Bio Rad Laboratories Inc v. California Institute Of Technology

1. Case Identification

• Case #: IPR2024-01178
• Patent #: 10,770,170
• Filed: July 15, 2024
• Petitioner(s): Bio-Rad Laboratories, Inc.
• Patent Owner(s): California Institute of Technology
• Challenged Claims: 1-20

2. Patent Overview

• Title: Signal Encoding and Decoding in Multiplexed Biochemical Assays
• Brief Description: The ’170 patent describes methods for detecting multiple polynucleotide analytes in a single experiment, such as a droplet-based digital PCR assay. The core concept involves using fewer types of fluorophore labels than the number of analytes being detected, distinguishing them by mapping unique combinations of signal colors and intensities to the presence or absence of specific analytes.

3. Grounds for Unpatentability

Ground 1: Obviousness of Claims 1-9 and 20 over Saxonov

• Prior Art Relied Upon: Saxonov (Application # US 2013/0040841).
• Core Argument for this Ground:
  • Prior Art Mapping: Petitioner argued that Saxonov teaches all key elements of the challenged claims. Saxonov discloses a digital assay method that partitions a sample into droplets for multiplexed detection of polynucleotide targets. This method uses fluorophore-labeled probes and distinguishes between multiple targets by detecting signals based on combinations of color and, critically, different signal intensities. Petitioner contended that Saxonov’s teaching of using multiple colors (e.g., three or more channels) and multiple intensity levels for each color (generating 2^N distinct populations, where N is the number of targets) makes the claimed detection of "at least five" analytes an obvious extension of the disclosed principles. For instance, using four widely available fluorophore colors with two distinct intensity levels per color would allow for the unambiguous detection of eight analytes.
  • Motivation to Combine (for §103 grounds): As a single-reference ground, the motivation was inherent in Saxonov’s own teachings. Petitioner asserted a person of ordinary skill in the art (POSITA) would have been motivated to scale Saxonov’s multiplexing method to detect more analytes, such as five or more, to improve assay efficiency and throughput, a well-understood goal in the field.
  • Expectation of Success (for §103 grounds): A POSITA would have had a reasonable expectation of success because Saxonov provides a detailed framework for multiplexing using intensity and color, and four-color detection instruments were widely available and commonly used at the time.

Ground 2: Obviousness of Claims 1-9 and 20 over Saxonov in view of Larson

• Prior Art Relied Upon: Saxonov (Application # US 2013/0040841) and Larson (Application # US 2011/0250597).
• Core Argument for this Ground:
  • Prior Art Mapping: This ground was presented as an alternative, arguing that if Saxonov alone is found insufficient, Larson explicitly supplies the missing elements. Petitioner asserted Larson teaches higher-plex digital PCR assays in droplets, providing experimental data for 5-plex and 9-plex assays using combinations of signal colors and intensities to create a unique signature for each target. Larson’s concrete examples of detecting five or more analytes directly address the core limitation of the independent claims.
  • Motivation to Combine (for §103 grounds): A POSITA would combine these references as they both address the same problem in the same field: increasing the multiplexing capacity of droplet-based digital PCR. A POSITA would have looked to Larson’s demonstrated success with higher-plex assays to implement or scale the foundational methods taught in Saxonov.
  • Expectation of Success (for §103 grounds): The expectation of success was high because Larson provides working experimental data for a 9-plex assay using only two fluorophores, proving the viability of the combined color-and-intensity encoding strategy for at least five targets.

Ground 3: Obviousness of Claims 10-12 over Saxonov and Nakamura

• Prior Art Relied Upon: Saxonov (Application # US 2013/0040841) and Nakamura (Application # US 2011/0160288).

• Core Argument for this Ground:

  • Prior Art Mapping: This ground targeted dependent claims reciting specific applications. Petitioner argued that Saxonov provides the core multiplexing method, while Nakamura teaches performing PCR assays on specific biological sample types—such as cell-free, tumor, and viral nucleic acids—for cancer diagnostics.
  • Motivation to Combine (for §103 grounds): A POSITA would combine the teachings to apply Saxonov’s advanced multiplexing assay to the clinically significant sample types described in Nakamura. The motivation was to improve diagnostic tools for diseases like cancer by simultaneously detecting multiple relevant biomarkers, a clear goal in the medical diagnostics field.
  • Expectation of Success (for §103 grounds): Success would be expected, as applying a known detection method to well-known, clinically relevant sample types was a routine and predictable practice in molecular diagnostics.

• Additional Grounds: Petitioner asserted additional obviousness challenges for claims 10-19 based on combining Saxonov (or Saxonov and Larson) with secondary references including Silverbrook (for claims related to network transmission and clinical decisions), Maltezos (for computer implementation), and Oh (for remote server implementation).

4. Key Claim Construction Positions

• “each [of said at least 5] hybridization probe[s]”: Petitioner proposed this term means "each collection of hybridization probes specific for a polynucleotide analyte."
• “cumulative intensity measurement”: Petitioner proposed this term means "the signal or collection of signals from the probes that contact the present analytes."
• Petitioner noted it applied these constructions, which were identified in parallel district court litigation, to its unpatentability analysis.

5. Arguments Regarding Discretionary Denial

• Petitioner argued against discretionary denial under both 35 U.S.C. §325(d) and the Fintiv factors.
• Under §325(d): Petitioner contended that although Saxonov was cited in an Information Disclosure Statement (IDS) during prosecution, the Examiner never substantively analyzed its teachings or used it in any rejection. Therefore, the arguments presented in the petition are not the same or substantially the same as those previously considered by the USPTO.
• Under Fintiv: Petitioner argued that the factors weigh in favor of institution. It stated a stay of the parallel district court litigation is likely if the IPR is instituted, the district court case is in its early stages with no trial date set (and an estimated trial date years after a Final Written Decision would issue), and investment in the parallel proceeding has been modest.

6. Relief Requested

• Petitioner requests institution of an inter partes review and cancellation of claims 1-20 of the ’170 patent as unpatentable.