CB1 Receptor Antibodies With Specific CDRs for Peripheral Targeting
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Solution Overview
Problem
Existing CB1 receptor antibodies lack specific CDR sequences and in vivo evaluation, leading to potential central side effects and limited therapeutic efficacy for conditions like obesity and diabetes.
Innovation Solution
Development of novel antibodies and fragments with specific CDR sequences in light and heavy chain variable regions that selectively bind to CB1 receptors, modulating signaling and minimizing brain migration, thereby providing therapeutic benefits for obesity, diabetes, and nonalcoholic steatohepatitis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If small molecule CB1 receptor antagonists are used to achieve anti-obesity effects and metabolic improvement, then appetite reduction and neutral fat value reduction are improved, but central side effects such as mental effects, depression, and suicidal desires occur
Solution Approach 1:
The invention segments the CB1 receptor distribution into central (brain) and peripheral (visceral adipose tissue, liver, kidney, lung) components. By designing a large molecule antibody that cannot cross the blood-brain barrier, the treatment selectively targets peripheral CB1 receptors while leaving central receptors unaffected, thereby achieving anti-obesity effects without central side effects
Solution Approach 2:
The antibody acts as an intermediary that blocks the interaction between endogenous cannabinoids and CB1 receptors in peripheral tissues. This intermediary approach prevents the activation of peripheral CB1 receptors that would otherwise lead to increased appetite and fat storage, while not interfering with central CB1 receptor function
2Object-affected harmful factors
If CB1 receptor antibodies are developed to minimize brain migration and reduce central side effects, then peripheral therapeutic effects are improved, but specific CDR sequences and in vivo evaluation data are lacking
Solution Approach 1:
The invention performs preliminary actions by providing complete CDR sequences for both light and heavy chains that are designed to bind peripheral CB1 receptors with high specificity. The patent also performs preliminary in vivo evaluation in obese diabetic mice, demonstrating improved insulin sensitivity, reduced visceral adipose tissue, and reduced liver fat before clinical application, thereby establishing reliability ahead of broader use
3Measurement precision
If antibodies with specific CDR sequences are designed to selectively bind CB1 receptors, then binding specificity is improved, but complexity of antibody structure increases
Solution Approach 1:
The invention applies local quality by providing specific CDR sequences (CDR1, CDR2, CDR3 for both light and heavy chains) with precisely defined amino acid compositions that confer high specificity for CB1 receptor binding. Each CDR region is optimized locally to recognize specific epitopes on the CB1 receptor, ensuring selective binding while maintaining overall antibody functionality
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
The antibodies effectively modulate CB1 receptor signaling, improving small intestine transport capacity and offering anti-obesity effects, making them useful for treating obesity and diabetes without central side effects.
Implementation Method 1
an antibody or an antibody fragment thereof that binds to a human cannabinoid type 1 (CB1) receptor
Data Source
AI summary
An object of the present invention is to provide a novel antibody or an antibody fragment thereof that binds to a cannabinoid type 1 (CB1) receptor. Disclosed is a CB1 receptor antibody or an antibody fragment thereof having six specific CDRs (CDR1 to CDR3 of the heavy chain and CDR1 to CDR3 of the light chain) or a specific heavy chain variable region/light chain variable region. The antibody and the like can be used for the treatment or prevention of obesity, diabetes, nonalcoholic steatohepatitis, and the like.