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

 

Feature

Benefit

Same high affinity and specificity as IgG

Low chance of off-target effects

Predictable mode-of-action

Multi-specific

T-cell recruitment

Target multiple pathways at once

Higher cell-specificity

Reduced acquired resistance (escape mutants)

Modular

Customisable half-life

Fusion with other bioactives (eg, ADCs)

Validated in clinic

Regulator awareness

Industry confidence

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. This email address is being protected from spambots. You need JavaScript enabled to view it. to start your antibody discovery partnership with Isogenica.

 

Download the infographic