The Challenge of Antibody Discovery
Despite recent advances in both antigen presentation and sequencing based antibody isolation techniques, the core platform approaches to antibody discovery - phage display and antigen immunization - often struggle to yield candidates with optimal functional, safety and developability profiles
Phage Display Library Panning
Using an antigen to “pan” a high-diversity library of phages genetically engineered to display different antibodies on their surface can quickly yield very large numbers of antibodies that bind diverse epitopes. However, without the ability to perform functional and other critical developability assays on all the potential candidates, potentially useful antibodies that may not initially have the best affinities are lost.
Repeatedly immunizing a host with the target antigen, and relying on host’s immune system to develop antibodies against the antigen can often yield antibodies with good affinities, however the host immune response will typically produce antibodies that bind a relatively small number of sites on a target protein (so-called immuno-dominant regions). Although antibodies developed in this way may by chance have some useful functional properties, it is highly unlikely they will bind the most therapeutically relevant epitopes, and as they so frequently cluster around the same immunodominant sites, it can be extremely challenging to identify antibodies with different mechanisms.
Hummingbird Bioscience’s proprietary Rational Antibody Development Platform enables precise targeting of epitopes and unlocks the potential to discover multiple mechanisms of action
Building on our proprietary computational structural biology platform (mAbPredict) and insights into systems immunology (mAbHits), the Rational Antibody Discovery Platform allows targeted identification and isolation of antibodies against almost any preferred site on a target protein - unlocking the potential of rational drug discovery to the antibody space for the first time.
Ability to choose where antibody binds is
- Explore multiple Mechanisms of Action in parallel in early development
- Develop antibodies against novel, better epitopes of validated targets
- Avoid cross reactive binding sites that may cause toxicity
- Ensure developability by matching epitope in suitable model organisms
- Optimal CDRs for Antibody-Drug Conjugates,
bi-specifics and TCRs