Wheeler offers flexible protein expression services and continually works to improve our enabling tools.   Our CHO-based transient expression system, delivering milligram to gram quantities of recombinant proteins from a CMC-relevant genetic background, often marks the first time that customers migrate to CHO in the discovery workflow — and away from HEK293 or some other transient expression system.   We use transient expression in CHO to rapidly screen molecular formats of the target protein, with the data being cycled back for further vector engineering (in our Boston R&D Center) to improve the final outcome. 

Transient Expression

Capabilities:

• Access to dedicated service team with over 50 years of combined protein expression expertise
• Access to state-of-the-art protein analytical lab
• Access to proven, high-titer transient expression systems (ExpiCHO and Expi293) 
• Highly automated transfection, outgrowth and transient pool generation workflow
• Compatibility with a full spectrum of therapeutic proteins including single-peptide ORFS, mAbs, Fabs, Fc fusions, cytokine fusions, bispecifics, etc.
• 0.5-5L shake-flask production (milligram quantities)
• 5-50L single-use bioreactor capacity (gram quantities)
• One-column affinity capture purification with ÄKTA protein purification system
• Second column polishing (optional)
• Buffer exchange into customer defined buffer or PBS
• Aliquot generation
• Final certificate of analysis (CoA)

Portable CMC™ Clone Selection (Cell Line Development)

Robust, consistent, agency-vetted cell lines are foundational to Wheeler’s cell line development (CLD) service called Portable CMC™ Clone Selection. Our CLD team members are seasoned practitioners of industry proven CHOSOURCE™ cell line from Horizon™ (Perkin Elmer) and companion transposon tool for high-fidelity, transposon-based gene delivery. Distinguished by cutting-edge genetic tools that are amenable to the expression of many classes of proteins including hard-to-express variants, what also makes our CLD service truly unique is its seamless integration with Wheeler’s non-exclusive method for the scalable preparation of mAbs (Portable CMC™ CDMO Selection). This inherent connection between cell substrate and drug substance process gives customers assurance that their final clone will be manufacturable and accepted by the FDA.

Capabilities:

• Access to dedicated service team with over 50 years of combined CLD expertise
• Access to proven, high-titer compatible CHO-K1 parental cell line with extensive regulatory track record
• Access to optimized Wheeler vector backbones with transposon based gene delivery tool  
• Highly automated transfection, outgrowth and pool generation workflow
• Efficient, consistent, and verifiable clone isolation
• Ambr® 15 based clone screening
• Genetic stability assessment of clones (60-generations)
• Ambr® 250 based manufacturability assessment (optional)
• Cell line development report that includes vector sequences, host banking information (not product specific), cloning traceability and documentation of clonality 

Process Development

We have a world-class development team dedicated to mammalian bioprocess design, development, characterization and intensification. Our leadership team has worked on hundreds of drug substance processes over the last two decades spanning a wide range of process modalities such as fed-batch, perfusion, microcarriers, and fiber-cell disks and a wide range of product types such as mAbs, bsAbs, fabs, scFvs, enzymes, vaccines, fusion proteins, cytokines, plasmids and CGTx. Whether beginning from ground level or optimizing a current process or using Wheeler’s platform for mAbs (Portable CMC™), our expert process development scientists can deliver a cost-effective scalable method for drug substance preparation. 

Capabilities:

• Basal and feed media screening and optimization
• Fed-batch or perfusion process intensification
• Chromatographic unit operation process development
• Filter unit operation process development 
• Process characterization and compatibility studies
• Liquid or lyophilized formulation development

Analytical Development

Our  wide range of analytical development capabilities support your product process development activities on a continuous basis. Robust measurement systems underlie a modern QbD approach to ensure that methods for preparation of drug substance meet your requirements for safety, integrity, strength, purity, and quality (SISPQ). Our capabilities include:

Capabilities:

• Release method development
• In-process control (IPC) method development
• Molecular and cellular bioassay and complement binding assay development
• Critical quality attributes (CQAs) design for glycosylation, oxidation, aggregates, activity, concentration
• Fed-batch validation, testing, lot release methods
• Perfusion analytical methods for in-process testing
• Analytical section for IND/BLA dossier preparation

Preclinical Material Supply & Testing

Our approach to preclinical material preparation leverages scaled-down models that are proven to meet prospective CQAs. Scaled-down model evaluations provide both data and materials for preclinical testing.  Our Oklahoma City Development Center features a 3,000 sq. ft. GLP-compliant protein sciences lab that gives our customers access to a scaled-down, standard method for the preparation and analysis of presumptive drug substances deriving from stable pools or clones. Our preclinical material supply services in Oklahoma City include:

Capabilities:

• Shake flask based seed expansion
• Small scale manufacturing for drug feasibility studies, process and method development, and early R&D material requirements
• Non-GMP production for process scalability and robustness evaluation
• IND-enabling toxicology study material generation
• Genetic and mammalian toxicology testing, using non-GLP assays for discovery, development and screening, and GLP assays for regulatory submissions