Anti-CD40 Antibody Viral Inactivation With Reduced Aggregation
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Solution Overview
Problem
The low-pH viral inactivation step during the purification process of anti-CD40 monoclonal antibodies leads to unexpected protein aggregation, posing a challenge in maintaining product quality and stability.
Innovation Solution
Adjusting the pH to a range of 3.6-3.9 during the viral inactivation step minimizes protein aggregation and stabilizes the anti-CD40 antibody, thereby reducing the formation of high molecular weight aggregates.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If low pH (≤3.6) is used for viral inactivation, then viral inactivation is achieved, but protein aggregation increases
Solution Approach 1:
The patent applies parameter changes by adjusting the pH range from the conventional ≤3.6 to a higher range of 3.6-3.9. This parameter modification allows the viral inactivation process to occur while preventing protein aggregation, as the elevated pH within this range stabilizes the protein structure against aggregation while still being sufficiently acidic to inactivate viruses.
2Reliability
If pH ≤3.6 is used during viral inactivation, then virus inactivation is effective, but high molecular weight aggregates form
Solution Approach 1:
The invention modifies the pH parameter from the standard ≤3.6 to 3.6-3.9, which effectively reduces the formation of high molecular weight aggregates while maintaining virus inactivation efficacy. This parameter adjustment resolves the contradiction between achieving effective viral clearance and preventing aggregate formation during the purification process.
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 approach results in a virus-inactivated antibody preparation with reduced high molecular weight aggregates and increased antibody monomers, enhancing product stability and quality.
Implementation Method 1
Low-pH viral inactivation often follows the Protein A capture step. The pool is titrated to a pH sufficiently acidic to disrupt viral envelopes and subjected to a static hold
Data Source
AI summary
The instant invention relates to compositions of, and methods for producing, a virus-inactivated antibody preparation having a reduced level of high molecular weight aggregates, and/or methods for minimizing formation of high molecular weight aggregates in a virus-inactivated antibody preparation, comprising an antibody, or antigen-binding portion thereof, e.g., an anti-CD40 antibody or antigen binding portion thereof.