Ablynx reveals power of Nanoclone™ - A high throughput method for isolating highly potent antibody-derived therapeutic proteins (Nanobodies™)

Speaking at the Drug Discovery Technology Europe 2006 Conference (London), Dr. Hennie Hoogenboom, CSO of Ablynx, for the first time presented data that reveal how Ablynx has been rapidly generating high affinity, picomolar potency Nanobodies™ using Ablynx’s proprietary Nanoclone™ discovery engine. Ablynx has been applying Nanoclone™ as part of its drug discovery efforts to generate Nanobodies™, a novel class of antibody-based therapeutics.

Using Nanoclone™, Ablynx is able to rapidly identify B-cells that produce heavy-chain antibodies that are not only specific for a particular target antigen, but also bind to the antigen with a very high affinity. Nanoclone™ is fast, easy to use and gives Ablynx a direct route to the identification of highly potent Nanobody™ leads.

Nanobodies™ are derived from heavy-chain antibodies that are found naturally in camels and llamas. Nanoclone™ involves the direct sorting of single antigen-specific B-cells (white blood cells that produce and secrete specific antibodies) from immunized llamas, without the need for phage display or any other complex screening platform. After sorting, the antibody variable genes from individual heavy chain B-cells are cloned into microbial hosts for further expression and analysis. Nanoclone™ is readily automated, further enhancing its speed and ease of use. Because Nanobodies™ comprise a single domain, they are easier to clone and express than fragments of conventional antibodies. By direct cloning antigen-specific single variable genes, Nanoclone™ avoids the biases often seen in repertoire cloning and with phage display technology.

Summarizing the results, Dr. Hoogenboom said: “These new data demonstrate the unexpected ease with which Nanoclone™ can be used to identify Nanobodies™ that are of picomolar potency. Although similar procedures have been described for screening and sorting of B-cells expressing conventional antibodies, it was in the past notoriously difficult to isolate monoclonal antibodies with the required potency for therapeutic use. The success of Nanoclone™ is probably due to a combination of a highly stringent selection for antigen-binding B-cells and a number of well-known strengths of our Nanobody™ platform, including the simplicity of cloning and formatting, and ease of expressing Nanobodies™.”

Commenting on the commercial potential Nanoclone™ offers, Dr. Simon Kerry, Director of Business Development said: “Nanoclone™ helps to create a competitive advantage for Ablynx, allowing us to easily identify highly potent Nanobody™ leads for our in-house programs and for our partners. Nanobody™-based therapeutics represent an exciting commercial opportunity as they combine the beneficial features of conventional antibodies, with desirable properties of small-molecule drugs.”