IL-17 Antibody Liquid Composition for Oxidation and Aggregation 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 a ready-to-use liquid pharmaceutical composition 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.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If liquid composition is prepared for ready-to-use administration, then convenience and ease of operation are improved, but protein stability and reliability deteriorate due to degradation 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 during storage, thereby maintaining protein stability while keeping the composition in ready-to-use liquid form. The inert gas atmosphere is maintained throughout storage and handling.
Solution Approach 2:
The patent employs parameter changes by carefully controlling multiple formulation parameters including pH (adjusted to specific ranges), ionic strength, temperature during storage, and oxygen concentration (reduced to less than 1% in headspace). These parameter optimizations collectively enhance protein stability in the liquid ready-to-use composition.
2Object-affected harmful factors
If oxygen levels are reduced in container headspace, then oxidation and protein degradation are reduced, but complexity of manufacturing increases
Solution Approach 1:
The patent reduces oxygen levels in the container headspace by replacing it with nitrogen or other inert gases. This inert atmosphere prevents oxidation of the IL-17 antibody during storage and handling. The manufacturing process involves purging the headspace with inert gas before sealing, which protects the protein from oxidative degradation.
Solution Approach 2:
The patent applies preliminary action by adjusting the pH and adding stabilizing excipients to the liquid composition before filling into the container. This pre-optimization of the formulation ensures the protein is in a stable state before exposure to the inert atmosphere and during subsequent storage, reducing the need for complex ongoing protective measures.
3Reliability
If stabilizing excipients are added to liquid composition, then protein stability is improved, but osmolality and viscosity may increase affecting syringeability
Solution Approach 1:
The patent optimizes the concentrations of stabilizing excipients to achieve the necessary protein stability while maintaining acceptable viscosity and osmolality. By carefully controlling the amounts of each excipient and adjusting pH to specific ranges, the formulation achieves a balance between stability and syringeability.
Solution Approach 2:
The patent uses a composite formulation containing multiple excipients including sugars (sucrose, trehalose), amino acids (methionine, histidine), and surfactants (polysorbate 80) in specific combinations. This composite approach provides synergistic stabilization while managing the physical properties like viscosity and osmolality to maintain syringeability.
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 long-term stability with reduced protein degradation and oxidation, maintaining stability for up to 13 months at 25°C with aggregate formation below 3.5% and degradation products below 34.5% by RP-HPLC, ensuring safety and efficacy for treatment of autoimmune disorders.
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
Implementation Method 3
a buffer, a surfactant, methionine, and a stabilizer
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).