Targeted glycoprotein-active cathepsins and methods of use
Glycoprotein-active cathepsins, stably associated with a targeting moiety, provide a targeted approach to degrading mucins, addressing the challenge of treating mucin-associated conditions in cancer by disrupting mucin functions.
WO2025064551A1 Publication Date: 2025-03-27THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV
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Patent Information
- Application Number
- PCT/US2024/047296
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2023-09-19
- Filing Date
- 2024-09-18
- Publication Date
- 2025-03-27
AI Technical Summary
Technical Problem
Mucins, which play a crucial role in cancer progression and immune modulation, have remained undruggable due to their unique structure and lack of a catalytic site or discrete extracellular epitope.
Method used
Development of glycoprotein-active cathepsins that are stably associated with a targeting moiety, allowing for targeted degradation of mucins on the cell surface, extracellular, or secreted forms.
Benefits of technology
The targeted degradation of mucins by glycoprotein-active cathepsins disrupts their protective and immunomodulatory functions, potentially reversing tumor aggressiveness and enhancing anti-cancer therapies.
✦ Generated by Eureka AI based on patent content.
Abstract
Provided are glycoprotein-active cathepsins, e.g., mucin-active cathepsins. According to some embodiments, the glycoprotein-active cathepsins are stably associated with a targeting moiety. In some instances, the glycoprotein-active cathepsin is stably associated with the targeting moiety via fusion of a protein domain comprising the glycoprotein-active cathepsin and a protein domain comprising the targeting moiety. In other embodiments, the glycoprotein-active cathepsin is stably associated with the targeting moiety via conjugation. In yet other embodiments, the glycoprotein-active cathepsin is stably associated with the targeting moiety via a non-covalent interaction. Also provided are methods of treating a glycoprotein-associated condition in a subject in need thereof, such methods comprising administering to the subject an effective amount of a glycoprotein-active cathepsin of the present disclosure. Upon administration of the glycoprotein-active cathepsin to the subject, the targeting moiety targets the glycoprotein-active cathepsin to cell surface, extracellular and / or secreted glycoproteins (e.g., mucins), and the glycoprotein-active cathepsin degrades the glycoproteins.
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