Anti-α4β7 Antibody Formulation for Stability and Low Aggregation
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Solution Overview
Problem
Existing formulations for anti-α4β7 antibodies are unstable, prone to deamidation, oxidation, and aggregation, leading to degradation and reduced efficacy in treating inflammatory bowel diseases.
Innovation Solution
A formulation comprising a non-reducing sugar and at least one free amino acid, with specific molar ratios, stabilizes the anti-α4β7 antibody, minimizing degradation and maintaining therapeutic effectiveness.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional formulations are used for anti-α4β7 antibodies, then the formulation can be simple and easy to manufacture, but the antibody stability and biological activity deteriorate due to deamidation, oxidation, and aggregation
Solution Approach 1:
The patent introduces specific excipients (sugars such as sucrose, trehalose, or lactose; amino acids such as histidine, arginine, or lysine; and polyols such as mannitol or sorbitol) as intermediary substances that mediate between the antibody and the destabilizing environment. These excipients act as protective intermediaries that prevent direct interaction between the antibody and harmful factors like oxygen, water, and metal ions, thereby reducing deamidation, oxidation, and aggregation while maintaining formulation stability.
Solution Approach 2:
The patent optimizes specific formulation parameters including pH (adjusted to 5.0-7.5 using buffers like phosphate or acetate), ionic strength, and excipient concentrations to create optimal conditions for antibody stability. By carefully controlling these parameters and their interactions, the formulation achieves enhanced stability without excessive complexity, as the optimized parameters work synergistically to protect the antibody.
2Reliability
If the formulation includes stabilizing excipients to prevent degradation, then the antibody stability improves, but the formulation complexity and manufacturing difficulty increase
Solution Approach 1:
The selected excipients serve multiple functions simultaneously: sugars and polyols provide both structural stabilization and protection against aggregation; amino acids serve as both stabilizers and pH buffers; and the formulation components work together to prevent multiple degradation pathways (deamidation, oxidation, aggregation) with a single integrated system, reducing the need for multiple separate additives and simplifying manufacturing.
3Duration of action of stationary object
If freeze-drying is used to preserve the antibody, then the shelf life and stability improve, but the manufacturing process complexity and time increase
Solution Approach 1:
The formulation is designed with pre-selected excipients and optimized parameters that prepare the antibody for freeze-drying in advance. The excipients are chosen to provide optimal freeze-drying characteristics, and the formulation is pre-adjusted to the correct pH and composition before processing, so that the freeze-drying step itself requires minimal intervention and produces consistent results, reducing process complexity and time.
4Reliability
If higher concentrations of excipients are used to maximize stability, then the antibody protection improves, but the formulation volume and dosage complexity increase
Solution Approach 1:
The patent optimizes excipient concentrations to achieve the minimum effective levels needed for stability protection. Through systematic optimization of pH, ionic strength, and excipient ratios, the formulation achieves maximum protection with minimal concentrations, avoiding excessive volume or dosage complexity while maintaining adequate stability.
Data Source
AI summary
Antibody formulations are described comprising a mixture of a non-reducing sugar, an anti-α4β7 antibody and at least one amino acid. The disclosed formulations have improved stability, reduced aggregate formation, and may retard degradation of the anti-α4β7 antibody therein or exhibit any combinations thereof. The present invention further provides a safe dosing regimen of these antibody formulations that is easy to follow, and which results in a therapeutically effective amount of the anti-α4β7 antibody in vivo.