A step by step demonstration of how we get the best candidates in just 21 days. Scroll your way through !
We first characterize your target: retrieve or model 3D structure, competitive analysis, suitable regions for antibody binding. Then we choose the epitope(s) with you.
We find antibodies binding to the chosen epitope. These antibodies can be designed completely in silico or they can come from different sources: your own antibody bank, MAbSilico’s antibody bank, NGS of enriched immune repertoires, NGS of patients repertoires.
The binders are optimized for affinity, developability, low off-targets number, diversity. The selected final candidates are your leads, ready for functional validations and pre-clinical studies.
The leads sequences are obtained by gene synthesis, cloned to be expressed as full-length IgGs, ready to be tested in binding (Cytometry, HTRF, BLI...) and in your functional assays.
Get antibodies binding to a determined region on your target
Get antibodies with nano-molar affinity
Get antibodies optimized and ready for pre-clinical developmement
MAbSilico enables our partners to accelerate and improve the success rate in identifying the best lead candidates. Our epitope-driven antibody design uses a multi-parameter approach to design antibodies while taking into account affinity, specificity, developability, and safety all at once.
Design new leads against your target.
Computational epitope-driven antibody design against TIGIT with nM affinity:
TIGIT is a major immune checkpoint target to develop new drugs for cancer treatment. More than 10 biotech and pharma companies are trying to design the drug for tomorrow’s breakthrough treatment. While 9 clinical trials are ongoing, more than 1000 of anti-TIGIT antibodies are described in patents. MAbSilico’s goal was to design, from a non-paired scFv naïve bank, antibodies directed against a predetermined epitope of TIGIT with nanomolar affinity.
"We discovered new drug candidates in a couple of days compared to several months"
Testimonial from Nicolas Poirier, CEO of OSE: What was impressive is the high success rate higher than 50%, compared to the usual 5%, which allows our company to accelerate, to decrease the risks and to develop new immunotherapies for the patients."
Out of trillions of possibilities, MAbSilico managed to design, in 21 days, 300 antibodies among which 90% were validated with bioassays to bind TIGIT. Computational affinity maturation was then performed on the best candidates and BLI showed that sub-nanomolar affinity was reached. During the design and optimization, MAbSilico evaluated the criteria to limit cross-reactivity and avoid liability issues, in order to get the best candidates fulfilling developability specifications and freedom-to-operate.
Optimize your hits.
The anti-FSH antibody was docked on the 3D structure of the FSH, and the epitope predicted. Experimental validation was tricky, since FSH is not a membrane protein, and is a notoriously difficult protein to produce. Indeed, FSH is constituted of two chains (⍺ and ß), assembled and linked by disulfide bonds. To validate the epitope prediction, a construct was designed, including the two chains fused to a trans-membrane helix domain, resulting in the membrane anchorage of the hormone. We validated that the antibody binds with high affinity to this construct. Mutations were then introduced at the positions predicted to belong to the epitope of the antibody. We showed experimentally that binding to the mutants was decreased or abolished, validating our predictions.
Results were presented at the conference “Writing the Future of Drug Discovery”.
3D structure of the ChemR23 receptor, a GPCR involved in Inflammatory Bowel Disease, was modeled from that of angiotensin receptor. The antibody developed by OSE Immunotherapeutics was docked on this model, and we predicted its epitope. Experimental validation of the epitope was performed using enzyme-linked immunosorbent assay (ELISA) binding assay. Results were published in Science Advances.
More information about ChemR23: https://www.ose-immuno.com/en/our-products/ose-230-modular/
Our technologies can be used for scaffold protein and peptides
Drop us a line if you want to know more about our technology or if you are willing to talk about your projects. We are always keen on discussing science!
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