Developing drug-like single-domain antibodies (VHH) from in vitro libraries

B cells. This library was further improved by eliminating long consecutive stretches of tyrosines in CDR3 and enriching for CDR1-2 diversity with elevated tolerance to high temperatures. A broad diversity of high affinity (100 pM-10 nM), developable binders was directly isolated, with developability evaluated for most assays using the isolated VHHs, rather than fused to Fc, which is customary. This represents the first systematic developability assessment of isolated VHH molecules.