IL-17 Antibody Liquid Formulation for Oxidation-Resistant Storage
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Solution Overview
Problem
Existing liquid pharmaceutical 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 oxygen presence, making them unsuitable for ready-to-use formulations.
Innovation Solution
Development of stable liquid compositions with controlled oxygen levels in the container headspace and inclusion of specific stabilizers like methionine, histidine, trehalose, and polysorbate 80, maintaining pH between 5.2 and 6.2, to enhance stability and prevent oxidation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If liquid pharmaceutical compositions of IL-17 antibodies are prepared for ready-to-use formulations, then convenience of administration is improved, but protein stability deteriorates due to oxidation and aggregation
Solution Approach 1:
The patent applies inert atmosphere by replacing oxygen in the container headspace with nitrogen or other inert gases. This creates an oxygen-free environment that prevents oxidation of the IL-17 antibody while maintaining the liquid formulation in a ready-to-use state. The inert gas displacement technique allows the composition to remain stable during storage and handling without requiring refrigeration or special packaging.
Solution Approach 2:
The patent uses oxygen-scavenging systems and antioxidants as intermediary substances that actively remove or neutralize oxygen from the liquid composition environment. These intermediaries protect the antibody protein from oxidation by converting reactive oxygen into stable, non-reactive forms, thereby maintaining protein stability in ready-to-use liquid formulations.
2Ease of manufacture
If oxygen is present in the container headspace, then ease of manufacturing is improved, but oxidation of the antibody occurs leading to degradation
Solution Approach 1:
The manufacturing process incorporates inert gas flushing to replace oxygen in the container headspace before sealing. This simple technique prevents oxidation during storage and transport while adding minimal complexity to the manufacturing workflow. The inert atmosphere is maintained throughout the product lifecycle from manufacturing to administration.
Solution Approach 2:
The patent implements preliminary oxygen removal through nitrogen flushing or vacuum sealing before the product is sealed and distributed. This preventive measure eliminates oxygen exposure before it can cause oxidation, ensuring product stability without requiring complex active protection systems during storage and handling.
3Reliability
If stabilizers are added to prevent protein degradation, then reliability is improved, but composition complexity increases
Solution Approach 1:
The patent prioritizes the inert atmosphere approach as the primary stabilization mechanism, which simplifies the composition compared to formulations requiring multiple stabilizers, buffers, and preservatives. By creating an oxygen-free environment, the need for extensive chemical protection systems is reduced, maintaining composition simplicity while ensuring reliability.
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, ensuring safety and efficacy for long-term storage and use.
Implementation Method 1
We have determined that 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
Implementation Method 3
maintaining pH between 5.2 and 6.2
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).