Anti-KIR3DL2 Antibody Formulation for Aggregation Control
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Solution Overview
Problem
Antibodies face challenges in maintaining stability during development, manufacture, and clinical use due to stresses that can lead to particle formation, aggregation, or denaturation, affecting efficacy and safety.
Innovation Solution
A stable aqueous pharmaceutical formulation comprising an anti-KIR3DL2 antibody with specific buffer, tonicity agent, and non-ionic surfactant ratios, such as polysorbate 80, is developed to minimize particle formation and aggregation, ensuring stability during storage and handling.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If antibodies are stored during development, manufacture, and clinical use, then the therapeutic must maintain stability, but particle formation, aggregation, or denaturation occurs due to various stresses
Solution Approach 1:
The patent introduces a specific formulation composition including buffers, tonicity agents, and non-ionic surfactants as intermediary substances that mediate between the antibody and environmental stresses. These formulation components create a protective environment that prevents direct interaction between the antibody and stressors such as shear force, interfacial stress, and temperature variations, thereby preventing particle formation and aggregation while maintaining therapeutic stability during storage and handling
2Quantity of substance
If the antibody concentration is increased to at least 15 mg/ml for effective dosing, then therapeutic efficacy is improved, but the formulation becomes more susceptible to aggregation and particle formation
Solution Approach 1:
The patent applies parameter changes by optimizing the formulation composition to include specific concentrations of buffers, tonicity agents, and non-ionic surfactants. These parameter adjustments create a chemical environment that stabilizes the high-concentration antibody solution (at least 15 mg/ml), preventing aggregation and particle formation despite the increased susceptibility that comes with higher concentrations. The specific ratios of formulation components are tuned to maintain solubility and stability at the required therapeutic concentrations
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 formulation significantly reduces particle formation and aggregation, maintaining antibody integrity and safety for prolonged storage and clinical use, with less than 200 particles ≥10 μm per mL after 6 months and reduced degradation, even under shear or interfacial stress.
Implementation Method 1
a non-ionic surfactant; wherein the ratio of the antibody concentration to non-ionic surfactant is about 20:0.1 to 40:0.4
Data Source
AI summary
The present disclosure relates to a stable aqueous formulation. The stable aqueous formulation may be used for an anti-KIR3DL2 antibody.