ADCs are a class of biopharmaceutical drugs that deliver cancer-killing agents directly to cancer cells – a far more targeted approach than conventional chemotherapy. Optimizing ADCs requires analytical technologies to comprehensively characterize the molecule, including its biochemical attributes like drug-to-antibody ratio (DAR) and sites of conjugation.
As biopharmaceutical organizations continue to explore the use of ADCs as a class of cancer therapies, they find significant challenges with analyzing their complex, heterogenous structures. However, a well-characterized ADC is critical to advance from discovery through clinical development and to commercialization.
Successfully address your characterization challenges with exceptional insight into your molecules from Waters fit-for-purpose ultra-performance liquid chromatography (UPLC), high resolution mass spectrometry (MS), column chemistries, and informatics solutions. Trust Waters to help simplify complex molecule analysis and accelerate your ADC characterization and monitoring of critical quality attributes.
Case Study: How Waters is Helping to Support the Development of Novel Therapies
Accelerate the journey from sample analysis to decision making using waters_connect for biopharmaceuticals, with tailored workflows designed for biopharma LC-MS applications, intact mass, peptide mapping, peptide MAM, and released N-glycan analysis.
Achieve high-quality LC-based analyses and determine DAR of cysteine-conjugated and highly hydrophobic ADCs using Waters Protein-Pak Hi Res Hydrophobic Interaction Chromatography (HIC) HPLC Columns for fast, efficient separations.
Reversed-Phase Columns for bio-conjugates and Antibody Drug Conjugates with MaxPeak HPS such as the ACQUITY and XBridge Premier Protein BEH C4 Columns are uniquely designed to minimize secondary interactions between ADCs and column hardware and suitable for the analysis of lysine-conjugated ADCs. Unlike cysteine-conjugated ADCs, the intra-chain disulfide bonds that maintain linkages between the heavy and light chains of the mAb for the lysine-conjugated ADCs are intact. Therefore, reversed-phase chromatography is suitable for the analysis of lysine-conjugated ADCs when linker chemistry is not labile at acidic pH. In addition, Waters offers Reversed-Phase Columns with solid-core particle technology, such as BioResolve RP mAb Polyphenyl for intact and subunit analysis to determine the localization of linked drugs at the domain level.
Eliminate the need to create multiple SEC eluent mobile phases with different proteins by using a platform method with phosphate buffered saline (i.e., PBS) for consistently accurate aggregate, monomer, and fragmented data with Waters SEC Columns. In addition, for bio-conjugates which can be hydrophobic creating unwanted secondary interactions, there is no need to add organic solvent with MaxPeak Premier Protein SEC Columns and it’s PEO bonded BEH particles.
Accurately measure charge variant profiles of cysteine-linked and lysine-linked ADCs with the BioResolve SCX mAb Column and BioResolve CX pH Buffer Concentrates for salt or pH gradients with minimal secondary interactions in optical detection. For structural insights with mass spectrometry in ion exchange, our MS-compatible buffers, IonHance CX-MS pH Buffer Concentrates, make online IEX-MS a reality with high-purity, volatile buffers suitable for mass spectrometry.
Antibody oligonucleotide conjugates (AOCs) are commonly used in protein diagnostics and are a promising therapeutic for targeted cell therapy. The net negative charge of an AOC expands with each additional conjugation site, resulting in increased retention on an anion exchange resin. The GenPak FAX Column contains a weak anion exchange sorbent that exhibits controlled retentivity and a unique selectivity for protein and oligonucleotide samples. Recent application work demonstrates that AEX can be coupled with MALS to generate absolute molecular weight information.
Hydrophilic Interaction Chromatography (HILIC) has been widely used to separate small polar compounds, yet its application to large biomolecules, other than released glycans, has been surprisingly limited. With Waters widepore Glycoprotein Columns, it is now possible to use HILIC to glean previously unattainable information from intact proteins (with or without glycosylation), protein fragments, and complex, released glycans.
Waters PeptideWorks Tryptic Protein Digestion Kits for manual or automated workflows uniquely provide your lab with high efficiency, reproducible peptide maps in under 2.5 hours—4x faster than average home-brew methods. Achieve 30-minute digestions with a 1:5 enzyme:peptide ratio, 78% reduction in missed cleavages, and a 98% reduction in contaminated autolysis peaks. PeptideWorks is ideal for drug conjugation site determination, protein structural characterization, protein identification, and protein modification monitoring including post-translation modifications.
Re-imagine a streamlined, fast, and highly sensitive way to profile N-glycans on ADCs with the GlycoWorks Kit. Achieve unprecedented fluorescent and mass spectrometric performance for released n-glycan analysis while maximizing productivity with a solution that is automatable on Waters Andrew+ Pipetting Robot. With just 3 easy steps in as little as 30 minutes, the GlycoWorks RapiFluor-MS N-Glycan Kit reduces complicated, time-consuming sample preparation.
Simplify and accelerate protein digestion with ProteinWorks eXpress Digest Kits. Pre-measured, lot-traceable reagents and standardized protocols for accurate, precise, and sensitive LC-MS quantification of proteins, including ADCs, in plasma and serum. Achieve unmatched performance and flexibility for reproducible protein digestion with kits optimized for various workflows, including protein bioanalysis/DMPK.
Streamline sample preparation for quantitative LC-MS analyses with verified workflows that help minimize variability, improve traceability, and simplify method transfer.
Optimize your laboratory's productivity and success with Waters Global Services to maintain peak system performance, minimize down time, address application challenges, and support stringent compliance requirements.
Maximize resources and minimize risk with payment options from Waters Capital, including upgrading aging equipment, getting customized support, and bundling services into one monthly payment.