Antibody-drug Conjugates Production

As an industry leading expert in antibody engineering and bio-pharmaceuticals, Creative Biolabs is committed to developing new generation of pharmaceuticals against various diseases for both scientific and clinical purposes. Antibody-drug conjugates (ADCs) are a class of novel APIs with high potency. Our experienced scientists and technicians can provide comprehensive custom services to develop numerous ADC products for every stage of development, from antibody expression to cGMP manufacturing.

Figure: Mechanism of action of ADCs (Nat Rev Drug Discov. 2006)

ADCs are composed of antibodies and cytotoxic drugs, conjugated by chemical linkers. They combine the abilities of mAbs and cytotoxic drugs, improving the control of drug pharmacokinetics and allowing specific drug delivery to target cells. A number of ADCs have been researched and entered clinical trials in recent years. And the successful FDA approval of brentuximab vedotin (Adcetris^®, SGN-35) and ado-trastuzumab emtansine (Kadcyla^®, T-DM1) further suggests that ADCs are promising therapeutic agents for oncotherapy. Our scientists from different disciplines, such as biochemical and chemistry, work together to design and perform optimized processes in ADC development.

Based on the proprietary ADC platform, Creative Biolabs provides a series of products and services:

• Antibody modification and conjugation:
  

  In ADC development, universal ADCs are used to select appropriate monoclonal antibodies and assess the function of designed ADCs. The antibody scaffold contains multiple native amino acids and suitable reactive groups for conjugation or modification to introduce additional reactive sites. Generally, the conjugation strategies can be classified into non-specific conjugation and site-specific conjugation.

• Payloads for ADCs
  

  Payloads are the crucial parts of therapeutic ADCs. Theoretically, agents contributing to treat diseases can be linked to an antibody, such as cytotoxins, protein toxins, enzymes, radionuclides, etc. Based on the modes of actions, payloads of cellular toxins fall into three categories: anti-mitotic (tubulin filaments damaging), DNA damaging or transcription inhibitors (RNA damaging).

• Linkers
  

  An ideal linker is fundamental in an ADC, it assists the ADC to retain intact in systemic circulation while it should be active at the specific site with payloads releasing to kill tumor cells. According to the mechanism of drug release, linkers can be classed into two categories: cleavable linkers and noncleavable linkers . Cleavable linkers include chemically cleavable linkers (e.g. acid-labile linkers, disulfide linkers, etc.) and enzymatically cleavable linkers (e.g. peptide linkers and β-Glucuronide linkers).

• ADC analysis
  

  The analysis services of ADC usually include biophysical/biochemical characterization, stability analysis, pharmacokinetics (PK) characterization, ADME characterization, DAR and drug distribution assessment. With various analytical methods, the characteristics of ADC are certified to facilitate the assessment of ADC function and make better ADC optimization.

• ADC manufacture
  

  Creative Biolabs can develop various types of ADC and transfer them to cGMP-compliant manufacturing to meet specific requirements. In collaboration with the worldwide partners, GMP team of Creative Biolabs provides services including biopharmaceutical contract R&D, process development, cGMP manufacturing, QA & QC solutions for scientific research, preclinical, clinical and commercial supply.

Reference

1. Schrama D, et al. Antibody targeted drugs as cancer therapeutics. Nat Rev Drug Discov. 2006 Feb; 5(2):147-59.

For research use only. Not intended for any clinical use.