Anti-IL-6R Antibody Formulation Stability via Arginine Extraction
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Solution Overview
Problem
Current formulations of anti-IL-6R antibodies, such as tocilizumab, sapelizumab, and sarilumab, face stability issues due to chemical or physical instabilities like denaturation and aggregation, leading to reduced efficacy over time, especially during storage, and require different excipients for varying concentrations and presentations, increasing complexity.
Innovation Solution
A liquid pharmaceutical composition comprising an anti-IL-6R antibody, a histidine buffer, a polyol (like mannitol), a free amino acid (such as methionine), and a surfactant (polysorbate 80), with optional salt, that is substantially free of arginine, maintaining stability and biological activity for extended periods across different concentrations and presentations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If different excipients are used for varying concentrations and presentations of anti-IL-6R antibodies, then the stability and efficacy of the formulation is improved, but the formulation complexity increases
Solution Approach 1:
The patent applies universality by developing a single formulation composition that can serve multiple purposes across different concentrations and administration routes. The composition includes specific excipients (polysorbate 80, histidine buffer, polyol, amino acid) that work synergistically to maintain stability and efficacy whether the antibody is formulated for intravenous, subcutaneous, or other injection routes, eliminating the need for separate formulations for different presentations
2Stability of the object's composition
If arginine is included in the formulation to enhance stability, then the protein stability is improved, but oxidation and aggregation issues arise
Solution Approach 1:
The patent applies the extraction principle by removing arginine from the formulation composition. Instead of including arginine as a stabilizing excipient, the invention uses alternative excipients (polysorbate 80, histidine buffer, polyol, and amino acid) that provide stability without causing oxidation or aggregation. This extraction of the problematic ingredient resolves the contradiction between stability enhancement and harmful side effects
3Duration of action of stationary object
If the formulation is designed for long-term storage stability, then the shelf-life is improved, but the formulation becomes more complex
Solution Approach 1:
The patent applies parameter changes by optimizing the concentration and interaction parameters of the excipients to achieve long-term stability. The specific combination of polysorbate 80, histidine buffer at controlled pH, polyol, and amino acid creates a formulation that maintains protein stability over extended periods (12 months or more) without requiring complex additional stabilizing agents or multiple formulation variants
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 retains at least 80% biological activity for 12 months or more, offering a stable and versatile formulation suitable for various concentrations and administration routes, simplifying the formulation process while matching or exceeding the performance of existing commercial formulations.
Implementation Method 1
a liquid pharmaceutical composition comprising an anti-IL-6R antibody, a histidine buffer
Implementation Method 2
a polyol (such as a sugar alcohol)
Implementation Method 3
a surfactant (polysorbate 80)
Implementation Method 4
a free amino acid (such as methionine)
Data Source
AI summary
The present invention relates to a novel protein formulation. In particular, the invention relates to a liquid pharmaceutical composition of an antibody directed to Interleukin-6 receptor, a method of manufacturing the composition, a kit including the composition, a package including the composition and to methods of treatment using the composition and/or package.