GM-CSF Antibody Formulation Stability
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Solution Overview
Problem
Current formulations of monoclonal antibodies neutralizing Granulocyte-macrophage colony stimulating factor (GM-CSF) face challenges with stability at high concentrations and during long-term storage, leading to aggregation and immunogenic responses, which complicates subcutaneous administration and storage at room temperature.
Innovation Solution
A stable aqueous formulation comprising a human monoclonal antibody or functional fragment binding to GM-CSF, with specific concentrations of sorbitol, histidine buffer, and polysorbate 80, which maintains stability for extended periods and reduces aggregation, allowing for subcutaneous administration and room temperature storage.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If monoclonal antibody concentration is increased for subcutaneous administration, then administration convenience is improved, but aggregation and immunogenic responses increase
Solution Approach 1:
The patent optimizes formulation parameters including pH (5.5-6.5), ionic strength, and excipient concentrations to maintain antibody stability at high concentrations (50-200 mg/ml), enabling subcutaneous administration without aggregation
Solution Approach 2:
Excipients such as histidine buffer, sorbitol, and polysorbate 80 act as intermediaries to prevent antibody aggregation and maintain solubility at high concentrations, thereby preventing immunogenic responses while enabling convenient administration
2Ease of operation
If liquid formulation is used for convenience, then ease of operation is improved, but protein stability deteriorates during long-term storage
Solution Approach 1:
The patent identifies optimal pH range (5.5-6.5) and excipient concentrations that simultaneously maintain protein stability during long-term storage and provide convenience for patient administration without requiring reconstitution
Solution Approach 2:
The formulation maintains continuous stability of the monoclonal antibody in liquid form during long-term storage through optimized excipients and buffer systems, eliminating the need for lyophilization and reconstitution steps while preserving protein integrity
3Ease of operation
If room temperature storage is implemented, then ease of operation is improved, but aggregation increases during storage
Solution Approach 1:
The patent optimizes formulation parameters including pH, ionic strength, and excipient selection to enable stable storage at room temperature by reducing the driving force for aggregation and maintaining antibody solubility without refrigeration
Solution Approach 2:
Specific excipients including histidine buffer, sorbitol, and polysorbate 80 act as protective intermediaries that prevent aggregation during room temperature storage by maintaining proper solvation and reducing intermolecular interactions that lead to 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 achieves high concentration stability, minimizing aggregation and maintaining bioactivity over long-term storage, facilitating convenient subcutaneous administration and room temperature storage without significant immunogenic reactions.
Implementation Method 1
The ingredients of the formulations preferably provide stability over long term storage and freeze-thaw cycles
Implementation Method 2
A stable aqueous formulation comprising a human monoclonal antibody or functional fragment binding to GM-CSF, with specific concentrations of sorbitol, histidine buffer, and polysorbate 80
Implementation Method 3
A stable aqueous formulation comprising a human monoclonal antibody or functional fragment binding to GM-CSF, with specific concentrations of sorbitol, histidine buffer, and polysorbate 80
Data Source
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AI summary
The present invention relates to aqueous formulations comprising a compound neutralizing GM-CSF in concentrations of at least 20 mg/ml, a tonicity modifier, a buffer and one or more of surfactants, amino acids, antioxidants and/or chelators, wherein the composition is stable. The ingredients of the formulation preferably provide stability to the compound neutralizing GM-CSF in view of long-term storage. In a preferred aspect, the formulation is for use in therapy, preferably for use in the treatment of inflammatory and autoimmune disorders, preferably including allergic and psoriatic disorders, as well as arthritic and asthmatic disorders.