Anti-IL-11Rα Antibody CDR Optimization for Potent Signaling Blockade
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing anti-IL-11Rα antibodies lack potency and optimal developability characteristics, necessitating the development of antibodies with improved binding affinity and manufacturing homogeneity for effective therapeutic applications.
Innovation Solution
Development of antibodies with specific VH and VL CDR sequences that bind to IL-11Rα, offering increased affinity and potency as IL-11 signaling inhibitors, along with reduced N-linked glycosylation heterogeneity, and humanized IgG Fc domains for enhanced therapeutic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing anti-IL-11Rα antibodies are used, then therapeutic applications can be pursued, but potency and binding affinity are insufficient
Solution Approach 1:
The patent applies parameter changes by systematically optimizing the CDR sequences of the antibody variable regions. Specific amino acid substitutions in VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 regions were made to enhance binding affinity to IL-11Rα. This direct modification of molecular parameters (amino acid sequences) resolves the contradiction by improving both therapeutic efficacy and binding affinity simultaneously.
2Productivity
If existing anti-IL-11Rα antibodies are used, then development can proceed, but manufacturing homogeneity is suboptimal
Solution Approach 1:
The patent reduces N-linked glycosylation heterogeneity by modifying amino acid residues at potential glycosylation sites in the antibody sequences. Specifically, serine and threonine residues that could serve as N-linked glycosylation sites were replaced with amino acids that do not undergo such modification, thereby improving manufacturing homogeneity while maintaining productivity.
3Reliability
If antibody potency is increased through CDR optimization, then signaling inhibition improves, but manufacturing complexity may increase
Solution Approach 1:
The patent applies local quality by making targeted amino acid substitutions only in the CDR regions of the antibody variable domains, rather than modifying the entire antibody structure. This localized optimization of binding regions enhances signaling inhibition potency while minimizing overall structural complexity and maintaining manufacturability.
Data Source
AI summary
Provided are antibodies and antigen binding fragments thereof that bind to human interleukin-11 receptor subunit α (IL-11Rα) and related compositions, which may be used in any of a variety of therapeutic or diagnostic methods, including the treatment or diagnosis of cancers, inflammatory diseases, autoimmune diseases, and others.