DCT
4:20-cv-08624
AbCellera Biologics Inc v. Bruker Cellular Analysis Inc
Key Events
Amended Complaint
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: Bruker Cellular Analysis, Inc. (Delaware)
- Plaintiff’s Counsel: Quinn Emanuel Urquhart & Sullivan, LLP
- Case Identification: 4:20-cv-08624, N.D. Cal., 10/20/2023
- Venue Allegations: Plaintiffs allege venue is proper because Defendant maintains a regular and established place of business in Emeryville, California, within the district. The complaint further notes that Defendant previously succeeded in transferring this litigation from the District of Delaware to the Northern District of California, thereby consenting to venue.
- Core Dispute: Plaintiffs allege that Defendant’s Beacon® line of optofluidic systems and related products, which are used for single-cell analysis, infringe fifteen patents covering methods for assaying and culturing individual cells in microfluidic devices.
- Technical Context: The technology relates to high-throughput microfluidic platforms that enable the isolation, culture, and analysis of individual biological cells, a process critical for modern antibody discovery, clone selection, and biopharmaceutical development.
- Key Procedural History: The litigation was initially filed in the District of Delaware and was transferred to the Northern District of California upon Defendant’s motion. Plaintiffs allege providing pre-suit notice of infringement to Defendant through a series of letters beginning on October 3, 2019. The complaint alleges that Defendant had knowledge of the patents-in-suit through these letters and also through a named inventor on the patents, Dr. Anupam Singhal, who was subsequently employed by Defendant.
Case Timeline
| Date | Event |
|---|---|
| 2010-07-07 | Earliest Priority Date (’408, ’936, ’018, ’270 Patents) |
| 2010-07-16 | Earliest Priority Date (’812, ’494, ’241, ’618, ’962, ’376, ’377, ’378, ’768, ’737, ’933 Patents) |
| 2017-01-01 | Defendant's original Beacon system launched (approx. date) |
| 2018-10-02 | U.S. Patent No. 10,087,408 Issued |
| 2018-10-23 | U.S. Patent No. 10,107,812 Issued |
| 2019-04-30 | U.S. Patent No. 10,274,494 Issued |
| 2019-09-24 | U.S. Patent No. 10,421,936 Issued |
| 2019-10-03 | Plaintiffs' first alleged notice letter to Defendant |
| 2019-11-05 | U.S. Patent No. 10,466,241 Issued |
| 2020-03-03 | U.S. Patent No. 10,578,618 Issued |
| 2020-06-30 | U.S. Patent No. 10,697,962 Issued |
| 2020-07-07 | U.S. Patent No. 10,704,018 Issued |
| 2020-07-21 | U.S. Patent No. 10,718,768 Issued |
| 2020-08-11 | U.S. Patent No. 10,738,270 Issued |
| 2020-08-18 | U.S. Patent No. 10,746,737 Issued |
| 2020-08-25 | U.S. Patent No. 10,753,933 Issued |
| 2020-09-15 | U.S. Patent Nos. 10,775,376, 10,775,377, and 10,775,378 Issued |
| 2023-01-01 | Defendant's Beacon Select and Beacon Quest launched (approx. date) |
| 2023-10-20 | Amended and Consolidated Complaint Filed |
II. Technology and Patent(s)-in-Suit Analysis
U.S. Patent No. 10,107,812 - “Methods for assaying cellular binding interactions”
- Issued: October 23, 2018
The Invention Explained
- Problem Addressed: The patent addresses the inefficiency of prior art methods for analyzing antibody-antigen binding kinetics, which required large numbers of cells and costly, time-consuming clonal expansion to produce sufficient antibodies for screening (’812 Patent, col. 2:12-19).
- The Patented Solution: The invention provides a method to assay binding interactions directly from a single cell. The method involves retaining a single protein-secreting cell in a microfluidic chamber, exposing the secreted protein to a capture substrate within the chamber, and then introducing a biomolecule to measure its binding interaction with the captured protein (’812 Patent, Abstract; col. 3:20-42). This allows for the direct measurement of binding properties from the protein as it is secreted by its source cell.
- Technical Importance: This approach enables high-throughput screening of millions of individual cells, such as antibody-producing B cells, to rapidly identify those with rare or desirable therapeutic properties (Compl. ¶¶ 18-19).
Key Claims at a Glance
- The complaint asserts at least independent claim 1 (Compl. ¶ 68).
- The essential elements of claim 1 include:
- Retaining a cell that secretes a protein within a chamber of a specific volume range (100 pL to 100 nL) which has an inlet, an outlet, and a solid wall.
- Exposing the secreted protein to a capture substrate that is in fluid communication with the cell and is capable of binding the secreted protein.
- Flowing a fluid containing a biomolecule through the chamber's inlet and outlet.
- Measuring a binding interaction between the secreted protein and the biomolecule.
- The complaint does not explicitly reserve the right to assert dependent claims for this patent.
U.S. Patent No. 10,274,494 - “Methods for assaying cellular binding interactions”
- Issued: April 30, 2019
The Invention Explained
- Problem Addressed: The patent, which is part of the same family as the ’812 patent, addresses the same technical challenge of enabling efficient, single-cell binding assays for antibody discovery (’494 Patent, col. 2:12-19).
- The Patented Solution: The invention is a method specifically for assaying an antibody produced by a single antibody-producing cell (APC). It recites retaining the APC in a chamber defined by a solid wall and an "aperture." A capture substrate binds the antibody secreted by the APC, and a biomolecule is then flowed into the chamber via the aperture to measure the binding interaction (’494 Patent, Abstract). The use of the term "aperture" rather than "inlet" and "outlet" is a notable distinction from the '812 Patent.
- Technical Importance: This method facilitates the rapid, individualized screening of antibody-producing cells, which is a key step in developing new antibody-based therapies (Compl. ¶¶ 18-19).
Key Claims at a Glance
- The complaint asserts at least independent claim 1 (Compl. ¶ 89).
- The essential elements of claim 1 include:
- Retaining a single antibody-producing cell (APC) within a chamber of a specific volume range (100 pL to 100 nL) which has a solid wall and an aperture.
- Exposing the antibody produced by the APC to a capture substrate that is in fluid communication with the antibody and is capable of binding it.
- Flowing a fluid containing a biomolecule into the chamber via the aperture.
- Measuring a binding interaction between the antibody produced by the APC and the biomolecule.
- The complaint does not explicitly reserve the right to assert dependent claims for this patent.
Multi-Patent Capsule: Additional Patents for Assaying Cellular Binding Interactions
- Patent Identification: U.S. Patent Nos. 10,466,241; 10,578,618; 10,697,962; 10,775,376; 10,775,377; 10,775,378; 10,718,768; 10,746,737; and 10,753,933. These patents share the same title and specification as the ’812 and ’494 patents.
- Technology Synopsis: These patents claim various methods for assaying binding interactions of proteins or antibodies secreted by single cells within microfluidic chambers. The claims vary in specific elements, such as the use of removable capture substrates, the specific type of cell (e.g., antibody-secreting cell), and additional steps like cell lysis and nucleic acid capture.
- Asserted Claims: The complaint asserts at least claim 1 of each patent (Compl. ¶¶ 109, 130, 153, 241, 264, 286, 310, 354, 378).
- Accused Features: The accused features are the antibody discovery and other single-cell assay workflows performed by the Accused Products and Services (Compl. ¶¶ 113, 134, 157, 245, 268, 290, 314, 358, 382).
Multi-Patent Capsule: Patents for Microfluidic Cell Culture
- Patent Identification: U.S. Patent Nos. 10,087,408; 10,421,936; 10,704,018; and 10,738,270. These patents are titled “System and method for microfluidic cell culture.”
- Technology Synopsis: These patents relate to methods for culturing and selecting cells in microfluidic devices. The inventions describe systems where cells are introduced into thousands of microfluidic chambers and retained for culturing and analysis, allowing for the creation and selection of individual clonal cell populations (’408 Patent, Abstract; Compl. ¶¶ 177-180).
- Asserted Claims: The complaint asserts at least claim 1 of each patent (Compl. ¶¶ 177, 198, 220, 333).
- Accused Features: The accused features are the cell culturing, clone selection, and cell recovery workflows performed by the Accused Products and Services (Compl. ¶¶ 181, 202, 224, 337).
III. The Accused Instrumentality
Product Identification
- The complaint identifies the accused instrumentalities as the Beacon® Optofluidic System, the Beacon Select™, the Beacon Quest™, and related technologies, including OptoSelect™ chips, reagents, software, and the Culture Station™ System (collectively, the "Accused Products and Services") (Compl. ¶¶ 37, 38, 41, 54, 58).
Functionality and Market Context
- The Accused Products and Services comprise an automated platform for single-cell analysis used in workflows such as antibody discovery and cell line development (Compl. ¶ 37). The system uses OptoSelect chips containing thousands of "NanoPen™" chambers to isolate, culture, and assay individual cells (Compl. ¶¶ 36, 48). The complaint alleges these chambers have a volume of 250 picoliters and a "narrow opening to the channel for nutrients and cellular waste diffusion" (Compl. ¶¶ 46, 50). The system is alleged to perform various bead-based and diffusion-based fluorescent assays to screen cells and measure protein secretion (Compl. ¶ 52). A diagram from Defendant's materials illustrates several assay types, including an 'Antigen Specific Bead Assay' where a secreted antibody from a plasma B cell binds to an antigen bead (Compl. p. 13). Defendant allegedly markets the Beacon Select™ and Beacon Quest™ devices as having the "same capabilities" as the original Beacon® system (Compl. ¶¶ 39, 40).
IV. Analysis of Infringement Allegations
10,107,812 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 uses NanoPen™ chambers on OptoSelect chips to retain individual cells. The complaint alleges these chambers have a volume of 250 picoliters (0.25 nL), which is within the claimed range, and have a narrow opening to a channel. | ¶¶ 46, 48, 50, 72 | col. 6:50-53 |
| (b) exposing the protein secreted by the cell to a capture substrate...operable to bind the protein secreted by the cell to produce a bound protein; | The system allegedly performs bead-based assays where proteins (e.g., antibodies) secreted by the isolated cell are captured on beads that function as capture substrates. A diagram in the complaint shows a secreted antibody binding to an "ANTI-IgG BEAD." | ¶¶ 52, 73, p. 13 | col. 3:25-33 |
| (c) flowing a first fluid volume comprising the biomolecule through the inlet into the chamber and out the outlet... | The system allegedly performs various assays by introducing reagents, which are biomolecules, into the NanoPen chambers to enable binding interactions. | ¶¶ 42, 43, 74 | col. 3:34-39 |
| (d) measuring a binding interaction between the protein secreted by the cell and the biomolecule. | The system allegedly uses fluorescent assays to measure binding and score secreted antibody on the chip, which corresponds to measuring a binding interaction. The complaint includes a schematic of a "fluorescent 'bloom'" being measured. | ¶¶ 52, 75, p. 16 | col. 3:40-42 |
10,274,494 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 uses NanoPen™ chambers to retain a single antibody-producing cell (APC). The chambers are alleged to have a volume of 250 pL (0.25 nL) and a "narrow opening" that functions as the claimed aperture. | ¶¶ 46, 50, 93 | col. 33:17-21 |
| (b) exposing the antibody produced by the APC to a capture substrate...operable to bind the antibody produced by the APC to produce a bound antibody; | The accused workflows allegedly use bead-based assays where capture substrates (beads) bind the antibody secreted by the retained APC. | ¶¶ 52, 94, p. 13 | col. 33:22-27 |
| (c) flowing a first fluid volume comprising the biomolecule into the chamber via the aperture... | The system allegedly introduces biomolecules (reagents) into the chamber via the "narrow opening" to perform binding assays. | ¶¶ 42, 43, 95 | col. 33:28-32 |
| (d) measuring a binding interaction between the antibody produced by the APC and the biomolecule. | The system allegedly uses fluorescence to measure the result of its binding assays, thereby measuring the claimed interaction. | ¶¶ 52, 96, p. 16 | col. 33:33-35 |
Identified Points of Contention
- Scope Questions: A primary question for the court may be whether the accused NanoPen's "narrow opening" (Compl. ¶ 50) satisfies the "inlet" and "outlet" limitation of the ’812 Patent. Defendant may argue that this limitation requires two distinct structures, whereas the single opening of the NanoPen does not. This raises a related question of whether the term "aperture" in the ’494 Patent, which lacks the dual "inlet/outlet" language, was a deliberate drafting choice that more accurately reads on a single-opening structure like the one alleged.
- Technical Questions: The complaint alleges that the accused workflows perform the claimed steps, often citing broad sections of the complaint for support (e.g., Compl. ¶¶ 71-75). A key technical question will be whether the evidence demonstrates that the accused system's largely diffusion-based mechanism for nutrient and reagent exchange (Compl. ¶ 50) constitutes "flowing a first fluid volume...through the inlet...and out the outlet" as required by claim 1 of the '812 patent, which may imply active, directed fluid movement.
V. Key Claim Terms for Construction
The Term: "chamber having an inlet, an outlet" (’812 Patent, Claim 1)
- Context and Importance: The construction of this phrase is central because the accused NanoPen™ is described as having a single "narrow opening" (Compl. ¶ 50). Whether this single structure can meet a limitation requiring both an "inlet" and an "outlet" will be a key point of dispute. Practitioners may focus on this term as it appears to be a potential mismatch between the claim language and the accused product architecture.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The patent specification describes that an inlet or outlet "can vary considerably in terms of structure and dimension, and may be reversibly switched between an open position...and a closed position" (’812 Patent, col. 9:16-21). This functional language may support an argument that a single physical structure can serve as both an inlet and an outlet at different times or for different purposes.
- Evidence for a Narrower Interpretation: The plain language of claim 1, reciting "an inlet, an outlet," suggests two distinct structural features. The specification states that "Each chamber will have at least one inlet...and at least one outlet," which also suggests the presence of separate structures (’812 Patent, col. 9:1-4).
The Term: "aperture" (’494 Patent, Claim 1)
- Context and Importance: This term appears in the ’494 patent in place of the "inlet" and "outlet" language of the earlier ’812 patent. Its construction is critical to determine if this patent family has a broader scope that more clearly covers the single "narrow opening" of the accused NanoPens. Practitioners may focus on this term to analyze whether it represents a successful design-around by the patentee to capture single-opening structures.
- Intrinsic Evidence for Interpretation:
- Evidence for a Broader Interpretation: The plain and ordinary meaning of "aperture" is an opening, hole, or gap. This interpretation would appear to directly read on the "narrow opening" of the accused NanoPen chambers (Compl. ¶ 50). The patent claims simply recite "an aperture that defines an opening of the chamber" (’494 Patent, col. 33:20-21).
- Evidence for a Narrower Interpretation: The patent discloses embodiments where the aperture is associated with a "sieve valve" used to trap cells or beads (’494 Patent, Fig. 2A). A defendant could argue that, in the context of the invention, an "aperture" is not merely a passive opening for diffusion but is a controllable feature integrated with a valve structure, which may not be descriptive of the accused product.
VI. Other Allegations
Indirect Infringement
- The complaint alleges that Defendant induces infringement by providing customers with instructions, user manuals, and support on how to use the Accused Products and Services to perform the patented methods (Compl. ¶¶ 55, 79). It also alleges contributory infringement, asserting the products have no substantial non-infringing uses and are a material part of the invention especially adapted for infringement (Compl. ¶ 81).
Willful Infringement
- The complaint alleges willful infringement based on both pre- and post-suit knowledge. Pre-suit knowledge is alleged based on a series of notice letters sent to Defendant beginning October 3, 2019 (Compl. ¶¶ 60, 78). The complaint further alleges that knowledge is imputed to Defendant through Dr. Anupam Singhal, a named inventor on the patents-in-suit and a former employee of Defendant (Compl. ¶¶ 62, 66). Plaintiffs further allege that Defendant, with Dr. Singhal's assistance, "copied" the patented technology (Compl. ¶ 86).
VII. Analyst’s Conclusion: Key Questions for the Case
- A core issue will be one of definitional scope: does the accused NanoPen's single "narrow opening" meet the "inlet, an outlet" limitation of the ’812 patent family, or does this structure fall only within the scope of the potentially broader term "aperture" used in the later ’494 patent family? The resolution will depend on how the court construes these terms in light of the patent specification and prosecution history.
- A central factual dispute will be one of intent and knowledge: what was the role of the named inventor, Dr. Singhal, during his employment at Defendant, and does the evidence support the complaint's allegation of deliberate "copying"? The outcome of this inquiry will be critical to the claim for willful infringement and potential enhanced damages.
- A key evidentiary question will be one of operational equivalence: across fifteen asserted patents, can Plaintiffs prove that the specific, multi-step workflows performed by the Accused Products and Services meet every limitation of at least one asserted claim? The case may turn on whether the accused system's use of primarily passive diffusion for reagent exchange constitutes "flowing a fluid volume," which could imply a more active process.