CD3-Binding Molecules Cross-Reactive with Human and Non-Human CD3
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Solution Overview
Problem
Current anti-CD3 antibodies are not specific enough for therapeutic use in humans due to their limited cross-reactivity with non-human CD3, such as that found in cynomolgus monkeys, which hampers their development as effective treatments for cancer, autoimmune, and inflammatory diseases.
Innovation Solution
Development of CD3-binding molecules, including antibodies and antigen-binding fragments, that are capable of binding to both human and non-human CD3, specifically cross-reactive with CD3 of non-human mammals like cynomolgus monkeys. These molecules are designed to be used in the treatment of various diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If current anti-CD3 antibodies are used, then they can bind to human CD3, but they lack cross-reactivity with non-human CD3 (e.g., cynomolgus monkey CD3)
Solution Approach 1:
The patent applies parameter changes by modifying the amino acid sequence of the antibody variable regions (specifically in the CDRs and framework regions) to alter the binding characteristics. This enables the antibody to maintain high affinity for human CD3 while gaining cross-reactivity with non-human CD3 isoforms, resolving the contradiction between specificity and adaptability
Solution Approach 2:
The invention creates an antibody that performs multiple functions: it binds to human CD3 with high specificity for therapeutic use, while also cross-reacting with non-human CD3 (particularly cynomolgus monkey CD3) to enable preclinical testing in animal models. This multi-functionality resolves the contradiction by making the antibody adaptable to different species while maintaining reliable human CD3 binding
2Adaptability or versatility
If anti-CD3 antibodies with limited cross-reactivity are used, then they show therapeutic effect in humans, but they cannot be effectively tested in non-human animal models
Solution Approach 1:
The patent modifies specific amino acid parameters in the antibody structure (particularly in the variable regions) to enable cross-species binding. This allows the antibody to be tested in non-human animal models while maintaining its therapeutic function, without requiring complete redesign of the molecular structure
Solution Approach 2:
The invention introduces partial modifications to the antibody sequence - not complete redesign but targeted changes in specific regions (CDRs and framework regions). This partial action is sufficient to gain cross-reactivity for animal modeling while preserving the core therapeutic mechanism and avoiding excessive structural complexity
Data Source
AI summary
The present invention relates to CD3-binding molecules capable of binding to human and non-human CD3, and in particular to such molecules that are cross-reactive with CD3 of a non-human mammal (e.g., a cynomolgus monkey). The invention also pertains to uses of such antibodies and antigen-binding fragments in the treatment of cancer, autoimmune and/or inflammatory diseases and other conditions.