Cynomolgus Monkey Oncostatin M Homolog for Human Toxicology Testing
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Solution Overview
Problem
Current toxicological testing strategies lack effective methods for evaluating the reactivity of therapeutic candidates against orthologous proteins from closely related animal species, particularly for cynomologous monkey models, due to the limitations of murine homologs in mimicking human Oncostatin M pathways.
Innovation Solution
The development of Macaca fascicularis polynucleotides and polypeptides, including vectors and host cells, to express and utilize cynomologous monkey Oncostatin M (OSM) proteins and antibodies, enabling more relevant models for human response evaluation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If murine OSM homolog is used for toxicological testing, then testing can be performed in mice, but the functional homology with human OSM pathways is insufficient
Solution Approach 1:
The patent creates a copy of the human OSM system by introducing human OSM cDNA into monkey kidney cells (COS-7 cells), generating a cell line that expresses human OSM protein. This allows toxicological testing to be performed in a system that closely mimics human OSM pathways, resolving the contradiction between using animal models and maintaining functional homology with human biology.
Solution Approach 2:
The patent uses monkey kidney cells as an intermediary system that can be engineered to express human OSM. This intermediary approach allows testing in a non-human system while maintaining human-specific pathway functionality, enabling reliable reactivity evaluation without requiring direct human testing.
2Reliability
If cynomologous monkey OSM system is developed, then functional homology with human OSM is improved, but system complexity and development effort increase
Solution Approach 1:
The patent develops a universal testing platform using COS-7 cells that can express human OSM and respond to various OSM-modulating compounds. This single cell line system serves multiple purposes: toxicological testing, reactivity evaluation, and pharmacological screening, reducing overall system complexity despite the initial development effort.
Solution Approach 2:
Instead of working with native cynomologous monkey OSM, the patent copies the human OSM system into a readily available monkey cell line (COS-7). This approach leverages existing cell line infrastructure while achieving the desired functional homology, reducing development complexity compared to creating entirely new monkey OSM expression systems.
Data Source
AI summary
Cytokine oncostatin M nucleic acids from Cynomolgus monkey are useful for expression of oncostatin M proteins that are functional homologs of human oncostatin M. The nucleic acids and proteins produced therefrom are useful in screening and safety testing of oncostatin M, the generation and testing of oncostatin M modulators and related activities.