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Company Updates : May 15, 2011 ( )
Mapping Epitopes with H/D-Ex Mass Spec
ExSAR Expands Repertoire of Technology Platform Beyond Protein Characterization
Epitope mapping is taking the spotlight in the race to develop new therapeutic monoclonal antibodies, a market expected to reach $33 billion by 2010. Identification and characterization of an epitope is key to this development process, as well as for vaccine design and mapping ligand binding sites in receptors using mAbs. A more recent application involves protecting the epitope from competitors, since the data is often used in patent filings.
Currently, the most popular H/D-Ex application is epitope mapping. This process involves separation of the antigen, then on-solution exchange experiments with the antigen by itself to determine the best time frame for on-/off-solution column exchange. The antibody is immobilized, and the binding capacity of the column against the antigen is determined. Then an on-/off-solution column exchange experiment is conducted to determine the antibody binding site.
The platform’s drug discovery applications include ligand binding-site identification, binding-site and pharmacology correlations (full agonist vs. partial antagonist), and enabling fragment-based drug discovery strategies in the absence of ligand-bound x-ray structures.
A biogeneric that has a different formulation or manufacturing process is suspected of being nonbioequivalent to the original. According to the company, H/D-Ex is able to detect subtle changes in protein structure within a few days. It recently identified a lot-to-lot difference in the protein dynamics of an antigen used by a client to generate therapeutic neutralizing antibodies.
A 20-residue region showed a differential rate of amide-hydrogen exchange in one of the lots. The lots were supposed to have exactly the same protein and the same manufacturing. The client expressed concern about unspecified modification and wanted additional data on equivalence. A difference was detected in hydrogen exchange rates, indicating a structure that had been compromised or changed.
Dr. Hamuro says that some of the future applications of the platform include epitope mapping of patients’ polyclonal antibodies against protein therapeutics when immunogenicity is observed. Another large potential area is the study of membrane protein-ligand interactions. “These are difficult to work with and we are just starting to see a few examples of using the H/D-Ex data with membrane proteins.”
In addition, the company sees opportunities for its technology in the biosimilars arena. “Our technology can be helpful to develop biosimilars when we want to see a direct comparison to the original,” Robert Johnston, president and CEO says.
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