Antibody fragments can be isolated rapidly using techniques such as phage d
isplay and can be expressed to high levels in microbial systems. However, t
o date such antibody fragments have been of limited use for many therapeuti
c applications because they are rapidly cleared from the body. We present a
strategy for the site-specific chemical modification of antibody fragments
with polyethylene glycol, which results in the production of antibody frag
ments with long in vivo half-lives and full retention of antigen-binding pr
operties. This technology should allow more rapid and economical production
of therapeutic antibodies for chronic disease therapy.