Anti-IL-5 Antibody Composition With Controlled Degradation Variants
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Solution Overview
Problem
Existing compositions for treating IL-5 mediated diseases, such as asthma and eosinophilic disorders, do not effectively maintain the biological function of the monoclonal antibody mepolizumab, which is critical for its therapeutic efficacy due to issues like deamidation, oxidation, and aggregation.
Innovation Solution
A composition comprising an anti-IL-5 antibody with specific heavy and light chain sequences (SEQ ID NO: 1 and SEQ ID NO: 2) and controlled levels of deamidated, oxidized, and aggregated variants, maintained within defined limits, to ensure optimal biological function and stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If mepolizumab is used to treat IL-5 mediated diseases, then therapeutic efficacy is achieved, but biological function is compromised due to deamidation, oxidation, and aggregation
Solution Approach 1:
The patent applies preliminary action by defining and controlling the formation of degradation variants (deamidated, oxidized, aggregated forms) during the manufacturing process. By establishing specific limits on these variants before the product is administered, the patent prevents biological function compromise before it occurs, rather than addressing it after degradation has happened.
Solution Approach 2:
The patent applies parameter changes by specifying precise compositional parameters (limits on deamidated, oxidized, and aggregated variants) to maintain protein structure stability. By controlling these chemical and structural parameters within defined ranges, the patent ensures reliable biological function while preventing degradation.
2Ease of manufacture
If deamidation, oxidation, and aggregation are present in mepolizumab, then manufacturing complexity is reduced, but biological function is compromised
Solution Approach 1:
The patent applies parameter changes by establishing specific compositional limits for degradation variants during manufacturing. By defining acceptable ranges for deamidated, oxidized, and aggregated forms, the patent balances manufacturing feasibility with maintaining biological function, allowing some variant formation while preventing excessive degradation.
3Reliability
If strict limits on variants are imposed to maintain biological function, then therapeutic efficacy is ensured, but composition complexity increases
Solution Approach 1:
The patent applies parameter changes by defining specific compositional limits for different variant types (deamidated, oxidized, aggregated forms). By establishing clear numerical criteria for acceptable variant levels, the patent maintains therapeutic efficacy while providing a structured framework for quality control that manages complexity systematically.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The composition effectively treats IL-5 mediated diseases by maintaining the biological function of mepolizumab, reducing exacerbations, improving lung function, and controlling eosinophil levels, thereby enhancing therapeutic outcomes.
Implementation Method 1
Mepolizumab is a monoclonal antibody that binds to soluble IL-5 and blocks the soluble IL-5 from binding to its receptor. These are a) binding to IL-5 in complementary determining region (CDR) which provides the mechanism of action
Implementation Method 2
b) binding to neonatal Fc receptor (FcRn) receptor in Fc region, which determines the half-life
Implementation Method 3
it has been found that deamidation, oxidation, and aggregation are critical quality attributes of mepolizumab. residue N31 of the light chain is deamidated to aspartic acid or iso-aspartic acid
Implementation Method 4
it has been found that deamidation, oxidation, and aggregation are critical quality attributes of mepolizumab. 3% or less oxidised antibody variant at W52 of the heavy chain amino acid sequence, 50% or less oxidised antibody variant at M64 of the heavy chain amino acid sequence
Implementation Method 5
it has been found that deamidation, oxidation, and aggregation are critical quality attributes of mepolizumab. 20% or less deamidated antibody variants at N31 of the light chain amino sequence
Data Source
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AI summary
The present disclosure relates to compositions, for treating interleukin 5 (IL-5) mediated diseases, and related methods.