AI POWERED ANTIBODY ENGINEERING
ADVANCED IMMUNIZATION STRATEGIES
FULLY HUMANIZED TRANSGENIC MICE
SINGLE B CELL TECHNOLOGY
Synthetic antibody technology has gained increasing attention in recent time. A well-designed synthetic antibody library is more efficient than conventional phage displayed library and its derived antibodies have the potential of better developability. Not only can it bypass the need for humanization and the limit of animal immune system, it is also better suited for engineering and screening method development. BioDuro now has built the antibody libraries in Fab and VHH format. We are expanding the libraries into different designs or formats to cover more widely epitopes and application
BioDuro-Sundia has established an antibody discovery platform that combines artificial intelligence (AI) and synthetic antibody discovery. The combined platform will enable our biopharma partners to shorten timelines and improve quality of antibody-based drug development programs, enabling faster path to the clinic.
The combined platform can screen tens of billions of high-impact sequences in a high-throughput manner. The sequences are all synthetic, meaning they are purposely designed antibodies with optimized affinity, specificity, stability, and therapeutic developability. The platform is especially useful for difficult targets, such as GPCRs, ion channels, and peptide-MHC complexes, that have consistently failed development as antibody-based therapeutics.
The AI powered antibody technology uses the latest artificial neural network algorithm, machine learning, and molecular dynamics to simulate the directed evolution of each antibody—ultimately generating optimized sequences that specifically and potently bind the target antigen. These AI-directed sequences are quickly advanced into experimental screens. Out of astronomical number of potential sequences, our platform selects the very best subset to advance into screens. A huge amount of AI computation is expended in order to select smaller, but optimal libraries with higher success rate of antibody discovery.
BioDuro-Sundia’s advanced synthetic antibody technology rapidly transforms the results of AI directed evolution into functional antibodies using high-speed DNA engineering, which can be used to create and screen more than 10 billion human synthetic antibodies in 3 – 4 weeks. Traditional non-synthetic approaches use the immune system of human or other animals to generate antibodies, resulting in antibody diversity and developability that is restricted. “BioDuro-Sundia’s synthetic antibody screening platform enables us to discover the most optimal antibodies, because we are not limited by a human or animal immune system; we can design any antibody with virtually infinite combinations of sequences that are optimized through directed evolution, and we make sure to start with a fully human antibody framework that has good development properties, meaning we have a much better likelihood of reaching the clinic—and doing so quickly.”
We are also working with several partners to extend the technology into antibody designs for immune cell therapies such as CAR-T and TCR-T, which are highly promising immuno-oncology therapeutics, but have had unexpected outcomes and strong side effects in clinical studies—largely attributed to suboptimal antibody and linker designs. The teams are applying their unique antibody discovery platform to rapidly discover and develop next-generation CAR-T therapy with improved safety and efficacy profiles.
The advanced immunization technologies such as immunizing animal with antigen coding DNA or surface antigen expressing cells which are preferred alternatives for targeting antigens that are difficult to express or purify. Usually, animal immunization can produce high affinity antibodies but the fusion efficiency by conventional method is low. At BioDuro we use electroporation for DNA immunization and fusion process to achieve better efficiency.
We have developed an immunization technology with multiple advantages, which is especially suitable for antigens such as membrane bound receptors, tumor associate antigens, immune regulators and GPCRs:
With the evolution of gene manipulation technology, the mouse antibody V genes can be replaced by human ones to create the humanized mice. Immunization of such mice to generate antibodies with human V region sequences has been widely adopted for therapeutic antibody discovery.
BioDuro-Sundia now has the humanized mice for human antibody generation. All the endogenous murine Ig segments have been deleted and replaced by human ones including V/D/J genes for VH and V/J genes for VL. The immunization response tests have shown that the humanized mice perform even slightly better than the normal mice. The expression of these Ig genes was analyzed by NGS and compared with their expression pattern in human. The results indicate that the expression levels are similar in humanized mice and in human. All the data support that the humanized mice is an ideal platform for human antibody generation. It can also be combined with our DNA or cell immunization method for better outcome
Single B cell technology has been widely used for antibody discovery for infectious diseases. The antigen reactive B cells from patients can be isolated by FACS and each B cell can be sorted into single wells. The VL and VH genes of the antigen reactive clones will be rescued for recombinant antibody production. Recently, the gene rescue procedure has been improved to achieve much higher rescue rate with lower cost.