AAV Buffer Composition for Long-Term Stability and Low Adsorption
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Solution Overview
Problem
Existing AAV compositions for intracerebroventricular, intraparenchymal, intrathecal, intravenous, sub-cutaneous, intramuscular, and intravitreal administrations face challenges in maintaining long-term stability and potency, preventing adsorption to containers and machinery, and minimizing particle formation during storage and manufacturing.
Innovation Solution
Aqueous compositions comprising stabilizing agents, pharmaceutically acceptable salts, non-ionic surfactants, and sugars or sugar alcohols, with optional buffering agents, are formulated to stabilize AAV vectors, preventing adsorption and maintaining potency for extended storage periods.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If AAV compositions are stored for extended periods, then availability for administration is improved, but AAV potency and stability deteriorate
Solution Approach 1:
The patent applies parameter changes by optimizing the buffer composition with specific concentrations of stabilizing agents (0.5-30 mM), salts (0-250 mM), non-ionic surfactants (0.0001-0.01% w/w), and sugars/sugar alcohols (0.1-20 mM). These compositional parameter adjustments maintain AAV potency while enabling extended storage stability.
Solution Approach 2:
The patent uses stabilizing agents, surfactants, and other buffer components as intermediary substances that protect AAV vectors from degradation during storage. These intermediaries prevent direct harmful interactions between AAV and storage conditions, maintaining potency over extended periods.
2Duration of action of stationary object
If AAV compositions are stored in containers, then storage is enabled, but adsorption to container surfaces occurs causing potency loss
Solution Approach 1:
Non-ionic surfactants (0.0001-0.01% w/w) and stabilizing agents act as intermediary substances that prevent direct adsorption of AAV vectors to container surfaces. These intermediaries form protective layers around AAV particles, eliminating harmful surface interactions while enabling standard container storage.
Solution Approach 2:
The patent modifies the chemical environment parameters by adding specific concentrations of surfactants and stabilizing agents to the buffer formulation. These parameter changes alter surface interaction properties, preventing adsorption while maintaining storage capability.
3Stability of the object's composition
If AAV compositions are formulated with multiple components, then stability is improved, but formulation complexity increases
Solution Approach 1:
The patent establishes specific concentration ranges for each buffer component (stabilizing agents: 0.5-30 mM, salts: 0-250 mM, surfactants: 0.0001-0.01% w/w, sugars: 0.1-20 mM) to achieve optimal stability. These defined parameter ranges provide guidance for formulation while ensuring consistent results.
Solution Approach 2:
The buffer formulation uses multi-functional components that simultaneously perform multiple roles: stabilizing agents provide both structural stabilization and adsorption prevention, while salts maintain osmotic balance and protein solubility. This multi-functionality reduces the need for additional specialized components.
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 compositions effectively maintain AAV vector stability and potency for at least six months, reducing degradation and particle formation, and are suitable for various administration routes, including intracerebroventricular and intraparenchymal routes.
Implementation Method 1
about 0.0001% (w/w) to about 0.01% (w/w) non-ionic surfactant
Implementation Method 2
prevent adsorption to the surfaces of the containers in which the AAV are packaged and stored and of the machinery used during manufacture
Implementation Method 3
about 0.5 mM to about 30 mM stabilizing agent
Implementation Method 4
about 0.1 mM to about 20 mM sugar, sugar alcohol, or combination thereof
Data Source
AI summary
The AAV compositions comprising an AAV and a buffer. These AAV compositions are appropriate for us in intracerebroventricular (ICV) and intraparenchymal (IPA) administration, as well as other routes of administration and can be provided in frozen, liquid or potentially freeze dried (lyophilized) state.