Anti-MASP-2 Antibody Formulation for High-Concentration Stability
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Solution Overview
Problem
Existing formulations for therapeutic antibodies, such as anti-MASP-2 monoclonal antibodies, lack stability during storage and administration, leading to degradation, aggregation, and undesirable chemical modifications, and do not support high concentrations suitable for clinical use.
Innovation Solution
A stable liquid pharmaceutical formulation comprising a monoclonal antibody that binds to human MASP-2, with a buffer system of histidine and/or acetate, a surfactant like polysorbate, and auxiliary materials like sucrose and trehalose, maintaining pH between 4.7 and 6.1, to ensure stability and suitability for intravenous or subcutaneous administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional formulations are used for therapeutic antibodies, then the formulations can be administered to patients, but the antibodies degrade, aggregate, and undergo undesirable chemical modifications during storage and administration
Solution Approach 1:
The patent optimizes multiple formulation parameters including pH (4.7-6.1), buffer composition (histidine and/or acetate), surfactant concentration (polysorbate 20, 40, or 80 at 0.01-0.1% w/v), and auxiliary materials (sucrose, trehalose, proline at specific concentrations) to achieve enhanced antibody stability. This systematic parameter optimization resolves the contradiction by finding the optimal balance point where the formulation maintains antibody integrity without causing degradation or aggregation.
Solution Approach 2:
The patent employs a composite formulation system combining multiple excipients working synergistically: buffers (histidine/acetate) for pH control, surfactants (polysorbates) for surface activity and aggregation prevention, and auxiliary materials (sucrose, trehalose, proline) for structural stabilization. This composite approach addresses the stability contradiction by creating a multi-functional formulation matrix that collectively protects the antibody throughout storage and administration.
2Quantity of substance
If the formulation is designed for high concentration to reduce administration volume, then clinical effectiveness is improved, but formulation complexity and stability maintenance become more difficult
Solution Approach 1:
The patent achieves high antibody concentrations (up to 150 mg/mL or higher) by optimizing formulation parameters particularly viscosity control through surfactant selection and concentration, pH adjustment to 4.7-6.1, and inclusion of auxiliary materials like sucrose and trehalose that prevent aggregation at high concentrations. This resolves the contradiction by creating a formulation that maintains physical and chemical stability even at therapeutic high concentrations.
Solution Approach 2:
The patent uses surfactants (polysorbate 20, 40, or 80) and auxiliary materials (sucrose, trehalose, proline) as intermediary substances that mediate between the high concentration antibody and the formulation environment. These intermediaries prevent direct antibody-antibody interactions that would lead to aggregation, while also controlling viscosity and maintaining solubility, thus enabling high concentration formulations without excessive complexity.
3Reliability
If the formulation uses multiple excipients to enhance stability, then antibody protection is improved, but the risk of chemical modifications and interactions increases
Solution Approach 1:
The patent carefully controls the concentration ranges of each excipient to minimize harmful interactions: buffers at 10-100 mM, surfactants at 0.01-0.1% w/v, and auxiliary materials at specifically optimized concentrations. By precisely controlling these parameters, the formulation achieves maximum protective effect while minimizing the risk of excipient-antibody chemical modifications.
Solution Approach 2:
The patent selects excipients with well-characterized compatibility profiles and established safety records in pharmaceutical formulations. The chosen excipients (histidine, acetate, polysorbates, sucrose, trehalose, proline) are commonly used, well-studied substances with minimal immunogenicity and predictable stability profiles, reducing the risk of unexpected chemical modifications while maintaining effective protection.
Data Source
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AI summary
The present invention provides stable pharmaceutical formualtions comprising a monoclonal antibody that specifically binds to human MASP-2, which is present in high and low concentrations, a kit comprising the formulation, a pharmaceutical composition comprising the formulation and a unit dosage form comprising the formulation, a treatment method for inhibiting MASP-2 dependent complement activation, a treatment method for treating related diseases with the formulation, the kit, the pharmaceutical composition and the unit dosage form, and as well as a use in manufacturing a corresponding medicaent. The present invention also provides a novel monoclonal antibody that specifically binds to human MASP-2.