Major strategies for mining human antibody repertoires are: a) non-combinatorial and b) combinatorial strategies. Non-combinatorial strategies retrieve human Monoclonal Antibodies (mAbs) from single B-cells with the original heavy and light chain pairs while combinatorial strategies involve human antibody library with randomly combined heavy and light chains. Both approaches have led to food and drug administration (FDA) and European medical agency (EMA) approved human mAbs. Among non-combinatorial approaches, the adaptation of hybridoma technology to the generation of human mAbs has seen sincere efforts over years, however, has been a slow and difficult process due to the limited number of B-cells stimulated with an antigen of interest and due to lack of its genetic stability. Therefore, generating viable hybridomas is typically challenging for practical applications and has not become a popular choice for mining human antibody repertoires. In contrast, rapidly discover unique antibodies against any target of interest with antibody library screening where display of the antibody on the surface of, either phages, yeast or on ribosomes is currently method of choice.
“INABLR”, (pronounce as Enabler, IN (Integrated) AB (Antibody) LR (Library)) Zumutor’s proprietary antibody discovery platform consists of two parts, highly diverse human antibody gene library and a super-efficient screening technology to discover novel monoclonal antibody of choice.
INABLRS® has three diverse kinds of human antibodies libraries:
a) Naïve library (generated form Indian subjects; library size 1010)
b) Synthetic library (Logical and statistical methods were used to modify CDR3H region; library size1010)
c) Semi-synthetic library (Achieved from naïve and synthetic library; library size 109-10)
In Synthetic Library, complete synthetic CDRH3 segments to the tune of billions of sequences which are grafted on naturally occurring human antibody genes. This synthetic human antibody library represents million folds more CDRH3 diversity compared to natural antibody repertoire.
“INABLR” is designed to deliver integrated solutions,
a) discover specific monoclonal antibody using a combination of phage and yeast surface display technology,
b) screening of either Fab and/or ScFv antibody formats,
c) confirmation of novelty,
d) direct transfer to mammalian expression system for further development.
Combined phage and yeast surface display technologies used to isolate human antibody molecules from above mentioned libraries as a screening platform. The rapid and robust “INABLRS” platform empowers Zumutor’s product pipeline and provides an end-to-end service for our partner’s programs – to discover and develop novel therapeutic mAbs against multiple disease targets.
Fig: Antibody library screening using both Phage and Yeast screening platform
INABLRS® are being used extensively to identify high affinity antibodies against wide range of targets such as ion channels, heteromeric proteins, sugar moieties, immuno-onco targets involved for various academic, industrial collaborations and for in-house discovery programs. Taken together, we have capabilities to fish out unique antibodies against any kind of targets by using our INABLRS® antibody library platform.