Humanized Antibodies for IL-12 and IL-23 Binding
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Solution Overview
Problem
Current antibodies targeting IL-12, such as murine monoclonal antibodies, face limitations due to short serum half-life and immune reactions in humans, necessitating the development of more effective and human-compatible IL-12 binding proteins.
Innovation Solution
The creation of CDR-grafted, humanized antibodies and fragments that specifically bind to the p40 subunit of IL-12 and IL-23 with high affinity, utilizing specific antigen binding domains and frameworks to neutralize IL-12 and IL-23 activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If murine monoclonal antibodies are used to target IL-12, then binding activity is achieved, but serum half-life is short and immune reactions occur in humans
Solution Approach 1:
The patent applies parameter changes by modifying the antibody's species origin from murine to humanized or fully human. This fundamental parameter change in the antibody's biological identity resolves the contradiction by extending serum half-life and reducing immune reactions while preserving IL-12 binding activity through careful design of the humanized antibody structures
2Reliability
If murine monoclonal antibodies are used to target IL-12, then binding activity is achieved, but immune reactions occur in humans
Solution Approach 1:
The patent changes the species parameter of the antibody from murine to humanized or fully human, which fundamentally reduces immunogenicity and immune reactions in human patients while maintaining the essential binding activity against IL-12 through preserved antigen-binding regions
3Object-affected harmful factors
If CDR-grafted humanized antibodies are designed to bind p40 subunit, then human compatibility is improved, but manufacturing complexity increases
Solution Approach 1:
The patent applies segmentation by dividing the antibody into distinct functional regions: CDRs for antigen binding and framework regions for structural support and human compatibility. This modular approach allows independent optimization of each region, simplifying the manufacturing process while maintaining human compatibility and binding activity
Data Source
AI summary
The present invention encompasses IL-12p40 binding proteins, particularly antibodies that bind human interleukin-12 (hIL-12) and/or human IL-23 (hIL-23). Specifically, the invention relates to antibodies that are chimeric, CDR grafted and humanized antibodies. Preferred antibodies have high affinity for hIL-12 and/or hIL-23 and neutralize h IL-12 and/or hIL-23 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting hIL-12 and/or hIL-23 and for inhibiting hIL-12 and/or hIL-23 activity, e.g., in a human subject suffering from a disorder in which hIL-12 and/or hIL-23 activity is detrimental.