Stable Liquid IL-17 Antibody Composition for Oxidation Control
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Solution Overview
Problem
Existing liquid compositions of IL-17 antibodies, such as secukinumab, face stability issues 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 headspace and specific stabilizers, including methionine, histidine, trehalose, and polysorbate 80, to maintain the stability of IL-17 antibodies like secukinumab, ensuring minimal degradation and aggregation over time.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If liquid compositions of IL-17 antibodies are prepared for ready-to-use formulation, then ease of operation and administration is improved, but stability of the antibody is worsened due to protein degradation, aggregation, and oxidation
Solution Approach 1:
The patent applies inert atmosphere by replacing oxygen in the headspace with nitrogen or other inert gases, creating an oxygen-free environment that prevents oxidation of the IL-17 antibody. This is achieved through nitrogen purging or vacuum sealing techniques, allowing the liquid composition to remain stable for extended periods without refrigeration while maintaining ready-to-use convenience
Solution Approach 2:
The patent employs parameter changes by optimizing pH levels (typically 5.0-7.0), temperature conditions (room temperature or refrigerated), and compositional parameters (adding stabilizers like methionine, histidine, trehalose, and polysorbate 80) to enhance antibody stability in liquid form. These parameter adjustments enable the composition to maintain stability while remaining in liquid ready-to-use form
2Stability of the object's composition
If stabilizers and controlled oxygen levels are implemented, then stability of the antibody is improved, but device complexity and manufacturing complexity increase
Solution Approach 1:
The patent uses stabilizers as intermediary substances that mediate between the antibody and the environmental stressors (oxygen, pH changes, temperature fluctuations). Specific stabilizers like methionine (scavenges oxygen), histidine (buffers pH), trehalose (prevents aggregation), and polysorbate 80 (reduces surface tension) act as protective intermediaries that simplify the overall system by handling stressor management
Solution Approach 2:
The patent applies preliminary action by pre-adjusting the composition parameters (pH, oxygen content, stabilizer concentrations) during manufacturing to optimize stability before the product reaches the patient. Nitrogen purging and vacuum sealing are performed during filling to establish protective conditions in advance, eliminating the need for complex storage infrastructure
3Loss of time
If long-term storage at room temperature is achieved, then loss of time and storage cost are reduced, but protein degradation and aggregation increase
Solution Approach 1:
The patent uses inert atmosphere (nitrogen or vacuum) in the headspace to prevent oxidation and reduce protein degradation during long-term storage. This allows room temperature storage for extended periods (months to years) while maintaining antibody stability, eliminating the need for continuous refrigeration and reducing storage time losses
Solution Approach 2:
The patent employs parameter changes by optimizing pH (5.0-7.0), temperature (room temperature or refrigerated), and compositional parameters (adding stabilizers like methionine, histidine, trehalose, and polysorbate 80) to enhance antibody stability in liquid form. These parameter adjustments enable the composition to maintain stability while remaining in liquid ready-to-use form
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 achieve long-term stability with less than 3.5% aggregate formation and less than 39.4% degradation products after 13 months at 25°C, maintaining bioactivity and safety for subcutaneous use.
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
an acceptable liquid antibody composition must enhance stability and minimize protein degradation, especially protein aggregation
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).