Stable Liquid IL-17 Antibody Composition With Low-Oxygen Headspace
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Solution Overview
Problem
Existing liquid compositions of IL-17 antibodies, such as secukinumab, face challenges in maintaining long-term stability due to protein degradation issues like aggregation, oxidation, and chemical reactions, which are exacerbated by high oxygen levels, making them unsuitable for ready-to-use pharmaceutical products.
Innovation Solution
Development of a ready-to-use liquid pharmaceutical composition with controlled oxygen levels in the container headspace, combined with specific stabilizers like methionine, histidine, trehalose, and polysorbate 80, to maintain the stability of IL-17 antibodies, reducing oxidation and aggregation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If liquid composition of IL-17 antibody is stored at room temperature or refrigerated conditions, then ease of operation is improved, but stability of the object's composition deteriorates due to protein degradation
Solution Approach 1:
The patent modifies the chemical parameters of the liquid composition by adjusting pH to a specific range (5.0-7.0) and incorporating stabilizing agents (sucrose at 2-10%, polysorbate 80 at 0.01-0.5%, methionine at 0.1-5%) to prevent protein degradation while maintaining liquid state storage convenience
Solution Approach 2:
The patent introduces stabilizing agents as intermediary substances that mediate between the protein and environmental factors. Specifically, sucrose acts as a stabilizer, polysorbate 80 prevents aggregation, and methionine prevents oxidation, thereby protecting the protein from degradation during storage
2Stability of the object's composition
If oxygen level in container headspace is reduced, then stability of the object's composition is improved by preventing oxidation, but device complexity increases due to headspace oxygen control requirements
Solution Approach 1:
The patent creates an inert environment in the container headspace by displacing oxygen with inert gases (nitrogen or carbon dioxide) to prevent oxidation of the IL-17 antibody. This is achieved by filling the headspace with these inert gases before sealing the container
Solution Approach 2:
The patent removes oxygen from the container headspace through purging with inert gases, extracting the harmful oxidizing agent from the system to prevent protein oxidation during storage
3Stability of the object's composition
If stabilizers like methionine and polysorbate 80 are added, then stability of the object's composition is improved, but quantity of substance increases
Solution Approach 1:
The patent optimizes the concentration parameters of stabilizing agents within specific ranges (sucrose: 2-10%, polysorbate 80: 0.01-0.5%, methionine: 0.1-5%) to achieve effective protein stabilization while minimizing the total quantity of additives in the formulation
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 achieves stability with less than 12% oxygen in the headspace, maintaining low aggregate formation and degradation products, ensuring the antibody's effectiveness over 13 months at 25°C, suitable for treating autoimmune disorders.
Implementation Method 1
various physical and chemical reactions can occur in solution (aggregation [covalent and noncovalent], deamidation, oxidation, clipping, isomerization, denaturation)
Implementation Method 2
various physical and chemical reactions can occur in solution (aggregation [covalent and noncovalent], deamidation, oxidation, clipping, isomerization, denaturation)
Data Source
AI summary
The disclosure is directed to pharmaceutical products and stable liquid compositions of IL-17 antibodies and antigen-binding fragments thereof, e.g., AIN457 (secukinumab), and processes of making these pharmaceutical products and compositions. The disclosure is also directed to the use of these pharmaceutical products and liquid compositions (e.g., as part of a kit having instructions for use) for the treatment of various IL-17-mediated disorders (e.g., autoimmune disorders, such as psoriasis, ankylosing spondylitis, psoriatic arthritis, and rheumatoid arthritis).