Multimeric Bicyclic Peptide Ligands for CD137 Tissue Activation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing therapeutic modalities, such as monoclonal antibodies and small molecules, struggle to effectively penetrate tissues and activate receptor signaling pathways, particularly in poorly vascularized areas like pancreatic cancer, and there is a need for alternative bicyclic peptides that can bind and activate targets like CD137 with high potency and efficacy.
Innovation Solution
Development of multimeric bicyclic peptide ligands that form covalent bonds with molecular scaffolds, allowing for synergistic binding and activation of targets like CD137, with varying chemical linkers and hinges to enhance potency and efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If monoclonal antibodies are used to bind and activate receptors, then high affinity and large interaction surface areas are achieved, but tissue penetration efficiency deteriorates
Solution Approach 1:
The patent segments the large monoclonal antibody structure into smaller bicyclic peptide units that retain the essential binding functionality. These segmented peptides can penetrate tissues more effectively while maintaining the ability to bind and activate target receptors through multimeric assembly.
Solution Approach 2:
The patent transitions from small molecules to a intermediate dimension - bicyclic peptides - which provide a larger interaction surface than small molecules but smaller size than antibodies. The multimeric structure adds another dimension by assembling multiple peptide units to achieve antibody-like binding affinity.
2Reliability
If multimeric bicyclic peptide ligands are developed to enhance binding potency, then binding avidity is improved, but molecular complexity increases
Solution Approach 1:
The patent employs universal scaffolds and modular linker designs that can be used across different bicyclic peptide ligands. This modularity allows systematic construction of multimeric structures with controlled complexity, where the same building blocks are reused to achieve enhanced binding potency through standardized assembly patterns.
Data Source
AI summary
The present invention relates to multimers of polypeptides which are covalently bound to molecular scaffolds such that two or more peptide loops are subtended between attachment points to the scaffold. The invention also describes the multimerization of polypeptides through various chemical linkers and hinges of various lengths and rigidity using different sites of attachments within polypeptides. In particular, the invention describes multimers of peptides which are high affinity binders and activators of CD137. The invention also includes drug conjugates comprising said peptides, conjugated to one or more effector and/or functional groups, to pharmaceutical compositions comprising said peptide ligands and drug conjugates and to the use of said peptide ligands and drug conjugates in preventing, suppressing or treating a disease or disorder mediated by CD137.