Anti-CSF-1R Antibody Formulation for High-Concentration Stability
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Solution Overview
Problem
Existing formulations of anti-CSF-1R antibodies are susceptible to physical and chemical degradation, making them unstable and difficult to administer in high concentrations without the need for in-line filters, which complicates their use in treating conditions like pigmented villonodular synovitis (PVNS) and tenosynovial giant cell tumors (TGCT).
Innovation Solution
A stable pharmaceutical formulation comprising 40 mg/ml to 200 mg/ml of an anti-CSF-1R antibody with specific amino acid sequences, 0.01% w/v to 0.1% w/v of a surfactant, 5 mM to 100 mM of a buffering agent, and 10 mM to 500 mM of a stabilizer, at a pH of 4.5 to 7.0, which maintains stability under refrigerated conditions and withstands physical stress during manufacturing and transportation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing formulations of anti-CSF-1R antibodies are used, then the antibody can be administered, but the formulation is susceptible to physical and chemical degradation, making it unstable
Solution Approach 1:
The patent applies parameter changes by optimizing the formulation composition with specific concentrations of excipients including 0.01% to 0.1% surfactant, 5 mM to 100 mM buffering agent, and 10 mM to 500 mM stabilizer at pH 4.5 to 7.0. These parameter adjustments resolve the contradiction by maintaining antibody stability while enabling administration without in-line filters.
2Quantity of substance
If the antibody is administered in high concentrations, then the treatment efficacy is improved, but the formulation becomes difficult to administer without in-line filters
Solution Approach 1:
The formulation achieves high antibody concentrations (40 mg/ml to 200 mg/ml) while maintaining ease of administration by optimizing excipient parameters. The specific combination of surfactant, buffering agent, and stabilizer at defined concentrations prevents aggregation and degradation, allowing direct intravenous administration without in-line filters despite the high protein concentration.
3Duration of action of stationary object
If the formulation is stored under refrigerated conditions, then the storage duration is extended, but the antibody may still degrade during manufacturing and transportation
Solution Approach 1:
The formulation incorporates stabilizers and surfactants that provide beforehand cushioning against physical and chemical degradation. These excipients protect the antibody during manufacturing processes and transportation conditions, ensuring biological activity is retained even before refrigerated storage begins, thus extending the effective storage duration while maintaining reliability.
Solution Approach 2:
The patent optimizes formulation parameters including pH (4.5 to 7.0), excipient concentrations (surfactant 0.01%-0.1%, buffering agent 5-100 mM, stabilizer 10-500 mM) to enhance the antibody's resistance to degradation. These parameter changes enable the formulation to withstand manufacturing and transportation stresses while maintaining biological activity for extended storage durations under refrigerated conditions.
Data Source
AI summary
The present invention relates to a stable liquid pharmaceutical formulation comprising 40 mg/ml to 200 mg/ml of an antibody against CSF-1R; 0.01 % (w/v) to 0.1% (w/v) of surfactant; 5 mM to 100 mM of a buffer agent; and 10 mM to 500 mM of at least one stabilizer; at a pH in the range from 4.5 to 7.0.