Lundbeck banks on shark antibody delivery tech to cross blood-brain barrier
Danish pharma firm H. Lundbeck has partnered Ossianix – a private held research company based in Philadelphia, Pennsylvania – since 2012, and has given the firm an undisclosed milestone payment for the successful completion of a number of objectives related to its CNS preclinical pipeline.
“The Lundbeck deal was our first collaboration with Pharma,” Ossianix CEO Frank Walsh told Biopharma-Reporter. “There has been a huge interest from Pharma in our technology as it delivers an elegant solution to a problem they have been working on for a long time but have not been able to deliver a good solution.
“The shark antibodies – because they are small and bind to this key receptor in a unique way – are arguably the best solution to the problem.”
VNAR technology
Ossianix’s technology platform is based on single domain variable new antigen receptor (VNAR) shark antibodies, and according to CEO Frank Walsh it can provide “an attractive way of delivering antibodies and other biologics” to the brain.
“The shark antibody is smaller than a human antibody and binds to the transferrin receptor in a very unique way utilising its large binding loop called the CDR3 region,” he told Biopharma-Reporter.
“This and a second site called HV2 allows the shark antibody to seek out sites on the receptor that are shared between laboratory animals and humans.”
This is important for translational studies, he continued, as it allows the firm to use the same antibody for studies in laboratory animals and to use the same reagent in primate studies and humans which significantly de-risks drug discovery projects.
“In addition this cross species reactivity is unique to the shark and has not been found by other pharmaceutical companies using human derived antibodies.”
Blood-Brain Barrier
The technology “hijacks” the Transferrin Receptor – one of a number of transport mechanisms in the blood-brain barrier – by using a single domain shark antibody that binds to a site different from the ligand transferrin site, he explained.
“This allows the transfer of agents that are attached to our shuttle into the brain at therapeutic doses.
“Normally antibodies get into the brain at very low levels but then attached to our single domain shuttle we can achieve brain plasma ratios of over 5 % which is sufficient for a therapeutic effect.”
Shark Ab production
Ossianix produces shark antibodies from synthetic antibody libraries from the shark.
“The basic antibody structure of the shark is well known and comprises of an invariable backbone plus key areas of hypervariability that gives us the specific antigen binding specificity,” Walsh told us.
“We make synthetic gene libraries by making all possible combinations of amino acids in the hypervariable regions called CDR3, CDR1 and HV2 and combine them into a master library over 10 trillion independent molecules. This we screen for binding to the transferrin receptor and it is by doing this screen we isolated the high affinity cross species binders that we used on the Lundbeck project.”
The gene cloning, screening and scale up of protein is carried out in Ossianix’s laboratories in Stevenage, UK, while animal experiments are carried out using a local CRO called Transpharmation.
