Anti-IL-33 Antibody Formulation Viscosity Reduction
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Solution Overview
Problem
Current formulations of anti-IL-33 antibodies, such as 33_640087-7B, face challenges with stability and bioavailability due to reversible self-association at high concentrations, leading to increased viscosity and aggregation, which complicates subcutaneous administration for chronic conditions.
Innovation Solution
A high-concentration formulation of anti-IL-33 antibodies with at least 100 mg/ml concentration, incorporating 170 mM arginine or 150 mM lysine, and a buffer, along with a surfactant like polysorbate 80, to reduce reversible self-association and viscosity, enhancing stability and bioavailability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If the concentration of anti-IL-33 antibody is increased to reduce administration volume, then the therapeutic efficacy is improved, but the viscosity increases and subcutaneous administration becomes difficult
Solution Approach 1:
The patent changes the pH parameter of the formulation to a lower range (pH 4.0-6.0, preferably pH 4.5-5.5) to reduce antibody viscosity and reversible self-association at high concentrations, enabling feasible subcutaneous administration while maintaining therapeutic efficacy
2Productivity
If the concentration of anti-IL-33 antibody is increased to achieve therapeutic dose in smaller volume, then the treatment efficiency is improved, but protein aggregation and reversible self-association increase
Solution Approach 1:
The patent adjusts the pH parameter to a lower range (pH 4.0-6.0) which stabilizes the antibody structure at high concentrations, reducing reversible self-association and aggregation while maintaining therapeutic efficacy
Solution Approach 2:
The patent introduces buffer systems (histidine, acetate, succinate, citrate) as intermediary substances that maintain the optimal pH environment, preventing protein aggregation and stabilizing the antibody formulation at high concentrations
3Ease of operation
If the concentration of anti-IL-33 antibody is increased to reduce administration volume for chronic conditions, then the patient compliance is improved, but the solution viscosity increases making delivery difficult
Solution Approach 1:
The patent lowers the pH parameter to (pH 4.0-6.0) which significantly reduces antibody viscosity at high concentrations, enabling delivery through devices with high back pressure while maintaining patient compliance for chronic treatment
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 achieves reduced reversible self-association and viscosity, improving the stability and bioavailability of anti-IL-33 antibodies, facilitating more comfortable and effective subcutaneous administration for chronic conditions.
Implementation Method 1
incorporating 170 mM arginine or 150 mM lysine, and a buffer, along with a surfactant like polysorbate 80, to reduce reversible self-association and viscosity
Implementation Method 2
incorporating 170 mM arginine or 150 mM lysine, and a buffer, along with a surfactant like polysorbate 80, to reduce reversible self-association and viscosity
Data Source
AI summary
The present disclosure is directed to compositions comprising greater than about 100 mg/ml of an anti-IL-33 antibody, a surfactant, arginine and a buffer. Methods for making the compositions and methods of treating disease in a subject are also disclosed.