Pepscan claims protein-locking technology significantly boosts bioactivity and enables antibody development against traditionally awkward targets.
Netherlands-based Pepscan Therapeutics and Crucell signed a research and license agreement through which the latter will be able to tap into Pepscan’s CLIPS™ (chemical linkage of peptides onto scaffolds) protein mimicking technology for the development of infectious disease vaccines. Pepscan will be eligible for research funding and could receive additional research and clinical milestones plus future sales royalties.
“We strongly believe that Pepscan’s CLIPS technology combined with Crucell’s expertise in vaccine development will yield breakthrough products,” remarks Wim Mol, Pepscan CEO. “We are convinced that Pepscan’s state-of-the-art epitope-mapping technology as well as our expertise in creating conformationally stabilized CLIPS peptides will greatly contribute to the development of novel vaccines.”
The deal with Crucell follows just a month after Pepscan inked a deal with Mercator Therapeutics, through which the firms will collaborate to optimize Mercator’s Homing Peptides using the CLIPS platform. Pepscan in addition has an ongoing collaboration with Tibotec focused on exploiting CLIPS for the development of therapeutic peptides.
Pepscan’s CLIPS technology allows proteins to be locked into a desired biologically active conformation including α-helix, loops, double loops, triple loops, and sheets, the firm explains. The technology involves the use of native or newly introduced cysteine residues in a peptide’s amino acid sequence to make single, double, or triple bridges. This enables the construction of molecules that behave as functional mimics of complex protein domains. The method requries no catalyst, involves single-step reactions and mild reaction conditions, and is compatible with standard peptide chemistry, Pepscan adds.
The CLIPS approach is applicable to either proteins in solution or peptides for microarrays, the firm claims. The technology can be used to significantly improve the bioactivity of therapeutic peptides and to generate stable, conserved antigens for antibody development. Pepscan says that for several targets it has demonstrated that introduction of CLIPS stabilizes the linear peptide and increases its activity up to 5,000-fold.
Pepscan also offers a CLIPS epitope-mapping service through its Pepscan Presto business. The approach uses a high-throughput synthesis of microarrays of overlapping structurally constrained (surface-immobilized) CLIPS peptides covering the complete sequence of a given protein. The firm says the technology effectively maps protein-protein interaction sites at the level of individual amino acids and can be applied to linear, conformational, and discontinuous epitiopes.
Pepscan’s in-house pipeline is primarily focused on the development of potential anticancer antibodies against disease-relevant GPCRs. It claims CLIPS immunogens mimicking the ligand-binding sites of potential targets have successfully been used to induce antibodies that recognize the native receptor and behave as functional antagonists.