Antibodies are essential therapeutic modalities for treating a plethora of different diseases, ranging from cancer, autoimmune disorders, degenerative diseases, and inflammation. The FDA approved the first antibody over three decades ago, and since more than 570 have been studied in clinical trials, over 80 have been FDA-approved.

The Need
Although antibodies have changed how many diseases are treated, they still have several limitations, including intracellular targeting, undruggable targets, protein-protein interactions, etc. One primary challenge of designing antibodies for intracellular targets is their structural dependence on conserved disulfide bonds that reduces the stability of and affinity to the target.

The Technology
This technology describes the design of antibodies using cysteine-free single-chain variable fragments (scFv) containing variable heavy and light domains fused together by a short artificial linker peptide. Thus far, the inventors have created a prototype and proof of concept data of the antibody using 3E8, a humanized antibody fragment specific to tumor-associated glycoprotein 72 (TAG-72).

Commercial Applications
This invention can be used as a platform for cysteine-free antibody development targeting intracellular antigens for cancer and other disease indications.

Benefits/Advantages
Compared to existing antibodies, this technology could enable more effective intracellular targeting of antibodies. As a result, it could lead to less off target toxicity and improved efficacy.

Patents

PCT Filed: PCT/US2023/071232