Anti-IL-31RA Antibody Formulation Stability via Arginine and Disaccharides
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Solution Overview
Problem
There is no stable formulation for the anti-IL-31RA antibody (CIM331) that effectively suppresses aggregate formation and charge heterogeneity, which are critical for maintaining antibody stability.
Innovation Solution
The addition of arginine or its salts, sucrose or trehalose, and a nonionic surfactant to formulations of the anti-IL-31RA antibody increases stability, whether in a lyophilized or solution state.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional formulation methods are used for anti-IL-31RA antibody, then the formulation can be prepared, but aggregate formation and charge heterogeneity occur which adversely affect antibody stability
Solution Approach 1:
The patent applies parameter changes by optimizing the formulation composition, specifically setting the concentration of arginine to 4.5-1500 mmol/L and sucrose/trehalose to 7.5-2500 mmol/L. These specific parameter ranges were determined to effectively suppress aggregate formation and charge heterogeneity while maintaining antibody stability in lyophilized formulations.
Solution Approach 2:
The patent uses arginine and sucrose/trehalose as intermediary substances that mediate between the antibody and the formulation environment. These additives act as stabilizing agents that prevent direct harmful interactions, suppress aggregate formation, and maintain charge homogeneity, thereby improving antibody stability without directly being the antibody itself.
2Stability of the object's composition
If lyophilized formulations are developed to improve stability, then storage stability is improved, but additional stabilizing agents and complex formulation processes are required
Solution Approach 1:
The patent achieves multi-functionality by selecting additives that perform multiple roles: arginine serves as both a stabilizing agent and a charge heterogeneity suppressor, while sucrose/trehalose provide both structural stability and protection against aggregation. This allows a single formulation system to address multiple stability concerns simultaneously, reducing the need for multiple separate additives.
Solution Approach 2:
The patent establishes specific concentration ranges for the stabilizing agents (arginine: 4.5-1500 mmol/L, sucrose/trehalose: 7.5-2500 mmol/L) that optimize the balance between formulation stability and complexity. These parameter optimizations ensure that the added agents provide maximum benefit while maintaining reasonable formulation simplicity.
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
These additives enhance the stability of the anti-IL-31RA antibody formulations by reducing aggregate formation and charge heterogeneity, thereby maintaining the antibody's effectiveness.
Implementation Method 1
the addition of arginine or a salt thereof to formulations comprising the above-described IL-31 antagonist increases stability of the formulations comprising the IL-31 antagonist
Implementation Method 2
the addition of sucrose or trehalose to the formulations increases stability of the formulations comprising the IL-31 antagonist when the formulations are in a lyophilized state
Implementation Method 3
the addition of a nonionic surfactant to the formulations increases stability of the formulations comprising the IL-31 antagonist when the formulations are in a solution state
Implementation Method 4
numerous lyophilized formulations for therapeutic proteins such as antibodies have been developed so far
Data Source
AI summary
In one non-limiting embodiment, the present disclosure relates to lyophilized formulations containing an IL-31 antagonist (for example, an anti-IL-31RA antibody) as an active ingredient, the lyophilized formulations further containing arginine and/or a salt thereof and sucrose and/or trehalose. In another non-limiting embodiment, the present disclosure relates to solution formulations containing an IL-31 antagonist as an active ingredient, the solution formulations further containing arginine and/or a salt thereof. In other non-limiting embodiments, the present disclosure relates to methods for stabilizing an antibody (for example, an anti-IL-31RA antibody) in an antibody-containing formulation, methods for suppressing antibody aggregation (aggregate formation) in an antibody-containing formulation, and methods for reducing components with charge heterogeneity in an antibody-containing formulation, the methods being characterized in that the formulation is prepared to contain arginine and/or a salt thereof, and/or sucrose and/or trehalose.