WuXi Biologics
Offering End-to-End Solutions
背景
某客户要求药明生物对他们提供的两个候选分子的关键表征做评估以决定一个可用作后续CMC开发的最终分子。
挑战
需要开发出一个成药性研究的平台,重点是需要遴选出能够决定成药性的关键筛选标准和关键产品表征,以挑出最终的分子和克隆。
解决方案/结果
标准 | 分子1 | 分子2 |
---|---|---|
是否适合上游开发 | 3.7 g/L | 3.7 g/L |
是否适合下游开发 |
在ProA纯化后有大于10%的高聚物; 阳离子交换层析的收率为52% |
阳离子交换层析的收率为87% |
制剂稳定性 | 平台方法得到的溶解度:100mg/ml | 平台方法得到的溶解度:>150mg/ml |
生物物理和生物化学的表征 | DSC: Tm2: 76.4oC | DSC: Tm2: 78.7oC |
背景
客户要求构建一个产量大于1.5g/L并且质量优异的细胞株。同时他们还要求被选出的克隆细胞株一定要保证单克隆性。
挑战
如何在非常紧凑的时间表内满足客户的要求。
解决方案/结果
标准 | 结果 |
---|---|
产量 |
细胞群产量:1.5 g/L 克隆产量:3.6 g/L |
单克隆率 |
保存并记录好铺板前细胞在ViCell拍出的图片以及用ClonePix挑出的克隆照片作为单克隆的证明 |
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背景
WuXi Biologics suggested using an FTE approach to meet critical bispecific antibody development timelines.
挑战
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.
解决方案/结果
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.
Table 3 – FTE program resultsFinal 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) |
背景
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.
挑战
Develop a high-throughput system that could quickly evaluate over 130 different molecules using multiple analytical methods to meet critical client timelines and budget.
解决方案/结果
A well-established, HT matrix-screening method in a fast, efficient way.
背景
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.
挑战
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.
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