Protein Production & Engineering Services

We offer a comprehensive, tiered production platform supporting projects from ultra-high-throughput screening to gram-scale material generation, balancing speed, scale, and flexibility:

• Ultra-High-Throughput Platform (1-3 mL): Ultra 96+ enables daily production of ~1,000 monoclonal antibodies, yielding 100-1,500 µg per well, suitable for in vitro assays and early screening.
• Customizable Mid-Scale Production (20-200 mL): 777 (20-200 mL) produces 1-100 mg of monoclonal antibodies for in vitro and in vivo studies; Quick & Clean (20 mL) supports high-throughput bispecific antibody production for optimal pairing identification, with a proven yield of 1-7 mg and capacity of ~300 unique molecules per run.
• Premium Large-Scale Production：GramExpress delivers 1-100 g of monoclonal antibodies within 3-4 weeks, enabling in vivo and preclinical studies; Premium BsAb, leveraging LC-MS-guided purification, enables high-quality production of diverse bispecific antibody formats and has demonstrated the capacity to produce ~100 bsAbs in parallel at 100 mL scale and ~20 bispecific antibodies simultaneously at 2 L scale.

We use a systematic, data-driven approach to troubleshoot complex production issues such as protein truncation, which is common in sensitive formats like VHH-Fc fusions:

• Mass Spec confirmation: MS analysis (Intact Mass, peptide mapping, etc.) is used to confirm truncation and precisely map the cleavage site.
• Target solution: Based on the findings, we implement corrective strategies, most commonly site-directed mutagenesis, to eliminate the cleavage hotspot and restore full-length, high-quality protein expression.
• Process optimization: If truncation occurs during expression, we can switch the expression host (e.g., HEK293) or shorten culture duration. If truncation occurs during purification, we optimize the process by removing host cell proteins (HCP) and accelerating purification.

Our primary expression platform is a proprietary, strategically selected CHO-K1 host (v3.0) that consistently delivers ~1.5 g/L baseline titers for project antibodies. We readily accommodate client-specific signal peptides or proprietary vectors. Clients provide the vector information (as part of the standard workflow), which we evaluate prior to transfection and expression. While titers from client-provided vectors may be lower than those achieved with our proprietary vectors, the produced material progresses seamlessly into our purification and analytical pipelines.

Our purification strategies are format-driven and tailored to molecular complexity. We have established, scalable workflows covering a wide range of bispecific antibody formats:

Our purification workflows are highly flexible and can be customized to meet specific project needs:

• Client-defined purity targets: Ultra-high purity (>95%) is not always required for early-stage work. We support custom purity thresholds (e.g., >90%) by starting with a streamlined workflow and adding polishing steps only if needed.
• Custom purification steps: We can integrate non-standard or client-specified steps, such as CH1XL affinity chromatography for select three-chain formats or flow-through Q columns for HCP reduction. Any impact on yield or timeline is discussed upfront.
• Intermediate data collection: Intermediate sampling is not feasible on fully automated, small-scale platforms. For ≥100 mL projects, purification is performed stepwise, enabling collection and reporting of intermediate data upon request.

A: We primarily use CHO cells for antibody production. We have made significant investments in optimizing our cell engineering and cell growth processes to achieve high titer expression of antibodies in the CHO cells, enhancing the antibody production efficiency.

A comprehensive suite of analytical services is available to characterize final products. For all bispecific antibody production projects, Intact MS is included by default to confirm molecular identity and integrity. Additional QC assays (e.g., endotoxin, purity, charge variants, glycosylation) can be added based on project requirements. Once produced and purified to specification, materials are ready for downstream preclinical evaluation.

Our protein production platform is supported by proprietary, high-performance expression technologies:

• Expression vector: We use a proprietary pXX4.1 vector, engineered for high-titer expression in our CHO host. It incorporates optimized elements, including REP and SEMI promoters, to support robust and consistent protein production.
• Codon optimization: We apply an in-house codon optimization algorithm developed and continuously refined. In multiple head-to-head evaluations, this algorithm has demonstrated superior expression performance compared with commercially available tools.

Project timelines are optimized for speed without compromising quality:

• High-throughput production (1-200 mL): ~3-5 weeks from construct generation to ship-ready protein for simple formats; ~1 week can be reduced when a common vector backbone is used.
• Large-scale production (1-100 L): ~3-6 weeks from construct generation to purified protein, based on project complexity.

A: Our unique advantage lies in providing valuable insights and guidance to customers throughout the entire antibody drug development process, enabling them to navigate around common pitfalls and overcome challenges effectively. This comprehensive end-to-end viewpoint and approach ensures a seamless and speedy journey from concept to market, making us a trusted and reliable partner for customers in need of antibody production services.

A: For projects involving new molecules, CHO cells are your ideal choice because of our well-established ultra-high-titer CHO expression platform. For projects encountering issues like truncation issues, HEK293 cells are recommended. In cases where your molecules have severe aggregation issues caused by disulfide bonds in CHO or HEK293, NS0 cells can be considered as a last option.

A: An optimal host expresses target antibodies with high titers, optimal glycosylation modifications, low levels of N-linked mannose-5 glycan and afucosylation, and minimal truncations. Additionally, the host should demonstrate efficient transfection, low lactate level, and rapid doubling time.

A: These potential risks include titer variations and different glycosylation and other PTMs, sometimes truncations. The difference may lead to inconsistent efficacy, PK, challenging CMC and late-stage developments. For molecules with therapeutic purposes, it’s highly desirable to use the same CHO host from early discovery to commercial manufacturing.

A: Antibody-dependent cellular cytotoxicity (ADCC) is one of the most important effector mechanisms of tumor-targeting antibodies. The need for ADCC depends on the specific therapeutic strategy and mechanism of action (MOA) of your molecule. You may leverage our CHO-Fut8 technology to enhance ADCC effects.  On the other hand, sometimes ADCC effects must be eliminated, such as T-cell engagers. Antibodies can be engineered to reduce or increase the ADCC effect. Consult our specialists for unique requirements of your project.

A: Afucosylation involves the reduction or removal of fucose in the Fc region of an antibody. This modification can significantly boost the antibody’s affinity for FcγRIIIa on natural killer (NK) cells, which in turn enhances ADCC. Careful MOA studies must be carried out to make the decision. You need to find a balance between efficacy and toxicity.

A: We have cultivated a rich pipeline comprising various drug modalities, including regular mAb, ADC, bsAb and fusion proteins. Leveraging our extensive experience, we can assist clients during the early research stage and accumulate valuable insights into the developability of different modalities. While we primarily focus on research-grade antibodies, WuXi Biologics’ extensive drug development expertise allows us to guide clients through a smooth transition from research to CMC.