Stable Liquid Anti-HER2 Formulations for Subcutaneous Delivery
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Solution Overview
Problem
Existing monoclonal antibody therapies for HER2-positive cancers, such as trastuzumab and pertuzumab, face challenges with conventional intravenous administration that are inconvenient and costly, and subcutaneous administration is limited by the amount that can be injected and requires stable liquid formulations with high antibody concentrations.
Innovation Solution
A stable liquid pharmaceutical composition for subcutaneous administration containing anti-HER2 antibodies like trastuzumab or pertuzumab, with buffering agents at pH 4.6 to 6.5, stabilizers such as methionine and glutamic acid, and tonicity agents like sucrose, allowing for high concentrations and improved stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If intravenous administration is used for monoclonal antibodies, then the antibodies can be delivered effectively, but the process is inconvenient for patients, requires long travel distances to medical facilities, and takes approximately 90 minutes
Solution Approach 1:
The patent changes the administration route parameter from intravenous to subcutaneous, and adjusts the antibody concentration parameter to achieve effective dosing in a smaller volume. This enables self-administration at home while reducing the time required compared to conventional IV infusions.
2Ease of operation
If subcutaneous administration is used to improve convenience, then patients can self-administer at home, but the amount of antibody that can be injected is limited to less than 1 to 2 mL
Solution Approach 1:
The patent increases the antibody concentration parameter in the formulation, enabling sufficient dosing within the limited subcutaneous injection volume. This maintains the self-administration advantage while delivering effective therapeutic amounts.
Solution Approach 2:
The patent optimizes the local properties of the formulation for subcutaneous injection, including pH, stabilizers, and tonicity, to ensure proper absorption and stability while maintaining high concentration within the constrained volume.
3Quantity of substance
If high concentration of monoclonal antibodies is used in subcutaneous formulation, then the injectable amount increases, but the formulation stability and solubility become challenging
Solution Approach 1:
The patent adjusts multiple formulation parameters including pH (4.6 to 6.5), stabilizer concentrations (methionine, glutamic acid, arginine), and tonicity agents to maintain stability at high antibody concentrations. These parameter optimizations prevent aggregation and degradation while achieving the required concentration levels.
4Quantity of substance
If conventional IV administration is used, then the full dose of monoclonal antibodies can be administered, but the cost and infrastructure requirements increase significantly
Solution Approach 1:
The patent changes the administration route from IV to subcutaneous and optimizes the formulation concentration and composition to enable effective dosing without requiring specialized medical infrastructure. This maintains therapeutic efficacy while eliminating the need for complex IV infusion facilities.
Data Source
AI summary
The present invention relates to stable liquid pharmaceutical formulations containing a high concentration of trastuzumab, pertuzumab or a mixture thereof for convenient subcutaneous administration. Formulations of the present invention can be administered to treat cancer, such as breast cancer and metastatic gastric or gastroesophageal junction adenocarcinoma.