Anti-CFH Antibody Selection for Cell-Associated CFH Specificity
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
There is a need for improved anti-Complement Factor H (CFH) antibodies that are broadly tolerated and have enhanced properties such as thermal stability, specificity for cell-associated CFH, and minimal off-target effects, while addressing the challenges of low yields in manufacturing.
Innovation Solution
The antibodies were generated by analyzing antibody repertoire data to identify convergent sequence clusters in viral and tumor cohorts, and further developed to improve desirable properties, resulting in antibodies like ATL5170 and ATL5155, which specifically bind to CFH with improved stability and specificity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional antibody generation programs are used to raise antibodies against specific antigens, then antibodies can be obtained, but they may have off-target effects and poor tolerability in vivo
Solution Approach 1:
The patent inverts the traditional antibody generation approach by starting with an analysis of broadly tolerated antibodies and working backwards to identify targets, rather than raising antibodies against specific antigens and then testing for tolerability. This inversion allows the selection of antibody sequences that are naturally tolerant across multiple disease states, thereby reducing off-target effects before clinical use.
Solution Approach 2:
The patent identifies convergent sequence clusters that are present across multiple disease states (viral, tumor, and other cohorts), suggesting that these antibody sequences have universal tolerability profiles. By selecting antibodies based on their presence across diverse disease cohorts, the patent achieves broad tolerability and minimizes off-target effects specific to any single disease state.
2Reliability
If antibody sequences are optimized for thermal stability and specificity, then desirable properties are improved, but manufacturing yield may be reduced
Solution Approach 1:
The patent employs parameter changes by systematically modifying antibody sequences to improve thermal stability and specificity while maintaining manufacturability. Through guided engineering and analysis of cohort diversity, the patent optimizes parameters such as amino acid sequences and structural characteristics to achieve desired properties without compromising production yield.
3Productivity
If antibody yields are improved in transient HEK293 cultures, then manufacturability is enhanced, but the original antibody sequence may lose desirable properties
Solution Approach 1:
The patent implements feedback mechanisms by extensively testing antibody variants and using cohort diversity analysis to guide further engineering. This feedback loop ensures that any modifications made to improve yield do not compromise the antibody's specificity and other desirable properties, allowing for iterative optimization.
Data Source
AI summary
Antibodies and fragments thereof capable of binding to Complement Factor H are described. Related products and therapeutic uses are also described.