Fibronectin Artificial Antibody Scaffold

Artificial Antibody Scaffolding

Human fibronectin Type III (FN3) has epitope-binding loops analogous to those in naturally occurring immunoglobulins. This gives the resulting molecule the binding properties of an immunoglobulin antibody and the improved chemical and biological properties of the smaller (~100 amino acids) human FN3 molecule. Artificial antibody scaffolds are being employed as substitutes for antibodies in immunotherapeutics, immunotoxins and immunodiagnostics.

The ribbon model below shows the structural similarities between FN3 and the variable heavy (VH) chain of immunoglobulin.

Patents are issued in the United States and Australia; patent applications are pending in the United States, Europe, Canada and Japan.

Inventor

Shohei Koide, University of Rochester

Improved Fibronectin Type III Scaffolds
for Artificial Antibody Polypeptides

An amino acid change in a non-loop region of the human fibronection Type III (FN3) molecule significantly increases its thermal and chemical stabilities.

In the engineering of artificial binding proteins, amino acid replacements, insertions and deletions (collectively referred to as mutations) are introduced to the FN3 scaffold. These mutations can possibly decrease the conformational stability of FN3. Because artifical binding proteins must maintain their three-dimensional structure to be functional, stability limits the number of mutations that can be introduced in the scaffold. The modification described in this technology increases the FN3 scaffold stability and allows more extensive mutations.

Patent applications are pending in the United States, Europe, Canada, Japan and Australia.

This technology is licensed exclusively.

Inventor

Shohei Koide, University of Rochester