Learn about how Mo used a revolutionary approach to quickly and efficiently discover novel antibody therapies. The SuperHuman antibody discovery platform is optimized for diversity and fitness. Watch the revolution.
Speaker (00:01) Moe loves his job as Director of Antibody Discovery at New ABCO because he knows antibodies are great drugs that help a lot of people. But sometimes he gets discouraged because making good ones can be really challenging and time-consuming. Moe and his team have been trying to develop an antibody against a difficult target. First, they panned a yeast display library, then a phage display library, then tried immunizing mice and spending months working to humanize a few hits without losing all affinity. When they had exhausted every avenue, their next attempt was with humanized mice. Despite their best efforts, even this method failed to produce functionally active binders against the target. (00:47) On his way to the annual MAB engineering conference, Moe sees in the abstracts online that his competitor is presenting preliminary data on the same target his team is working on. The stakes just got higher. Moe knows that if he can't produce viable hits soon, his competitors might beat him to the market. Now the clock is ticking. Moe is stressed on the first day of the conference. When he bumps into his friend Sophia, she tells Moe about the company she's working for now, Distributed Bio, an immuno engineering company in San Francisco. She invites Moe to check out her presentation the next day at the conference. Moe is impressed with Sophia's poster presentation. Instead of finding a few antibodies and working hard to fix them, Distributed Bio locates a lot of antibodies and picks the best of them. Their library has produced thousands of hits against every single antigen they have ever tried in just a few weeks. When D Bio offers him a guarantee that he will have development ready antibodies in weeks, he decides to send them a sample of his antigen. (01:56) Four weeks later, the D Bio team shares their results. As Moe reviews the data, a huge weight is lifted off his shoulders. The properties of the hundreds of best hits they have picked out for characterization have surpassed his expectations. Not only are they high affinity, non immunogenic, aggregation resistant, and thermostable, but many of them also cross-react with mice, nonhuman primates, and human antigens, promising an easier development process. Moe is thrilled, and calls Sophia to thank her. She explains that the success of D Bio's library is attributed both to its diversity and to the principles of developability that are applied to enrich the library. The D Bio team sequenced the antibody repertoires of thousands of healthy volunteers to understand how to make a radically more diverse library. They then deconstructed and recombined human CDRs from 140 healthy human controls on the best therapeutic heavy and light scaffolds in nearly a hundred billion combinations to develop a massively diverse library of new fully human antibodies. (03:08) The best therapeutic heavy and light therapeutic scaffolds were determined by assessing the biophysical and biological characteristics of successful therapeutic antibodies, the thousand genome project, and other data sources to learn their strengths and weaknesses, identifying features that predispose antibodies to liabilities, like immunogenicity, aggregation, and thermal instability, and then avoiding them in the design. During construction, the library was heated to select only the best behaving and most thermostable and aggregation resistant molecules. (03:44) Finally, they employ automated robotic panning and high throughput kinetics and FACS screening to scale and accelerate the process, allowing them to search through the library to recover and characterize thousands of hits within days. The result? A revolution of massive numbers of hits against any target, and a changed paradigm for antibody discovery. Moe and his team are so happy. With their antibodies in the clinic, Moe's team is no longer discouraged and they're thinking about even more difficult targets they want to tackle, by mining the vast depths of the D Bio library. To learn more, visit www.criver.com/antibody, or email [email protected]