Phosphate based linkers for intracellular delivery of drug conjugates

US10550190B2 · kind B2 · utility

Assignees

• Merck Sharp & Dohme LLC · US
• Ambrx, Inc. · US

Inventors

• Robert M. Garbaccio · Lansdale, US
• Jeffrey Kern · Gilbertsville, US
• Philip E. Brandish · Needham, US
• Sanjiv Shah · Wakefield, US
• Linda Liang · Mountain View, US
• Ying Sun · Waltham, US
• Jianing Wang · San Diego, US
• Nick Knudsen · San Diego, US
• Andrew H. Beck · Brookline, US
• Anthony Manibusan · San Diego, US
• Dennis Gately · Philadelphia, US

Key dates

• Filing date: Mar 30, 2015
• Grant date: Feb 4, 2020
• Expiry date: Mar 12, 2036

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K16/2866
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Phosphate-based linkers with tunable stability for intracellular delivery of drug conjugates are described. The phosphate-based linkers comprise a monophosphate, diphosphate, triphosphate, or tetraphosphate group (phosphate group) and a linker arm comprising a tuning element and optionally a spacer. A payload is covalently linked to the phosphate group at the distal end of the linker arm and the functional group at the proximal end of the linker arm is covalently linked to a cell-specific targeting ligand such as an antibody. These phosphate-based linkers have a differentiated and tunable stability in blood vs. an intracellular environment (e.g. lysosomal compartment).