AvantGen is a San Diego-based biotechnology company founded in 2006 with Therapeutic and Research & Diagnostic divisions. Its Therapeutic Division is dedicated to novel human antibody discovery, antibody humanization, antibody affinity maturation and optimization for therapeutic development. AvantGen has a proprietary and robust yeast display system, large natural human antibody database, fully human antibody (Germliner™) libraries and screening technologies and collaborates with pharmaceutical and biotechnology companies to facilitate and speed their path to antibody-based therapeutic development through services, partnerships, and licensing.
Additionally, AvantGen has developed a novel platform to generate rabbit monoclonal antibodies with very high affinity and specificity by combining AvantGen’s yeast display system and the alternate diversity obtained from the immune responses in rabbits. With this platform, AvantGen’s Research & Diagnostic Division develops high quality rabbit monoclonal antibodies for high value diagnostic targets for NIH’s proteomic projects. AvantGen also provides services to pharmaceutical and biotech companiesas well as academic researchers for their needs in obtaining superior rabbit monoclonal antibodies.
The power of AvantGen’s technology platform has been well recognized by the National Institutes of Health (NIH). AvantGen has received 18 SBIR Phase I and Phase II grant and contract awards to date from the NIH to develop novel antibodies against multiple targets for therapeutic, diagnostic and research reagent development. AvantGen has also successfully completed de novo antibody discovery, antibody humanization and optimizations for pharmaceutical, biotech companies, and academic institutions.
AvantGen has constructed 30 human antibody libraries (Germliner™) with multiple human antibody germline frameworks. These were selected based on their high stability, solubility and expression level. Diversity is focused in the CDR regions and mimics the diversity of the natural human antibody repertoire for that variable region family. The framework sequences are left as fully human germline sequences. AvantGen’s proprietary libraries are comprised of >100 billion members, are well expressed and displayed with AvantGen’s yeast display system allowing efficient human antibody discovery.
Coupled with AvantGen’s proprietary screening technologies, we can rapidly isolate fully human antibodies against not only the antigen, but also the epitope of interest and with other desired characteristics, such as high affinity (sub-nM to low nM), high specificity, and functional activity from the libraries within weeks.
Starting with the target of interest, AvantGen can perform a complete antibody discovery service. AvantGen will perform the screening, isolation, identification, and characterization of the novel antigen-positive antibody clones. The VH and Vκ/λ antibody fragments can be readily subcloned into the full-length IgG format of choice.
AvantGen can also produce antigens and develop and run functional assays to support the human antibody discovery program.
Therapeutic antibodies need to meet stringent criteria for development and testing. Antibodies from many discovery methods may have interesting properties but not meet the required profile. Affinity maturation and optimization of a pre-existing antibody can preserve the epitope specificity and its functional activity. Optimization can also boost the antibody’s potency to the desired level. In addition, it can be useful to remove potential modification sites for improved developability. With AvantGen’s antibody database and yeast display system, AvantGen is able to quickly design focused libraries based on the antibody to be optimized, and simultaneously screen for antibodies with higher affinity and higher levels of expression, while removing undesirable post-translational modification sites. Our system routinely yields affinity improvement of 10-1,000 times or greater compared to the parental antibodies.
Although fully human antibodies are ideal for therapeutic development, humanized antibodies currently dominate the therapeutic antibody market, since historically, many murine antibodies generated as research reagents were later shown to have properties of interest for therapeutic development. These antibodies were then humanized to minimize immunogenicity and to provide effector functions in humans. There are many approaches to humanize murine antibodies. The most common approach is to graft the 6 CDRs from a murine antibody onto a human antibody acceptor framework. However, such CDR grafting often results in partial or complete loss of affinity of the humanized antibody. Also, some residues from the murine framework sequences need to be retained to replace the human residues at the corresponding positions (back mutations) in order to restore some of the lost affinity.
Therefore, it is critically important to accurately pinpoint the key residues to be retained and to select a suitable human antibody germline acceptor that can support the structure of humanized antibodies with goodthermo-stability and solubility for downstream development. AvantGen has extensive antibody modeling and engineering expertise to successfully restore and, if necessary, improve on the binding affinity of the humanized antibody with superior developability.
In addition, AvantGen has also developed an improved antibody humanization technology using its advanced yeast display system. Using this technology, the CDR3-H region alone from an antibody to be humanized is grafted into the relevant VH antibody sublibrary in place of the existing human CDR3-H regions. This is in turn is coupled with the relevant existing human VL library to generate a focused library of humanized antibodies. This library is then screened for higher affinity binders using a FACS epitope-guided approach. The resulting humanized antibodies will have fully human antibody sequences in the variable regions, except for CDR3-H which is from the original non-human monoclonal antibody. Therefore, the humanized antibody greatly reduces potential immunogenicity, while maintaining or improving affinity of the original antibody.
The rabbit immune system generates and affinity matures antibodies by mechanisms that differ from those of mice and other rodents. Rabbit monoclonal antibodies normally have 10 to 100-fold higher affinity for antigen than mouse monoclonal antibodies. In addition, the rabbit immune system can generate antibodies that are able to distinguish between very similar molecules with subtle structural variations.
Advantages of AvantGen’s technology for generation of rabbit monoclonal antibodies
We combine an optimized rabbit immunization protocol and AvantGen’s robust yeast display system. Thus, we are able to generate a yeast display library of sufficient size allowing us to isolate very high affinity monoclonal antibodies. The yeast display system is uniquely suited for rabbit antibodies, which have an additional disulfide bond in their light chain. This disulfide bond formation is believed to be important for the high affinity and specificity observed for rabbit antibodies. In contrast, phage display normally does not support such modifications.
Our approach overcomes issues associated with rabbit hybridoma-based technology, such as low fusion efficiency, unstable cell lines and low antibody yield. It also greatly shortens the time required to generate monoclonal antibody producing stable cells. Finally, antibodies generated with our technology often exhibit affinities in the range of 0.001-1.0 nM as demonstrated by a recently completed contract project for the National Cancer Institute (NCI)[HHSN261201300023C].
Harness the advantages of rabbit monoclonal antibody for your research needs
AvantGen’s custom services offer you:
Fluorescence-activated cell sorting (FACS) is a specialized type of flow cytometry which can be used to sort a heterogeneous mixture of cells into different homogeneous subpopulations of interest based upon the specific light scattering and fluorescent characteristics of each cell. In such a mixture of cells, the different subpopulations may have different antigenic or other markers on their surface. These markers can be tagged by the means fluorescently-labeled antibodies which can then be detected by laser and light detectors.
This powerful and versatile technology can provide rapid, accurate, and high throughput cell analysis. It can be used to study cell cycle, cell proliferation, cell viability, cell phenotyping, cell signaling, intracellular cytokine secretion, etc. The advanced equipment in our laboratory allows us to conduct accurate experiments with high efficiency. We have experienced scientists that can provide ideal and customer-tailored experimental designs and our team can offer you the professional data analysis you need.
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