Aqueous Anti-IL5R Antibody Formulation Without Lyophilization
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Solution Overview
Problem
Challenges exist in stabilizing antibodies for transport and storage, with issues such as denaturation, aggregation, contamination, and particle formation, and existing formulations often require lyophilization and reconstitution, which can introduce contaminants and are not ideal for administration.
Innovation Solution
A stable, aqueous antibody formulation comprising specific concentrations of antibodies with defined CDR sequences, polysorbate-20, and uncharged excipients like trehalose and arginine, which maintains antibody stability and prevents aggregation and particle formation during storage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If lyophilization and reconstitution are used to stabilize antibodies, then antibody stability during transport and storage is improved, but the formulation process becomes more complex and contaminants may be introduced
Solution Approach 1:
The patent changes the formulation parameters by using aqueous solutions with specific excipients (polysorbate-20 at 0.002-0.01%, uncharged excipients at 20-400 mM) instead of lyophilization, maintaining stability through chemical composition optimization rather than physical state changes
Solution Approach 2:
The patent extracts the stabilizing function from the lyophilization process and implements it through specific excipients in aqueous formulation, eliminating the need for freeze-drying while maintaining antibody stability
2Stability of the object's composition
If lyophilization and reconstitution are used, then antibody stability is improved, but additional administration steps are required
Solution Approach 1:
The patent removes the reconstitution step entirely by formulating antibodies in stable aqueous solutions that can be administered directly, extracting the stability function and implementing it through excipient selection rather than physical processing
Solution Approach 2:
The patent segments the administration process by providing ready-to-administer aqueous formulations that eliminate the need for reconstitution, allowing direct intravenous, subcutaneous, or intramuscular injection
3Quantity of substance
If high concentration antibodies are formulated, then dosage efficiency is improved, but aggregation and particle formation increase
Solution Approach 1:
The patent introduces polysorbate-20 and uncharged excipients as intermediary substances that mediate between high antibody concentration and aggregation prevention, allowing 2-100 mg/mL formulations to remain stable through surfactant protection
Solution Approach 2:
The patent changes the formulation parameters by optimizing excipient concentrations (polysorbate-20 at 0.002-0.01%, uncharged excipients at 20-400 mM) to enable high antibody concentrations without aggregation
4Stability of the object's composition
If antibody formulations are optimized for one antibody, then stability is improved, but versatility across different antibodies decreases
Solution Approach 1:
The patent creates a universal formulation platform using aqueous solutions with polysorbate-20 and uncharged excipients that can stabilize multiple different antibodies, achieving both stability and versatility through a common formulation approach
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 maintains at least 80-95% binding ability to IL-5R polypeptides after storage at various temperatures for extended periods, with minimal aggregation and particle formation, making it suitable for intravenous, subcutaneous, or intramuscular administration.
Implementation Method 1
about 0.002% to about 0.01% polysorbate-20
Implementation Method 2
uncharged excipient like trehalose and arginine
Data Source
AI summary
The present invention relates to stable, aqueous antibody formulations. In some embodiments, the stable, aqueous formulations comprise about 2 mg/mL to about 100 mg/mL of an anti-IL5R antibody, and about 0.002% to about 0.01% polysorbate-20. Also provided are methods of making and methods of using such antibody formulations.