Locked antibodies

Antibodies are traditionally depicted as Y-shaped molecules, with the Fab arms pointing away from the Fc region. In locked antibodies, the antibody is found in a compact closed m-shaped structure, where the Fab arms fold along the Fc region. In the closed structure, the Fab arms control the effector functions of the antibody by shielding the Fc region.

The advantages of locked antibodies are that:

• Half-lives are significantly longer compared to traditional antibodies, as antibody halv-lifes are determined by the binding of the Fc region to Fc receptors

• Locked antibodies are retained at the site of interaction, where they interact with targets for a longer time period, due to reduced clearance

• Locked antibodies are less prone to induce anti-drug antibodies

Locked antibodies are typically generated by recombinant expression technology, where necessary modifications are introduced to ensure the generation of a locked antibody.