Anti-hTNFalpha Antibody Crystallization via Inorganic Phosphate Salts
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Solution Overview
Problem
Current methods for crystallizing anti-hTNFalpha antibodies are inefficient and often require toxic agents, making it difficult to produce stable, industrially scalable crystals for pharmaceutical applications.
Innovation Solution
A batch crystallization method using physiologically acceptable inorganic phosphate salts as crystallization agents, specifically at pH levels between 3 to 5, to induce crystallization of anti-hTNFalpha antibodies, allowing for the production of stable crystals suitable for pharmaceutical use.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional crystallization methods are used for anti-hTNFalpha antibodies, then crystals can be obtained, but toxic agents are required and industrial scalability is limited
Solution Approach 1:
The patent changes the pH parameter to a physiological range (pH 3-5) and uses inorganic phosphate salts instead of traditional toxic crystallization agents. This parameter change enables crystallization without harmful substances while maintaining crystal stability, directly resolving the contradiction between reliability and harmful factors.
Solution Approach 2:
The patent employs inexpensive, biocompatible inorganic phosphate salts (such as sodium phosphate, potassium phosphate) that can be easily removed from the final product. These replace expensive, toxic agents that require extensive purification, thereby eliminating harmful factors while maintaining crystallization effectiveness.
2Volume of moving object
If high concentration antibody solutions are used, then dosing volume is reduced, but viscosity increases and aggregation tendency exponentially increases
Solution Approach 1:
The patent utilizes phase transition by crystallizing the antibody from high concentration solution. The crystallization process transforms the dissolved antibody into solid crystal phase, enabling high concentration formulation (reduced dosing volume) while the crystal lattice structure prevents aggregation, maintaining stability even at high concentrations.
Solution Approach 2:
The patent segments the antibody molecules into ordered crystal lattices. This segmentation into regular structural units prevents random aggregation while maintaining high local concentration, thereby reducing dosing volume without increasing aggregation tendency.
3Reliability
If crystallization conditions are optimized for stability, then crystal quality improves, but manufacturing complexity increases
Solution Approach 1:
The patent employs a self-service crystallization system where inorganic phosphate salts naturally induce antibody crystallization at physiological pH without requiring complex equipment or multiple processing steps. The system uses the inherent properties of the components to achieve crystallization, reducing manufacturing complexity while maintaining crystal stability.
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
This method enables the reproducible production of stable anti-hTNFalpha antibody crystals on an industrial scale, avoiding the use of toxic agents and ensuring pharmaceutical applicability, thus addressing the challenges of stability and scalability in existing technologies.
Implementation Method 1
A batch crystallization method using physiologically acceptable inorganic phosphate salts as crystallization agents, specifically at pH levels between 3 to 5, to induce crystallization of anti-hTNFalpha antibodies
Data Source
AI summary
The present invention relates to a batch crystallization method for crystallizing an anti-hTNFalpha antibody which allows the production of said antibody on an industrial scale; antibody crystals as obtained according to said method; compositions containing said crystals as well as methods of use of said crystals and compositions.