G-Protein coupled receptors, or GPCRs, are attractive drug targets. Today, more than 30% of current drug targets are GPCRs and they cover a range of indications. GPCRs are Hard-to-Drug with only 2 FDA approved antibodies today. Current antibody drug development methods often do not work against GPCRs and such antigens immunizations often produce binders to epitopes not available biologically. Panning with random mutagenesis libraries is too inefficient to explore the effective sequence space and more focused library approaches are required.
Synthetic antibody phage display libraries that utilize oligo pools have the following advantages over traditional synthetic antibody and immunization approaches:
- No immunization required
- Design and synthesis of explicit mAb libraries to focus on effective sequence space
- Simultaneous screening against multiple targets
- CDR diversity can be designed to match the natural CDR repertoire
- Liabilities can be removed, e.g. isomerization, cleavage, deamidation, glycosylation sites
- Accurate representation, e.g. motif sequences can be explicated encoded in oligos
Utilizing its proprietary DNA writing technology to create oligo pools, genes, and synthetic libraries, Twist Biopharma, a division of Twist Bioscience, uses large diverse oligo pools (upwards of 106) to develop a range of antibody phage display libraries that are either broadly applicable to any target or focused on a specific class of tough targets, e.g. GPCRs. In this presentation, we will introduce how we can easily discover anti-GPCR antibodies from a range of synthetic antibody phage display libraries. As a case study, we will highlight the discovery of antibodies against GLP1R, CRTH2, and CXCR5 from multiple Twist Biopharma libraries.
- Current case studies of validated antibodies discovered by Twist Biopharma
- Advantages of using Twist Biopharma synthetic phage display libraries for antibody discovery, particularly for hard-to-drug targets like GPCRs
Aaron K. Sato, Ph.D.
Biopharma, A division of Twist Bioscience
Aaron is a proven biologics leader adept at managing teams to discover and develop novel first-in-class antibody therapeutics. Prior to Twist Bioscience, he served as Chief Scientific Officer of LakePharma, leading the California Antibody Center, which discovers novel antibody therapeutics for its clients. Prior to LakePharma, he oversaw all discovery research functions both as Vice President of Protein Sciences at Surrozen, and previously, as Vice President of Research at Sutro Biopharma, Inc. He also served as Senior Director of Antibody Engineering at OncoMed Pharmaceuticals, where he was responsible for human antibody lead discovery and he served as project team leader on several key antibody projects through IND filing. Before OncoMed, Aaron held positions of increasing responsibility at Dyax Corp., most recently as Senior Director of Lead Discovery, leading antibody, peptide, and small protein discovery using their proprietary phage display technology. He earned his Ph.D. from the Massachusetts Institute of Technology where he studied MHC class II structure-function relationships. He is an author of over 30 peer reviewed papers and 40 issued patents in the antibody space.
Cost: No Cost!