Bispecific Antibody Formulation Stability at High Concentration
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Solution Overview
Problem
There is a need for stable pharmaceutical compositions of bispecific EGFR/c-Met antibodies that remain effective for long periods at refrigerated and ambient temperatures, optimized for subcutaneous administration, as existing compositions face challenges in maintaining stability and reducing infusion-related reactions.
Innovation Solution
The development of stable aqueous pharmaceutical compositions comprising a bispecific EGFR/c-Met antibody, hyaluronidase, and specific excipients such as polysorbate 80, methionine, and EDTA, formulated to maintain stability and reduce infusion-related reactions through subcutaneous administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If high concentration bisspecific antibody formulations are used, then productivity is improved, but stability of the composition deteriorates
Solution Approach 1:
The patent applies parameter changes by systematically optimizing multiple formulation parameters including pH (adjusted to specific ranges), ionic strength (controlled through buffer composition), temperature (storage conditions), and excipient concentrations (sucrose, polysorbate 80, methionine, EDTA). These parameter adjustments enable the formulation to maintain stability at high antibody concentrations (100-500 mg/mL) while preventing aggregation and degradation.
Solution Approach 2:
The patent employs composite materials by creating a complex formulation system that combines the bispecific antibody with multiple excipients serving different functions: sucrose (stabilizer), polysorbate 80 (surfactant), methionine (antioxidant), and EDTA (chelating agent). This composite formulation approach allows the high concentration antibody solution to remain stable by addressing multiple degradation pathways simultaneously.
2Stability of the object's composition
If refrigerated storage is used, then stability of the composition is improved, but loss of time increases
Solution Approach 1:
The patent applies parameter changes by formulating the antibody solution with specific buffers (acetate or histidine at controlled pH), stabilizers (sucrose at optimized concentrations), and surfactants (polysorbate 80) that collectively enable the formulation to maintain stability across a broader temperature range. This allows extended storage at ambient temperatures while preserving antibody integrity and activity.
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 provide a stable and effective delivery of the bispecific EGFR/c-Met antibody, reducing infusion-related reactions and maintaining potency over time at various temperatures, enhancing the therapeutic efficacy for cancer treatment.
Implementation Method 1
The composition comprises about 1,050 mg to about 3,360 mg of the bispecific EGFR/c-Met antibody and about 13,000 U to about 28,000 U of the hyaluronidase
Implementation Method 2
stable aqueous pharmaceutical compositions comprising a bispecific EGFR/c-Met antibody, hyaluronidase, and specific excipients such as polysorbate 80, methionine, and EDTA
Implementation Method 3
about 6.8% (w/v) to about 10.2% (w/v) of sucrose
Implementation Method 4
about 16 μg/mL to about 24 μg/mL of ethylenediaminetetraacetic acid (EDTA)
Implementation Method 5
about to 0.8 mg/mL to about 1.2 mg/mL of methionine
Data Source
AI summary
Provided herein are stable aqueous pharmaceutical compositions comprising high concentration formulations of a bispecific epidermal growth factor receptor (EGFR)/hepatocyte growth factor receptor (c-Met) antibody and methods of preparing the same. Also provided herein are methods of treating cancer in a subject in need thereof by subcutaneously administering to the subject the stable aqueous pharmaceutical compositions as disclosed herein.