TECHNOLOGY

Harnessing the power of fully human libraries for antibody discovery

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

Advantages of in vitro libraries

  • 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 antibody libraries offer several advantages over traditional animal immunization strategies for the discovery and development of therapeutic antibodies.

These libraries are key for generating diverse and high-quality antibodies, featuring the following benefits:

  • High diversity: In vitro antibody libraries can achieve immense diversity, with sizes reaching up to 1011 independent clones. This significantly enhances the likelihood of identifying antibodies with high affinity and specificity for a wide range of antigens. Moreover, they enable the selection of antibodies against virtually any antigens including challenging targets such as GPCRs and ion channels.
  • Generating fully human antibodies: Combinatorial antibody libraries can directly generate fully human antibodies, by-passing the immunogenicity concerns often associated with animal-derived antibodies.
  • Direct selection for specific features: In vitro selection allows for screening antibodies with desired specific characteristics such as stability, species cross-reactivity, and high binding affinity, all within the selection process itself.
  • Engineering flexibility: Antibodies produced in vitro can easily be converted into various formats such as: standard IgG, engineered IgGs (Fc-enchanced/Fc-silenced), Fab, single-chain variable fragments (scFv), ADC, bsAb). This versatility allows customization for specific therapeutic or diagnostic applications.

Mabqi has designed a suite of fully human synthetic naive HuscI2™ antibody libraries based on a highly developable scaffold.

Husci2TM: Proprietary human synthetic antibody 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 (co-founder of Mabqi) 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 patented and used successfully to derive highly specific and stable therapeutic antibodies to a wide range of different targets (proteins, protein complexes, peptides and cells).

Mabqi offers a suite of human antibody libraries that integrate data from 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.

Proprietary ready-to-use antibody libraries

  • HuscI2TM: scFv phage display library
  • FabIgTM: Fab phage display library
  • Next generation pHuscI2TM: pH-sensitive phage display library

We leverage on key advantages of our antibody discovery platform:

  • delivers fully human antibody hits
  • with high-developability and stability: hyper-stable scaffold
  • in any format of interest: IgG, scFv, Fab, ADC, bsAb,…
  • enhanced diversity (1011 clones)
  • superior affinity: ranges from picomolar (pM) to nanomolar (nM)
  • cross-species coverage: cross reactivity with key preclinical species meeting the sponsor’s requirements
  • fully characterized and validated with improved characteristics (e.g., pH-sensitivity, internalization, cytotoxicity, stability, antagonist activity,… ).
 

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 (functional diversity >1010 with minimal risk for immunogenicity) has been carefully designed to retain the scaffold remarkable properties resulting in collections of selected antibodies with homogeneous high expression and stability.

AN OPTIMIZED LIBRARY FOR STABILITY, AFFINITY AND EPITOPE COVERAGE

Through extensive  in silico 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 CDR residue usage and lengths variations are consistent with human antibodies.

Antibody selection worflow : AI-powered phage/yeast display

Mabqi has extensive experience in in vitro phage and yeast display technologies combined with highly optimized proprietary humanized synthetic antibody libraries from which antibody leads have been obtained for challenging targets: GPCR, ion channel, peptides, pMHC, …

 

AI-empowered antibody discovery engine unlocking new frontiers in antibody therapeutic discovery

 

Mabqi leverage its discovery engine with artificial intelligence and ML powerful cutting-edge tools for:

  • Advanced antibody library design
  • Comprehensive target antigen analysis and engineering
  • Precise antibody-antigen docking simulations
  • Efficient antibody optimization

 

These AI-driven approaches significantly accelerate the antibody discovery process, improve the quality of candidates, and enhance the overall efficiency of therapeutic antibody development.