photodetectors; and Maltezos and Slepnev for coupling a display to the system for data visualization.

4. Key Claim Construction Positions

• For the purposes of the petition, Petitioner stated it would adopt the claim interpretations used by the Patent Owner in parallel district court litigation.
• Petitioner noted that the claim term "F" (maximum cumulative intensity) appears to be indefinite due to inconsistencies between claims (e.g., claim 1 requires a minimum F=3, while claim 4 allows F=1). However, Petitioner argued this does not preclude an obviousness determination, as the prior art teaches values of F that fall squarely within the scope of the claims.
• The term "analyte specific hybridization probes" was construed according to its express definition in the ’797 patent as "a reagent capable of generating a signal in the presence of a particular analyte and that hybridizes to the analyte."
• The phrase "associating, for each analyte, a first value" was construed to mean associating analytes with signal intensity values corresponding to a geometric progression (e.g., 1, 2, 4, 8), as dictated by the patent’s disclosure and mathematical formulas.

5. Relief Requested

• Petitioner requests institution of an inter partes review and cancellation of claims 1-2, 5-11, 13-15, and 18 of Patent 12,168,797 as unpatentable under 35 U.S.C. §103.