ENGINEERED ANTIBODY SCAFFOLDS

摘要

The invention described herein features methods and compositions for generating an antibody specific to post-translational modifications (PTMs). The methods and compositions provide a renewable synthetic antibody strategy that installs a novel motif-specific hot spot into an antibody scaffold that functions independently of the surrounding scaffold. Such antibodies provide a rapid and robust development of antibodies for signaling, diagnostic, and therapeutic applications.

主权项

1. A method of identifying antibodies that specifically bind a protein comprising a post translational modification, the method comprising the steps of:
(1) identifying a noncovalent post translational modification-binding motif in a protein; (2) inspecting known antibody CDRs for an anchoring pocket sequence that adopts the conformation of the noncovalent post translational modification-binding motif; (3) preparing an antibody scaffold comprising a CDR, wherein amino acid residues from the CDR comprise the anchoring pocket; (4) preparing a library comprising the antibody scaffold, wherein the CDR is randomized outside of the anchoring pocket; and (5) identifying antibodies in the library that specifically bind to a protein comprising a post translational modification.