Recombinant VHH libraries from Specifica deliver:
- Fully humanized VHHs – not just the frameworks, but also the CDRs are humanized
- Providing improved safety and therapeutic efficacy
- Broad diversity – our phage display libraries far exceed the diversity of immunization, and sorting via yeast display provides additional capabilities to enable selection for desired properties
- High specificity – controlled selection conditions allow you to focus on specific regions of your target antigen
- High affinity – exceptional binding due to the preserved CDR regions, often reaching into the sub-nanomolar range
- >50% of campaigns yield at least one subnanomolar binder
- >50% of binders <10nM and ~5% of binders are subnanomolar
- High affinity and specificity – combined, high affinity and desired specificity can provide a drug-like VHH straight from selection, often without the need for additional improvement
- High developability – over 70% of VHHs have two or fewer biophysical liabilities
The Specifica approach to building VHH libraries
- Our VHH libraries are based on well-behaved therapeutic VHH molecules
- HCDR1 and 2 natural replicated diversity from rearranged VH3 family genes are inserted into CDR1-2 of the therapeutic VHH scaffolds
- HCDR1 and 2 natural replicated diversity is bioinformatically curated to remove sequence liabilities
- Each individual CDR is filtered for display
- Amplified HCDR3s from a unique donor set are inserted into CDR3 of the therapeutic VHH scaffolds
- HCDR3 natural diversity, provides the vast diversity which allows the identification of specific, high affinity binders towards virtually any target
- Multiple rounds of phage and yeast display are used to screen our vast libraries and select only candidates with properties of interest to our clients
Advantages of VHH antibodies
- VHHs are single-domain antibodies based on camelid antibodies
- VHHs are much smaller than traditional antibodies, enabling them to bind to challenging targets including “hidden” epitopes, less easily accessible by traditional antibodies
- VHHs are generally more diverse than other antibody fragments, due to their unique structure, with elongated CDR1 and CRD3 loops
- VHHs are stable and soluble, making them well suited to meet the developability requirements of consistent quality and reduced variability
