Antibody Structure & Comparability Analysis Services
Antibody Structure & Comparability Analysis Services
SARomics Biostructures' team has extensive experience in X-ray and NMR spectroscopic analysis of monoclonal antibody and antibody-antigen complex structures. Our services also include structural characterization and comparability studies of biosimilars' higher-order structure (HOS) using 13C-natural abundance 2D-NMR spectroscopy. All our studies include biophysical characterization of the state of the monoclonal antibodies and biosimilars in solution.
More detailed, our monoclonal antibody structure services can help you with the following:
Please see our blog series on monoclonal antibodies and biosimilars for additional information. Our X-ray crystallography and NMR spectroscopy services platform is equipped to handle projects of all types, including challenging projects. To discuss your project, please do not hesitate to contact us.
Case studies
The PDF file below provides a short company introduction and shows several case studies involving antibody-antigen complex structures. They were published recently in leading journals such as PNAS, Nat Comm, Cell Reports, iScience, Cancer Ther, Blood Ad, and Structure. The determined structures include:
Our publications page provides additional examples.
For an overview of our services, please download the white paper below.
More detailed, our monoclonal antibody structure services can help you with the following:
- Epitope definition to file stronger IP
- Understanding the mode of action
- Structure-based antibody engineering: affinity maturation, humanization, antibody-drug conjugates (ADC), etc.
- Structural characterization of protein drugs for regulatory purposes
Please see our blog series on monoclonal antibodies and biosimilars for additional information. Our X-ray crystallography and NMR spectroscopy services platform is equipped to handle projects of all types, including challenging projects. To discuss your project, please do not hesitate to contact us.
Case studies
The PDF file below provides a short company introduction and shows several case studies involving antibody-antigen complex structures. They were published recently in leading journals such as PNAS, Nat Comm, Cell Reports, iScience, Cancer Ther, Blood Ad, and Structure. The determined structures include:
- Bispecific anti-Met/EpCAM mAb MM-131 in complex with its antigens (Merrimack Pharmaceuticals).
- ALPN-202 (An engineered CD80 variant fusion therapeutic) in complex with PD-L1 (Alpine Immune Sciences).
- SRF388 Fab in complex IL-27 (Surface Oncology Inc.),
- ActRIIB-Alk4-Fc in complex with activin A and anti-ActRIIB Fab (Acceleron Pharma).
- ALG.APV-527 (Fab1618) in complex with 4-1BB (CD137) (Alligator Bioscience AB).
- Glenzocimab Fab in complex with platelet glycoprotein VI (Acticor Biotech),
- DutaFab (Roche) in complex with its antigens PDGF and VEGFA.
- Dusquetide in complex with p62 (SQSTM1) ZZ domain (Soligenix, Inc.).
Our publications page provides additional examples.
For an overview of our services, please download the white paper below.
On the image: Martin Welin, PhD, Senior Scientist, Team Leader, Protein Crystallography.
Higher order structure & comparability analysis of Biosimilars
Assessing the comparability of a therapeutic monoclonal antibody's higher-order structures (HOS) and its biosimilar is critical to developing new products that adhere to patient safety principles. The NMR-based approach offered by SARomics Biostructures is currently the most efficient HOS comparability assessment approach at atomic resolution. Please see our latest blog post on which experimental method is best for assessing the structural comparability of a biosimilar and its reference antibody.
Our analyses are based on advances in NMR spectroscopy that have made it possible to acquire a unique fingerprint representation of the 3D conformation of large, complex molecules like biologics. For biosimilar comparability assessment, 2D 13C NMR spectra of the methyl region of the biomolecules are acquired, and the biosimilar and originator spectra are compared. The method is based on natural abundance and does not require additional expensive labeling. Molecules as large as full antibodies can be analyzed using this approach. By directly matching the NMR fingerprint of a given protein to its high-resolution 3D structure, determined, e.g., by X-ray crystallography, or to a fingerprint of another protein batch of the therapeutic monoclonal antibody or its biosimilar, we can rapidly assess and analyze comparability and show that the molecules, for example, a biosimilar and its originator, or different batches or alternative preparations of the same biologic, have identical HOS. In addition, for formulation optimization and batch comparison, the biomolecules can be studied in the formulation buffer. Depending on the biomolecule, around 1-2 mg of protein can be sufficient for HOS analysis.
Our method can substantially accelerate the characterization of monoclonal antibody structures, helping you save both time and money. Additional details on the NMR experiments can be found on our NMR services page.
Our analyses are based on advances in NMR spectroscopy that have made it possible to acquire a unique fingerprint representation of the 3D conformation of large, complex molecules like biologics. For biosimilar comparability assessment, 2D 13C NMR spectra of the methyl region of the biomolecules are acquired, and the biosimilar and originator spectra are compared. The method is based on natural abundance and does not require additional expensive labeling. Molecules as large as full antibodies can be analyzed using this approach. By directly matching the NMR fingerprint of a given protein to its high-resolution 3D structure, determined, e.g., by X-ray crystallography, or to a fingerprint of another protein batch of the therapeutic monoclonal antibody or its biosimilar, we can rapidly assess and analyze comparability and show that the molecules, for example, a biosimilar and its originator, or different batches or alternative preparations of the same biologic, have identical HOS. In addition, for formulation optimization and batch comparison, the biomolecules can be studied in the formulation buffer. Depending on the biomolecule, around 1-2 mg of protein can be sufficient for HOS analysis.
Our method can substantially accelerate the characterization of monoclonal antibody structures, helping you save both time and money. Additional details on the NMR experiments can be found on our NMR services page.
Recent publications
Skladanowska K, Bloch Y, Strand J, White K, Hua J, Aldridge D, Welin M, Logan DT, Soete A, Merceron R, Murphy C, Provost M, Bazan JF, Hunter C, Hill J & Savvides SN. Structural basis of activation and antagonism of receptor signaling mediated by interleukin-27.
Cell Reports, 41, 111490. doi:https://doi.org/10.1016/j.celrep.2022.111490
Cell Reports, 41, 111490. doi:https://doi.org/10.1016/j.celrep.2022.111490
Interleukin-27 (IL-27) uniquely assembles p28 and EBI3 subunits to a heterodimeric cytokine that signals via IL-27Rα and gp130. To provide the structural framework for receptor activation by IL-27 and its emerging therapeutic targeting, the crystal structures of mouse IL-27 in complex with IL-27Rα and human IL-27 in complex with SRF388, a monoclonal antibody undergoing clinical trials with oncology indications, were determined.
For the complete publication list, please visit our publications page.
For related services please follow the respective link
X-ray crystallography services
Protein NMR spectroscopy services
Structure-based design of biological drugs