DCT
1:20-cv-01230
AbCellera Biologics Inc v. Berkeley Lights Inc
I. Executive Summary and Procedural Information
- Parties & Counsel:
- Plaintiff: AbCellera Biologics Inc. (British Columbia) and The University of British Columbia (British Columbia)
- Defendant: Berkeley Lights, Inc. (Delaware)
- Plaintiff’s Counsel: Morris, Nichols, Arsht & Tunnell LLP; Quinn Emanuel Urquhart & Sullivan, LLP
- Case Identification: 1:20-cv-01230, D. Del., 09/16/2020
- Venue Allegations: Venue is alleged to be proper in the District of Delaware because Defendant is a Delaware corporation and therefore resides in the state.
- Core Dispute: Plaintiffs allege that Defendant’s "Beacon®" Optofluidic System, used for antibody discovery, infringes patents related to microfluidic methods for assaying single-cell antibody secretions and linking them to genetic data.
- Technical Context: The technology involves high-throughput microfluidic screening of individual antibody-secreting cells, a process critical for accelerating the discovery of therapeutic antibodies and other biopharmaceuticals.
- Key Procedural History: The complaint alleges that Plaintiffs put Defendant on notice of its patent estate via correspondence beginning in October 2019. It further alleges that a named inventor on the patents-in-suit is an employee of the Defendant and was involved in developing the accused product. Plaintiffs have also filed prior lawsuits against Defendant asserting infringement of related patents.
Case Timeline
| Date | Event |
|---|---|
| 2010-07-16 | Priority Date for ’376, ’377, and ’378 Patents |
| 2019-10-03 | AbCellera alleges it sent a notice letter to Berkeley |
| 2019-12-30 | Berkeley allegedly responded to AbCellera's letter |
| 2020-01-28 | AbCellera alleges it sent a second letter to Berkeley |
| 2020-02-25 | Berkeley allegedly responded to AbCellera's letter |
| 2020-04-28 | AbCellera alleges it sent a third notice letter to Berkeley |
| 2020-07-09 | AbCellera filed a prior complaint against Berkeley on related patents |
| 2020-08-25 | AbCellera filed a second prior complaint against Berkeley on related patents |
| 2020-09-15 | Issue Date for U.S. Patent No. 10,775,376 |
| 2020-09-15 | Issue Date for U.S. Patent No. 10,775,377 |
| 2020-09-15 | Issue Date for U.S. Patent No. 10,775,378 |
| 2020-09-16 | Complaint Filing Date |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 10,775,376 - "Methods for assaying cellular binding interactions"
The Invention Explained
- Problem Addressed: The patent’s background section describes the inefficiency of conventional antibody production, such as hybridoma technology, which is time-consuming and requires costly clonal expansion to produce sufficient antibodies for screening (’376 Patent, col. 1:47-66, col. 2:1-22). Existing devices could estimate antibody dissociation constants but could not measure full binding kinetics from single cells (col. 2:23-28).
- The Patented Solution: The invention provides a microfluidic method to analyze antibodies from a single antibody-secreting cell (ASC). The method involves retaining a single ASC within a very small chamber, allowing it to secrete antibodies, and exposing those antibodies to a "removeable capture substrate" (such as a bead) within the same chamber (col. 2:32-46; Abstract). A fluid containing a target antigen is then flowed through the chamber, and the binding interaction between the captured antibody and the antigen is measured to determine binding characteristics (col. 2:40-46).
- Technical Importance: This technology allows for the rapid, high-throughput screening and functional characterization of antibodies from millions of individual cells without the need for traditional, slow cultivation and expansion methods (Compl. ¶10).
Key Claims at a Glance
- The complaint asserts independent claim 1 (Compl. ¶41).
- The essential elements of claim 1 include:
- retaining a single ASC within a chamber of less than 500 pL with a solid wall and an aperture.
- incubating the ASC to produce a secreted antibody.
- bringing a fluid with an antigen into communication with the secreted antibody.
- exposing the secreted antibody to a removeable capture substrate that is in fluid communication and can bind the antibody.
- incubating the antibody with the substrate to produce a bound antibody.
- measuring the binding interaction between the secreted antibody and the antigen.
- The complaint does not explicitly reserve the right to assert dependent claims for this patent.
U.S. Patent No. 10,775,377 - "Methods for assaying cellular binding interactions"
The Invention Explained
- Problem Addressed: The patent addresses the same problem as the ’376 Patent: the inefficiency of prior art methods for screening single antibody-producing cells for desired functional properties (’377 Patent, col. 1:47-66).
- The Patented Solution: This invention builds upon the method of the ’376 Patent by adding a crucial final step. After assaying the secreted antibody's binding to an antigen on a first capture substrate, the method involves lysing the single cell and capturing its nucleic acids on a second removeable capture substrate (’377 Patent, Claim 1, col. 32:20-22). This process directly links the observed antibody function (e.g., binding affinity) with the genetic sequence that codes for that specific antibody, all from the same single cell (col. 3:24-35).
- Technical Importance: By pairing functional data with genetic data from the same cell, this method enables the rapid identification and subsequent cloning of rare, high-performing antibodies for therapeutic development (Compl. ¶10).
Key Claims at a Glance
- The complaint asserts independent claim 1 (Compl. ¶64).
- The essential elements of claim 1 include:
- retaining a single antibody producing cell (APC) in a chamber (100 pL to 100 nL).
- incubating the APC to produce a secreted monoclonal antibody.
- exposing the antibody to a first removeable capture substrate bound to an antigen.
- determining if the antibody binds the antigen.
- lysing the single APC and capturing its nucleic acids on a second removeable capture substrate.
- The complaint does not explicitly reserve the right to assert dependent claims for this patent.
U.S. Patent No. 10,775,378 - "Methods for assaying cellular binding interactions"
Technology Synopsis
This patent claims a method similar to the ’376 and ’377 patents for analyzing a secreted antibody from a single cell in a microfluidic chamber. The claimed method involves capturing the secreted antibody on a first removeable substrate, incubating them to form a bound antibody, and then exposing that bound antibody to an antigen to determine binding (’378 Patent, Claim 1). Like the ’377 patent, it also includes the subsequent step of lysing the cell and capturing its nucleic acids on a second removeable capture substrate (col. 20:1-4).
Asserted Claims
Independent claim 1 is asserted (Compl. ¶86).
Accused Features
The complaint alleges that Berkeley's "Beacon®" system, which isolates single cells, performs binding assays, and can lyse cells for nucleic acid capture, infringes this patent (Compl. ¶¶15-32, 89-96).
III. The Accused Instrumentality
Product Identification
The accused products and services include the Berkeley Lights, Inc. "Beacon®" Optofluidic System, associated "OptoSelect™" chips (e.g., 1750, 3500, and 11k models), the "Culture Station™" System, and related reagents and software (Compl. ¶¶16, 23, 27).
Functionality and Market Context
- The complaint alleges the "Beacon®" system is an automated platform for antibody discovery that isolates individual antibody-secreting cells in thousands of micro-chambers called ""NanoPen™"" chambers on its "OptoSelect" chips (Compl. ¶¶16, 22). Each chamber is alleged to have a volume of 250 picoliters (Compl. ¶20). The complaint includes a diagram illustrating various assays, such as a "Ligand Blocking Assay" and "Antigen Specific Bead Assay," performed within these chambers (Compl. p. 6).
- Within these chambers, the system is alleged to screen plasma B cells using binding and functional assays to identify promising antibody candidates (Compl. ¶18). The system allegedly uses a "bead-based, two-color fluorescent binding assay" to detect antigen-specific antibodies (Compl. ¶26). The complaint further alleges that after identification, individual cells can be lysed within the NanoPens, and their nucleic acids captured for analysis and sequencing (Compl. ¶26). A schematic in the complaint depicts this bead-based assay design for detecting IgG secretion and antigen specificity (Compl. p. 9).
- The complaint positions the "Beacon®" system as a direct competitor in the high-throughput, single-cell antibody discovery market (Compl. ¶¶9-10, 16).
IV. Analysis of Infringement Allegations
10,775,376 Infringement Allegations
| Claim Element (from Independent Claim 1) | Alleged Infringing Functionality | Complaint Citation | Patent Citation |
|---|---|---|---|
| retaining the single ASC within a chamber having a volume of less than 500 pL, a solid wall, and an aperture that defines an opening of the chamber | The "Beacon®" system isolates a single antibody-secreting cell in a "NanoPen™" chamber, which has a volume of 250 pL and an opening to a channel. | ¶¶20, 24, 45 | col. 14:39-42 |
| incubating the single ASC within the chamber to produce a secreted antibody | The system holds the single cell in the "NanoPen" chamber, where it is cultured to allow for secretion of antibodies for subsequent analysis. | ¶¶18, 22, 46 | col. 14:5-10 |
| bringing a first fluid volume comprising the antigen in fluid communication with the secreted antibody | The "Beacon®" system performs assays, including an "Antigen Specific Bead Assay," which involves introducing antigens into the "NanoPen" chambers containing the secreted antibodies. | ¶¶19, 26, 47 | col. 12:1-4 |
| exposing the secreted antibody to a removeable capture substrate...operable to bind the secreted antibody | The system uses bead-based fluorescent assays where beads (the capture substrate) are used to detect secreted antibodies from cells sequestered in the NanoPens. | ¶¶25, 26, 48 | col. 15:3-14 |
| incubating the secreted antibody with the removeable capture substrate to produce a bound antibody | The system incubates the cells and beads together to allow secreted antibodies to bind to the beads. | ¶¶18, 26, 49 | col. 12:15-20 |
| measuring a binding interaction between the secreted antibody and the antigen | The system performs "bead and diffusion-based fluorescent assays" to score secreted antibodies, which can produce a "characteristic fluorescent bloom" indicating a binding interaction. | ¶¶25, 26, 50 | col. 13:42-54 |
Identified Points of Contention
- Scope Questions: A potential point of dispute may be the interpretation of "chamber." The complaint alleges the NanoPens have a "narrow opening to the channel" (Compl. ¶24). The defense may argue this constant fluidic communication differs from the "enclosed space" with a distinct "aperture" described in the patent, potentially impacting how the assay steps are performed and isolated.
- Technical Questions: The claim requires exposing the "secreted antibody" to a capture substrate. The complaint describes the "Beacon" workflow where cells and beads are loaded and incubated (Compl. ¶¶18, 26). The precise sequence of events within the automated "Beacon®" system—whether beads capture antibodies that are already free in solution versus capturing them as they are secreted—may become a key factual question.
10,775,377 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... | The "Beacon®" system isolates a single cell in a "NanoPen™" chamber, which has a volume of 250 pL (0.25 nL), falling within the claimed range. | ¶¶20, 68 | col. 8:14-16 |
| incubating the single APC within the chamber to produce a secreted monoclonal antibody | The system cultures the single cell in the "NanoPen" chamber, allowing it to secrete antibodies for assaying. | ¶¶18, 22, 69 | col. 14:5-10 |
| exposing the secreted monoclonal antibody to a first removeable capture substrate bound to an antigen | The "Beacon®" system is alleged to use bead-based assays, such as the "Antigen Specific Bead Assay," where beads are functionalized with antigens to capture secreted antibodies. | ¶¶19, 26, 70 | col. 3:5-9 |
| determining whether the secreted monoclonal antibody binds the antigen | The system uses fluorescent assays that produce a "fluorescent bloom" to detect and score the binding of secreted antibodies to the antigen-coated beads. | ¶¶25, 26, 71 | col. 2:43-46 |
| lysing the single APC and capturing the nucleic acids of the single APC on a second removeable capture substrate | The complaint alleges that after identification, cells of interest can be lysed in the NanoPens and their nucleic acids captured for further analysis and sequencing. | ¶¶26, 72 | col. 3:24-35 |
Identified Points of Contention
- Scope Questions: The claim recites a "first removeable capture substrate" and a "second removeable capture substrate." The complaint alleges the "Beacon" system can capture both antibodies and nucleic acids (Compl. ¶26). It does not specify if this is done using two distinct substrates as recited in the claim, or a single substrate with dual functionality. This raises the question of whether a single dual-function bead can meet the "first" and "second" substrate limitations.
- Technical Questions: The infringement allegation hinges on whether the "Beacon®" system is used to perform the full sequence of claimed steps, including both the functional antibody assay and the subsequent cell lysis and nucleic acid capture. Evidence of customers using the system for this complete workflow will be central.
V. Key Claim Terms for Construction
Term: "removeable capture substrate"
(appears in asserted claims of ’376, ’377, and ’378 patents)
- Context and Importance: This term is central to the infringement theory, which relies on Defendant's use of bead-based assays (Compl. ¶26). The definition will determine if Berkeley's beads qualify and if the claims require a physically distinct, particulate substrate that can be removed from the chamber, or if other structures could suffice.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The specification states a capture substrate "is meant to encompass a wide range of substrates capable of capturing a protein or biomolecule of interest," including microspheres, nanospheres, or other microparticles (’376 Patent, col. 15:3-9). This language suggests flexibility beyond a single type of object.
- Evidence for a Narrower Interpretation: The patent’s detailed examples and figures consistently depict beads as the capture substrate (e.g., ’376 Patent, Fig. 12, Fig. 15, col. 11:35-42). A defendant may argue that the invention, as actually described and enabled, is limited to these specific embodiments.
Term: "a first removeable capture substrate" and "a second removeable capture substrate"
(’377 Patent, Claim 1)
- Context and Importance: Practitioners may focus on this phrasing because the infringement case for the ’377 Patent requires showing that the accused system uses two distinct capture substrates—one for the antibody and another for the nucleic acids. If Berkeley's system uses a single bead with dual functionality (capturing both), the case may turn on whether one object can satisfy two separate claim limitations.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation (One Bead Can Be Both): The specification describes preparing "dual-capture (i.e., dual-function) beads" capable of capturing both antibodies and mRNA, suggesting the inventors contemplated a single substrate performing both roles (’376 Patent, Fig. 14; col. 11:35-38). Plaintiffs may argue that one dual-function bead can be considered to meet both limitations sequentially.
- Evidence for a Narrower Interpretation (Two Beads Required): The plain language of the claim recites "a first" and "a second" substrate, which typically implies two structurally distinct items. A defendant may argue that this language requires two separate beads or substrates to be used in the process, and that a single dual-function bead does not meet the limitation.
VI. Other Allegations
Indirect Infringement
The complaint alleges inducement of infringement, stating that Berkeley provides instructions, marketing materials, and technical support that encourage and guide its customers to use the "Beacon®" system in a manner that directly infringes the patents-in-suit (Compl. ¶¶54, 76, 100).
Willful Infringement
The complaint alleges willful infringement based on both pre- and post-suit knowledge. It cites a series of notice letters sent to Berkeley starting nearly a year before the complaint was filed (Compl. ¶¶33, 35, 37). More significantly, it alleges that a named inventor on the patents-in-suit, Dr. Anupam Singhal, is a Berkeley employee who was involved in developing the "Beacon®" system and allegedly "copied the '376 patent despite knowing that the Beacon® is covered by the '376 patent" (Compl. ¶¶35, 61, 83, 107).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of claim construction and scope: can a single, dual-function micro-bead, as may be used in the accused system, satisfy the limitations of claims that recite "a first removeable capture substrate" and "a second removeable capture substrate," or does the plain language require two physically distinct substrates?
- A key evidentiary question will be one of direct infringement: what is the precise, automated sequence of steps performed by the accused "Beacon®" system when used by customers for antibody discovery, and does this sequence map onto the specific order of steps recited in the asserted method claims, which vary slightly between the asserted patents?
- The case may also heavily feature the question of willful infringement: given the allegation that a named inventor on the patents is now a key employee at the defendant company, the dispute will likely focus on the extent of his knowledge and influence on the design of the accused product, and whether this constitutes the egregious conduct necessary for enhanced damages.