AvantGen Awarded SBIR Phase II Grant to Develop High-Affinity Rabbit Monoclonal Antibodies for Neuroscience Related Antigens from the NIH/NIDA

AvantGen Awarded SBIR Phase II Grant to Develop High-Affinity Rabbit Monoclonal Antibodies for Neuroscience Related Antigens from the NIH/NIDA

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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faq Want to learn more?

  • Why Yeast?

    Yeast, or Saccharomyces cerevisiae aka brewer’s yeast to be exact, has the best of both worlds as a model organism for drug discovery. In selecting the right model, two opposing factors are: 1) finding an organism that can be used cost-effectively and ethically, and 2) being physiologically relevant by having it as similar as humans, the intended patients. This is where yeast has all the advantages: 1) it is unicellular, grows incredibly fast at a doubling rate of 90 minutes, and is easy and safe (non-pathogenic) to culture, meanwhile 2) as a eukaryote it can properly express, fold, and glycosylate proteins such as antibodies similar to mammals.

  • Yeast is “similar” but not the same as in humans with regards to post-translation modification (PTM) of proteins such as glycosylation?

    Correct, there are slight differences in the PTM profiles of proteins expressed in yeast versus mammals. However, we recombinantly express our lead antibodies in HEK293 or CHO cells and rarely observe a loss in activity. This is in stark contrast with E. coli-based systems like phage or cell-free, where bacteria lack protein glycosylation machinery.

  • Is affinity maturation required after using one of your platforms?

    Due to our large size rationally-designed Germliner™ library collection coupled with our rapid cell sorting based screening, we consistently obtain single-digit and subnM affinity antibodies with optimal developable characteristics. Interestingly, our popular AvantGeneer affinity maturation platform has been frequently used to optimize client antibodies that were originally discovered with hybridoma and human transgenic mouse platforms.

  • My target is a GPCR. Will your platform work?

    We have had success with multi-transmembrane proteins such as GPCRs, by using virus-like-particles (VLPs), nanodiscs, and client-designed variants with increased solubility.

  • What materials should I provide?

    We typically use various amounts of biotinylated, DyLight™ 650 conjugated, and unlabeled antigens for all projects. It’s important that both labeled and unlabeled antigens are QC’ed by provider, third party, and/or AvantGen. >0.5 mg/mL concentration, >80% monomer percentage, and >90% purity. Preferred buffer is PBS and no tris-based buffers please.

    Estimated Material Amounts*

    Application Stage Discovery Affinity Maturation Rabbit mAb
    All stages 1.5-2 mg biotinylated or 2-3 mg unlabeled 0.5 mg biotinylated or 1 mg unlabeled 2 mg unlabeled and 1 mg biotinylated
    FACS and screening 0.5-1 mg biotinylated or 1-2 mg unlabeled 0.2-0.5 mg biotinylated or 0.5-1 mg unlabeled 1 mg biotinylated and 0.2 mg unlabeled
    Screening only 0.2 mg biotinylated or 0.2-0.5 mg unlabeled 0.2 mg biotinylated or 0.2-0.5 mg unlabeled 0.2-0.5 mg unlabeled

    *Assuming 50 kDa antigen. AvantGen can bioconjugate and QC as needed.

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