Antibody-Antigen Complex Structure
Biosimilars Structure Characterization
SARomics Biostructures' team has gathered extensive experience in crystallization and X-ray structure determination of antibodies, biosimilars and antibody-antigen complex structures. We also provide services in characterisation of biosimilars' higher order structure (HOS) and comparability studies. This includes biophysical characterization of the biosimilar in solution, crystallization and crystal structure determination (see a case study below) as well as NMR spectroscopy studies.
Our crystallography and protein NMR spectroscopy services plattform includes all necessary equipment and tools for handling projects of this type.
Testing, analysis and validation of higher order structures (HOS) of biosimilars is critical to the development of 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 both global structural information and detailed atomic position analysis, which will detect any differences in the structures of the samples.
Our biosimilars testing and analysis services are based on recent revolutionary advances in NMR spectroscopy that have made it possible without expensive isotope labeling to acquire a unique fingerprint representation of the 3D conformation of large, complex molecules like biologics. By directly matching the NMR fingerprint of a given protein to its high-resolution 3D structure, e.g. determined 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 higher order structure.
A recent publication that include contribution from SARomics Biostructures:
Casaletto JB, et.al. (2019). MM-131, a bispecific anti-Met/EpCAM mAb, inhibits HGF-dependent and HGF-independent Met signaling through concurrent binding to EpCAM. Proc Natl Acad Sci U S A 116, 7533-7542. https://doi.org/10.1073/pnas.1819085116
The paper reports the design and preclinical development of a purely antagonistic anti-Met antibody that potently blocks both ligand-dependent and ligand-independent signaling by exploiting the concept of avidity. MM-131 is a bispecific antibody that is monovalent for Met, but exhibits high avidity by concurrently binding to the tumor-specific antigen epithelial cell adhesion molecule. SARomics Biostructures has contributed to the determination of the crystal structure of the antibody.
To view a full list please visit our publications page.