Tuesday, September 24, 2024 - Day One of Main ConferenceTuesday, 24 September 2024 - ET (Eastern Time, GMT-05:00)

A team of BioPhorum members have developed and executed surveys focused on the activities and effort involved in a typical Cell Line Development (CLD) campaign. An average of 27 members from different companies that participate in the BioPhorum CLD working group answered surveys covering a standard CLD workflow from vector design to single cell clone selection. The surveys were very extensive, including a total of 341 questions split between antibody and complex molecule CLD processes. They provide a comprehensive industry perspective on the typical time and effort required to develop a CHO production cell line

Transposase/Transposon platforms have become increasingly common for the development of robust high-expressing CHO cell lines for protein therapeutic manufacturing. Notably, these techniques use a single transposase/transposon pair to enable such outcomes. ATUM, as part of the Leap In Transposase platform, has developed a number of mutually orthogonal transposase/transposon pairs that can be used to serially engineer CHO, and other, cell lines in a robust manner. Indeed, this engineering can be used to not only increase the expression of transgenes, as is the case for a mAb therapeutics, but also knock-down the expression of endogenous genes to affect cellular physiology and/or product quality attributes … or both. This talk will provide examples of such engineering including a case study wherein three orthogonal Leap In Transposase/Transposon systems were implemented for the creation of a mAb expressing cell line with specific product quality attributes.

In the biopharma industry, various techniques are utilized to enhance yield and quality of the target protein produced by stable cell pools and accelerate overall CLD timeline. In this presentation, we will show a case study of a method for minipool productivity enrichment via co-expression of the target protein with a fluorescent biosensor protein using an IRES, combined with state-of-the-art automation tools to allow productivity enhancement and reduce timeline for overall cell line development efforts.

Cell Line Development plays a crucial role in establishing Master Cell Banks for clinical and commercial biomanufacturing. This involves creating subclones and undergoing multiple stages of rigorous assessment, leading to the selection of a final clone used for the project's entire duration. Decision-making in this process hinges on extensive datasets obtained from advanced analytical methods. The introduction of high-throughput platforms like the Berkeley Light Beacon and automated micro-bioreactor systems has resulted in generating vast datasets, which often consist of thousands of data points in each experiment. Moreover, the need to integrate process and performance data from various scales, including deep-well plates, shake flasks, and bioreactor processes, is essential for a thorough analysis. Collectively, these factors pose significant challenges in data processing and analysis, which are critical for informed decisionmaking in Cell Line Development. Here, we propose a holistic method for digitizing the entire cell line development and selection process. Our approach begins with implementing laboratory and data automation tools to streamline the generation and handling of raw data. We then establish automated data pipelines using the Databricks platform, enabling the integration of various data types and data of different scales into a specially designed database. This database comprehensively encompasses data on cell line creation, assessment, and selection. Additionally, we develop visualization dashboards linked in real-time to the database, significantly reducing time spent on data processing. Finally, we leverage this streamlined data to build predictive models using open-source Python machine-learning algorithms, enhancing the cell line selection process. Our proposed digital framework ensures a data-driven approach, optimizing the selection of highquality cell lines for clinical and commercial manufacturing purposes.

Great Bay Bio is a tech-bio company integrating big data analysis, AI, and automation into biologics development processing. We have developed an intelligent ecosystem covering biological drug discovery and CMC, including:

1. Antibody molecule development and optimization (AlfaDAX): within 1-2 weeks, the platform can develop and optimize antibody molecules with less wet-lab work in the aspects of humanization, affinity maturation, and developability assessment.

2. Site-specific integration technology for cell line development (AlfaCell): the stable monoclone with high titer (6-15 g/L) can be obtained within 1.5 months instead of the traditional process of 6 months, particularly solving two pain points of bispecific antibody development – lower titer and higher missing paring.

3. Non-screening cell culture media development (AlfaOPA): the customized cell culture media can be developed within 1 month only using 1 mL of the supernatant at the end of fed-batch processing.

The presentation will use obesity treatment target development, ACTRII, as a case study to show how the intelligent ecosystem developed a preclinical asset from drug discovery to CMC enabling within 7-9 months.

CRISPR, a molecular technology developed by adapting a protective bacterial response to virus infection, provides previously unknown power and sophistication in editing genes in organisms from bacteria to man. Consequently, control over this technology, principally by patent protection, has engendered several waves of contested proceedings in the US and European patent offices, many of which are ongoing. Because there are multiple partied and multiple proceedings a definitive determination of who owns CRISPR patent rights and the accompanying royalties on licenses is something that will not be finally concluded for several years.

Nevertheless, or perhaps because of this situation the assignees of CRISPR inventors at several universities have engaged in a broad licensing regime covering application of the technology in medicine, agriculture, and other fields. This talk will walk through these regimes in light of the various academic and commercial interests and provide a glimpse at what may arise in future when these rights are more certainly established, as well as briefly touching on the existing companies that have already licensed CRISPR technology.

• Summarize key takeaways from discussions on accelerating CLD and FIH studies
• Encourage further exploration of innovative technologies and strategies for bioprocess development
• Highlight the importance of collaboration and shared learnings in advancing the field

• Grab a 'Cloud Spritz' (Aperol Spritz)
  • Culture Bioscience's booth (328)
• Grab a SmartLabs 75 (French 75)
  • SmartLabs Booth (1824)