Fully Human Antibodies Binding CD147 Epitopes
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Solution Overview
Problem
Current treatments for CD147-related disorders, such as cancer and inflammatory diseases, face challenges due to limited efficacy and specificity of existing antibodies, which often fail to effectively target CD147 on both resting and activated T-cells, and have variable affinity and specificity.
Innovation Solution
Development of fully human antibodies, antibody fragments, and single-chain antibodies with high affinity (at least 10^-6 M) that specifically bind to CD147 epitopes, utilizing sequences identified in SEQ ID NOs, to treat CD147-expressing tumors and non-oncology diseases like rheumatoid arthritis and heart failure.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing antibodies are used to target CD147, then treatment can be administered, but binding affinity and specificity are insufficient leading to limited efficacy
Solution Approach 1:
The patent applies parameter changes by developing fully human antibodies with optimized variable region sequences (SEQ ID NOs: 1-63) that achieve binding affinity of at least 10^-6 M to CD147. The antibodies utilize specific complementarity determining regions (CDRs) with modified amino acid sequences to enhance both affinity and specificity for CD147 epitopes, directly resolving the contradiction between reliable binding and treatment efficacy
Solution Approach 2:
The patent creates composite antibody structures combining heavy chain variable domains (SEQ ID NOs: 1-31) with light chain variable domains (SEQ ID NOs: 32-63) to form fully human IgG molecules. This composite approach integrates multiple sequence elements that work synergistically to achieve high-affinity binding to CD147 while maintaining therapeutic effectiveness
2Adaptability or versatility
If existing antibodies are used, then treatment coverage is provided, but they fail to effectively target CD147 on both resting and activated T-cells
Solution Approach 1:
The patent develops antibodies with universal binding capability across different T-cell states through optimized CDR sequences. The variable regions (SEQ ID NOs: 1-63) are designed to recognize conserved epitopes on CD147 that are present on both resting and activated T-cells, enabling a single antibody formulation to effectively target multiple cell states without sacrificing binding reliability
3Reliability
If antibody sequences are optimized for higher affinity, then binding strength increases, but manufacturing complexity increases
Solution Approach 1:
The patent segments the antibody into distinct functional regions with assigned sequences: heavy chain variable domains (SEQ ID NOs: 1-31), light chain variable domains (SEQ ID NOs: 32-63), and constant regions. This segmentation allows systematic optimization of affinity through specific CDR sequences while maintaining standardized framework regions, thereby managing complexity through modular design
Data Source
AI summary
There is disclosed compositions and methods relating to or derived from anti-CD147 antibodies. More specifically, there is disclosed fully human antibodies that bind CD147, CD147-binding fragments and derivatives of such antibodies, and CD147-binding polypeptides comprising such fragments. Further still, there is disclosed nucleic acids encoding such antibodies, antibody fragments and derivatives and polypeptides, cells comprising such polynucleotides, methods of making such antibodies, antibody fragments and derivatives and polypeptides, and methods of using such antibodies, antibody fragments and derivatives and polypeptides, including methods of treating or diagnosing subjects having CD147 related disorders or conditions. There is also disclosed a method for treating CD147-expressing tumors, including hepatocellular carcinomas and squamous carcinomas, and non-oncology diseases selected from the group consisting of rheumatoid arthritis, experimental lung injury, atherosclerosis, chronic liver disease induced by hepatitis C virus, ischemic myocardial injury and heart failure.