Auristatin drugs having highly stable hydrophilic linker units and conjugates thereof
By linking auristatin derivatives to an enzyme peptide unit via an aminomethylene structure, the new ADCs improve safety and efficacy, addressing neurotoxicity and hematotoxicity, and enhancing plasma stability, thus achieving better tumor inhibition with lower doses.
JP2025532285APending Publication Date: 2025-09-29SYSTIMMUNE INC
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Patent Information
- Application Number
- JP2025518396
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2023-09-25
- Filing Date
- 2023-09-28
- Publication Date
- 2025-09-29
AI Technical Summary
Technical Problem
Current auristatin-based antibody-drug conjugates (ADCs) face challenges with neurotoxicity, hematotoxicity, and poor plasma stability due to hydrophobic linkers, leading to limited DAR and efficacy, and existing linker modifications suffer from instability and off-target toxicity.
Method used
Auristatin or its derivatives are linked to an enzyme peptide unit via an aminomethylene structure at the hydroxyl site, increasing DAR to 8, enhancing hydrophilicity and plasma stability, and reducing neurotoxicity and hematotoxicity.
Benefits of technology
The new linker-payload conjugates achieve superior efficacy with lower doses, improved maximum tolerated dose (MTD), and reduced side effects, while maintaining tumor-inhibiting effects.
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Abstract
The present invention relates to the medical technology field and relates to auristatin drugs and conjugates thereof having highly stable hydrophilic linker units. In particular, the present invention relates to ligand-drug conjugates or pharmaceutically acceptable salts or solvates thereof, and methods for preparing and using the same. The present invention also relates to linker-drug compounds or their isomers, meso-isomers, racemates, enantiomers, or mixtures thereof, or pharmaceutically acceptable salts or solvates thereof, and methods for preparing and using the same.
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