Cross-Species CD3 Binding Domain for Primate Testing
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Solution Overview
Problem
Current CD3 antibodies are species-specific, limiting their therapeutic application across primates, including humans, due to their recognition of conformational epitopes that require specific subunit arrangements, and their use in preclinical testing is hindered by the need for chimpanzee models, which are ethically and financially restrictive.
Innovation Solution
A context-independent CD3 epsilon polypeptide binding domain, specifically the N-terminal 1-27 amino acid residue fragment, maintains its three-dimensional structure and binds to human and non-chimpanzee primate CD3 epsilon chains, allowing for cross-species specificity and reduced allosteric changes, enabling its use in both preclinical and clinical settings without the need for chimpanzee testing.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If species-specific CD3 antibodies are used for preclinical testing, then binding specificity to human CD3 is achieved, but application across non-human primates is limited and chimpanzee models are required
Solution Approach 1:
The patent creates a universal CD3 binding domain that can recognize and bind to CD3 epsilon chains across multiple primate species including humans, chimpanzees, rhesus monkeys, and cynomolgus monkeys. This single binding domain sequence (SEQ ID NO: 2) serves multiple functions: it binds to CD3 in different species, enables preclinical testing in non-chimpanzee primates, and maintains therapeutic relevance for human applications, thereby achieving cross-species versatility without sacrificing binding specificity.
2Measurement precision
If chimpanzee models are used for preclinical testing, then relevant physiological data is obtained, but ethical constraints and financial costs increase
Solution Approach 1:
The patent uses non-chimpanzee primates (rhesus monkeys and cynomolgus monkeys) as intermediary species for preclinical testing. These intermediaries share sufficient physiological and immunological characteristics with humans to provide relevant predictive data, while avoiding the ethical restrictions associated with chimpanzee experimentation. The cross-species CD3 binding domain ensures that the same molecule can be tested in these intermediary species and then applied to human therapy.
3Reliability
If context-dependent CD3 epitopes are targeted, then high binding affinity to human CD3 is achieved, but the epitope requires specific subunit arrangements that limit cross-species binding
Solution Approach 1:
The patent segments the CD3 epsilon chain into a specific N-terminal region (amino acids 1-27) that forms a context-independent epitope. This segmented approach allows the binding domain to recognize a specific structural motif that is conserved across primate species regardless of the full CD3 complex assembly. The segmentation isolates the critical binding interface from the context-dependent subunit arrangements, enabling high binding affinity while maintaining cross-species recognition capability.
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
This approach provides a safer and more effective therapeutic option with reduced CNS adverse events and increased predictive power in human trials, as the same molecule can be used for both animal testing and human administration, avoiding ethical and financial constraints associated with chimpanzee testing.
Implementation Method 1
A context-independent CD3 epsilon polypeptide binding domain, specifically the N-terminal 1-27 amino acid residue fragment, maintains its three-dimensional structure and binds to human and non-chimpanzee primate CD3 epsilon chains
Data Source
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).