Human soluble VH and VL single-domain antibody libraries for human therapeutic applications (L-11686, L-11965)
Camelid VHH and shark VNAR single-domain antibodies have the drawback of being immunogenic because of their non-human nature. This limits their applications in human therapy. Fully human VH and VL single-domain antibodies would be ideal molecules for human therapy because of their expected lower (or lack of) immunogenicity. However, since they are generally insoluble, methods need to be developed to select non-aggregating domains of the antibody molecule. NRC's non-aggregating human single-domain antibodies possess all the desirable properties of naturally occurring ones, with the added advantage of being non-immunogenic, and are applicable to a broad spectrum of therapeutic applications, e.g. cancer or infectious diseases.
- A commercial exploitation licence for the technology.
- Development of this technology through a joint collaboration.
Therapeutic monoclonal antibodies (mAbs) are used to treat wide range of diseases, from cancer to rheumatoid arthritis. MAbs are the fastest growing molecule segment in the prescription pharmaceutical industry; global sales of mAbs are growing at a compound annual rate of 9.5 %, from $36B in 2009 to reach $62.7B by 2015 (source: Datamonitor).
How it works and benefits for partners
The invention addresses the exceedingly large size and/or poor biophysical properties such as low stability, irreversible unfolding and low expression and, therefore, limited clinical applications of human conventional antibodies and antibody fragments.
The technology offers:
- a selection method for the isolation of non-aggregating binders from phage mid vector-based single-domain antibody phage display libraries; and
- two novel randomization strategies that:
- make VH synthetic libraries a good source of enzyme inhibitors and binders to cryptic sites; and
- increase the proportion of non-aggregating VHs and VLs in synthetic VH libraries.
NRC file 11686: Patents granted in the US, Canada, Europe, Japan, Singapore
NRC file 11965: Patents pending
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