This process for engineering human antibodies results in sequences very close
and in some cases identical to human germline. The property of closeness-to-human-germline
(and not merely 'fully human') has implications beyond immunogenicity. Unlike
other technologies, Humaneering™ yields large panels of antibodies with the
identical binding specificity; therefore, clones can be chosen that fulfill not
only classic issues of antibody engineering (e.g., affinity and specificity),
but also DSP issues (e.g., expression level, stability, etc.) as shown below:
V-region sequences
High amino-acid sequence identity with human germ-line, including CDRs 1+2 from each chain
V-regions sequences are mainly from a human source and are close to germline in sequence
CDR lengths and sequences are 'natural'
Important for low immunogenicity
Affinity
Binding affinity and selectivity is high
Kinetics on/off rates can be selected
Important for potency/dose/cost of goods
Express level
Antibodies are screened for high level expression
Important for cost of goods
Physicochemical properties
Mainly determined by V-region sequences
Solubility, stability and lack of aggregation
Important for low immunogenicity, cost of goods and route of delivery
