RANKL-Binding Antibodies with Modified CDR Regions
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current RANKL inhibitors, such as Denosumab, while effective in treating osteoporosis and bone metastases, exhibit adverse effects like pain, anemia, and skin problems, necessitating the development of more potent and safer RANKL binding moieties with improved binding affinity and blocking capacity.
Innovation Solution
Development of isolated monoclonal antibodies or antigen-binding portions that specifically bind to RANKL with high affinity, including mouse, chimeric, or humanized antibodies, with specific amino acid sequences in their variable regions, capable of blocking RANK-RANKL interactions, and potentially used in bispecific molecules for enhanced therapeutic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If Denosumab is used to treat osteoporosis and bone metastases, then bone protection effect is improved, but adverse effects such as pain, anemia, and skin problems occur
Solution Approach 1:
The patent applies parameter changes by modifying the antibody structure to create variants with altered binding characteristics. Specifically, the patent describes modifying amino acid residues in the CDR regions of the antibody to change binding affinity and specificity, thereby achieving improved therapeutic effects with reduced adverse effects while maintaining the core bone protection function
2Reliability
If RANKL binding affinity is increased to improve blocking capacity, then therapeutic efficacy is improved, but specificity and safety may be compromised
Solution Approach 1:
The patent applies local quality by making targeted modifications to specific regions of the antibody molecule, particularly the CDR (complementarity determining region) amino acid residues. This allows the antibody to have enhanced binding capacity at the antigen-binding site while maintaining appropriate specificity through careful selection of which residues to modify and which to preserve
Data Source
AI summary
An isolated monoclonal antibody that specifically binds human RANKL, or the antigen-binding portion thereof. A nucleic acid molecule encoding the antibody or the antigen-binding portion thereof, an expression vector, a host cell and a method for expressing the antibody or the antigen-binding portion thereof are also provided. A treatment method using an anti-RANKL antibody or the antigen-binding portion is provided.