VHH antibodies as biotherapeutics
Camelid heavy-chain only antibodies were discovered in the early 1990’s. Often referred to as VHH antibodies, they are a well characterized alternative to therapeutic IgG’s.
Camelid heavy-chain only antibodies have no light chain. The VHHs or Nanobodies constitute the binding domain of heavy-chain only antibodies. Nanobody technology was patented in mid-1990’s with patents expiring in 2014. They are now widely used and developed for therapeutics, diagnostics, and laboratory reagents. Camelid VHH antibodies are typically obtained via the immunisation of camelids (e.g Llama) or by using in vitro libraries.
Why choose a synthetic antibody library, over immunising a Llama?
- Large size – Over 1 million fold larger than libraries generated from natural sources, increasing the opportunity to source multiple novel biological candidates with high specificity and affinity
- Diversity – Constructed de novo, using state-of-the-art synthetic biology approaches. No animal immunisation or use of natural human repertoires from B cells.
- Innovative – Immunologically naïve maximising the discovery of potential therapeutic antibodies against a greater range of target epitopes
Features and benefits of VHH single domain antibodies
|Same high affinity and specificity as IgG||Low chance of off-target effects
Target multiple pathways at once
Reduced acquired resistance (escape mutants)
Fusion with other bioactives (eg, ADCs)
|Validated in clinic||Regulator awareness
|Small size||Tissue penetration (ADCs)
Targeting of inaccessible epitopes (GPCRs, Ion Channels, Enzymes)
|High sequence homology to human VH||High homology = lower immunogenicity|
|pH and temperature stability||Shelf-life
Alternative delivery routes (eg, inhaled)
|Simple production||Low cost of goods
Ease of manufacturing and technology transfer
VHH – Clinical landscape: Increasing clinical validation of platform in multiple settings
There are currently 12 VHH antibodies in pre-clinical to phase III validation worldwide (souce Ablynx*).
In summary, a synthetic antibody offers greater opportunity to find a developable therapeutic antibody candidate within a short timeframe. Contact us to start your antibody discovery partnership with Isogenica.
Isogenica is developing LlamdA® (single domain VHH) and Alexandria™ (human Fab) therapeutic antibodies from its proprietary fully synthetic antibody libraries and leveraging its CIS Display and Colibra™ technologies to accelerate the discovery and development process. Over the last four years
Isogenica has entered into eight significant partnerships, leveraging its libraries, technologies and expertise to build a broad pipeline of programs that are now advancing into pre-clinical and early clinical development with our partners.”
T +44 1799 533 680