Due to their small size and unique structure, single domain camelid VHH antibodies are ideal for labeling/targeting studies and for use as building blocks for the generation of novel biological drugs with multiple advantages. Using our proprietary antibody generation SDALibTM platform, VHH antibodies against established and emerging targets can be rapidly generated with desired attributes.
Key advantages of camelid VHH include:
• Building blocks: VHHs serve as building blocks to create multivalent therapeutic molecules capable of binding multiple targets including cross-linking T-cells to cancer cells. The different VHH building blocks are linked together with flexible Glycine-Serine linkers of different lengths.
• Difficult targets: Due to its small size and long CDR3, VHH can interact with cryptic epitopes on targets which are hidden or shielded from much larger conventional antibodies. VHHs are an excellent choice against cell surface and membrane proteins or large protein targets with a pocket such as GPCRs, ion-gated, ligand-gated, and voltage-gated ion channels.
• Alternative route of administration: The small size and exceptional stability of VHH allows administration through multiple delivery routes including: intravenous and subcutaneous injection, nebulization directly into the respiratory tract, and potentially through the ocular route or orally for local treatment in the gut
• Customized half-life: As a building block, VHH can be expressed as a fusion with Fc or anti-albumin VHH to extend its serum half-life from hours to days or weeks
• Antibody-drug conjugates: Due to their small size, VHH possess properties optimal for ADCs such as rapid tissue penetration and accumulation while clearing quickly from circulation system to minimize systemic toxicity
• High yield production: VHH including multivalent and multi-specific fusions are encoded by single genes and are efficiently produced in various prokaryotic and eukaryotic hosts, including bacteria, yeast, and mammalian cells.
Advantages of Abzyme’s antibody discovery platform include:
Patented inducible triple-mode system: Our system uses inducible in vivo antibody affinity maturation, and a switchable antibody surface display or antibody secretion mode to accelerate the antibody selection, optimization and production processes.
In vivo antigen-directed antibody affinity maturation: A direct mimic of mammalian antibody diversification and affinity maturation processes
Eukaryotic-based selection system: Filters for well-expressing and manufacturable antibody candidates
Antibody generation against difficult targets: The animal-free system enables us to develop antibodies to a variety of difficult targets including, non-immunogenic or highly toxic antigens as well as cell surface multi-pass membrane protein antigens.
Hybrid approach: Where appropriate, Abzyme will utilize an animal immunization-derived immune library/yeast triple-mode hybrid approach to isolate developable domain antibodies with desired attributes.
Unsurpassed diversity: Unprecedented diversity of antibodies thanks to inducible somatic hypermutation.
FACS-based approach identifies desired antibodies: Advanced processes for rapid identification of antibodies with desired attributes
Advanced antibody optimization capabilities: Combination of combinatorial libraries with defined amino acid substitutions at selected sites of existing antibodies with FACS-based approach screening allows to rapidly optimize leads into best-in-class therapeutic candidates. We have developed a robust platform to optimize existing antibodies to targeting the tumor micro-environment and reducing the potential on-target off-tumor side effects via developing antibodies that have high affinity at low pH (pH in the tumor microenvironment) but have low or weak target binding at the normal pH. Such pH dependent antibodies would be desirable for treatment of solid tumor, especially in T-cell mediated immunotherapy.
Abzyme’s antibody discovery platform incorporates the ability to select for key properties such as epitopic diversity, binding affinity, antibody pH-dependent binding preference, expressibility, solubility, developability, broad-reactivity and target-specificity into real-time screening.