The present invention is directed to recombinant human antibodies specific
for Cn2 toxin from C. noxius scorpion venom. The antibodies are able to
recognize the toxin and preferably neutralize it as well as the whole
venom of C. noxius scorpion. This invention is also directed to a human
non-immune phage display library. One clone that specifically binds the
Cn2 toxin was affinity matured by directed evolution. Three cycles of
maturation were performed and several scFv clones were isolated which
specifically recognize toxin Cn2 with increased Kd of 446 fold. All
variants were monomeric and only variants 6009F, 6105F and 6103E showed
to be capable of neutralizing toxin Cn2 and the whole venom. Variant
6009F recognizes a different epitope than that of BCF2, a murine
monoclonal antibody raised against scorpion toxin Cn2 which is also
capable of neutralizing both Cn2 toxin and the whole venom when tested in
mice, as well as that of commercially available polyclonal antibody
fragments antivenom from horse. The scFv 6009F is the first reported
recombinant human antibody fragment capable of neutralizing a scorpion
venom. These results pave the way for the generation of safer autologous
recombinant neutralizing antivenom against scorpion stings. The
antibodies of the present invention can be used as part of a composition
to treat those in need of treatment including those already stung by one
or more scorpions, particularly C. noxius scorpions.