PTAB

IPR2019-00566

Bio Rad Laboratories Inc v. 10X Genomics Inc

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Methods for Droplet-Based Sample Preparation
  • Brief Description: The ’468 patent discloses methods for preparing nucleic acid samples for downstream analysis. The core technology involves tagging nucleic acid analytes with oligonucleotide "barcodes" inside aqueous droplets generated by a microfluidic device, where the barcodes are provided on beads within the droplets.

3. Grounds for Unpatentability

Ground 1: Claims 1-4, 6-9, 11, 12, 21, and 22 are obvious over Samuels in view of Hinz

  • Prior Art Relied Upon: Samuels (Application # 2012/0220494) and Hinz (Application # 2010/0304982).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Samuels taught the core method of independent claim 1, including labeling nucleic acids in droplets using barcoded oligonucleotides attached to beads, employing a microfluidic co-flow system to generate the droplets, and using a sufficient number of oligonucleotides to encompass the claimed "at least 1,000,000" limitation. Samuels also disclosed that the barcodes are releasably attached and that all barcodes within a droplet share the same sequence. However, Petitioner contended Samuels did not explicitly require the use of porous beads. Hinz was introduced to supply this limitation, as it expressly taught the construction and use of porous gel beads (e.g., polyacrylamide) for nucleic acid analysis to increase the loading capacity of attached polynucleotides compared to non-porous beads.
    • Motivation to Combine: A POSITA practicing the method of Samuels would seek to optimize the number of barcode molecules attached to each bead to ensure sufficient signal for downstream analysis. Petitioner asserted that Hinz directly addressed this need by teaching that porous beads provide a higher loading capacity. A POSITA would therefore combine Hinz’s porous beads with Samuels’s system as a simple substitution of one known element for another to achieve the predictable result of increased barcode loading.
    • Expectation of Success: Petitioner argued a POSITA would have a high expectation of success because both references were in the same field of endeavor (droplet-based nucleic acid analysis) and Hinz’s porous beads were used for the identical purpose of acting as a support for oligonucleotide molecules. Hinz also provided detailed methods for preparing and functionalizing the beads.

Ground 2: Claims 1-4, 6-9, 11, 12, 21, and 22 are obvious over Samuels in view of Abate

  • Prior Art Relied Upon: Samuels (Application # 2012/0220494) and Abate (a 2009 journal article on Poisson encapsulation statistics).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground presented an alternative to Hinz for teaching the use of porous beads. As in Ground 1, Samuels provided the foundational method. Abate was cited for its disclosure of using porous, cross-linked polyacrylamide gel beads in microfluidic devices for biological assays. Abate taught that such beads can be functionalized with DNA fragments and are suitable for encapsulation in droplets. Further, Abate's disclosure of a microfluidic device with two cross-channel junctions—one to space particles and a second to add oil for encapsulation—was argued to map directly onto the claimed method of combining aqueous streams at a first junction before generating a droplet with an immiscible phase at a second junction.
    • Motivation to Combine: The motivation was similar to that for combining with Hinz. A POSITA implementing Samuels's method would be motivated to use the porous polyacrylamide beads from Abate to increase barcode capacity and improve the efficiency of biological assays, a specific focus of Abate. Abate’s teachings on using gel particles to overcome inefficient encapsulation would provide a further reason to incorporate its methods into the Samuels system.
    • Expectation of Success: A POSITA would have a high expectation of success because Abate provided detailed methods for preparing its gel particles, including the precise composition (10% polyacrylamide with 10% cross-linker). The application of these beads as supports for DNA fragments in droplet-based assays was directly analogous to their proposed use in the Samuels method.

4. Key Claim Construction Positions

  • "releasably attached": Petitioner proposed this term meant "wherein said bead is configured to release said at least 1,000,000 oligonucleotide molecules." Petitioner noted this was consistent with its position in a parallel ITC proceeding and argued the patent was invalid under this construction or the construction adopted by the Administrative Law Judge in that proceeding ("attached in a manner that allows the attached object to be released"). The argument relied on prior art teachings of cleaving biotin-streptavidin linkages with heat or using cleavable linkers.
  • "gel": Petitioner proposed that "gel" meant "a cross-linked material, whether linked by chemical bonds or crystallites or some other kind of junction, that exhibits no steady state flow." This construction was argued to be consistent with examples in the patent (polyacrylamide) and the plain and ordinary meaning a POSITA would understand, thereby encompassing the polyacrylamide gel beads taught by Hinz and Abate.

5. Relief Requested

  • Petitioner requested the institution of an inter partes review and the cancellation of claims 1-4, 6-9, 11, 12, 21, and 22 of the ’468 patent as unpatentable.