DCT
1:20-cv-01116
AbCellera Biologics Inc v. Berkeley Lights Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: AbCellera Biologics Inc. (British Columbia, Canada) and The University of British Columbia (British Columbia, Canada)
- Defendant: Berkeley Lights, Inc. (Delaware)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP; Quinn Emanuel Urquhart & Sullivan, LLP
- Case Identification: 1:20-cv-01116, D. Del., 09/04/2020
- Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant is incorporated in Delaware.
- Core Dispute: Plaintiffs allege that Defendant’s Beacon® Optofluidic System, which is used for single-cell analysis and antibody discovery, infringes four patents related to microfluidic methods for assaying and culturing single cells.
- Technical Context: The technology relates to high-throughput microfluidic platforms that enable the rapid isolation, culture, and analysis of individual biological cells, a critical capability for accelerating pharmaceutical and antibody drug discovery.
- Key Procedural History: The complaint alleges that Plaintiffs put Defendant on notice of its patent estate via correspondence beginning on October 3, 2019. It further alleges that a named inventor on all four patents-in-suit, Dr. Anupam Singhal, is an employee of Defendant Berkeley Lights, a fact Plaintiffs assert is relevant to Defendant's knowledge of the patents. An initial complaint was filed by AbCellera on July 9, 2020, and was subsequently amended to add The University of British Columbia as a co-plaintiff.
Case Timeline
| Date | Event |
|---|---|
| 2010-07-07 | Earliest Priority Date for ’270 Patent |
| 2010-07-16 | Earliest Priority Date for ’768, ’737, and ’933 Patents |
| 2019-10-03 | AbCellera sends letter to Berkeley regarding its patent estate |
| 2020-07-09 | AbCellera files initial complaint against Berkeley |
| 2020-07-21 | U.S. Patent No. 10,718,768 issues |
| 2020-08-11 | U.S. Patent No. 10,738,270 issues |
| 2020-08-18 | U.S. Patent No. 10,746,737 issues |
| 2020-08-25 | U.S. Patent No. 10,753,933 issues |
| 2020-09-04 | Plaintiffs file Amended Complaint |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 10,718,768 - “Methods for assaying cellular binding interactions”
Issued July 21, 2020 (’768 Patent)
The Invention Explained
- Problem Addressed: The patent’s background section describes the low efficiency and time-consuming nature of conventional hybridoma technology for discovering and producing monoclonal antibodies, which requires sampling a vast diversity of antibody-secreting cells from an immune response (’768 Patent, col. 2:1-24).
- The Patented Solution: The invention provides a microfluidic method for rapidly assaying the binding interaction between a protein (e.g., an antibody) produced by a single cell and a biomolecule (e.g., an antigen). A single antibody-producing cell is retained in a micro-chamber, where its secreted antibody is exposed to a capture substrate; a fluid containing the target biomolecule is then flowed through the chamber to measure the binding kinetics, allowing for high-throughput screening directly from single cells (’768 Patent, col. 2:33-51, Abstract). Figure 12 of the patent illustrates a single antibody-secreting cell within a microfluidic chamber alongside antibody capture beads (’768 Patent, Fig. 12).
- Technical Importance: This method allows for the direct measurement of binding kinetics from antibodies secreted by single cells, bypassing the need for time-consuming clonal expansion required by traditional methods (Compl. ¶10).
Key Claims at a Glance
- The complaint asserts independent claim 1 (Compl. ¶42-44).
- The essential elements of claim 1 are:
- A method of assaying for a binding interaction between a secreted monoclonal antibody from a single antibody producing cell (APC) and an antigen.
- Retaining the single APC within a chamber with a specific volume (100 pL to 100 nL), a solid wall, and an aperture.
- Incubating the APC in the chamber to produce the antibody.
- Exposing the antibody to a first removeable capture substrate bound to an antigen capable of capturing the antibody.
- Incubating the antibody with the substrate to produce a bound antibody.
- Measuring the binding interaction between the bound antibody and the antigen.
- Lysing the single APC and capturing its nucleic acids on the removeable capture substrate.
U.S. Patent No. 10,738,270 - “System and method for microfluidic cell culture”
Issued August 11, 2020 (’270 Patent)
The Invention Explained
- Problem Addressed: The patent background describes the difficulty in obtaining robust, long-term growth of mammalian cells, particularly non-adherent suspension cells, in microfluidic devices, which is a barrier to high-throughput, single-cell biological studies (’270 Patent, col. 1:29-41; col. 2:20-34).
- The Patented Solution: The invention provides a microfluidic device with thousands of micro-chambers for culturing single cells. A key feature is a design where a single introduction port feeds a flow channel connected to the inlets of the numerous chambers, allowing for the delivery and exchange of cell culture medium to sustain cell growth and create clonal populations from single parent cells (’270 Patent, Abstract; col. 3:10-23). This architecture is designed to retain non-adherent cells while enabling nutrient perfusion.
- Technical Importance: This technology enables the long-term, high-throughput culture and analysis of individual non-adherent cells and their progeny, facilitating detailed studies of cellular heterogeneity and clonal selection (Compl. ¶10).
Key Claims at a Glance
- The complaint asserts independent claim 1 (Compl. ¶65-67).
- The essential elements of claim 1 are:
- A method for culturing single cells.
- Introducing a population of cells via a single introduction port into a microfluidic device comprising 1,600 to 20,000 microfluidic chambers.
- Each chamber has an inlet in fluid communication with a flow channel, which is in fluid communication with the single introduction port.
- Retaining single cells from the population in different chambers.
- Providing a cell culture medium to the chambers via the flow channel.
- Exchanging the cell culture medium in the chambers via the flow channel to create individual clonal cell populations, which are retained in the same chamber as their parent cell.
U.S. Patent No. 10,746,737 - “Methods for assaying cellular binding interactions”
Issued August 18, 2020 (’737 Patent)
- Technology Synopsis: The ’737 Patent addresses the same technical problem as the ’768 Patent: the inefficiency of traditional antibody discovery. It provides a similar microfluidic method for assaying binding interactions from a single cell retained in a chamber, but details a different sequence of steps for exposing the secreted antibody, capture substrate, and antigen (’737 Patent, Abstract).
- Asserted Claims: Independent Claim 1 (Compl. ¶86-88).
- Accused Features: The accused features are the antibody discovery workflows performed by Defendant’s Beacon® system, which allegedly involve assaying binding interactions of antibodies secreted from single cells in microfluidic chambers (Compl. ¶89-96).
U.S. Patent No. 10,753,933 - “Methods for assaying cellular binding interactions”
Issued August 25, 2020 (’933 Patent)
- Technology Synopsis: Like the ’768 and ’737 patents, the ’933 Patent addresses the inefficiency of traditional antibody discovery. It claims a method of assaying a binding interaction between an antibody from a single cell and an antigen within a microfluidic chamber, focusing on the core steps of retaining the cell, incubating it, exposing the secreted antibody to a capture substrate, and measuring the interaction (’933 Patent, Abstract).
- Asserted Claims: Independent Claim 1 (Compl. ¶110-112).
- Accused Features: The accused features are the single-cell antibody screening workflows performed by the Beacon® system (Compl. ¶113-118).
III. The Accused Instrumentality
Product Identification
- The accused instrumentalities are Defendant’s Beacon® Optofluidic System, associated OptoSelect™ Chips, the Culture Station™ System, and related software and reagents (Compl. ¶17, 23-24, 28).
Functionality and Market Context
- The complaint alleges the Beacon® system is an automated platform for antibody discovery and cell therapy development (Compl. ¶17). It is alleged to work by isolating individual cells in thousands of “NanoPen™” chambers on disposable OptoSelect™ chips (Compl. ¶16, 23). The complaint states that within these chambers, the system performs various assays on secreted proteins, such as antibodies, using bead-based and diffusion-based fluorescent techniques to characterize cell function (Compl. ¶26). A diagram included in the complaint illustrates bead-based assays for functional analysis and antigen specificity occurring within the NanoPen chambers (Compl., p. 6). The associated Culture Station™ is described as a module that allows for moving the OptoSelect™ chips out of the Beacon® system for longer-term culturing before returning them for further analysis (Compl. ¶28).
IV. Analysis of Infringement Allegations
’768 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| 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 isolates a single cell within a discrete NanoPen™ chamber, which allegedly has a volume of 250 picoliters (pL) and an opening to a channel. | ¶21, ¶46 | col. 14:18-24 |
| incubating the single APC within the chamber to produce a secreted monoclonal antibody | The system holds the single cell in the NanoPen™ chamber, allowing it to secrete antibodies for subsequent analysis. | ¶16, ¶47 | col. 4:4-6 |
| exposing the secreted monoclonal antibody to a first removeable capture substrate bound to an antigen, wherein the antigen is capable of capturing the secreted monoclonal antibody | The system utilizes bead-based assays where beads, allegedly functioning as a removeable capture substrate, are used to detect antigen-specific antibodies secreted by the cell. | ¶20, ¶27, ¶48 | col. 3:14-16 |
| incubating the secreted monoclonal antibody with the first removeable capture substrate to produce a bound antibody | The secreted antibodies are allowed to interact with and bind to the antigen-specific beads within the NanoPen™ chamber. | ¶19, ¶49 | col. 4:7-9 |
| measuring a binding interaction between the bound antibody and the antigen | The system performs fluorescent assays to measure the binding of the secreted antibody to the antigen on the bead substrate. | ¶26, ¶50 | col. 4:15-16 |
| lysing the single APC and capturing the nucleic acids of the single APC on the removeable capture substrate | The system is capable of lysing the cell within the NanoPen™ and capturing its nucleic acids for further analysis. | ¶27, ¶51 | col. 3:18-21 |
- Identified Points of Contention:
- Scope Questions: A central question may be whether the accused system’s process for analyzing nucleic acids meets the limitation "capturing the nucleic acids of the single APC on the removeable capture substrate." The claim language suggests the same substrate used for the antibody capture is used for nucleic acid capture. The complaint alleges the system can perform both functions (Compl. ¶27), but it will be a factual question whether it does so on the same substrate as required by the claim.
- Technical Questions: What evidence does the complaint provide that the accused bead-based assay uses a substrate "bound to an antigen" as opposed to a substrate that binds the antibody first, which is then exposed to a separate antigen solution? The complaint includes a diagram of an "Antigen Specific Bead Assay" that appears to show a bead coated with an antigen (Compl., p. 6), which may support the plaintiff's theory.
’270 Patent Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| introducing a population of cells via a single introduction port into a microfluidic device comprising a 1,600 to 20,000 of microfluidic chambers... | The accused OptoSelect™ chips allegedly contain thousands of NanoPen™ chambers (e.g., 1758, 3500, or 11k), which falls within the claimed numerical range. | ¶23, ¶25, ¶69 | col. 4:10-15 |
| wherein each microfluidic chamber comprises an inlet, the single introduction port is in fluid communication with a flow channel that is in fluid communication with the inlets of the microfluidic chambers | The NanoPen™ chambers are described as being arrayed along continuous channels and having a narrow opening to the channel, which allegedly serves as the inlet. | ¶25, ¶69 | col. 3:10-14 |
| wherein single cells of the population are retained in different microfluidic chambers... | The Beacon® system allegedly isolates individual cells and sequesters them into individual NanoPens™ for screening. | ¶16, ¶27, ¶70 | col. 3:10-14 |
| providing a cell culture medium to the plurality of microfluidic chambers via the flow channel and the inlets of the microfluidic chambers | The channels connected to the NanoPens™ allegedly allow for "nutrients and cellular waste diffusion," and the Culture Station™ provides media and fluidics. | ¶25, ¶28, ¶71 | col. 3:15-20 |
| exchanging the cell culture medium in the microfluidic chambers via the flow channel and the inlets... to create a plurality of individual clonal cell populations... | The system allegedly allows cells to grow into clonal populations within the NanoPen™ chambers while being supplied with nutrients from the channels. | ¶16, ¶72 | col. 3:20-23 |
- Identified Points of Contention:
- Scope Questions: The claim requires "exchanging the cell culture medium in the microfluidic chambers." The complaint alleges the accused system provides nutrients via "diffusion" from a continuous channel (Compl. ¶25). A likely point of dispute will be whether this passive diffusion of nutrients into the chamber and waste out of the chamber constitutes "exchanging" the medium in the chamber, or if the claim requires a more active flushing or replacement of the chamber's contents.
- Technical Questions: Representative images of the NanoPens on the nanofluidic chips show chambers arrayed along larger channels (Compl., p. 8). The complaint alleges these channels facilitate nutrient diffusion (Compl. ¶25). Evidentiary questions may arise regarding the actual rate and completeness of this diffusion process and whether it is sufficient to meet the "exchanging" limitation.
V. Key Claim Terms for Construction
Term from the ’768 Patent: "capturing the nucleic acids of the single APC on the removeable capture substrate"
- Context and Importance: This limitation appears in the final step of claim 1. The infringement case depends on whether the accused Beacon® system, after lysing a cell, captures its genetic material on the same substrate that was previously used for the antibody binding assay. The construction of this phrase, particularly whether "the" substrate refers back to the "first" substrate, will be critical.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: A party might argue that "the" does not strictly require the exact same physical object, but rather the same type of substrate, allowing for a two-bead process (one for antibody, one for nucleic acids) to meet the limitation.
- Evidence for a Narrower Interpretation: The patent specification describes "dual-function" beads capable of capturing both antibodies and nucleic acids (e.g., oligo(dT) beads conjugated with anti-mouse pAbs), and refers to collecting mRNA from the cell after the binding assay (’768 Patent, col. 11:41-52). This description of a single, dual-purpose substrate may support a narrower construction requiring both capture events to occur on the same physical bead.
Term from the ’270 Patent: "exchanging the cell culture medium in the microfluidic chambers"
- Context and Importance: This term is central to the method of culturing cells. Infringement will depend on whether providing nutrients via diffusion from an adjacent channel, as alleged in the complaint, satisfies this limitation. Practitioners may focus on this term because it distinguishes between passive nutrient refreshment and active fluid replacement.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent’s overall goal is to enable long-term cell culture. A party could argue that any method disclosed that achieves this goal, including diffusion from a channel that effectively refreshes the medium, falls within the scope of "exchanging."
- Evidence for a Narrower Interpretation: The term "exchanging" may imply a more active process of removing old medium from the chamber and replacing it with new medium. The specification discusses "perfusing a cell" and "flowing a perfusing fluid through the chamber," which could be interpreted as requiring active flow through the chamber itself, rather than just diffusion from an external channel (’270 Patent, Abstract; col. 4:10-15).
VI. Other Allegations
- Indirect Infringement: The complaint alleges both induced and contributory infringement for all four patents. Inducement is based on allegations that Defendant provides customers with instructions, user manuals, and support on how to operate the Beacon® system in an infringing manner (Compl. ¶29, 53, 74). Contributory infringement is based on allegations that the Beacon® system is a material part of the claimed inventions, is not a staple article of commerce suitable for substantial non-infringing use, and is especially adapted for infringing the patents (Compl. ¶57, 78).
- Willful Infringement: The complaint alleges willful infringement based on both pre-suit and post-suit knowledge. Pre-suit knowledge is alleged based on correspondence initiated by AbCellera on October 3, 2019 (Compl. ¶34, 59). Willfulness allegations are further supported by the assertion that a named inventor on all patents-in-suit, Dr. Anupam Singhal, is an employee of Defendant, and that his knowledge is attributable to the company (Compl. ¶36, 54, 62). The complaint also makes the factual allegation that Defendant "copied" the patents (Compl. ¶62, 83).
VII. Analyst’s Conclusion: Key Questions for the Case
The resolution of this dispute may turn on the following key questions:
- A core issue will be one of definitional scope: For the ’270 patent, can the claim term "exchanging the cell culture medium," which suggests fluid replacement, be construed to cover a process of passive nutrient and waste "diffusion" between the NanoPen™ chambers and an adjacent flow channel?
- A key question of claim interpretation and factual proof will arise for the ’768 patent: Does the limitation requiring the capture of nucleic acids "on the removeable capture substrate" require the use of the same physical substrate that captured the antibody, and if so, what evidence demonstrates that the accused Beacon® system performs the method in this specific manner?
- Finally, the case presents a significant question of intent and knowledge: Given the allegation that a named inventor on all asserted patents is an employee of the Defendant, the issue of willful infringement will likely be a central focus, raising the possibility of enhanced damages should infringement be found.