New peptide-based strategy for the generation of monoclonal antibodies against so-called ‘intractable’ targets like GPCR’s

SAN DIEGO, CA, USA I December 6, 2011 I Speaking today at the plenary session of the IBC’s International Antibody Conference in San Diego , Dr. Klaus Schwamborn , CDO of Pepscan Therapeutics, presented Pepscan’s protein mimicry platform for the discovery of therapeutic antibodies.

In his presentation ‘CLIPS meets GPCRs’ Dr. Schwamborn introduced the CLIPS technology and the most recent developments of immunogen design. He showed data demonstrating that Pepscan’s synthetic immunogens induce potent antibodies against GPCRs and therefore are able to mimic the native receptor. Resulting antibodies do not only bind strongly to the native receptor, but also show functionality with neutralizing activity in different cell based assays. Pepscan’s approach was applied to different targets, supporting the concept of a generic platform for antibody generation for any given GPCR.

Monoclonal antibody therapy is very successful and has major advantages compared to small molecule therapy. However, it is very difficult to generate monoclonal antibodies for certain important drug targets, due to technical constraints, and so far no generic approach has been documented. This is in particular valid for G-protein coupled receptors (GPCR’s), for which no FDA approved antibody exists. Over the last years, Pepscan Therapeutics has validated and optimized its CLIPS technology which enables the design and synthesis of conformationally stabilized peptides with a well-defined 3D-structure, resembling the native functional protein surface. New immunogen design strategies were established which allow grafting extracellular domains of any given GPCR onto a synthetic template, mimicking the native receptor structure in an optimal way.

The platform provides a systematic and efficient way of making synthetic immunogens which induce antibodies against the native target. With these immunogens, monoclonal antibodies can be generated by using common antibody technologies, like phage display libraries or hybridoma generation procedures.

Dr. Schwamborn stated: "Our approach has proven to be successful and the fact that we have the possibility to tailor antibodies to certain GPCR domains enables us to engineer antibodies which fulfill certain biological requirements. The immunogen design concept for mimicking extracellular domains of discontinuous epitopes might be also applicable to other important target classes like ion channels".

About Pepscan Therapeutics

Pepscan Therapeutics is a privately held company based in Lelystad, The Netherlands . Pepscan is using its proprietary high throughput CLIPS protein mimicking technology for the development of novel constrained therapeutic peptides and immunogens. Besides its pipeline of proprietary anti-GPCR monoclonal antibody products, Pepscan has various ongoing collaborations with leading pharmaceutical and biotech companies to develop novel therapeutics based on the proprietary CLIPS technology.

About CLIPS

CLIPS (Chemical LInkage of Peptides onto Scaffolds) is a technology to present one or more peptides in a structurally constrained configuration. These molecules behave as functional mimics of structurally complex protein domains. CLIPS therapeutic peptides have been shown to exert improved activity and stability. CLIPS peptides are also used as superior immunogens for antibody generation against disease relevant protein targets. This is especially valuable in the case of proteins that are inaccessible as recombinant proteins, such as GPCRs.

SOURCE: Pepscan