Complexes comprising transmembrane receptors and antibodies that bind the receptors in a conformationally selective manner

US10520516B2 · kind B2 · utility

Assignee

• The Board of Trustees of the Leland Stanford Junior University · US

Inventors

• Aaron Michael Ring · New Haven, US
• Aashish Manglik · Menlo Park, US
• Andrew Kruse · Brookline, US
• Brian Kobilka · Palo Alto, US

Key dates

• Filing date: Dec 15, 2017
• Grant date: Dec 31, 2019
• Expiry date: Dec 15, 2037

Classification

• Technology area (CPC G): Physics
• CPC primary: G01N2570/00
• WIPO field: Measurement
• WIPO sector: Instruments

Abstract

Provided herein are several methods for selecting agents that bind to transmembrane receptors in a conformationally-selective way. In some embodiments, the method may comprise producing: a transmembrane receptor in an active conformation; and said transmembrane receptor in an inactive conformation and using cell sorting to select, from a population of cells comprising a library of cell surface-tethered extracellular capture agents, cells that are specifically bound to either the transmembrane receptor in its active conformation or the transmembrane receptor in its inactive conformation, but not both. In other embodiments, the method may comprise: contacting a GPCR with a population of cells that comprise a library of surface-tethered extracellular proteins; labeling the cell population with a conformationally-specific binding agent, e.g., a G-protein or mimetic thereof; and using cell sorting to select from the cell population cells that bind to the agent.