Anti-CD19 Antibody Fed-Batch Process for Glycan Profile Control
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Solution Overview
Problem
Existing manufacturing processes for biologic therapeutics like antibodies face challenges in achieving desired product quality attributes such as yield and purity efficiently and economically, particularly in producing anti-CD19 antibodies with favorable N-glycan profiles and reduced low molecular weight species impurities.
Innovation Solution
A method for manufacturing anti-CD19 antibodies with specific CDR sequences and Fc region substitutions, combined with a fed-batch production process that maintains high cell viability and controlled conditions, results in a composition with a high sialylation and low mannose-5 N-glycan profile, reducing low molecular weight species.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If standard manufacturing processes are used for anti-CD19 antibodies, then production efficiency and economy are maintained at conventional levels, but the desired product quality attributes (N-glycan profile, purity, yield) cannot be achieved
Solution Approach 1:
The patent applies parameter changes by modifying culture conditions including temperature profiles (37°C for 7 days followed by 34°C for 3 days), pH control (7.0-7.4), dissolved oxygen levels (30-60%), and fed-batch feeding strategies. These parameter adjustments optimize the cellular environment to produce antibodies with desired N-glycan profiles (≥20% sialylated, ≤5% mannose-5) while maintaining high cell viability (≥95%) and production efficiency
Solution Approach 2:
The patent implements dynamic process control through fed-batch cultivation where media composition is adjusted over time. The protocol includes sequential media changes, temperature shifts based on day number, and real-time monitoring of cell density and viability. This dynamic approach allows the system to adapt conditions throughout the 10-day production cycle to maximize both quality and productivity
2Manufacturing precision
If manufacturing processes are optimized for high cell viability and desired N-glycan profiles, then product quality improves, but process complexity and production time increase
Solution Approach 1:
The patent maintains continuous useful action through a 10-day fed-batch process where cells are continuously fed with optimized media containing specific amino acids (glutamine, asparagine, serine, tyrosine, cystine, galactose) and supplements. The continuous provision of nutrients and controlled conditions ensures sustained high cell viability (≥95%) and consistent N-glycan profile throughout the production cycle without requiring intermediate harvests or process interruptions
3Manufacturing precision
If conventional production methods are used, then production time and cost are reduced, but low molecular weight species impurities remain high
Solution Approach 1:
The patent applies preliminary action by pre-optimizing the cell line (CHO cells with specific integration sites) and media formulation before production. The media is pre-formulated with specific amino acid compositions and supplements that promote proper glycosylation from the start. This preliminary preparation prevents the formation of low molecular weight species impurities during the 10-day production cycle, achieving ≥95% purity without requiring extended purification time
Data Source
AI summary
The present invention provides compositions and methods of producing antibodies or antigen-binding fragment that specifically bind human CD19.