Cross-Species CD3 Binding Domain for Primate Therapeutics
Solution Overview
Problem
Current CD3 antibodies are species-specific, limiting their therapeutic application across primates, including humans, due to their ability to recognize only specific epitopes, and require extensive testing in various species, which is costly and ethically challenging, especially with the use of chimpanzees.
Innovation Solution
A polypeptide with a context-independent binding domain that targets the N-terminal 1-27 amino acid residue of the CD3 epsilon chain, maintaining its structural integrity and binding affinity across human and non-chimpanzee primates, allowing for cross-species specificity and reduced need for multiple testing models.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If species-specific CD3 antibodies are used, then binding specificity to human CD3 is achieved, but cross-species applicability is limited
Solution Approach 1:
The patent creates a universal CD3 binding domain that can recognize and bind to CD3 molecules across multiple primate species including humans, chimpanzees, monkeys, and mice. This single binding domain design enables the same therapeutic molecule to be used across different species without requiring species-specific variants, thereby achieving both high binding specificity to human CD3 and broad cross-species applicability simultaneously
2Reliability
If multiple species testing is performed, then safety and efficacy are validated, but cost and ethical challenges increase
Solution Approach 1:
By designing a universal CD3 binding domain that works across multiple species, the patent eliminates the need to develop and test separate species-specific antibodies for each preclinical model. This single binding domain can be used in human efficacy studies, non-human primate safety studies, and mouse mechanistic studies, thereby reducing the overall cost and complexity of multi-species testing while maintaining comprehensive safety validation
Solution Approach 2:
The patent uses a simplified binding domain structure that copies the essential binding functionality of full-length species-specific antibodies without requiring the full antibody repertoire to be maintained across multiple species. This allows the core binding function to be replicated and tested across different species using the same molecular design, reducing resource requirements
3Measurement precision
If chimpanzee testing is used, then human-relevant data is obtained, but ethical concerns and availability are reduced
Solution Approach 1:
The universal CD3 binding domain enables the use of alternative non-human primate species (such as rhesus monkeys, baboons, or macaques) that are more ethically acceptable and more readily available for preclinical testing. These alternative species still provide human-relevant data due to their physiological similarities to humans, while avoiding the ethical concerns and availability issues associated with chimpanzee testing
Solution Approach 2:
The patent creates a simplified binding domain that copies the essential binding functionality needed for human-relevant data without requiring the use of chimpanzees. This allows the same level of scientific validity to be achieved using ethically preferable alternative species, thereby maintaining data quality while reducing harmful factors
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
Enables preclinical and clinical use of the same molecule in humans and primates, enhancing predictive power and safety profiles by minimizing species differences and avoiding the use of chimpanzees, thus reducing costs and ethical concerns.
Implementation Method 1
A polypeptide with a context-independent binding domain that targets the N-terminal 1-27 amino acid residue of the CD3 epsilon chain, maintaining its structural integrity and binding affinity across human and non-chimpanzee primates
Data Source
Figure 1
Figure 2
Figure 3
AI summary
The present invention relates to a polypeptide comprising a human binding domain capable of binding to an epitope of human and non-chimpanzee primate CD3 (epsilon) chain as well as to a process for the production of the mentioned polypeptide. The invention further relates to nucleic acids encoding for the polypeptide, to vectors comprising the same and to host cells comprising the vector. In another aspect, the invention provides for a pharmaceutical composition comprising the mentioned polypeptide and medical uses of the polypeptide. In a further aspect the invention provides a method for the identification of polypeptides comprising a cross-species specific binding domain capable of binding to an epitope of human and non-chimpanzee primate CD3ε (CD3 epsilon).