Synthetic Canine Antibody Libraries for Stable Therapeutic Leads
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Solution Overview
Problem
There is a lack of fully synthetic canine antibody libraries with a predefined and diverse VH/VL composition, and existing methods do not adequately address the need for antibodies with favorable biophysical properties for therapeutic applications in dogs.
Innovation Solution
Development of synthetic canine antibody libraries using germline sequences, specifically selecting VH and VL regions based on canine immunoglobulin gene repertoires, optimizing for high monomeric content and thermal stability, and removing post-translational modification sites to enhance expression and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing methods are used to generate canine antibodies, then antibody production is achieved, but the antibodies lack favorable biophysical properties for therapeutic applications
Solution Approach 1:
The patent applies preliminary action by pre-selecting and optimizing VH and VL gene sequences from canine germline repertoires before antibody production. Specific germline sequences are chosen based on their predicted biophysical properties, and the library is constructed with predefined VH/VL compositions that ensure favorable characteristics such as high monomeric content and thermal stability before the actual antibody generation process begins.
2Stability of the object's composition
If canine antibodies are generated without predefined VH/VL composition, then diversity is achieved, but monomeric content and thermal stability are insufficient
Solution Approach 1:
The patent applies parameter changes by systematically varying the VH and VL gene segment combinations within defined germline families. Different VH genes from specific canine germline families are paired with different VL genes, creating a diverse library where each combination maintains optimized biophysical parameters such as monomeric content and thermal stability through the predefined germline sequence selection.
3Productivity
If post-translational modification sites are retained in canine antibody sequences, then natural sequence fidelity is maintained, but expression and stability are reduced
Solution Approach 1:
The patent applies the extraction principle by systematically removing post-translational modification sites from the canine antibody sequences. Specific amino acid residues that serve as PTM sites are identified and eliminated from the germline sequences during library construction, while the rest of the sequence fidelity is maintained to preserve the natural canine antibody characteristics.
Data Source
AI summary
The present invention provides synthetic canine antibody libraries, as well as polypeptides, nucleic acids, vectors, host cells and methods used in conjunction with these libraries. The present invention also provides antibodies isolated from such libraries.