Humanized Anti-IL17BR Antibody Expression Optimization
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Solution Overview
Problem
Current humanized antibodies targeting interleukin-17 receptor B (IL17BR) face challenges in maintaining expression levels without compromising specificity or affinity.
Innovation Solution
The development of humanized antibody molecules with specific mutations in the heavy chain and light chain variable domains, which improve expression while maintaining binding specificity and affinity to IL17BR.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If humanized antibody molecules are developed to improve expression levels, then expression is improved, but specificity or affinity may be compromised
Solution Approach 1:
The patent applies parameter changes by introducing specific amino acid mutations at defined positions (Kabat framework regions 1-4) in the variable domains of the antibody. These parameter changes in the primary structure enable improved expression levels while the patent demonstrates that specificity and affinity are maintained through careful selection of mutation sites that do not interfere with antigen binding.
2Productivity
If mutations are introduced in variable domains to improve expression, then expression is improved, but binding properties may deteriorate
Solution Approach 1:
The patent applies local quality by restricting mutations to specific framework regions (Kabat positions 1-4) that are spatially separated from the CDR regions responsible for antigen binding. This localized approach allows expression improvement through framework mutations while preserving the precise binding properties determined by the CDR loops, which remain unchanged.
Data Source
AI summary
This invention relates to humanised versions of the murine anti-IL17BR antibody D9.2 which comprise mutations of certain residues within the heavy chain and/or light chain variable domains that display improved expression without deleterious effects on specificity or affinity. The humanised antibodies may comprise a heavy chain variable (VH) domain which comprises a VHCDR1 of SEQ ID NO: 1, a VHCDR2 of SEQ ID NO: 2, and a VHCDR3 of SEQ ID NO: 3, for example, a VH domain of SEQ ID NO: 9, SEQ ID NO: 10 or SEQ ID NO: 11. The humanised antibodies may comprise a light chain variable (VL) domain which comprises a VLCDR1 of SEQ ID NO: 4, a VLCDR2 of SEQ ID NO: 5, and a VLCDR3 of SEQ ID NO: 6, for example a VL domain of SEQ ID NO: 13. Antibodies, pharmaceutical compositions and methods of use, for example in the treatment of cancer are provided.