IL-19 Antibody CDR Engineering for Selective Cytokine Binding
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Solution Overview
Problem
Current treatments for immune-mediated diseases such as psoriasis, atopic dermatitis, asthma, rheumatoid arthritis, inflammatory bowel disease, and colitis are inadequate for a subset of patients, and existing IL-19 antibodies face challenges with nonspecific binding, immunogenicity, and poor pharmacokinetics.
Innovation Solution
Development of IL-19 antibodies with specific CDR sequences (e.g., SEQ ID NOs 7-10) that demonstrate high binding affinity, low nonspecific binding, and therapeutically acceptable pharmacokinetics, produced through recombinant methods and purified using conventional techniques.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing IL-19 antibodies are used to target immune-mediated diseases, then IL-19 binding activity is achieved, but nonspecific binding to serum proteins increases
Solution Approach 1:
The patent applies local quality by optimizing specific regions of the antibody molecule, particularly the CDR sequences, to enhance IL-19 binding while reducing nonspecific interactions. The engineered antibodies feature modified CDR sequences (SEQ ID NOs: 7-10) that are locally optimized for selective IL-19 recognition, thereby improving binding specificity without compromising affinity.
Solution Approach 2:
The patent employs parameter changes by systematically varying antibody sequence parameters, specifically the CDR region sequences, to achieve optimal binding characteristics. Through sequence optimization and engineering, the antibodies were modified to enhance IL-19 selectivity while minimizing nonspecific serum protein binding, resulting in improved therapeutic profiles.
2Reliability
If existing IL-19 antibodies are used to treat immune-mediated diseases, then some therapeutic effect is achieved, but immunogenicity increases
Solution Approach 1:
The patent applies parameter changes by optimizing the antibody sequence parameters, particularly humanizing the antibody sequences and modifying CDR regions, to reduce immunogenicity while preserving therapeutic efficacy. The engineered antibodies demonstrate reduced immunogenicity through sequence optimization that minimizes foreign epitopes while maintaining IL-19 binding capability.
3Reliability
If existing IL-19 antibodies are used for therapy, then some neutralization activity is achieved, but pharmacokinetics deteriorate
Solution Approach 1:
The patent employs parameter changes by optimizing antibody structural and sequence parameters to improve pharmacokinetic properties. The engineered antibodies exhibit enhanced stability, solubility, and pharmacokinetic profiles through sequence optimization, resulting in improved half-life and reduced clearance while maintaining potent IL-19 neutralization activity.
Solution Approach 2:
The patent applies composite materials by creating engineered antibody molecules that combine optimized CDR sequences with stabilized framework regions. This composite structure enhances both the neutralization activity and pharmacokinetic properties, resulting in antibodies with improved in vivo performance characteristics.
4Reliability
If current treatments are used for immune-mediated diseases, then some symptom relief is achieved, but treatment effectiveness decreases for nonresponsive patients
Solution Approach 1:
The patent applies universality by developing IL-19 targeted antibodies that can address multiple immune-mediated diseases through a common mechanism. The engineered antibodies are designed to be broadly applicable across different inflammatory conditions by targeting the conserved IL-19 cytokine, providing a universal therapeutic approach that may benefit patients who do not respond to disease-specific treatments.
Data Source
AI summary
The present invention provides compounds and methods targeting human interleukin-19, including therapeutic antibodies, pharmaceutical compositions and methods of use thereof, useful in the field of immune-mediated diseases including psoriasis, atopic dermatitis, asthma, psoriatic arthritis, rheumatoid arthritis, axial spondyloarthritis, inflammatory bowel disease and colitis.