MAIN CONFERENCE DEC. 18Wednesday, 18 December 2024 - PT (Pacific Time, GMT-08:00)

It is relatively straightforward to select antibodies or VHHs that bind targets, but much more challenging to generate antibodies with functional activity. Here we describe the use of TripleBar’s microfluidics system to select functional CD3 activating antibodies from Specifica’s Generation 3 library platform.

Discovery of biotherapeutics against challenging targets such as integral membrane proteins, membrane protein complexes, and heavily glycosylated surface proteins using display technologies remains a challenge. We have utilized therapeutic-ready phage- and yeast-display platforms expressing a diversity of formats to pan against both cells and virus-like particles. Using these novel reagents and protocols, we have managed to discover biotherapeutics to traditionally display "unfriendly" targets.

We have developed a droplet-microfluidic single-cell-based platform for the repertoire biobanking and expression of the antibodies of up to one million human B cells in HEK cells. This cognate biobank represents 80% of the input cells, the robustness of this format enables any screening process including droplet microfluidic sorting.

This technology is applied for the direct discovery of tumor-reactive antibodies from tumor-infiltrating B cells in cell-based assays.

Abalone Bio’s Functional Antibody Selection Technology (FAST) platform combines biology and machine learning (ML) to identify and design functionally active antibody drugs. FAST simultaneously tests the entire diversity of antibody libraries directly for the desired function and produces library-scale sequence-function datasets that uniquely power generative protein language models to design novel active antibody sequences. FAST-discovered antibodies have been demonstrated to have agonist activity in vitro and in vivo.

Characterizing the binding parameters (ka, kd, KD) of antibody:receptor interactions is crucial in drug discovery. However complex Abs and/or receptors are not always amenable to traditional biophysical methods (i.e., SPR, BLI, etc.), necessitating cell-based binding assays. We developed a pre-equilibrium assay to simultaneously determine the binding kinetics of up to 30 therapeutic Abs on living cells.

Protillion combines ML-guided antibody design technology with purpose-built chip-based high-throughput instrumentation to tackle challenging problems in therapeutic protein engineering. The platform is capable of characterizing the binding affinity of up to 10^6 antibody variants in a 2-day automated run. This unique approach enables identification of better antibody candidates that meet challenging product profiles, including pH-dependent binding, cross-species reactivity, and stringent developability.