This workshop will provide an overview of the nuts and bolts of antibody development and developability assessment to help you accelerate antibody drugs to the clinic. it will explore various strategies to discovering and designing antibodies with properties that are more likely to be successful in development. Building in “developability” and “manufacturability” assessments is crucial in any antibody discovery program, and this workshop will discuss case studies and lessons learned from a variety of antibody projects. Developability considerations to be discussed include: developability modeling and prediction, developability assessment methods, biophysical properties and PK, delivery, cell line development and more.
Antibody-display Libraries in Mammalian Cells Created Using CRISPR/Cas9 and TALE Nucleases
Using directed integration of antibody genes by CRISPR/Cas9 and TALE nucleases we have constructed large libraries in mammalian cells containing a single antibody gene/cell. This has permitted construction of populations of millions of monoclonal stable cell lines displaying antibodies on their surface from which novel binders including IgG formatted antibodies, have been isolated. This together with transcriptional “normalization” from a single locus and expression in cell lines used for production enable aspects of developability to be incorporated during antibody discovery.
John McCafferty, Ph.D., CEO, IONTAS, United Kingdom
Biophysical Properties of the Therapeutic Antibody Landscape
Max Vasquez, Ph.D., Vice President, Computational Biology, Adimab LLC
Fc Engineering for Improved Developability and Retained Biological Activity
Modifications of the IgG Fc have allowed for serum persistence and immune engagement to become tunable properties for therapeutic mabs and Fc fusions. Nevertheless, these mutation combinations are rarely “plug-and-play” and can introduce developability problems not present in the parental antibody. This talk will focus on strategies to assess the stability of Fc mutants and outline our engineering approach to improve the developability of antibodies containing Fc mutations while retaining tailored biological activity.
M. Jack Borrok, Ph.D., Scientist II, Medimmune
Antibody Engineering with Optimized Developability – Modulation of Effector Function
While biological activity always trumps the developability assessments, there is also the need to ensure adequate productivity to meet the future commercial demand and product quality that leads to favorable safety and efficacy. This presentation will review engineering strategies for modulating the antibody effector function and discuss engineering of an IgG scaffold with optimized developability. Extensive biophysical analyses and pharmacokinetic studies were utilized to assess the developability of the engineered scaffold.
Guna Kannan, Ph.D., Director, Biologics-Antibody Engineering, Pharmaceutical Development, Santen, Inc.