Monoclonal antibodies are used for treatment of a wide range of diseases from cancer to infectious diseases. However, development of antibodies with high affinity and specificity is still time-consuming, labor-intensive and unpredictable. Abzyme Therapeutics LLC is actively developing animal-free antibody discovery platforms to accelerate generation of therapeutic antibodies. In Phase I, we will create a so-called Self-Diversifying Antibody Library or SDALib as a monoclonal antibody generating system that will provide a diverse array of complete antibodies in vitro, without using immunization. The main feature of the system is the ability to self-generate a cell library with diversified antibodies by means of hypermutation induction in antibody encoding genes. Using the SDALib system, generation time of monoclonal antibodies against any antigen will be reduced to about two weeks as compared to 6 to 9 months normally required using conventional techniques. The platform is adaptable for simultaneous screening for multiple antibodies specific for different target antigens. Since there is no need to immunize whole animals, the SDALib system can generate specific antibodies against toxins, pathogens, self-antigens, and the like which were by nature difficult to obtain in the past. As a proof-of-principle, we will develop camelid single domain antibodies capable of inhibiting the enzymatic activity of influenza A virus neuraminidases (NA) of different suptypes. Once obtained, candidate antibodies will be humanized to reduce immunogenicity in humans. Multivalent and multi-specific antibodies will be produced as linear fusions to increase anti-NA potency and cross-reactivity. Such anti-NA antibodies can be used as a component of a nasal spray for flu treatment by stopping the spread of the flu virus in Phase II.
The vision of this work is to develop an animal-free, cost-effective and high throughput platform for rapid generation of monoclonal antibodies. The fully developed technology will have broad impact on the discovery and development of monoclonal antibodies for research and human therapy. As a specific result of this project, multivalent broadly cross- reactive antibodies with a potential use for flu treatment will be created.