TECHNOLOGY

In Vitro Human Display

Mabqi’s technology is based on proprietary fully human synthetic antibody libraries and highly innovative, flexible and robust display technology, especially fitted for challenging targets.

In Vitro Display: Our Technology of Choice

  • Speed
    First result in a few weeks (ELISA, FACS...)
    Direct access to antibody sequence
  • Human antibodies*
    Fully human scaffold 
  • Powerful in vitro selection
    Peptides, proteins, whole cells
    Depletion, epitope exlcusion, ...
  • No immune restriction
    Access to epitopes "hindered" in mouse
    Species cross-reactivity
  • High specificity
    Domain/epitope
    Conformation
    Post-translational modification
    Isoform
  • Homogeneous library*
    Expression, stability

* Mabqi library

In vitro display technologies, brewing for years in the academic environment, have recently been unleashed from patent restrictions allowing Mabqi to make its optimal use for the rapid generation of antibodies virtually against any target of any type (peptides, proteins, whole cells) and with high control over the antibodies selected.

Unique advantages offered by this technology over the traditional hybridoma approach includes: the ability to define specific selection conditions allowing the derivation of antibodies recognizing predefined epitopes or conformations, the immediate availability of genes encoding the selected antibodies, and their further improvement (e.g. affinity maturation, engineered developability).

Furthermore, the starting naive antibody library can already be made human (no more humanization needed) and selections can be designed to obtain species crossreactive antibodies (eg. mouse-human) allowing better assessment of therapeutic efficacy and toxicity in animal models.

Mabqi benefits from strong experience accumulated over the years by Pierre Martineau’s team at IRCM Montpellier, in in vitro phage display technology coupled with highly optimized proprietary humanized synthetic antibody libraries from which antibody leads have been obtained for challenging targets: GPCR agonists, enzyme inhibitors, antipost-translational-modification, anti-splicingvariants, Tyr-Kinase Receptors, anti-ligand, …

Our Human Synthetic Libraries

The discovery of an antibody fragment that could retain its functionality inside cells and be produced stably in very high yields by Pierre Martineau and Sir Greg Winter (Nobel Prize in 2018) in Cambridge in 1998 opened up the doors to the generation of antibody fragment libraries and corresponding full antibodies with high developability properties. Over the years, these so called “naïve” or “single pot” antibody phage libraries derived from this unique clone have been used successfully by Inserm to derive highly specific and stable antibody reagents to a wide range of different target proteins, protein complexes, peptides and cells.

The latest libraries, HuscI2TM (scFv phage display library), FabIgTM (Fab phage display library), and pHuscI2TM (pH-sensitive phage display library) – Inserm and Mabqi joint ownership – combine the data gathered from the use of this scaffold, bioinformatics and structure modeling to optimize stability, paratope diversity, and affinity. Rational structure-based design and best-in-class precision technology have been used for accurate synthesis to maximize functionality and developability.

 

OUR SCAFFOLD: A KEY STRUCTURAL ELEMENT FOR HOMOGENEOUS HIGH EXPRESSION AND STABILITY

Our libraries are based on a single optimized scaffold reaching remarkably high levels of expression and stability.

Furthermore, the library diversity on this framework has been carefully designed to retain these properties resulting in collections of selected antibodies with homogeneous high expression and stability.

AN OPTIMIZED LIBRARY FOR STABILITY, AFFINITY AND EPITOPE COVERAGE
Through extensive bioinformatics analysis of hundreds of antibody-antigens crystal structures and model structures integrating the hyper-stable scaffold, key positions and residues were identified to optimize diversity for stability, affinity, and epitope coverage.
BILLIONS OF HUMAN ANTIBODIES

The human scaffold, diversification and hypervariable loop lengths variations are consistent with human antibodies.

Therefore, all antibodies from our libraries, which reach a diversity of 3-10 billion, are classified as human under the new INN nomenclature scheme (Geneva, November 2021).

Our Processes

Besides the library, key to successful antibody recovery is clearly dependent on the process and screening protocols adopted to fit the projects specificities.

Over the years, we developed a robust toolbox for antigen preparation, a broad range of selection schemes including pH-sensitive antibody selections using our proprietary pH-sensitive antibody library, scFv-Fab-mAb rapid reformating, screening, and numerous advanced bioanalytics to characterize and validate the Ab hits we provide for final lead selection. Our in-depth knowledge of phage display and scientific expertise in antigen preparation, assay development, and screening protocols, has resulted in successful delivery in all our projects.