Cystine knot peptides that bind alpha-V-beta-6 integrin

US9206237B2 · kind B2 · utility

Assignee

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

Inventors

• Richard H. Kimura · Stanford, US
• Sanjiv S. Gambhir · Portola Valley, US
• Benjamin Hackel · Edina, US
• Robert Teed · Menlo Park, US
• Bin Shen · Mountain View, US
• Frederick T. Chin · Ceres, US
• Zhen Cheng · 红钢城街道, CN

Key dates

• Filing date: May 21, 2014
• Grant date: Dec 8, 2015
• Expiry date: May 21, 2034

Classification

• Technology area (CPC G): Physics
• CPC primary: G01N2333/70546
• WIPO field: Measurement
• WIPO sector: Instruments

Abstract

Disclosed are peptides comprising a molecular scaffold portion and a loop portion that binds to integrin αvβ6. This integrin is expressed on pancreatic tumors, making the peptides useful as imaging agents, among other uses. The peptides showed single-digit nanomolar dissociation constants similar to antibodies used clinically for imaging and therapy. The peptides rapidly accumulated in αvβ6-positive tumors, which led to excellent tumor-to-normal contrast. The peptides are specific for the targeted integrin αvβ6 receptors expressed on orthotopic pancreatic tumors and various xenografts used. Additionally, pharmacokinetic-stabilization strategies endowed knots with rapid renal clearance, which significantly reduced off-target dosing.