AI-based antibody discovery platform identifies novel, diverse and pharmacologically active therapeutic antibodies against multiple SARS-CoV-2 strains (preprint)

ABSTRACT

A critical aspect of a successful pandemic response is expedient antibody discovery, manufacturing and deployment of effective lifesaving treatments to patients around the world. However, typical drug discovery and development is a lengthy multi-step process that must align drug efficacy with multiple developability criteria and can take years to complete. In this context, artificial intelligence (AI), and especially machine learning (ML), have great potential to accelerate and improve the optimization of therapeutics, increasing their activity and safety as well as decreasing their development time and manufacturing costs. Here we present a novel, cost-effective and accelerated approach to therapeutic antibody discovery, that couples AI-designed human antibody libraries, biased for improved developability attributes with high throughput and sensitive screening technologies. The applicability of our platform for effective therapeutic antibody discovery is demonstrated here with the identification of a panel of human monoclonal antibodies that are novel, diverse and pharmacologically active. These first-generation antibodies, without the need for affinity maturation, bind to the SARS-CoV-2 spike protein with therapeutically-relevant specificity and affinity and display neutralization of SARS-CoV-2 viral infectivity across multiple strains. Altogether, this platform is well suited for rapid response to infectious threats, such as pandemic response. IMPORTANCEExpedient discovery and manufacturing of lifesaving therapeutics is critical for pandemic response. The recent COVID pandemic has highlighted the current inefficiencies and the need for improvements. To this end, we present our therapeutic antibody discovery platform that couples artificial intelligence (AI) and innovative high throughput technologies, and we demonstrate its applicability to rapid response. This platform enabled the isolation, characterization, and rapid identification of effective broadly neutralizing SARS-CoV-2 antibodies with good developability attributes, anticipated to fit our current process development and manufacturing platform. As such, this would benefit cost-of-goods and improve therapeutic access to patients. The AI-derived antibodies represent an advantageous therapeutic modality that can be developed and deployed fast, thus well suited for rapid response to infectious threats, such as pandemic response.