Anti-FGFR2 Antibody Liquid Formulation Stability
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Solution Overview
Problem
Current formulations of anti-FGFR2 antibodies face challenges in maintaining stability and effectiveness over time, particularly during storage and administration, as they often require lyophilization and have issues with protein aggregation and charge variants, which affect their potency and usability in intravenous applications.
Innovation Solution
The development of pharmaceutical formulations that include anti-FGFR2 antibodies with specific concentration ranges of 10-30 mg/mL, buffered with histidine, citrate, or phosphate, and containing arginine or sucrose, along with polysorbate 20 or 80, which maintain stability and prevent protein aggregation and charge variant changes, allowing for intravenous administration without lyophilization.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If anti-FGFR2 antibodies are formulated in liquid form for intravenous administration, then ease of operation and administration is improved, but protein aggregation and charge variant changes occur during storage, reducing stability
Solution Approach 1:
The patent applies parameter changes by optimizing the formulation composition with specific concentrations of histidine buffer (5-50 mM), arginine (100-500 mM), sucrose (100-500 mM), and polysorbate 20/80 (0.002-0.1%), along with controlling pH (5.0-6.5) and ionic strength, to maintain antibody stability in liquid form during storage and administration
Solution Approach 2:
The patent uses arginine and sucrose as intermediary substances that mediate between the antibody and storage conditions, preventing protein aggregation and charge variant formation while maintaining the antibody in stable liquid formulation for intravenous administration
2Loss of time
If anti-FGFR2 antibodies are stored as liquid formulations, then loss of time for preparation is reduced, but protein aggregation increases during storage, affecting potency
Solution Approach 1:
The patent applies preliminary action by pre-formulating the antibody with stabilizing agents (arginine, sucrose, polysorbate) and buffer systems before storage, so that the formulation is ready for immediate intravenous administration without requiring lyophilization or complex preparation, while maintaining potency through the protective formulation environment
3Ease of operation
If anti-FGFR2 antibodies are administered intravenously without lyophilization, then ease of operation is improved, but protein aggregation and charge variants increase, reducing therapeutic efficacy
Solution Approach 1:
The patent converts the potential harm of liquid storage (which could lead to aggregation) into a benefit by using the liquid state to enable ready-to-use formulations, while incorporating arginine and sucrose that actively prevent aggregation, thus turning what could be a detrimental condition into an advantageous delivery format
Data Source
AI summary
This disclosure relates to a formulation of an anti-fibroblast growth factor receptor 2 (FGFR2) antibody that, in some embodiments, is capable of being stored as a liquid, for example in a ready-to-use form, and that, in some embodiments, may be administered intravenously such as by intravenous (IV) infusion.