Rabbit antibodies – high yield of high affinity

While our human acceptor scaffold and MATCH^TM-formats are in principle applicable to antibodies from any source (human, rodent, etc.), our proprietary pipeline is fuelled by a powerful combination of rabbit immunization and an ultra-high throughput flow cytometry procedure to exhaustively characterize the full rabbit antibody repertoire of hundreds of millions of antibodies, in a few days. Our discovery process typical yields panels of hundreds of high-affinity monoclonal antibodies.

Our proprietary λ-Cap^TM technology is the basis of our highly stable, fully human variable region fragment, or Fv, acceptor scaffold onto which complementary-determining regions, or CDRs, from conventional antibodies can be engrafted.

Numab stabilizes its antibody Fv fragments by exchanging a notoriously unstable part of the scaffold (FW4 of Vϰ) by a stability conferring sequence referred to as λ-Cap^TM (FW4 of Vλ).

A scaffold with unmatched stability

Traditionally, antibody Fv fragments have proven intractable to therapeutic use due to their inherent instability. With an elegant engineering step, Numab has overcome this hurdle by replacing a short stretch of a human variable light kappa-chain with the equivalent λ-chain stretch at the C-terminus of the light chain. This results in a fully human Fv acceptor scaffold with unmatched stability on which CDRs (complementarity determining regions) from any monoclonal antibody can be engrafted, irrespective of their origin, be it human, rodent, or rabbit. The so-called λ-Cap^TM constitutes a true breakthrough and endows our human acceptor scaffold with hitherto elusive stability. The resulting favorable properties have effectively turned the humanization/stabilization procedure into a routine procedure for most antibodies while maintaining their affinity and on the whole, adopting the favourable human acceptor scaffold’s biophysical properties.

Multispecific Antibody-based Therapeutics by Cognate Heterodimerization (MATCH^TM) is a modular scaffolding technology with unprecedented stability, and the ability to generate highly stable multispecific antibody formats.

The proprietary, highly flexible, multi-specific format has the potential to incorporate up to six λ-Capped^TM Fv fragment building blocks and, consequently, to allow for up to six binding specificities.

The MATCH^TM format is a heterodimer that can contain up to six different antigen-binding sites. The variable heavy (VH) and light (VL) chains of the two core domains are placed in two separate protein chains, and their highly stable VH-VL interfaces drive the MATCH^TM format’s heterodimerization.

MATCH^TM formats can incorporate up to six λ-capped^TM Fv building blocks and binding specificities in a true plug-and-play fashion. Most importantly, the stability of the λ-capped Fv fragments and the fact that they do not aggregate confer excellent CMC properties on MATCH^TM molecules.