HGF Binding Antibody Humanization for Reduced Immunogenicity
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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), particularly to inhibit the growth and proliferation of cancer cells associated with HGF activity, 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, utilizing complementarity determining regions (CDRs) to confer binding specificity, which can be engineered to minimize immune response and conjugated with other moieties for therapeutic and diagnostic applications, including inhibition of tumor growth.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing anti-HGF antibodies are used as therapeutic agents, then HGF activity can be inhibited, but immune response may be induced against the antibody
Solution Approach 1:
The patent applies parameter changes by modifying the antibody sequence parameters through humanization processes. The variable regions are engineered to have higher homology with human antibodies, changing the amino acid sequence parameters to reduce immunogenicity while maintaining HGF binding capability. This resolves the contradiction by altering the antibody's molecular parameters to eliminate harmful immune responses while preserving therapeutic effectiveness.
2Reliability
If antibody binding specificity is increased to target HGF, then therapeutic efficacy is improved, but manufacturing complexity increases
Solution Approach 1:
The patent applies segmentation by dividing the antibody into distinct functional regions: variable regions (VL, VH) responsible for binding specificity and constant regions (CL, CH1, CH2, CH3) responsible for effector functions. This segmentation allows independent optimization of binding specificity through variable region engineering while maintaining standardized constant regions that simplify manufacturing processes.
Solution Approach 2:
The patent uses parameter changes by systematically modifying amino acid sequences in the variable regions to achieve desired binding specificity. Through computational design and iterative mutagenesis, specific amino acid parameters are optimized at positions critical for HGF interaction, thereby improving therapeutic efficacy without proportionally increasing manufacturing complexity.
3Reliability
If antibody affinity for HGF is increased, then therapeutic effectiveness is improved, but the risk of off-target effects increases
Solution Approach 1:
The patent applies local quality by concentrating the binding interface at specific local regions (the complementarity determining regions or CDRs within the variable regions) while keeping the rest of the antibody structure generic. This localized binding approach ensures high affinity for HGF at the interaction site while the overall antibody structure remains compatible with human immune system, thereby reducing off-target effects.
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
The binding proteins effectively neutralize HGF activity, inhibiting cancer cell proliferation and tumor growth by binding to HGF, reducing the risk of immune response and maintaining high specificity and affinity, making them suitable for therapeutic and diagnostic use.
Implementation Method 1
The binding proteins are based upon the antigen binding sites of certain monoclonal antibodies that have been selected for their ability to bind, and neutralize the activity of, HGF
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.