Expression of functional antibody fragments

Abstract

Methods for the high yield production of antibody Fv-containing polypeptides, especially Fab′ and F(ab′) 2 antibody fragments are provided. Expression of heavy and light chain Fv in a microbial secretory system is followed by recovery of Fv from the periplasm under conditions that maintain a cysteine residue as a free thiol. The free thiol is reacted with free thiol of an antibody fragment of the same or differing specificity, or with agents such as diagnostic labels or therapeutic moieties. The products offer advantages of homogeneity and purity not available through the use of known methods for preparing such derivatives.

1 - 21 . (canceled)  
     
     
         22 . A method for high yield production of an immunoglobulin polypeptide comprising culturing a host cell transformed with nucleic acid encoding an immunoglobulin polypeptide under the transcriptional control of an inducible promoter/operator system wherein the promoter/operator system is subsequently induced, thereby resulting in polypeptide levels in the cell culture of greater than about 1 gram of polypeptide per liter of cell culture.  
     
     
         23 - 24 . (canceled)