BCMA Antibodies with Optimized CDR Sequences
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Solution Overview
Problem
Current therapies for multiple myeloma lack effective targeting of B-cell maturation antigen (BCMA) due to limited specificity and affinity of existing antibodies, necessitating the development of antibodies with enhanced binding capabilities.
Innovation Solution
Development of isolated antibodies or antigen-binding fragments with specific heavy and light chain variable regions that are at least 80% homologous to sequences provided, ensuring high affinity binding to human BCMA, including specific CDR sequences for enhanced specificity and efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing antibodies are used to target BCMA, then treatment can be provided, but the binding affinity and specificity are insufficient for effective therapy
Solution Approach 1:
The patent applies parameter changes by systematically optimizing antibody sequence parameters including CDR region sequences, amino acid compositions, and homology percentages (at least 80% homologous to SEQ ID NOS: 1-66). This involves modifying specific sequence parameters to achieve enhanced binding affinity to BCMA while maintaining manufacturability through defined sequence specifications
Solution Approach 2:
The patent applies local quality by focusing optimization on specific CDR regions (heavy chain CDR1-3 and light chain CDR1-3) rather than the entire antibody sequence. This allows targeted improvement of binding affinity in the antigen-binding regions while keeping other portions of the antibody standardized for ease of manufacture
2Reliability
If existing antibodies are used to target BCMA, then treatment can be provided, but the specificity is insufficient for effective therapy
Solution Approach 1:
The patent applies parameter changes by defining specific sequence identity thresholds (at least 80% homology to reference sequences) and optimizing CDR region sequences to enhance binding specificity to BCMA. This systematic parameter optimization ensures high specificity while managing sequence complexity through defined parameters
Solution Approach 2:
The patent applies local quality by concentrating specificity-enhancing features in the CDR regions (complementarity determining regions) of the antibody variable domains. This localized optimization of binding interface sequences improves specificity without requiring complexity throughout the entire antibody structure
Data Source
AI summary
The presently disclosed subject matter provides antibodies that bind to B-cell maturation antigen (BCMA) and methods of using the same.