Posted on March 1, 2015

AvantGen, a leader in novel antibody discovery and engineering, was awarded a SBIR Phase II grant from the National Institute on Drug Abuse (NIDA) of the National Institutes of Health (NIH) to develop novel rabbit monoclonal neuroscience antibodies against 120 targets.

Neuroscience related proteins are highly conservative and homologous among different species, making them difficult targets to generate high quality antibodies.  Therefore, we need novel methods to yield neuroscience antibodies and one that can distinguish between related family members.

AvantGen has developed its proprietary yeast display system and rabbit antibody libraries. This will allow the discovery of novel antibodies for research, diagnostic and therapeutic development. AvantGen’s technology bypasses the low efficiency (1 in 1 million) of fusion between antibody-producing cells (B cells) and myeloma used with hybridoma technologies. Following this, we will sequence the antibodies isolated with AvantGen’s technology and express them in mammalian cell systems. This prevents the instability and low antibody yield issues of rabbit monoclonal antibody cell lines.

The most widely used reagents to detect and quantify proteins are mouse monoclonal antibodies . However, a recent study showed that only about 25% of antibodies on the market are specific, due to the vastly different characterization criteria used by different providers. In addition, the affinities for antigen of the current antibody clones on the market vary considerably, ranging from μM to sub nM.  Rabbits generate much stronger immune responses than mice to antigens in general, but small peptides and haptens in particular. This is due to their unique use of both gene conversion and somatic hypermutation and the diversity of light chain variable regions, including germline encoded Vκ variability in CDR-3 length. Finally, rabbit monoclonal antibodies generally exhibit 10-100 fold higher affinity for antigens than murine monoclonal antibodies.

Antibody clones developed with AvantGen’s technologies are highly specific. We can readily select them to distinguish between related family members, different isoforms, post-translational modified variants, and different conformations.

This Phase II grant will allow AvantGen to develop highly quality rabbit monoclonal neuroscience antibodies against such challenging targets. The developed antibodies will be fully characterized by AvantGen’s collaborators at the Mount Sinai Icahn School of Medicine.


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