Stable IL-17 Antibody Liquid Composition With Low-Oxygen Headspace
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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
Development of stable liquid pharmaceutical compositions with controlled oxygen levels in the container headspace, combined with specific stabilizers like methionine and buffers, to maintain the stability of IL-17 antibodies 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 administration is improved, but protein stability deteriorates due to degradation, aggregation, and oxidation
Solution Approach 1:
The patent applies inert atmosphere by replacing oxygen in the container headspace with nitrogen or other inert gases, creating an oxygen-free environment that prevents oxidation of the IL-17 antibody while maintaining liquid formulation stability for long-term storage
Solution Approach 2:
The patent modifies chemical parameters by adding specific stabilizers (methionine at 2.5-20 mM, sucrose at 5-50%, polysorbate 80 at 0.01-0.1%) and controlling pH (5.0-7.0) and osmolality (200-600 mOsm/kg), which collectively prevent protein degradation, aggregation, and oxidation while maintaining ready-to-use liquid formulation
2Productivity
If long-term storage at room temperature or refrigerated conditions is attempted, then productivity is improved, but physical and chemical stability deteriorates leading to aggregation, deamidation, oxidation, clipping, isomerization, and denaturation
Solution Approach 1:
The patent replaces oxygen with nitrogen or other inert gases in the container headspace, creating an oxygen-free environment that prevents oxidation and other oxygen-dependent degradation reactions, enabling long-term storage stability
Solution Approach 2:
The patent uses a composite formulation system combining multiple stabilizers (amino acids like methionine, sugars like sucrose, surfactants like polysorbate 80, and buffers) that work synergistically to prevent various degradation mechanisms (aggregation, deamidation, oxidation, clipping, isomerization, denaturation) simultaneously
3Object-affected harmful factors
If protein aggregation is prevented to avoid immunogenic reactions, then safety is improved, but formulation complexity increases due to multiple stabilizers and controlled oxygen levels
Solution Approach 1:
The patent combines multiple stabilizing functions into a single integrated formulation system where amino acids, sugars, surfactants, and inert atmosphere work together synergistically to prevent aggregation and other degradation, avoiding the need for separate protective measures
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 exhibit minimal protein aggregation and degradation, maintaining stability for up to 13 months at 25°C, ensuring effective and safe administration of IL-17 antibodies.
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).