Stable IL-17 Antibody Liquid Composition With Low-Oxygen Headspace
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Existing liquid compositions of IL-17 antibodies, such as secukinumab, suffer from instability due to protein degradation, aggregation, and oxidation, making long-term storage and administration challenging, especially in ready-to-use formulations.
Innovation Solution
Developing stable liquid pharmaceutical compositions with controlled oxygen levels in the container headspace and specific stabilizers, including methionine, histidine, trehalose, and polysorbate 80, to maintain the stability of IL-17 antibodies like secukinumab, ensuring minimal oxidation and aggregation over time.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If liquid compositions of IL-17 antibodies are formulated for ready-to-use administration, then ease of operation is improved, but stability deteriorates due to protein degradation, aggregation, and oxidation
Solution Approach 1:
The patent applies inert atmosphere by removing oxygen from the headspace of the container and using oxygen-scavenging agents within the formulation. This creates an oxygen-depleted environment that prevents oxidation of the IL-17 antibody, thereby maintaining protein stability while enabling ready-to-use liquid formulation for ease of administration.
Solution Approach 2:
The patent uses stabilizing agents (such as sugars, amino acids, and surfactants) as intermediaries between the antibody and harmful environmental factors. These intermediaries protect the antibody from degradation, aggregation, and oxidation, allowing the liquid composition to remain stable during storage and administration.
2Stability of the object's composition
If oxygen levels in the container headspace are reduced to prevent oxidation, then protein stability is improved, but device complexity increases due to additional requirements for oxygen control
Solution Approach 1:
The patent applies preliminary action by pre-establishing an oxygen-depleted environment in the container headspace before filling the liquid composition. Oxygen-scavenging agents are incorporated into the formulation in advance, and the container is designed with features that maintain low oxygen levels, thereby preventing oxidation before it can occur without requiring complex active control systems.
Solution Approach 2:
The patent uses disposable oxygen-scavenging agents and single-use containers that are designed to maintain low oxygen levels during the product's intended shelf life. This approach avoids the need for complex, reusable oxygen control systems while effectively preventing oxidation throughout the product's lifecycle.
3Stability of the object's composition
If stabilizers are added to the liquid composition to prevent aggregation and degradation, then protein stability is improved, but manufacturing complexity increases
Solution Approach 1:
The patent applies parameter changes by optimizing the concentration and type of stabilizing agents (such as selecting specific sugars, amino acids, or surfactants) and adjusting formulation parameters like pH, ionic strength, and temperature. This systematic optimization achieves effective aggregation control and protein stability while maintaining manufacturability through defined parameter ranges.
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 compositions demonstrate excellent stability with aggregate formation below 3.5% and degradation products less than 39.4% after 13 months at 25°C, suitable for long-term storage and administration.
Implementation Method 1
the combined use of particular stabilizers with a low oxygen level in the headspace of the container contributes significantly to long-term stability of the liquid pharmaceutical product, and prevents oxidation of the IL-17 antibody
Implementation Method 2
various physical and chemical reactions can occur in solution (aggregation [covalent and noncovalent], deamidation, oxidation, clipping, isomerization, denaturation), leading to an increase in degradation product levels
Implementation Method 3
a container having a headspace with less than about 12% oxygen... the combined use of particular stabilizers with a low oxygen level in the headspace of the container contributes significantly to long-term stability
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).