DCT

1:20-cv-00931

AbCellera Biologics Inc v. Berkeley Lights Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 1:20-cv-00931, D. Del., 09/01/2020
  • Venue Allegations: Venue is alleged to be proper in the District of Delaware because the Defendant is incorporated in the State of Delaware.
  • Core Dispute: Plaintiffs allege that Defendant’s Beacon® Optofluidic System, used for high-throughput single-cell analysis, infringes eight patents related to methods and systems for microfluidic cell culturing and for assaying cellular binding interactions.
  • Technical Context: The technology at issue involves microfluidic devices that can isolate, culture, and analyze single biological cells in nano-volume chambers, a process critical for accelerating antibody discovery and biopharmaceutical development.
  • Key Procedural History: The complaint details pre-suit correspondence beginning on October 3, 2019, wherein Plaintiffs allegedly put Defendant on notice of several of the patents-in-suit. The complaint also alleges that a named inventor on all asserted patents, Dr. Anupam Singhal, is an employee of the Defendant, a fact which may be central to allegations of pre-suit knowledge and willful infringement.

Case Timeline

Date Event
2010-07-07 Priority Date for ’408, ’936, ’018 Patents
2010-07-16 Priority Date for ’812, ’494, ’241, ’618, ’962 Patents
2018-10-02 U.S. Patent No. 10,087,408 Issues
2018-10-23 U.S. Patent No. 10,107,812 Issues
2019-04-30 U.S. Patent No. 10,274,494 Issues
2019-09-24 U.S. Patent No. 10,421,936 Issues
2019-10-03 Plaintiff sends first notice letter to Defendant
2019-11-05 U.S. Patent No. 10,466,241 Issues
2019-12-30 Defendant responds to Plaintiff's letter
2020-01-28 Plaintiff sends second notice letter to Defendant
2020-02-25 Defendant responds to Plaintiff's second letter
2020-03-03 U.S. Patent No. 10,578,618 Issues
2020-04-28 Plaintiff sends third notice letter to Defendant
2020-06-30 U.S. Patent No. 10,697,962 Issues
2020-07-07 U.S. Patent No. 10,704,018 Issues
2020-09-01 Complaint Filed

II. Technology and Patent(s)-in-Suit Analysis

U.S. Patent No. 10,107,812 - "Methods for assaying cellular binding interactions"

  • Patent Identification: U.S. Patent No. 10,107,812, titled "Methods for assaying cellular binding interactions", issued October 23, 2018 (Compl. ¶11).

The Invention Explained

  • Problem Addressed: The patent’s background section describes the inefficiency of conventional antibody production methods, such as hybridoma technology, which are time-consuming and expensive and do not permit the measurement of antibody-antigen binding kinetics from single cells (’812 Patent, col. 1:26-2:19).
  • The Patented Solution: The invention provides a method for assaying binding interactions at the single-cell level using a microfluidic device. A single protein-secreting cell is retained in a nano-volume chamber, and the secreted protein is captured on a substrate within the chamber. A fluid containing a biomolecule of interest is then flowed through the chamber, allowing for the measurement of the binding interaction between the secreted protein and the biomolecule (’812 Patent, Abstract; col. 3:23-36).
  • Technical Importance: This method enables high-throughput screening of potentially millions of cells to identify and characterize antibodies with specific therapeutic properties, significantly reducing the time required for drug discovery (Compl. ¶¶9-10).

Key Claims at a Glance

  • The complaint asserts infringement of at least independent claim 1 (Compl. ¶45).
  • The essential elements of claim 1 are:
    • A method of assaying for a binding interaction between a protein secreted by a cell and a biomolecule.
    • (a) Retaining the cell within a chamber having an inlet, an outlet, a solid wall, and a volume from 100 pL to 100 nL.
    • (b) Exposing the secreted protein to a capture substrate operable to bind the protein.
    • (c) Flowing a fluid containing the biomolecule through the inlet and out the outlet.
    • (d) Measuring a binding interaction between the secreted protein and the biomolecule (Compl. ¶47).

U.S. Patent No. 10,274,494 - "Methods for assaying cellular binding interactions"

  • Patent Identification: U.S. Patent No. 10,274,494, titled "Methods for assaying cellular binding interactions", issued April 30, 2019 (Compl. ¶12).

The Invention Explained

  • Problem Addressed: The patent addresses the same technical problem as the ’812 Patent: the limitations of conventional methods for generating and screening monoclonal antibodies, which are inefficient and cannot measure binding kinetics at the single-cell level (’494 Patent, col. 1:26-2:19).
  • The Patented Solution: The invention is a method for assaying a binding interaction using a microfluidic chamber, but it is structurally distinct from the ’812 Patent’s claims. This method retains a single antibody-producing cell (APC) within a chamber defined by a solid wall and an "aperture." A secreted antibody is exposed to a capture substrate, and a fluid containing a biomolecule is flowed into the chamber "via the aperture" to measure the binding interaction (’494 Patent, Abstract; col. 3:35-50).
  • Technical Importance: This patented solution offers an alternative microfluidic architecture for performing high-throughput, single-cell analysis, which is fundamental to modern antibody discovery platforms (Compl. ¶¶9-10).

Key Claims at a Glance

  • The complaint asserts infringement of at least independent claim 1 (Compl. ¶66).
  • The essential elements of claim 1 are:
    • A method of assaying for a binding interaction between an antibody produced by a single antibody producing cell (APC) and a biomolecule.
    • (a) Retaining the single APC within a chamber having a volume from 100 pL to 100 nL, a solid wall, and an aperture defining an opening.
    • (b) Exposing the antibody to a capture substrate operable to bind the antibody.
    • (c) Flowing a fluid containing the biomolecule into the chamber via the aperture.
    • (d) Measuring a binding interaction between the antibody and the biomolecule (Compl. ¶68).

Multi-Patent Capsules

  • U.S. Patent No. 10,466,241

    • Patent Identification: U.S. Patent No. 10,466,241, "Methods for assaying cellular binding interactions", issued November 5, 2019 (Compl. ¶13).
    • Technology Synopsis: This patent describes a method for assaying a binding interaction between an antibody from a single cell and a biomolecule. The method involves retaining the cell in a chamber with an aperture, exposing the antibody to a capture substrate, and then "bringing a fluid volume" comprising the biomolecule into communication with the captured antibody to measure the interaction (Compl. ¶89).
    • Asserted Claims: At least independent claim 1 (Compl. ¶87).
    • Accused Features: The accused features are the use of the Beacon® system to perform single-cell binding assays in its NanoPen™ chambers (Compl. ¶¶90-94).

  • U.S. Patent No. 10,578,618

    • Patent Identification: U.S. Patent No. 10,578,618, "Methods for assaying cellular binding interactions", issued March 3, 2020 (Compl. ¶14).
    • Technology Synopsis: This patent claims a method for assaying a binding interaction between an antibody from a single antibody secreting cell (ASC) and an antigen. The method includes incubating the cell to produce an antibody, bringing an antigen into fluid communication, and exposing the antibody to a "removeable capture substrate" to measure the binding (Compl. ¶110).
    • Asserted Claims: At least independent claim 1 (Compl. ¶108).
    • Accused Features: The use of the Beacon® system with its NanoPen™ chambers and bead-based assays, which allegedly use removable capture substrates, to perform single-cell binding analysis (Compl. ¶¶111-117).

  • U.S. Patent No. 10,697,962

    • Patent Identification: U.S. Patent No. 10,697,962, "Methods for assaying cellular binding interactions", issued June 30, 2020 (Compl. ¶15).
    • Technology Synopsis: This patent describes a method for assaying a binding interaction that combines antibody analysis with genetic analysis. It claims exposing a secreted monoclonal antibody to a removable capture substrate "capable of binding the secreted monoclonal antibody and nucleic acids of the single APC," and then lysing the cell to capture its nucleic acids on the same substrate (Compl. ¶133).
    • Asserted Claims: At least independent claim 1 (Compl. ¶131).
    • Accused Features: The accused features are workflows on the Beacon® system that allegedly involve both detecting antibodies and then lysing the cell of interest in the NanoPen™ to capture nucleic acids for sequencing (Compl. ¶¶134-141, 31).

  • U.S. Patent No. 10,087,408

    • Patent Identification: U.S. Patent No. 10,087,408, "System and method for microfluidic cell culture", issued October 2, 2018 (Compl. ¶16).
    • Technology Synopsis: This patent claims a method of culturing a cell in a microfabricated device where the cell is retained in a chamber. The method requires that "gravitational forces acting on the cell to keep it at or near the retaining position exceed hydrodynamic forces acting on the cell to move it toward the outlet," allowing for perfusion without dislodging the cell (Compl. ¶157).
    • Asserted Claims: At least independent claim 1 (Compl. ¶155).
    • Accused Features: The use of the Beacon® system to sequester cells in NanoPens via gravity for screening and culturing, where fluid exchange occurs in the main channel without disturbing the retained cell (Compl. ¶¶158-162, 31).

  • U.S. Patent No. 10,421,936

    • Patent Identification: U.S. Patent No. 10,421,936, "System and method for microfluidic cell culture", issued September 24, 2019 (Compl. ¶17).
    • Technology Synopsis: This patent claims a method for selecting a cell by introducing a population into 1,600 to 20,000 microfluidic chambers via a single introduction port and flow channel. The method includes exchanging culture medium to create clonal populations and measuring a secreted cell product (Compl. ¶178).
    • Asserted Claims: At least independent claim 1 (Compl. ¶176).
    • Accused Features: The use of the Beacon® system's OptoSelect chips, which allegedly contain thousands of chambers (e.g., 1758 NanoPen chambers on one chip type), to introduce, culture, and screen large populations of cells (Compl. ¶¶179-184, 29).

  • U.S. Patent No. 10,704,018

    • Patent Identification: U.S. Patent No. 10,704,018, "System and method for microfluidic cell culture", issued July 7, 2020 (Compl. ¶18).
    • Technology Synopsis: This patent claims a method for culturing single cells by introducing them into a plurality of microfluidic chambers via a single port and flow channel. The method involves retaining single cells in different chambers and exchanging culture medium to create and culture individual clonal cell populations (Compl. ¶200).
    • Asserted Claims: At least independent claim 1 (Compl. ¶198).
    • Accused Features: The use of the Beacon® system and its OptoSelect chips to perform single-cell introduction, retention, and culturing in thousands of individual NanoPen chambers (Compl. ¶¶201-205, 27).

III. The Accused Instrumentality

  • Product Identification: The accused instrumentalities are Defendant’s Beacon® Optofluidic System, its associated OptoSelect™ Chips, reagents, software, and the Culture Station™ System (collectively, "the Beacon® system") (Compl. ¶¶21, 28, 32).
  • Functionality and Market Context: The complaint alleges the Beacon® system is an automated platform used for antibody discovery, cell line development, and other cell therapy workflows (Compl. ¶21). The system utilizes OptoSelect chips which contain thousands of micro-chambers called "NanoPen™ chambers" (Compl. ¶27). The complaint alleges that these chambers have a volume of 250 picoliters and are designed to isolate a single cell for culturing and assaying (Compl. ¶25). The complaint includes an image from Defendant's website illustrating the Beacon® system as a self-contained unit intended to replace a "roomful of equipment" (Compl. p. 6). The system allegedly performs various assays, including bead-based fluorescent binding assays, to screen cells that secrete specific antibodies (Compl. ¶¶24, 31). A provided schematic from Defendant's materials illustrates several "Assays That Run In Our NanoPen Chambers," including a Functional Assay and an Antigen Specific Bead Assay (Compl. p. 7). The complaint alleges that after screening, individual cells of interest can be lysed within the NanoPens to capture nucleic acids for sequencing or can be exported from the chip (Compl. ¶31).

IV. Analysis of Infringement Allegations

’812 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
(a) retaining the cell secreting the protein within a chamber having an inlet, an outlet, and a solid wall defining the chamber, wherein the volume of the chamber is from 100 pL to 100 nL The Beacon® system allegedly retains a single cell within a NanoPen™ chamber, which has a solid wall and an alleged volume of 250 picoliters. The chamber's opening to a channel allegedly serves as the inlet and outlet. ¶¶25, 29, 49 col. 13:17-25
(b) exposing the protein secreted by the cell to a capture substrate, wherein the capture substrate is in fluid communication with the protein secreted by the cell and wherein the capture substrate is operable to bind the protein secreted by the cell to produce a bound protein The system allegedly uses bead-based assays where polystyrene beads coated with antibodies act as capture substrates to bind proteins (e.g., antibodies) secreted by the cell in the NanoPen™. ¶¶30-31, 50 col. 3:37-43
(c) flowing a first fluid volume comprising the biomolecule through the inlet into the chamber and out the outlet, wherein the first fluid volume is in fluid communication with the capture substrate and the bound protein The system's microfluidics allegedly introduce fluids containing biomolecules (e.g., antigens) into the channels connected to the NanoPen™ chambers for performing binding assays. ¶¶24, 31, 51 col. 3:44-49
(d) measuring a binding interaction between the protein secreted by the cell and the biomolecule The system allegedly uses fluorescent assays to measure binding, which is detected as a "characteristic fluorescent bloom" on the capture beads. The complaint includes a schematic showing a "Fluorescent 'bloom' on polystyrene bead" (Compl. p. 10). ¶¶31, 52 col. 4:1-5
  • Identified Points of Contention:
    • Scope Questions: A primary question may be whether the NanoPen™ chamber, described as having a single "narrow opening to the channel" (Compl. ¶29), meets the claim limitation of "a chamber having an inlet, an outlet." Defendant may argue that a single opening cannot be both an inlet and an outlet as required by the plain language of the claim.
    • Technical Questions: The claim requires "measuring a binding interaction." The complaint alleges the accused system detects a "fluorescent bloom" (Compl. ¶31). A potential dispute is whether this qualitative detection of binding satisfies the "measuring" limitation, or if the claim requires a more quantitative analysis (e.g., of affinity or kinetics).

’494 Patent Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
(a) retaining the single APC within a chamber having a volume of from 100 pL to 100 nL, a solid wall, and an aperture that defines an opening of the chamber The Beacon® system allegedly retains a single antibody producing cell (APC) in a NanoPen™ chamber with a volume of 250 picoliters. The "narrow opening to the channel" is alleged to be the claimed aperture. ¶¶25, 29, 70 col. 13:26-30
(b) exposing the antibody produced by the APC to a capture substrate, wherein the capture substrate is in fluid communication with the antibody produced by the APC and wherein the capture substrate is operable to bind the antibody produced by the APC to produce a bound antibody The system allegedly uses bead-based assays where beads act as capture substrates to bind antibodies secreted by the single APC in the NanoPen™. ¶¶30-31, 71 col. 3:41-47
(c) flowing a first fluid volume comprising the biomolecule into the chamber via the aperture, wherein the first fluid volume is in fluid communication with the capture substrate and the bound antibody The system's microfluidics allegedly introduce fluids containing biomolecules into the channels, which then enter the NanoPen™ chamber via its opening (the alleged aperture) to perform binding assays. ¶¶24, 31, 72 col. 3:48-53
(d) measuring a binding interaction between the antibody produced by the APC and the biomolecule The system allegedly uses fluorescence to detect the binding of biomolecules to the antibodies captured on beads, observed as a fluorescent signal or "bloom." ¶¶31, 73 col. 4:1-5
  • Identified Points of Contention:
    • Scope Questions: The central dispute may focus on the term "flowing...via the aperture." Defendant may argue that the fluid exchange between the main channel and the NanoPen™ chamber occurs primarily via passive diffusion, not active "flowing" as required by the claim. The complaint describes the opening as being for "nutrients and cellular waste diffusion" (Compl. ¶29), which may support such an argument.
    • Technical Questions: As with the ’812 Patent, a question is whether the detection of a "fluorescent bloom" constitutes "measuring a binding interaction" as the claim may be construed to require.

V. Key Claim Terms for Construction

For the ’812 Patent

  • The Term: "a chamber having an inlet, an outlet"
  • Context and Importance: This term is critical because the accused NanoPen™ chamber is described as having a single "narrow opening" (Compl. ¶29). The infringement analysis will turn on whether this single physical structure can satisfy the claim requirement for two distinct elements: "an inlet" and "an outlet." Practitioners may focus on this term because it represents a potential structural mismatch between the claim language and the accused product.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification of the ’812 patent states that "The inlet and outlet may be the same or different channels" (’812 Patent, col. 13:17-18). This language may support an argument that a single physical port can function as both an inlet and an outlet at different times.
    • Evidence for a Narrower Interpretation: The plain language of "an inlet" and "an outlet" suggests two separate structures. Furthermore, figures in the patent, such as Figure 2, depict embodiments with physically distinct channels serving as the inlet and outlet, which may support a narrower construction requiring two separate ports (’812 Patent, Fig. 2).

For the ’494 Patent

  • The Term: "flowing a first fluid volume...into the chamber via the aperture"
  • Context and Importance: While the term "aperture" in the ’494 patent may better describe the accused NanoPen's "narrow opening" than the "inlet, an outlet" language of the ’812 patent, the infringement question shifts to the nature of fluid movement. The complaint itself describes the opening as being for "diffusion" (Compl. ¶29). The case may depend on whether passive diffusion constitutes active "flowing" as required by the claim.
  • Intrinsic Evidence for Interpretation:
    • Evidence for a Broader Interpretation: The specification of the ’494 patent may describe fluid communication broadly, stating that it can occur "through diffusion" (’494 Patent, col. 13:41-43). This could be used to argue that "flowing" encompasses diffusion-driven movement from the main channel into the chamber.
    • Evidence for a Narrower Interpretation: In other contexts, the specification may distinguish between active, pressure-driven flow and passive diffusion. Standard technical usage often implies that "flowing" involves bulk fluid movement, which could support an argument that diffusion is not included and that the accused system therefore does not meet this limitation.

VI. Other Allegations

  • Indirect Infringement: The complaint alleges both induced and contributory infringement for all asserted patents. Inducement is based on allegations that Defendant provides instructions, user manuals, and technical support that encourage customers to use the Beacon® system in an infringing manner (Compl. ¶¶33, 54, 56). Contributory infringement is based on allegations that the Beacon® system is a material part of the claimed inventions, is especially adapted for infringing use, and is not a staple article of commerce with substantial non-infringing uses (Compl. ¶58).
  • Willful Infringement: The complaint alleges willful infringement based on Defendant's alleged pre-suit knowledge of the patents. This knowledge is alleged to derive from two sources: (1) a series of notice letters sent by Plaintiff to Defendant beginning on October 3, 2019 (Compl. ¶38), and (2) the employment by Defendant of Dr. Anupam Singhal, who is a named inventor on all eight patents-in-suit and is alleged to have been involved in the development of the Beacon® system (Compl. ¶¶40, 55, 63).

VII. Analyst’s Conclusion: Key Questions for the Case

  • A core issue will be one of claim construction and scope: can the accused "NanoPen" chamber, which is described with a single "narrow opening," be found to meet the distinct structural limitations of the asserted claims? Specifically, this will involve determining whether a single opening can be both "an inlet, an outlet" (’812 patent) and whether passive exchange of reagents constitutes "flowing...via the aperture" (’494 patent).
  • A second key question will be one of scienter and damages: what is the legal impact of the Defendant's alleged pre-suit knowledge, particularly through its employment of a named inventor on the patents-in-suit? The resolution of this issue will be central to the claims of indirect and willful infringement and could substantially affect the potential damages award.
  • Finally, the case will present an evidentiary question of technical operation: does the accused system's method of detecting a "fluorescent bloom" to indicate a positive result satisfy the claim requirement of "measuring a binding interaction"? The court may need to determine if this constitutes a qualitative indication or a quantitative measurement, and which of these the claims require.