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 and ion channels.
• Alternative route of administration: The small size and exceptional stability of VHHs allow administration through multiple delivery routes, including intravenous or subcutaneous injection; nebulization directly into the respiratory tract or eye or orally for local treatment in the gut.
• Customized half-life: As a building block, VHHs can be expressed fused to an Fc domain or to an anti-albumin VHH, to extend its serum half-life from hours to days or weeks.
• Antibody-drug conjugates: Due to their small size, VHHs possess properties optimal for ADCs, such as rapid tissue penetration and accumulation while clearing quickly from circulation, resulting in less systemic toxicity.
• High yield production: VHHs, even in multivalent and multi-specific fusions, are encoded by single genes and are efficiently produced in various 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.
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, such as well-expressing and manufacturable antibody candidates.
Advanced antibody optimization capabilities: Our combinatorial libraries with defined amino acid substitutions at selected sites and FACS-based screening allow us to rapidly optimize existing antibodies into best-in-class therapeutic candidates. We have developed a robust platform for optimizing existing antibodies to the tumor micro-environment by screening candidates with high affinity to its target in the tumor microenvironment, but with weak target binding at normal pH outside the tumor microenvironment. Such pH-dependent antibodies would be especially desirable for the treatment of solid tumors mediated by T-cell immunotherapy.
Abzyme’s antibody discovery platform incorporates the ability to select for key properties such as epitopic diversity, binding affinity, pH selectivity, expressibility, solubility, developability, and broad-reactivity in real time.