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ADC Development & Manufacturing

CellMosaic offers a complete antibody-drug conjugate (ADC) discovery and development program for its customer with classical or clinical approved drug linkers. For novel and complex ADC development with proprietory AqT® linker, please check here. For other types of bioconjugate drug such as antibody-oligo, olgio-drug conjugate, please check here.

Each antibody is unique, as the particular drug linker and chemistry that works for one ADC may not apply to others. CellMosaic has the in-house capability and expertise to devise and execute appropriate strategies to fit customer's ADC development plan. Specifically, CellMosaic will provide custom design and development of drug linker and conjugation strategies to fit customer’s needs. CellMosaic has various in-house ADC processes to quickly synthesize ADCs for initial proof-of-concept studies with minimum development efforts/time. CellMosaic advances its customer's ADC projects under the following three incremental stages:

• ADC Discovery (Stage I):
  • Screening small molecule drugs/toxin and optimizing ADC performance
    • • PerKit™ ADC: MMAE, Deruxtecan, MMAF with or without VC-PAB, DM1, SN38, Doxorubicin, Methotrexate
      • Customer specific toxins or drugs can be added depending on the properties of the drugs
  • Evaluation and decide on the antibody labeling sites
    • • PerKit™ ADC: surface amines and reduced thiols
      • Other supported: single Cys mutated antibody, glycolysation sites, N-terminal amino site, enzymatic labeling sites
  • Optimize the linkage chemistry
    • • PerKit™ ADC with different chemistries
        • Stable bond via maleimide thiol coupling or amide
        • Releasable linkage via Val-C-PAB or ester bond
      • Other supported chemistries
        • Releasable oxime, hydrazone bond, pyrophosphate
        • Stable bond via DBCO-azide click chemistry, amide direct linkage, thiol ether
        • Other selections developed at CellMosaic or customer recommended
  • Evaluation of the linker type & length
    • • PerKit™ ADC: ethylene, PEG, peptide
      • Other selections of conventional linker developed at CellMosaic
      • In the event an ADC cannot be made using classical linkers or the effectiveness of the ADCs are compromised by the number of toxins loaded onto the antibody, Customer has the option to try super-hydrophilic and water soluble proprietary AqT™ Linkers under licensing/collaboration
• ADC Development (Stage II):
  • Stability and formulation studies
    • • Stability study design & protocol
      • Formulation to stabilized ADC
      • Instrumentation and setup to perform the study.
      • Stabilities of various ADCs prepared from standard human IgG1 have been established at CellMosaic
  • Purity profile establishment and characterization
    • • Established bio-analytical methods for ADC at CellMosaic
        • HPLC: reversed-phase, HIC, SEC, cation or anion exchange
        • Mass Spectrometric: MALDI-TOF MS, LC/MS Profiling
        • DAR determination by UV/Vis, HPLC, and MS
        • Gel
  • Purification optimization
    • • Established purification methods for ADCs that can be extrapolated to customer ADCs
      • Capacity to purify ADC in large scale using various media.
  • Pharmacokinetic and pharmacodynamic study
    • • pK studies of ADCs in blood and tissue extracts
      • As benchmark, pK studies of ADCs with many of CellMosaic selected linkages/linkers have been established in preclinical or clinical studies
• Process Development, Sacle Up & Manufacturing (Stage III)
  • Supply Chain and Manufactruing Strategy
    • • Material sourcing from qualified CellMosaic’s vendors
      • Identify site of manufacturing based on GMP/non-GMP requirement (CellMosaic or Partner)
      • Forecast production scale using info from Stage II
      • Define process development and manufacturing pathway
  • Safety, Quality, and Compliance
    • • Safety assessment and documentations: establishment of hazard categorization and control system, SDS
      • Risk Assessments
      • Technical and process auditing
      • Pre-approval inspection preparation and remediation
      • Cleaning and sterility validation
      • Quality management system development
  • Process Development and Optimization
    • • Incoming raw materials QC: Antibody, Drug, Linker (or Linker-Drug), Crosslinkers (using QC methods from Stage II)
      • Process development from mg to gram scale (info from Stage II)
      • Process optimization and validation at the desired scale
      • Formulation, stability, analytical testing, product specifications
      • SOP documentation
      • Prototype lot manufacturing
  • Non-GMP/GMP Manufacturing and Technology/Process Transfer
    • • Non-GMP manufacturing
      • GMP SOP documentation and approval
      • Technology/process transfer if necessary
      • GMP manufacturing
        • Setting up the QC instrumentation and process
        • Manufacturing and purification instrumentation
        • Planning and oversight of manufacturing
        • Packaging and labeling
        • Inventory and distribution

Depending on the needs of a customer’s project, the typical turn-around time for synthesizing an ADC for initial proof-of-concept is 4-6 weeks. Please contact us to discuss your project.