Humanized Anti-IL-31 Antibody Reducing Immunogenicity
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Solution Overview
Problem
There is a need for humanized antibodies that can effectively bind to human IL-31 to treat IL-31 mediated inflammation and dermatitis-like symptoms, as existing mouse anti-human IL-31 monoclonal antibodies can cause immunogenicity and have a short half-life in humans.
Innovation Solution
Development of humanized antibodies with specific amino acid sequences in the heavy and light chain variable domains that are at least 90% identical to certain sequences, including those with leucine at position 29 in FR1 and phenylalanine at position 32 in FR3, which are fused with human immunoglobulin constant domains like IgG4 for improved affinity and potency.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If mouse anti-human IL-31 monoclonal antibodies are used, then binding affinity to IL-31 is achieved, but immunogenicity increases and half-life decreases
Solution Approach 1:
The patent applies parameter changes by modifying the antibody structure from mouse to humanized format. Specifically, the constant regions are changed to human immunoglobulin constant regions (IgG1, IgG2, IgG3, or IgG4), and the variable regions are humanized by grafting CDRs from mouse antibodies onto human framework regions. This structural parameter change resolves the contradiction by extending half-life to match human physiological conditions while reducing immunogenicity through human sequence homology.
Solution Approach 2:
The patent creates composite antibody structures combining mouse CDR sequences with human framework and constant region sequences. This chimeric construction allows the antibody to maintain IL-31 binding capability from the mouse CDRs while acquiring the favorable pharmacokinetic properties of human antibodies, including extended half-life and reduced immunogenicity.
2Object-affected harmful factors
If chimeric antibodies are used, then some human compatibility is achieved, but immunogenicity remains and effector function may be compromised
Solution Approach 1:
The patent applies local quality by selectively humanizing only the necessary regions of the antibody. The CDRs retain mouse sequences to preserve binding affinity and specificity, while the framework and constant regions are humanized to reduce immunogenicity. This localized approach ensures that effector functions mediated by human Fc regions (such as ADCP, ADC, and CDC) are maintained while minimizing immune recognition of foreign sequences.
3Reliability
If humanized antibodies with specific amino acid sequences are developed, then affinity and potency are improved, but manufacturing complexity increases
Solution Approach 1:
The patent applies segmentation by dividing the antibody into distinct functional modules: mouse CDRs for binding, human framework regions for structural stability, and human constant regions for effector functions. This modular construction allows each segment to be optimized independently and assembled through standard recombinant DNA techniques, balancing improved affinity and potency with feasible manufacturing processes.
Data Source
AI summary
The invention provides humanized mouse anti-human IL-31 antibodies and antibody fragments that are capable of binding IL-31 and thereby neutralizing, inhibiting, limiting, or reducing the proinflammatory or pro-pruritic effects of IL-31.