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Katherine Harris, PhD
Multi-Specific Antibody Development Using Sequence-Based Antibody Discovery
William Pardridge, M.D.
Brain Drug Delivery of Therapeutic Antibodies with Blood-Brain Barrier Penetrating Bi-Specific Antibodies:
UCLA / ArmaGen
Utilizing it’s proprietary DNA writing technology to create oligo pools, genes, and synthetic libraries, Twist Pharma, a division of Twist Bioscience, provides the biotechnology industry with an end-to-end antibody discovery solution. This solution includes (1) a panel of high diversity synthetic antibody libraries, (2) a proprietary human anti-GPCR antibody phage display library focused on this validated target class, and (3) a Twist Antibody Optimization (TAO) platform for antibody affinity and developability optimization.
We have developed a novel, sequenced-based approach for the rapid and high-throughput discovery of antibodies from our human transgenic rat (UniRat) platform. UniRats express fully human heavy chain only antibodies called UniAbs. UniAbs are ideal building blocks for antibody-based biologics because they can be genetically fused to other proteins and can be arranged to make multi-specific antibodies without the complication of heavy and light chain pairing. Our results show UniAbs have biochemical properties similar to conventional antibodies and have distinct advantages for developing next-generation multi-specific therapeutic antibodies.
Glenmark Pharmaceuticals’ BEAT® platform is a robust and versatile bispecific antibody platform based on heavy chain heterodimerization. The technology relies on biomimicry wherein the protein-protein interfaces of two different immunoglobulin constant domain pairs are exchanged to design new heterodimeric CH3 domains. In transient transfections, at equimolar chain ratios, engineering allows for ≥ 95% heterodimerization in the bispecific Fab scFv and the Fab Fab common light chain antibody formats. Using our platform, we have engineered and in-house manufactured two clinical stage bispecific antibodies. Engineering concept, manufacturing, and latest improvements to the platform will be presented.
IL-10 is a key negative regulator of inflammation, however, development of IL-10 in the clinic for suppression of inflammation has been challenging. APVO210, an anti-CD86 scFv x monoIL10 fusion, offers key advantages over other IL-10 based drugs, due to its unique MOA: selective stimulation of the IL-10R on APC, without stimulating T and B cells. Potent biological activity has been demonstrated preclinically in vivo.