Anti-FXI/FXIa Antibody Formulation Stability via pH Optimization
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Solution Overview
Problem
Therapeutic proteins like anti-FXI/FXIa antibodies are prone to degradation and instability due to their large molecular weights and complex structures, making them challenging to administer effectively and maintain stability during storage and use.
Innovation Solution
A pharmaceutical composition comprising an anti-FXI/FXIa antibody or its antigen-binding fragment, formulated with a self-buffering system that includes basic amino acids like histidine and a surfactant such as poloxamer 188, to enhance stability and suitability for administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If anti-FXI/FXIa antibody is formulated as liquid pharmaceutical formulation for injection, then it can be administered effectively, but it is prone to degradation, aggregation, and unwanted chemical modifications due to large molecular weight and complex structure
Solution Approach 1:
The patent applies parameter changes by optimizing the pH of the liquid pharmaceutical formulation to a specific range (pH 5.0-7.5, preferably pH 6.0-7.0) to enhance the stability of the anti-FXI/FXIa antibody. This pH optimization prevents degradation, aggregation, and chemical modifications while maintaining the antibody's therapeutic efficacy and administerability as a liquid formulation for injection.
2Ease of operation
If antibody drugs are administered by injection as liquid pharmaceutical formulations, then they can be delivered to patients, but they are unstable during storage and subsequent use due to great molecular weights and complex structures
Solution Approach 1:
The patent optimizes the pH parameter of the liquid pharmaceutical formulation to a specific range (pH 5.0-7.5, preferably pH 6.0-7.0) to enhance the stability of the anti-FXI/FXIa antibody during storage and subsequent use. This parameter optimization prevents degradation, aggregation, and unwanted chemical modifications while maintaining the antibody's therapeutic efficacy and administerability.
3Productivity
If existing oral anticoagulants (NOACs) are used, then treatment can be provided, but they do not provide sufficient safety profile with visible bleeding risk
Solution Approach 1:
The patent extracts and targets the specific coagulation factor FXI/FXIa in the coagulation cascade, rather than using broad-spectrum oral anticoagulants (NOACs). By developing an anti-FXI/FXIa antibody that specifically inhibits this single factor, the treatment achieves effective antithrombotic effects while minimizing bleeding risk, as FXI is not essential for hemostasis under normal physiological conditions.
Solution Approach 2:
The patent uses an anti-FXI/FXIa antibody as an intermediary agent to selectively inhibit the FXI/FXIa coagulation pathway. This antibody mediator provides precise control over coagulation inhibition, achieving therapeutic antithrombotic effects while sparing other coagulation factors necessary for normal hemostasis, thereby reducing bleeding risk compared to broad-spectrum NOACs.
Data Source
AI summary
A pharmaceutical composition comprising an anti-FXI/FXIa antibody and the use thereof. The specific pharmaceutical composition to which the present disclosure relates comprises an anti-FXI/FXIa antibody or an antigen-binding fragment thereof, and a buffer.