IL-36 Antibody Formulation Stability via Intermediary Excipients
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Solution Overview
Problem
Antibody formulations, particularly those containing interleukin-36 (IL-36) antibodies, face challenges with stability during storage and use due to denaturation, oxidation, and aggregation, especially at high concentrations, which affects their pharmaceutical and therapeutic efficacy.
Innovation Solution
A stable liquid aqueous pharmaceutical formulation comprising an antibody or antigen binding antibody fragment, a histidine buffer, proline and/or sorbitol as stabilizers, and a non-ionic surfactant like polysorbate, which maintains stability and effectiveness.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If high concentration of antibody is used in formulation, then therapeutic efficacy is improved, but stability deteriorates due to denaturation, oxidation, and aggregation
Solution Approach 1:
The patent introduces multiple intermediary substances (excipients) including buffers, stabilizers, and surfactants that mediate between the high antibody concentration and the antibody molecules themselves. These intermediaries create a protective environment that prevents direct harmful interactions between antibody molecules, thereby maintaining stability at high concentrations.
Solution Approach 2:
The formulation systematically adjusts multiple parameters including pH (using histidine buffer), ionic strength, and molecular crowding conditions (using stabilizers like proline and sorbitol). These parameter changes create optimal conditions that simultaneously support high antibody concentration and prevent denaturation, oxidation, and aggregation.
2Quantity of substance
If high concentration of antibody is used in formulation, then therapeutic efficacy is improved, but aggregation increases
Solution Approach 1:
Surfactants and stabilizers act as intermediary molecules that occupy space and interact with antibody surfaces, preventing direct antibody-antibody interactions that lead to aggregation. These intermediaries create steric and electrostatic barriers that maintain molecular dispersion at high concentrations.
Solution Approach 2:
The formulation creates different local environments around antibody molecules through the use of multiple excipients with different functions. Buffers maintain local pH stability, while stabilizers and surfactants provide local protective layers, ensuring each antibody molecule experiences favorable local conditions that prevent aggregation.
3Quantity of substance
If high concentration of antibody is used in formulation, then therapeutic efficacy is improved, but oxidation increases
Solution Approach 1:
The formulation creates a chemically inert environment through the use of buffers and stabilizers that resist oxidation and can scavenge reactive oxygen species. This inert environment protects the high concentration of antibodies from oxidative damage while maintaining their therapeutic activity.
4Quantity of substance
If high concentration of antibody is used in formulation, then therapeutic efficacy is improved, but denaturation increases
Solution Approach 1:
The formulation optimizes multiple parameters including pH control through histidine buffer, ionic strength, and osmotic pressure through stabilizers. These parameter changes create a buffered environment that maintains the native conformation of antibodies even at high concentrations, preventing denaturation.
Solution Approach 2:
Stabilizers and surfactants act as intermediary molecules that interact with antibody surfaces and maintain their native structure. These intermediaries prevent unfolding and aggregation by providing steric and electrostatic protection, allowing high concentration formulations to remain stable.
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 provides enhanced stability and effectiveness of IL-36 antibodies, reducing denaturation, oxidation, and aggregation, ensuring their suitability for pharmaceutical use and therapeutic applications.
Implementation Method 1
a buffer
Implementation Method 2
a stabilizer comprising proline and/or sorbitol
Implementation Method 3
a non-ionic surfactant
Data Source
AI summary
The invention relates to a stable liquid aqueous pharmaceutical formulation comprising an anti-interleukin 36 receptor (IL-36R) antibody or antigen binding antibody fragment; a buffer; a stabilizer; and a surfactant, and methods of treating a subject with the pharmaceutical formulation.