DCT

8:22-cv-00220

Lonza Walkersville Inc v. Miltenyi Biotec North America Inc

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I. Executive Summary and Procedural Information

  • Parties & Counsel:
  • Case Identification: 8:22-cv-00220, D. Md., 09/20/2022
  • Venue Allegations: Plaintiffs allege venue is proper in the District of Maryland because Defendant Miltenyi resides in, has committed acts of infringement in, and maintains a regular and established place of business at its headquarters in Gaithersburg, Maryland.
  • Core Dispute: Plaintiffs allege that Defendant’s CliniMACS Prodigy® System, an automated cell processing platform, infringes six patents related to automated cell therapy manufacturing systems and methods.
  • Technical Context: The technology concerns automated, closed-system bioreactors that enable the complex process of cell therapy manufacturing to be performed consistently, with minimal human intervention, and potentially at the point-of-care.
  • Key Procedural History: The complaint alleges that Plaintiff Lonza sent a letter to Defendant on May 12, 2021, providing actual notice of infringement for four of the six asserted patents, a fact which may be relevant to the allegation of willful infringement.

Case Timeline

Date Event
2002-04-08 Priority Date for ’932, ’195, ’986, and ’338 Patents
2014-07-01 Collaborative discussions between Lonza and Octane allegedly begin
2016-08-30 Lonza and Octane enter into a Collaboration and Commercialization agreement
2017-01-03 U.S. Patent No. 9,534,195 Issues
2017-07-11 U.S. Patent No. 9,701,932 Issues
2017-09-01 Priority Date for ’018 and ’745 Patents
2018-10-30 Lonza acquires controlling stake in Octane
2020-07-28 U.S. Patent No. 10,723,986 Issues
2020-11-24 U.S. Patent No. 10,844,338 Issues
2021-05-12 Lonza sends notice letter to Miltenyi
2022-06-28 U.S. Patent No. 11,371,018 Issues
2022-09-20 U.S. Patent No. 11,447,745 Issues
2022-09-20 Second Amended Complaint Filed

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

U.S. Patent No. 9,701,932 - “Automated Tissue Engineering System”

  • Issued: July 11, 2017

The Invention Explained

  • Problem Addressed: Conventional cell and tissue culturing methods are described as labor-intensive and susceptible to contamination and human error, which creates variability in outcomes and restricts the cell culture process (U.S. 10,844,338 B1, col. 2:55-65). These methods are often incapable of adequately monitoring and modifying the cellular environment to support the complex developmental stages required for producing functional tissue implants (U.S. 10,844,338 B1, col. 2:1-4).
  • The Patented Solution: The invention is a portable, automated cell culture module that integrates the necessary components for cell and tissue engineering into a single system (Compl. ¶22). It comprises at least one bioreactor, a fluid containment system, a heating chamber, and sensors that provide feedback to a microprocessor, which in turn actively monitors and adjusts environmental conditions to support cell growth through different developmental stages (Compl. ¶22; U.S. 10,844,338 B1, Abstract).
  • Technical Importance: This automated, "all-in-one" approach facilitates the manufacturing of cell therapies at the point-of-care, which can significantly reduce the time between cell extraction and patient administration, a critical factor for terminally ill patients (Compl. ¶¶15, 19).

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶77).
  • The essential elements of claim 1 include:
    • A portable tissue and/or cell culture engineering module;
    • at least one bioreactor for cell culture and/or tissue engineering functions;
    • a fluid containment system in fluid communication with the bioreactor;
    • a heating and/or mixing chamber to heat and/or mix fluids flowing to the bioreactor; and
    • one or more sensors configured to detect environmental conditions and cell metabolic turnover, which generate signals for a microprocessor to actively monitor and adjust the changing environmental conditions until completion of cell growth.
  • The complaint asserts dependent claims 2-3, 10-11, and 13-22 (Compl. ¶77).

U.S. Patent No. 9,534,195 - “Automated Tissue Engineering System”

  • Issued: January 3, 2017

The Invention Explained

  • Problem Addressed: The patent addresses the same general problems as the ’932 Patent regarding the limitations of manual cell culture (U.S. 10,844,338 B1, col. 2:55-65).
  • The Patented Solution: This patent focuses specifically on the bioreactor component of an automated system (Compl. ¶24). The claimed bioreactor includes a housing, ports for media flow, at least one chamber for cell culture, and one or more sensors for monitoring and automatically adjusting parameters such as temperature, pH, dissolved gases, and metabolic turnover. The bioreactor is explicitly adapted to use sensor feedback to maintain optimal conditions and readjust parameters in response to the status of cell proliferation to generate a desired cell population (Compl. ¶24).
  • Technical Importance: The invention enables precise, automated feedback and control over the microenvironment within a bioreactor, which is intended to improve the consistency, reliability, and yield of cell therapy manufacturing processes (U.S. 10,723,986 B2, col. 3:5-10).

Key Claims at a Glance

  • The complaint asserts independent claim 1 (Compl. ¶85).
  • The essential elements of claim 1 include:
    • A bioreactor for facilitating cellular functions and/or generating tissue constructs;
    • a bioreactor housing with one or more ports for media flow;
    • at least one chamber within the housing for supporting cellular functions; and
    • one or more sensors for monitoring and automatically adjusting specific parameters (temperature, pH, dissolved gases, metabolic turnover, etc.);
    • wherein the bioreactor is adapted to automatically monitor parameters from the sensors to maintain optimal conditions and to automatically re-adjust parameters responsive to cell proliferation status.
  • The complaint asserts dependent claims 2, 7, 9, 13, 18-19, 21, 26, and 28 (Compl. ¶85).

U.S. Patent No. 10,723,986 - “Automated Tissue Engineering System”

  • Issued: July 28, 2020
  • Technology Synopsis: The ’986 Patent is directed to an automated method for cell culture or tissue engineering. The claimed method comprises loading cells into a sensor-equipped bioreactor, seeding the cells onto a substrate, proliferating or differentiating the cells, and using a microprocessor to actively monitor and automatically adjust culture parameters to obtain the desired cells or tissue (Compl. ¶26).
  • Asserted Claims: Independent claim 1 is asserted (Compl. ¶¶26, 93).
  • Accused Features: The complaint alleges that the use of the CliniMACS Prodigy System to perform automated cell culture constitutes infringement of the claimed method (Compl. ¶¶42, 49).

U.S. Patent No. 10,844,338 - “Automated Tissue Engineering System”

  • Issued: November 24, 2020
  • Technology Synopsis: The ’338 Patent claims a cell culture engineering module. The module comprises at least one bioreactor, a fluid containment system, and one or more sensors configured to detect changing environmental conditions and generate signals to a microprocessor to automatically monitor and alter those conditions throughout the cell culture process (Compl. ¶28).
  • Asserted Claims: Independent claim 1 is asserted (Compl. ¶¶28, 101).
  • Accused Features: The complaint identifies the CliniMACS Prodigy Instrument as the infringing cell culture engineering module (Compl. ¶¶36, 43).

U.S. Patent No. 11,371,018 - “End-to-End Cell Therapy Automation”

  • Issued: June 28, 2022
  • Technology Synopsis: The ’018 Patent claims a method for the automated production of a genetically modified T cell culture. The method comprises steps of activating T cells, transfecting the activated cells via an electroporation unit, expanding the transfected cells, concentrating the expanded cells, and harvesting the final culture. A key limitation is that the automated expansion process produces at least 20% more cells than a manual culture process using a flexible, gas permeable bag (Compl. ¶30).
  • Asserted Claims: Independent claim 1 is asserted (Compl. ¶¶30, 109).
  • Accused Features: The complaint alleges that the use of the CliniMACS Prodigy System, including its Electroporator module, infringes the claimed method (Compl. ¶¶3, 44, 49, 57).

U.S. Patent No. 11,447,745 - “End-to-End Cell Therapy Automation”

  • Issued: September 20, 2022
  • Technology Synopsis: The ’745 Patent claims methods for the automated production of genetically modified T cell cultures, including CAR T cells. The method comprises steps of activating, transducing with a viral vector, expanding, concentrating, and harvesting T cells. The steps are performed within a fully enclosed cell engineering system, and the automated expansion is recited as producing at least 20% more cells than a manual culture process using a flexible, gas permeable bag (Compl. ¶¶32-34).
  • Asserted Claims: Independent claims 1, 8, and 11 are asserted (Compl. ¶¶32-34, 117).
  • Accused Features: The complaint alleges that the use of the CliniMACS Prodigy System for cell therapy manufacturing infringes the claimed methods (Compl. ¶¶45, 49).

III. The Accused Instrumentality

Product Identification

  • The CliniMACS Prodigy® System, which includes the CliniMACS® Prodigy Instrument, related CliniMACS Prodigy® Tubing Sets, and the CliniMACS® Electroporator (Compl. ¶3).

Functionality and Market Context

  • The Accused Products are described as an "automated cell processing platform that enables scalable GMP-compliant manufacturing of cell therapy products, on a single device and within a single process setup" (Compl. ¶36). The system is alleged to be a "[f]ully-automated, sensor-controlled" and "[c]losed system" that uses its sensors to maintain optimal conditions via "sensor-controlled, cell processing capabilities" (Compl. ¶38). An annotated image provided in the complaint identifies key components of the Instrument, including a bioreactor, a fluid containment system, a heating chamber, and sensors (Compl. ¶37). A further schematic illustrates a setup for hematopoietic stem cell engineering using the Instrument and a tubing set (Compl. ¶50). Plaintiffs allege that they and Defendant are direct competitors in this market (Compl. ¶35).

IV. Analysis of Infringement Allegations

U.S. Patent No. 9,701,932 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A portable tissue and/or cell culture engineering module The CliniMACS Prodigy Instrument is described as a "module for cell engineering" and an "automated cell processing platform" ¶36 U.S. 10,844,338 B1, col. 7:8-14
at least one bioreactor The Instrument is alleged to have a bioreactor. ¶37 U.S. 10,844,338 B1, col. 6:52-56
a fluid containment system in fluid communication with said at least one bioreactor The Instrument is alleged to have a fluid containment system, shown in an annotated image to be connected to other components. ¶37 U.S. 10,844,338 B1, col. 6:57-59
a heating and/or mixing chamber to heat and/or mix fluids flowing to said at least one bioreactor The Instrument is alleged to have a heating chamber. ¶37 U.S. 10,723,986 B2, col. 16:26-33
one or more sensors configured to actively detect environmental conditions... and... generate signals to a... microprocessor to actively monitor and actively adjust the changing environmental conditions The Instrument is alleged to be designed for "[f]ully-automated, sensor-controlled processes" and uses its sensors and a control system to maintain optimal conditions. ¶38 U.S. 10,844,338 B1, col. 8:1-9

U.S. Patent No. 9,534,195 Infringement Allegations

Claim Element (from Independent Claim 1) Alleged Infringing Functionality Complaint Citation Patent Citation
A bioreactor for facilitating and supporting cellular functions and/or the generation of tissue constructs The CliniMACS Prodigy Instrument is alleged to have a bioreactor for cell engineering. ¶¶36-37 U.S. 10,723,986 B2, col. 7:54-58
a bioreactor housing The annotated image of the Instrument points to a "Housing." ¶37 U.S. 10,723,986 B2, col. 7:59
one or more ports for media flow The annotated image of the Instrument points to "Ports." ¶37 U.S. 10,723,986 B2, col. 7:60-61
at least one chamber defined within said bioreactor housing for facilitating and supporting cellular functions The annotated image of the Instrument identifies a "Bioreactor" component, which contains such a chamber. ¶37 U.S. 10,723,986 B2, col. 7:62-65
one or more sensors for monitoring and automatically adjusting parameters... wherein: the bioreactor is adapted to automatically monitor parameters... and to automatically re-adjust the parameters The Instrument is alleged to be "sensor-controlled" and uses its sensors and control system to "maintain optimal conditions" and perform "cell processing." ¶38 U.S. 10,723,986 B2, col. 8:1-9

Identified Points of Contention

  • Technical Questions: The complaint's allegations are based on high-level marketing statements and annotated product photos (Compl. ¶¶36-38). A central technical question will be what specific "environmental conditions and cell metabolic turnover" the accused sensors actually detect, and what specific "active adjustments" the accused control system actually performs in response. The complaint provides little detail on the actual, operational logic of the accused system's feedback loop.
  • Scope Questions: The dispute may involve the scope of the term "microprocessor." It will be a question for the court whether the accused "Control system" (Compl. ¶37) meets the "microprocessor" limitation as understood in the context of the patent specification, or if the accused system utilizes a different control architecture.

V. Key Claim Terms for Construction

  • The Term: "microprocessor"

    • Context and Importance: This term appears in the independent claims of the ’932, ’986, and ’338 Patents and is central to the automation and active control elements of the invention. The infringement analysis will depend on whether the defendant's "Control system" (Compl. ¶37) falls within the scope of this term. Practitioners may focus on this term because the complaint identifies the accused feature with a generic label from a marketing photo, leaving open questions about its specific hardware and software architecture.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patents refer to the microprocessor as being linked to sensors to control the system, and can be a "central microprocessor" or an "onboard microprocessor," suggesting the term is not limited to a single, specific type or location (Compl. ¶22; U.S. 10,723,986 B2, col. 4:58-64).
      • Evidence for a Narrower Interpretation: The specification distinguishes between a "central microprocessor" and a "secondary onboard microprocessor" (U.S. 10,723,986 B2, col. 4:62-64). A defendant may argue this distinction implies the primary "microprocessor" must be a single, central processing unit with comprehensive control, as opposed to a distributed system of controllers.

  • The Term: "actively... adjust"

    • Context and Importance: This term from claim 1 of the ’932 Patent defines the nature of the system's response to sensor data. The dispute may turn on whether the accused system's control logic constitutes "active" adjustment in response to detected conditions, or if it primarily follows pre-programmed protocols that are not "responsive" in the manner claimed.
    • Intrinsic Evidence for Interpretation:
      • Evidence for a Broader Interpretation: The patent describes a system that "automatically monitors the progression of the cell culture ... and adjusts the environmental conditions to meet the requirements of the different stages" (U.S. 10,723,986 B2, col. 4:48-52), which suggests a broad scope of automated, responsive control.
      • Evidence for a Narrower Interpretation: The specification provides specific examples of adjustments, such as altering pH, temperature, and dissolved gases based on sensing "metabolic turnover as a function of time (e.g. pH, O2, CO2, lactic acid and glucose consumption)" (U.S. 10,723,986 B2, col. 4:56-61). A party could argue that "actively adjust" requires this specific type of feedback-driven chemical or physical alteration of the culture environment, not merely advancing a pre-set schedule.

VI. Other Allegations

Indirect Infringement

  • The complaint alleges inducement of infringement of the method claims of the ’986, ’018, and ’745 Patents (Compl. ¶¶46, 111, 119). The allegations are based on Defendant's publication of materials that allegedly instruct customers on how to use the Accused Products in an infringing manner, such as a brochure for "Manufacturing of gene-engineered hematopoietic stem cells" (Compl. ¶¶46-48). A diagram from a brochure allegedly shows the infringing process workflow (Compl. ¶48).

Willful Infringement

  • The complaint alleges willful infringement based on Defendant's alleged knowledge of the patents (Compl. ¶71). For the ’932, ’195, ’986, and ’338 Patents, this knowledge is alleged to arise no later than a May 12, 2021 notice letter (Compl. ¶67). For the more recently issued ’018 and ’745 Patents, knowledge is alleged based on awareness of the pending applications and notice via the filing of the complaint itself (Compl. ¶¶114, 122).

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

  • A core issue will be one of functional operation: does the accused system's "sensor-controlled" functionality perform the specific feedback-driven monitoring and "active adjustment" of environmental conditions required by the claims, or does it operate on a different, primarily pre-programmed basis that falls outside the claim scope?
  • A key evidentiary question will be one of technical mapping: what evidence will demonstrate that the components of the Accused Products, identified in the complaint through marketing materials and annotated photos, actually perform each limitation of the asserted claims, particularly regarding the internal logic and operation of the "Control system" and "Sensors"?
  • For the method patents, a central question will be one of induced acts: can Plaintiffs demonstrate that Defendant's instructional materials led customers to perform all steps of the claimed methods for automated cell culture, including the specific steps of activating, transfecting, and expanding cells to achieve a yield that is quantifiably superior to manual methods?