Case examples

Epitope fine mapping: revealing fine details of anti-HIV-1 F425-B4e8

Having a detailed understanding of the binding specificity of an antibody surely is appealing from the perspective of basic science, but also to secure IP or ensure freedom to operate.  Epitope fine mapping defined the fine features of an anti-HIV-1 antibody and provided a unique insight into the breadth of HIV strains that can be recognized by this antibody.

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FDA breakthrough therapy designation for two Pepscan-mapped antibodies

Two antibodies for which Pepscan was asked to perform the epitope mapping, recently received breakthrough therapy designation by the FDA. It concerns Roche/Genentech’s anti-CD20 mAb obinutuzumab and Genmab/Johnson & Johnson’s anti-CD38 mAb daratumumab. We are proud to have contributed to these projects and congratulate our clients with their success.

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Revealing the discontinuous epitope of human anti-SIRPα in full detail

The epitope of an anti-SIRPα antibody, which cannot be mapped either with linear peptides or with structural mimics, was successfully elucidated via CLIPS Precision Epitope Mapping using a comprehensive library of combinatorial CLIPS peptides based on the sequence of SIRPα.

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Determining the discontinuous epitope of the anti-CD38 antibody daratumumab

CD38 is a 46kDa trans-membrane glycoprotein highly expressed in hematological malignancies. A two-stage CLIPS Precision Epitope Mapping strategy precisely determined the discontinuous epitope for daratumumab on the membrane-bound CD38.

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Conformational Epitope Mapping of a Flu Virus Antibody

FI6 is a monoclonal antibody that potentially neutralizes all influenza viruses. To reveal the molecular basis of this pan-influenza cross-reactivite antibody, we fine-mapped the conformational epitope recognized by FI6. (Corti et al, Science 2011).

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The molecular basis for distinction between GA-101 and Rituximab

Rituximab, a monoclonal antibody targeting CD20, has improved the treatment of malignant lymphomas. Therapeutic CD20 antibodies are classified as either type I or II based on different mechanisms of killing malignant B cells. To reveal the molecular basis of this distinction, we fine-mapped the epitopes recognized by Rituximab (Type I) and novel GA101 (Type II).

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Conformational Protein-Protein Interaction Mapping of etanercept (Enbrel®)

The CLIPS Epitope Mapping technology has been shown an effective tool for mapping of conformational and discontinuous epitopes of therapeutic antibodies. This case study demonstrates that the technology can also be used to identify the interaction site between hormones and cell-bound receptors. Etanercept (Enbrel®) is a chimeric TNFa receptor that is used to treat autoimmune disease by interfering with TNFa (tumor necrosis factor). The interaction between Etanercept and the TNFa trimer was studied in full detail through the CLIPS Mapping technology.

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Epitope Fingerprinting of large sets of disease-related polyclonal sera

Pepscan’s CLIPS Epitope Mapping not only suitable for precision mapping of one single antibody , but also for detailed epitope fingerprinting analysis of large sets of antibodies or polyclonal sera. This case report demonstrates the application in profiling the epitope landscapes of large numbers of sera from diseased and healthy origin to identify epitopes linked to protection.

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