Humanized Antibodies for Peripheral CB1 Receptor Modulation
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Solution Overview
Problem
There is a need for new CB1 receptor antagonists and agonists with reduced central nervous system (CNS) penetration to minimize psychiatric adverse effects associated with existing CB1 receptor modulation, particularly for therapeutic and diagnostic purposes.
Innovation Solution
Development of antibodies and antigen-binding fragments that selectively bind to the cannabinoid 1 (CB1) receptor, offering reduced brain penetration and modified effector functions, which are at least as potent as small molecule modulators like AM6545 or rimonabant, while providing therapeutic benefits with minimized CNS side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If small molecule CB1 receptor modulators (e.g., rimonabant) are used, then CB1 receptor signaling is effectively modulated, but CNS penetration occurs leading to psychiatric adverse effects
Solution Approach 1:
The patent uses antibodies as intermediary molecules that bind to CB1 receptors on the cell surface, mediating the therapeutic effect without requiring CNS penetration. The antibodies act as a bridge between the administered therapeutic and the target receptor, achieving modulation while remaining confined to peripheral circulation.
Solution Approach 2:
The patent changes the molecular parameters of the CB1 modulator from small molecule characteristics (high lipid solubility, blood-brain barrier penetration) to antibody characteristics (large molecular size, peripheral confinement). This parameter change transforms the drug's distribution profile to eliminate CNS exposure while maintaining peripheral CB1 receptor modulation.
2Object-affected harmful factors
If antibodies are designed to bind CB1 receptor extracellular epitopes, then CNS penetration is reduced, but binding affinity and potency must be maintained
Solution Approach 1:
The patent segments the CB1 receptor binding interface into distinct epitope regions on the extracellular domain. By targeting specific segmented epitopes (such as the N-terminal region or transmembrane domain extracellular portions), the antibodies achieve high affinity binding without requiring access to intracellular or CNS-localized binding sites.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
These antibodies and fragments effectively modulate CB1 receptor signaling with enhanced potency and reduced CNS side effects, offering a therapeutic and diagnostic tool for conditions such as obesity, diabetes, and pain, while avoiding the psychiatric adverse effects of traditional small molecule CB1 receptor modulators.
Implementation Method 1
antibodies and antigen-binding fragments that bind to cannabinoid receptor 1 (CB1) receptor
Data Source
AI summary
The present invention relates to novel antibodies and fragments thereof that binds cannabinoid 1 (CB1) receptor. The antibodies and fragments thereof as disclosed herein include humanized antibodies that bind CB1 receptor. The invention also includes uses of the antibodies for treating a disease or disorder responsive to antagonism or agonism of the CB1 receptor.