Fc-silenced Anti-oxMIF Antibodies with Reduced Aggregation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current therapies targeting oxMIF are limited by protein aggregation and hydrophobicity issues, which affect stability, immunogenicity, and efficacy, and there is a need for Fc-silenced antibodies with reduced aggregation potential and hydrophobicity to treat oxMIF-related conditions.
Innovation Solution
Development of Fc-silenced anti-oxMIF antibodies with specific amino acid substitutions and glycosylation modifications in the variable domains, reducing aggregation propensity and hydrophobicity, and altering Fc region interactions to minimize effector functions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional anti-oxMIF antibodies are used, then therapeutic efficacy is achieved, but protein aggregation and hydrophobicity increase
Solution Approach 1:
The patent applies parameter changes by systematically modifying amino acid residues at specific positions (e.g., L234, L235, L328, P329, A330, P331) in the Fc region of the antibody. These substitutions alter the physicochemical parameters of the antibody, specifically reducing hydrophobicity and aggregation propensity while preserving therapeutic efficacy against oxMIF-targeted conditions.
Solution Approach 2:
The invention applies local quality by making targeted amino acid substitutions at specific positions within the Fc region rather than throughout the entire antibody structure. This localized modification approach allows the antibody to maintain its overall structure and antigen-binding capability while specifically addressing aggregation-prone regions in the Fc domain.
2Reliability
If conventional anti-oxMIF antibodies are used, then therapeutic efficacy is achieved, but immunogenicity increases
Solution Approach 1:
The patent reduces immunogenicity by modifying parameters such as glycosylation patterns (removing N-linked glycans at Asn297) and amino acid compositions in the Fc region. These parameter changes make the antibody more similar to human proteins, thereby reducing the immune system's recognition and response to the therapeutic antibody.
Solution Approach 2:
The invention employs copying by creating humanized versions of the antibody Fc region that closely mimic human IgG structure and properties. By copying human amino acid sequences and glycosylation patterns, the antibody becomes less foreign to the human immune system, reducing immunogenicity while maintaining therapeutic function.
3Object-generated harmful factors
If Fc region is modified to reduce aggregation, then aggregation potential decreases, but effector function may be affected
Solution Approach 1:
The patent applies local quality by selectively modifying specific amino acid positions (L234, L235, L328, P329, A330, P331) in the Fc region that are responsible for aggregation-prone interactions, while preserving other regions critical for effector functions. This localized approach allows differentiation between aggregation-prone areas and functionally critical areas.
Solution Approach 2:
The invention uses parameter changes to modify hydrophobicity and aggregation propensity at specific Fc positions while maintaining parameters related to effector function (such as FcγR binding capability). By carefully selecting amino acid substitutions that alter local hydrophobicity without disrupting overall Fc structure, the patent achieves reduced aggregation with preserved effector function.
Data Source
Figure 1A~1B
Figure 1C~2
Figure 3~4A
AI summary
The invention refers to Fc silenced anti-oxMIF antibodies with improved properties such as reduced aggregation potential and reduced hydrophobicity due to selected amino acid substitutions in the light and heavy chain variable domains, and their use in the treatment of oxMIF-related conditions.