Higher Order Structure of Antibodies & Comparability Analysis

SARomics Biostructures' team has extensive experience in X-ray and NMR spectroscopic analysis of antibody and antibody-antigen complex structures. Our services also include structural characterization and comparability studies of biosimilars' higher order structure (HOS). We use a combination of X-ray crystallography and NMR spectroscopy for comparability analysis of HOS. All our studies include biophysical characterization of the state of antibodies and biosimilars in solution.

X-ray crystallography 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 white paper pdf below shows case studies involving antibody-antigen complex structures contributed by our team. 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.).

For details, please, download the white paper below. You may also visit our
publications page.

On the image: Martin Welin, PhD, Senior Scientist, Team Leader, Protein Crystallography.

Higher order structure analysis & characterization of Biosimilars

Testing, analysis, and validation of higher order structures of biosimilars are critical to developing products that adhere to patient safety principles. SARomics Biostructures offers a multidisciplinary approach for the best possible comparability assessment and analysis of HOS at atomic resolution. By combining NMR spectroscopy and X-ray crystallography, we can provide global structural information and detailed atomic position analysis, which will detect any differences in the structures of the antibodies. Details can be found on our NMR services page.

Our biosimilar characterization and analysis 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 without expensive isotope labeling. 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 or a 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.

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

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.

You may also visit our publications page for the full publication lists.

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X-ray crystallography services

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