How to Find Antibodies That Only Detect Bound Drug Targets

This patent describes a method to create and use special antibodies that only detect when a therapeutic or diagnostic antibody is bound to its target, ignoring both the target and the unbound antibody.

What it covers

This invention provides a method for creating and using unique antibodies, called "complex-specific antibodies." These special antibodies are designed to only attach to a "complex" (Claim 1) – which is formed when a "cognate antibody" (the original antibody being studied) is already bound to its "antigen" (its target molecule). The method involves screening a library of potential antibodies (Claim 1a) and then isolating specific ones that bind only to this complex, explicitly not binding to the cognate antibody alone or the antigen alone (Claim 1c). Once identified, these complex-specific antibodies can be used to contact a sample (Claim 1d) and detect how much of the original cognate antibody is actually bound to its target, for example, to monitor a therapeutic antibody drug's activity in a patient's body.

What it doesn't cover

• —Does not cover antibodies that bind to the cognate antibody when it is not attached to its antigen.
• —Does not cover antibodies that bind to the antigen when it is not attached to the cognate antibody.
• —Does not cover detection methods where the identifying antibody binds to both the complex and the individual cognate antibody or antigen.
• —Does not cover methods for detecting the complex that do not involve first screening a library of antibodies as described in Claim 1a.
• —Does not cover detection methods that do not use an isolated monoclonal antibody or functional fragment thereof.

The clever bit

The novelty lies in creating an antibody that *only* recognizes the specific shape formed when an original antibody is already bound to its target, ignoring the individual components. This "complex-specific" binding allows for direct and precise measurement of active drug engagement, which was previously challenging.

Why it matters

This technology could significantly improve the development and monitoring of antibody-based drugs. By precisely measuring how much of a therapeutic antibody is actually bound to its target in a patient (Claim 4), doctors and researchers can better understand drug effectiveness and adjust dosages. This could lead to more personalized and effective treatments, especially in areas like cancer therapy or autoimmune diseases, by providing clear data on drug-target engagement.

Real-world examples

• 1.Monitoring therapeutic antibody drug levels bound to their targets in patients during clinical trials.
• 2.Developing diagnostic tests to confirm active drug-target engagement in a patient's bloodstream.
• 3.Research tools to study how specific antibody-antigen interactions occur within living systems.