HGF Binding Proteins with Optimized Specificity
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Solution Overview
Problem
There is a need for additional modulators that can be used as therapeutic and diagnostic agents targeting human hepatocyte growth factor (HGF), as existing agents may induce an immune response and have limitations in specificity and affinity.
Innovation Solution
Development of a family of antibody-based binding proteins that specifically bind to HGF, engineered to minimize immune response and optimized for binding specificity and affinity, which can neutralize HGF activity and inhibit cancer cell proliferation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing HGF modulating agents are used, then HGF activity can be inhibited, but they may induce immune responses and have limitations in binding specificity and affinity
Solution Approach 1:
The patent applies parameter changes by modifying the binding protein sequence to achieve optimal binding characteristics. Specifically, the patent identifies and modifies residues in the complementarity determining regions (CDRs) and framework regions (FRs) to enhance binding affinity and specificity for HGF while maintaining low immunogenicity. The patent provides specific amino acid sequences and structural parameters that optimize the interaction between the binding protein and HGF.
Solution Approach 2:
The patent applies local quality by focusing modifications on specific regions of the binding protein, particularly the CDRs and FRs, while maintaining the overall antibody structure. The patent identifies specific residues within the variable regions that are critical for HGF binding and modifies only those local areas, leaving the constant regions and overall protein fold unchanged, thus preserving functionality while optimizing binding properties.
2Object-affected harmful factors
If antibody-based binding proteins are engineered to minimize immune response, then therapeutic safety is improved, but manufacturing complexity increases
Solution Approach 1:
The patent applies segmentation by dividing the binding protein into distinct functional regions: complementarity determining regions (CDRs) responsible for antigen binding, framework regions (FRs) providing structural support, and constant regions maintaining immunoglobulin characteristics. This segmentation allows independent optimization of each region's properties, enabling minimization of immunogenicity in FRs and constant regions while preserving high-affinity binding in CDRs.
Solution Approach 2:
The patent applies copying by utilizing known immunoglobulin family structures and conserved motifs as templates for designing the binding protein. The patent copies the overall antibody fold and key structural features from well-characterized immunoglobulins, then introduces specific sequence variations in the variable regions to achieve the desired binding properties and reduced immunogenicity, leveraging existing structural knowledge to simplify the design process.
Data Source
AI summary
The present invention provides a family of binding proteins that bind and neutralize the activity of hepatocyte growth factor (HGF), in particular human HGF. The binding proteins can be used as diagnostic and/or therapeutic agents. With regard to their therapeutic activity, the binding proteins can be used to treat certain HGF responsive disorders, for example, certain HGF responsive tumors.