Updated Conjugation Protocols for PerKit ADC with Reduced Thiol Chemistry

Updated Conjugation Protocols for PerKit ADC with Reduced Thiol Chemistry

Posted by Yumei Huang on 2nd Nov 2024

At CellMosaic, we are committed to delivering high-quality, cutting-edge bioconjugation solutions. We invest significantly in R&D to continuously optimize our bioconjugation processes, ensuring that our products offer the latest advancements and meet the highest standards of quality. Recently, we enhanced our PerKit® ADC kits by refining protocols for reduced thiol chemistry, a key advancement that strengthens our market-leading position in ADC.

Key Improvements in Updated Protocols 

The new protocols streamline the conjugation process and enhance ADC kit performance, benefiting customers by:

  1. Reduced overall preparation time: A streamlined process, now completed in just four hours, allows for same-day bioassay use. 
  2. Enhanced antibody stability: Some antibodies are unstable at 37°C for extended periods. The new protocol minimizes the time antibodies remain at 37°C, significantly reducing chemical degradations (e.g., oxidation, deamidation) of sensitive residues (such as methionine and asparagine). 
  3. Expanded kit compatibility and reduced variability across IgG types: Previous protocols were optimized for human IgG1 to achieve an average drug-to-antibody (DAR) of 4. The new protocol removes the need for an optional labor-intensive thiol assay, providing consistent results across all IgG types. 
  4. Improved homogeneity and reduced unreacted antibodies: For challenging antibodies, the previous protocol may yield low DARs with over 10% of unreacted antibodies with a wide DAR distribution. The new protocol achieves over 95% conjugation with a predominant DAR of 3 to 5 conjugates. 

The following product part numbers are affected by this update: 

No changes have been made to the components themselves. If you are obtaining satisfactory results with the previous protocol, you may continue to use it. 

About PerKit® Antibody-Drug Conjugation (ADC) Kits 

Historically, antibody-drug conjugation was performed solely by drug developers, occasionally in collaboration with contract research organization (CRO). The cost of these services can be prohibitive for academia institutions and small biotech companies. During the screening stages, researchers often need to prepare various ADCs with different antibodies and drugs. In December 2017, CellMosaic launched its first ADC kit product line, enabling customers to prepare ADCs in-house and eliminating high CRO labor costs. CellMosaic's ADC PerKits® are designed for antibody-drug conjugation via surface amines or reduced thiols. Some kits are applicable for general payloads with specific functional groups, while others provide selected standard linker molecules conjugated to a chosen payload. Each kit includes the necessary reagents and protocols for attaching the selected payload to the customer’s antibody and purifying the final ADC. Customers only need to supply their antibody and standard lab equipment. As of August 2024, more than 112 organizations have purchased CellMosaic’s ADC kits. 

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About CellMosaic® Inc. 

CellMosaic is a Massachusetts-based biotech company specializing in the research and drug bioconjugate market. Bioconjugates are widely used as research tools, diagnostic reagents, and novel drug modalities, such as antibody-drug conjugates (ADCs), antibody-oligo conjugates (AOCs). Since its founding in 2008, CellMosaic® has invested significant research efforts in developing core technologies to address two major challenges in the field: advanced bioconjugation processes for producing high-quality bioconjugates and AqT® technologies for efficiently loading large amounts of hydrophobic small molecules onto biomolecules. Operating from its U.S. facility, CellMosaic® currently offers bioconjugation-related reagents and kits, customer bioconjugation services, contract bioconjugate development and manufacturing, and strategic partnerships for developing proprietary innovative AqT® ADC using its novel AqT® linker-modified drugs.