Anti-RSV Monoclonal Antibody Formulation with Ionic Excipient
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Anti-RSV monoclonal antibodies with low or neutral isoelectric points (pI) face challenges in colloidal stability due to lack of electrostatic charge, leading to aggregation, precipitation, and instability at commercially desirable concentrations, particularly in pH ranges outside the 5.5 to 7.5 range.
Innovation Solution
A formulation comprising an anti-RSV monoclonal antibody with an ionic excipient at concentrations of 50-150 mM, maintaining a pH of 5.5 to 7.5, which colloidally stabilizes the antibody by shielding charges and reducing aggregation, allowing for higher concentrations without physical instabilities.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Stability of the object's composition
If the pH of the formulation is set within the range of 5.5 to 7.5 (close to the antibody pI), then the formulation maintains colloidal stability and prevents aggregation, but the antibody concentration must be limited to avoid physical instabilities
Solution Approach 1:
The patent changes the pH parameter to be within 1 pH unit of the antibody pI (range 5.5-7.5), which is unconventional as formulations are typically set at least 1 pH unit away from pI. This parameter change enables colloidal stability while allowing higher antibody concentrations (50 mg/ml or greater) by balancing the electrostatic charge conditions to prevent aggregation.
2Stability of the object's composition
If the pH is set outside the range of 5.5 to 7.5 (at least 1 pH unit away from pI), then colloidal stability is improved, but chemical stability deteriorates due to increased fragmentation, oxidation, and deamidation
Solution Approach 1:
The patent changes the pH parameter to be within 1 pH unit of the antibody pI (range 5.5-7.5), which is unconventional as formulations are typically set at least 1 pH unit away from pI. This parameter change enables colloidal stability while allowing higher antibody concentrations (50 mg/ml or greater) by balancing the electrostatic charge conditions to prevent aggregation.
3Stability of the object's composition
If the pH is set more acidic than 5.5, then colloidal stability is improved, but conformational stability decreases and aggregation increases
Solution Approach 1:
The patent changes the pH parameter to be within 1 pH unit of the antibody pI (range 5.5-7.5), which is unconventional as formulations are typically set at least 1 pH unit away from pI. This parameter change enables colloidal stability while allowing higher antibody concentrations (50 mg/ml or greater) by balancing the electrostatic charge conditions to prevent aggregation.
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 improved stability and reduced self-aggregation of anti-RSV antibodies, enabling their use at commercially useful concentrations within the desired pH range, enhancing their suitability for pharmaceutical applications.
Implementation Method 1
these molecules present unique formulation challenges. Colloidal instability at a molecules pI is due to a lack of an electrostatic charge on the molecule, which allows closer protein-protein interactions (so-called 'self-association') that lead to physical instabilities
Data Source
AI summary
The present invention provides a formulation comprising: (i) an anti-RSV monoclonal antibody; and (ii) an ionic excipient; wherein the monoclonal antibody is present at a concentration of about 50 mg/ml or greater and the ionic excipient is present at a concentration of between 50 and 150 mM and the formulation has a pH of about 5.5 to about 7.5.