Prolonged in vivo residence times of antibody fragments associated with albumin

Antibody fragments can be expressed at a high level in microbial systems, but they may have limited therapeutic value because they are rapidly eliminated from the body. We demonstrate here that site-specific conjugation or binding of bacterially derived Fab ' to the long-lived protein serum albumin allows full retention of the antibody's binding characteristics while imparting the albumin's longevity in vivo. In rats the area under the curve for Fab ' conjugated to rat serum albumin was 17-fold greater than for the control of Fab ' conjugated to cysteine. Again, a bispecific F(ab ')(2) with specificity for rat serum albumin showed an area under the curve about 8-fold greater than did a F(ab ')(2) without specificity to albumin. Genetic fusions of scFv to albumin were similarly long-lived and could be expressed in yeast to provide the basis of a cost-effective production system.