INTERCALATED SINGLE-CHAIN VARIABLE FRAGMENTS

摘要

Single chain antibody polypeptides with engineered peptide bond crossovers in the light chain and/or heavy chain variable domains, compositions comprising the same, and methods of making and using the same are provided. The antibody polypeptides can be intercalated (crossover) single chain variable fragments (scFvs) or any antibody frameworks which comprise such scFvs, such as diabodies, bispecific antibodies or bssFvs. The single chain antibody polypeptides may or may not contain a linker. The single chain antibody polypeptides are useful in applications where standard (conventional) scFvs are useful, such as in the development of scFv libraries for screening, as therapeutic antibodies, or in in vitro and in vivo targeting applications.

主权项

1. A single chain antibody polypeptide comprising a heavy chain variable domain and a light chain variable domain, wherein the antibody polypeptide comprises at least one interdomain crossover, at least one intradomain crossover, or at least one intradomain crossover and at least one interdomain crossover, wherein each crossover is an engineered peptide bond producing an intercalated structure (arrangement or organization) selected from the group consisting of:
a) at least one portion of the heavy chain variable domain intercalated (inserted) into the light chain variable domain; b) at least one portion of the light chain variable domain intercalated (inserted) into the heavy chain variable domain; c) at least one portion of the light chain variable domain intercalated (inserted) into a different portion of the light chain variable domain; and, d) at least one portion of the heavy chain variable domain intercalated (inserted) into a different portion of the heavy chain variable domain.