Ubiquitin-Based Artificial Binding Proteins for Stable Antibody Substitution
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current methods for producing antibody fragments, such as scFv and Fab fragments, face challenges including high production costs, low yields, reduced thermodynamic stability, and aggregation issues due to unfavourable folding properties and slow blood clearance, limiting their therapeutic applications.
Innovation Solution
Modification of ubiquitin-like proteins by altering amino acids in the alpha helical region to create high-affinity binding variants that can be used as substitutes for antibodies, allowing for specific recognition and binding of target molecules without the disadvantages of traditional antibodies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If antibody fragments (scFv, Fab) are produced using conventional methods, then specific binding capability is achieved, but production costs are high and yields are low
Solution Approach 1:
The patent creates artificial binding proteins that copy the specific binding capability of antibodies by displaying antibody variable regions (VH and VL domains) on the surface of ubiquitin-based display particles. This allows the binding function to be replicated in a simpler, more producible system, achieving high yields while maintaining specific binding capability.
2Reliability
If antibody fragments are produced using conventional methods, then specific binding capability is achieved, but thermodynamic stability is reduced
Solution Approach 1:
The patent uses ubiquitin-based display particles as an intermediary scaffold to present antibody variable regions. The ubiquitin core provides robust thermodynamic stability while the displayed variable regions maintain binding capability. This intermediary structure resolves the contradiction by separating the stability function (ubiquitin core) from the binding function (variable regions).
3Reliability
If antibody fragments are produced using conventional methods, then specific binding capability is achieved, but aggregation issues occur
Solution Approach 1:
The patent segments the antibody structure into separate variable regions (VH and VL) that are independently displayed on the surface of ubiquitin particles. This segmentation prevents the aggregation problems associated with conventional antibody fragments by isolating the binding regions on stable, discrete particle surfaces rather than relying on fragile fragment structures.
Data Source
Figure 1
Figure 2
Figure 3
AI summary
The present invention is directed to a method for the generation of binding proteins derived from the protein superfamily of ubiquitin like proteins with modifications in their alpha helical region as well as to a protein obtainable by said method. Furthermore, the invention provides the use of a protein for the specific recognition, binding and neutralization of a predescribed target molecule, for the detection, quantitative determination, separation and/or for the isolation of a corresponding binding partner and the use of a protein of the invention, for diagnosis, prophylaxis and treatment of diseases in which the corresponding binding partner is directly or indirectly involved.