Fully Human Anti-IL-25 Antibody with High Affinity Binding
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Solution Overview
Problem
Current anti-IL-25 antibodies are insufficient for effectively treating diseases associated with IL-25 expression and signaling, as they lack novel antagonistic properties to target various disorders such as asthma, inflammatory bowel disease, and autoimmune diseases effectively.
Innovation Solution
Development of a fully human monoclonal antibody or antigen-binding fragment specifically binding to human IL-25, comprising a heavy chain variable region (HCVR) and light chain variable region (LCVR) with specific amino acid sequences, which can be used in pharmaceutical compositions to treat a range of diseases by blocking IL-25 signaling.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing anti-IL-25 antibodies are used, then some IL-25 binding activity is achieved, but they lack sufficient antagonistic properties to effectively treat various IL-25 associated disorders
Solution Approach 1:
The patent applies parameter changes by modifying the antibody structure to achieve optimal binding affinity and antagonistic activity. Specifically, the antibody is engineered with a Kd of less than 120 pM for IL-25, and Fc region modifications (such as M428L and N434S mutations) are introduced to alter effector function while maintaining binding. These parameter optimizations resolve the contradiction by creating an antibody that simultaneously achieves high reliability in binding and enhanced versatility in therapeutic application across multiple IL-25 associated disorders
2Reliability
If a fully human monoclonal antibody with specific sequences is developed, then therapeutic efficacy is improved, but development complexity and manufacturing challenges increase
Solution Approach 1:
The patent applies segmentation by dividing the antibody into distinct functional regions with specific sequences. The heavy chain variable region (SEQ ID NO: 114) and light chain variable region (SEQ ID NO: 122) are separately defined and optimized for IL-25 binding, while the Fc region contains specific mutations (M428L, N434S) for altered effector function. This segmentation allows each region to be independently optimized and manufactured, resolving the contradiction between therapeutic efficacy and manufacturing ease
Solution Approach 2:
The patent specifies precise amino acid sequences for the variable regions and introduces defined mutations in the Fc region. The heavy chain variable region has specific amino acid sequence SEQ ID NO: 114 and the light chain variable region has specific amino acid sequence SEQ ID NO: 122. These parameter specifications ensure consistent therapeutic efficacy while providing clear manufacturing guidelines for producing the fully human monoclonal antibody
Data Source
Figure 1
AI summary
The present invention provides antibodies that bind to human interleukin-25 (IL-25) and methods of using the same. According to certain embodiments, the antibodies of the invention bind human IL-25 with high affinity. In certain embodiments, the invention includes antibodies that bind human IL-25 and block IL-25-mediated cell signaling. The antibodies of the invention may be fully human, non-naturally occurring antibodies. The antibodies of the invention are useful for the treatment of various disorders associated with IL-25 activity or expression, including asthma, allergy, chronic obstructive pulmonary disease (COPD), inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, atopic dermatitis (AD), and Eosinophilic Granulomatosis with Polyangiitis (EGPA), also know as Churg-Strauss Syndrome.