Our VHH Nanobody Discovery Platform

Flexible by Design. Powerful in Execution.

At Cortalix, we built our platform around one simple principle: no single discovery route fits every target. That’s why we offer two fully integrated, complementary approaches for VHH discovery:

  • Synthetic libraries for speed, modularity, and animal-free selection
  • Immune libraries for target-specific binders with natural affinity maturation

You can choose either route, or combine them, we help you make that decision based on target complexity, timeline, and goals.

Our Discovery Libraries

At Cortalix, we initially created immune libraries from llamas immunized with a mixture consisting of extracellular domains of membrane receptors overexpressed in fibrosis and various cell types present in fibrotic tissue and fibrotic cancers.
Starting from these immune sdAb libraries, we were able to select a large number of attractive sdAb candidates which can be developed into clinical candidates after various in vitro and in vivo studies.
Based on our previous experiences with immune libraries, we have invested in the design and construction of animal-free synthetic sdAb libraries.
For this purpose, we selected robust sdAb frameworks in which the antigen-binding regions in the three CDRs were (partially) randomized using trimeric phosphoramidites to avoid, for example, unwanted stop codons or cysteines.

Synthetic Library Platform

Our synthetic VHH Nanobody libraries are designed for:

  • High diversity (>10⁸ unique clones)
  • Rapid screening (within days)
  • Modular design for engineering flexibility
  • Fully animal-free discovery workflows

Synthetic panning allows you to quickly identify VHH Nanobodies with favorable properties — e.g. for targets that are difficult to immunize. It’s ideal for diagnostic or time-critical applications, or when ethical or regulatory constraints limit animal use.

Immune Library Platform

For complex or highly specific targets, our immune library route is the preferred choice. We immunize llamas with your antigen of interest and generate VHH Nanobody libraries from the B-cell response.

Benefits include:

  • Naturally high-affinity binders
  • Conformational epitope recognition
  • Matured specificity through the immune system

Immune panning is ideal for targets such as GPCRs, ion channels, or low-abundance proteins.

Shared Engineering & Optimization Layer

Regardless of the discovery route, all projects benefit from our advanced VHH Nanobody engineering capabilities:

  • CDR grafting & humanization for therapeutic readiness
  • Affinity maturation using rational design or display systems
  • Stability engineering for harsh environments (e.g., in vitro diagnostics)
  • Conjugation with fluorophores, chelators, toxins, other drugs, Fc domains or enzymes

These tools allow us to optimize any lead for downstream use — in the lab, the clinic, or in commercial applications.

VHH Nanobody Engineering & Optimization

Humanization

It is actually not possible to make a 100% humanized VHH Nanobody as that would disrupt the integrity and therefore the functionality of the single domain antibody. It is possible to approximate that situation as best as possible by replacing some amino acids of the framework, applying residue optimization, CDR grafting and finally evaluating the potential immunogenicity assessment with in silico prediction tools.
By following these activities, we ultimately end up with synthetic nanobody libraries with an optimized framework and variable CDRs that produce molecules with limited immunogenicity, while retaining their antigen-binding properties and good expression properties.

Cloning & Engineering

In the early days, when recombinant antibody technology – mainly focused on scFvs – emerged, VHH Nanobodies did not attract much attention. However, over the years, a steadily growing number of publications illustrated the benefits of VHH Nanobodies in certain research niches. To identify practically applicable VHH Nanobodies, it is important to start from a high-quality gene bank of VHH Nanobodies, focused on the final application and with a great diversity. Our screening and selection procedure using phage display techonology allows us to extract the most promising nanobodies for a particular target from this diverse library. Then, various options for genetic engineering and post-translational modification, including specific spacers and linkers, can be used to tailor the VHH Nanobodies for its final application. For instance, we are experienced with the conjugation of VHH Nanobodies to radionuclide chelators, including NOTA and DOTA derivatives. We use the latest techniques to control the PK and plasma clearance, which is different for a diagnostic and a therapeutic application/VHH Nanobodies. 

3D Modelling

Through 3D simulation we are able to make predictions, within certain limits, about the applicability of selected VHH Nanobodies. 
Now that the first therapeutic VHH Nanobodies have been admitted to the market, other pharmaceutical companies will quickly join in and this will certainly lead to even broader applications, including in the field of radiopharmaceuticals and immunotherapeutics. 
At Cortalix we want to participate in this development, and we will evolve into a party that will accelerate the application of VHH Nanobodiess. Cortalix aims to present solutions that offer prospects for patients who currently do not have them. 

Flexible Routes, Integrated Output

You can start with a synthetic library for speed and parallelize with immune panning later, or vice versa. We adapt the discovery strategy to your target, not the other way around.

All leads, from either route, feed into the same downstream pipeline for characterization, optimization, and production preparation.

Let’s Talk

Let’s contact how we can introduce our Platform Technology to support your antibody discovery program.

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