WuXi Biologics
Offering End-to-End Solutions
Background
Client asked WuXi Biologics to assess the key attributes of two candidate molecules to determine the lead molecule for further product CMC development.
Challenge
Design developability platform, identify key selection criteria and key product attributes to determine the lead clone and molecule.
Solution/Results
Table 1 – Results
Criteria | Molecule 1 | Molecule 2 |
---|---|---|
Fit to Upstream | 3.7 g/L | 3.7 g/L |
Fit to Downstream |
>10% HMW level after ProA 52% CEX step yield |
87% CEX step yield |
Formulation and Stability |
Platform Solubility: 100mg/ml | Platform Solubility: >150mg/ml |
Biophysical and Biochemical Characterization |
DSC: Tm2: 76.4oC | DSC: Tm2: 78.7oC |
Background
Client requested a cell line with good titer and product quality.
Challenge
With the third party codon, high titer clones tend to have more aggregates.
Solution
Results
Criteria | Result |
---|---|
Titer |
Pool Titer: 1.5 g/L Clone Titer: 3.6 g/L |
Monoclonality |
Documented pre-plating ViCell pictures and ClonePix colony pictures |
Background
Challenge
Solution/Results
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Solution/Results
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Solution/Results
Background
WuXi Biologics suggested using an FTE approach to meet critical bispecific antibody development timelines.
Challenge
Previous client attempts to produce and purify the protein led to undesirable expression levels of a bispecific antibody due to low expression of one of the antibody chains which resulted in only 10% of desired protein product from the entire protein production campaign. These challenges were delaying product CMC development and thus time was critical as original IND filing date was in jeopardy.
Solution/Results
After discussion with the client and outlining the DOE study required to potentially solve the problem, client-dedicated personnel via an FTE program was established. The client-dedicated FTE team generated and evaluated 42 different constructs and evaluated expression levels of the bispecific antibody in over 1,000 minipools using a high-throughput methodology. Minipools demonstrating best results were moved to clone screening and eventual final clone selection. Results provided in Table 3.
Final Titer of bispecific Ab clone | Main product expression levels before purification | Main product purity after purification | Date of client IND filing |
---|---|---|---|
3.8 g/L | 90% | 98% | (On-time filing) |
Background
Client struggled with developing the tools to understand if a recombinant cytokine product produced in e. coli had refolded correctly after removal from inclusion bodies post fermentation.
Challenge
Develop a high-throughput system that could quickly evaluate over 130 different molecules using multiple analytical methods to meet critical client timelines and budget.
Solution/Results
A well-established, HT matrix-screening method in a fast, efficient way.
Background
Client could not get a consistent product quality or GMP manufacturing process performance at current vendor. Requested WuXi Biologics assemble a team from multiple functional areas to trouble-shoot manufacturing process and provide solutions.
Challenge
Product had high HMW and dimer content and low enzymatic activity. Had to evaluate over 800 pages of batch records, perform technical transfer and trouble-shoot based on investigation master plan in short time frame.
Solution/Results
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