In Vivo DAR Characterization
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Characterization analyses that measure the drug-antibody ratio (DAR) play an important role in the discovery, development, and manufacture of ADCs. Due to the complex structure of ADCs and non-specific de-coupling after drug administration, it leads to dynamic changes in DAR in vivo. Therefore, the characterization of in vivo DAR of ADCs is extremely challenging. Creative Proteomics has established a variety of high-precision DAR analytical characterization methods that can accurately analyze this property of ADCs and help customers better evaluate the safety and efficacy of ADCs in drug development.
Introduction of In Vivo DAR Characterization
DAR is an important physicochemical parameter characterizing ADCs, which determines the loading of small-molecule drugs and also affects the safety and efficacy of ADCs. The analysis of DAR consists of 2 aspects, i.e., average DAR value and DAR distribution. The average DAR value is defined as the average number of drug molecules that are conjugated to the antibody. The DAR distribution mainly determines the proportion of ADC molecules with different DARs to the total ADC molecules, respectively. Although ADCs are designed to remain stable until internalized, non-specific deconjugation occurs after ADCs administration, resulting in altered DAR in vivo. Therefore, monitoring DAR changes after drug administration is important in determining ADC stability and assessing therapeutic effects.
In Vivo DAR Characterization Services at Creative Proteomics
Creative Proteomics' capabilities in DAR characterization include providing advanced analytical techniques and in vivo models to accurately quantify the average DAR values of ADCs and determine the distribution of different drug payloads in ADCs. Our experienced team of experts performs comprehensive DAR characterization using a variety of advanced techniques, including spectroscopic assays, chromatography-UV assays and mass spectrometry.
At Creative Proteomics, we reflect the average DAR value by determining the ratio of the molar concentration of total drug molecules to antibody molecules in the system. Currently, DAR value is measured using the following methods:
- Ultraviolet-Visible (UV/Vis) spectroscopy
- Cathepsin-B enzyme-based digestion method
DAR distribution is defined as the stoichiometric distribution of the amount of the conjugated drug present on the antibody carrier. We used different Capillary electrophoresis (CE) methods to characterize ADCs, including:
In addition, we have developed a series of methods that are more advantageous for the analysis of DAR, allowing us to simultaneously measure the average DAR and determine the DAR distribution in the ADC. These methods include:
Creative Proteomics' experts clearly understand the strengths and limitations of various methods, and we offer our customers a portfolio of complementary assays. Customized DAR characterization solutions can help customers obtain more accurate information on average DAR, drug loading distribution, un-spliced antibody content, and free payload linker content to ensure proper and extensive characterization in ADCs. Contact us to learn more about our service and we will be happy to serve you.
