Activating the body's antiviral defense system: A novel RIG-I ligand developed at the Medical Faculty of the University of Bonn and the University Hospital Bonn (UKB) helps the body to recognize and fight off certain viruses at an early stage. This molecular structure has potential for the prevention and treatment of viral infections. Based on the research results, there are now plans to develop and market an antiviral nasal spray to protect against viral respiratory infections.
In this interview, Prof. Gunther Hartmann, Director of the Institute for Clinical Chemistry and Clinical Pharmacology – Immunology in Translation at the UKB, and co-inventor Dr. Christine Wübben discuss their experiences in patenting and further developing the invention into a marketable product.
(The interview was conducted by PROvendis. As the central service provider of the innovation2business.nrw network, PROvendis supports the team of inventors in securing intellectual property rights for the research results, obtaining funding for further development, and marketing the invention.)
What is your invention about?
Prof. Dr. Hartmann: The invention involves a special short artificially produced RNA that activates a receptor (RIG-I: retinoic acid-induced gene I), which stimulates the body's own antiviral immune response. Cells in which RIG-I is activated send alarm signals in the form of cytokines (e.g., type I interferon) to neighboring cells and systemically to the entire organism to warn of a spreading viral infection. The underlying molecular principle of RIG-I activation, the structure of the RNA ligand, was identified by my research group in 2006 and further specified in subsequent work.1–5
Dr. Wübben: Our newly developed RNA ligand has two major advantages: First, it is considerably shorter than conventional RIG-I ligands and, in addition to being inexpensive to manufacture, it is also easier to absorb into the cell; chemical modifications further increase the stability of the molecule. Second, the ligand has a guanine-rich overhang. Several guanine building blocks can lead to a special folding that forms complex stacked structures known as G-quadruplexes. Due to our guanine overhang, the RNA is present outside the cell as a monomer, while inside the cell it assembles into a multimeric structure due to the change in the ions present, allowing the RIG-I signaling cascade to be activated.
What potential does the invention hold for which areas of application?
Dr. Wübben: The use of RIG-I ligands for immunotherapy of tumors6–15 or for the prevention and treatment of viral infections16–21 has been documented in numerous publications by Professor Hartmann's group and other groups. However, no product has yet reached the market. We want to change that with our invention and demonstrate the potential of RIG-I ligands.
When did you realize that you needed to protect your invention with intellectual property rights? Was the topic of patents new to you, or did you already have experience with it?
Prof. Dr. Hartmann: My research group has already filed a number of patents. Two patent groups were of particular importance to us: In 2017, we worked with partners in the US to identify a small endogenous signaling molecule that activates an antiviral immune response. We patented this molecular key to activating the receptor responsible for this, STING, together with our partners, and then successfully licensed it to a US company. The other is a group of patents on RIG-I ligands, with which we founded the spin-off Rigontec from the University of Bonn in 2013. Rigontec has developed RIG-I ligands for the immunotherapy of tumors, such as malignant melanoma. In 2017, Rigontec was sold to Merck Sharp & Dohme (MSD), which evaluated the principle in clinical trials. As part of a PostDoc Innovation Fund from the ImmunoSensation² Cluster of Excellence, Ms. Wübben took the opportunity to further develop an idea for an improved RIG-I ligand. Ms. Wübben and I made the decision to file a patent for the novel RIG-I ligand during a data review meeting, which showed that the newly constructed RNA is a highly potent ligand for RIG-I.
You have successfully obtained funding through the GO-Bio initial funding program—how did you find out about it, and how does the program benefit you?
Dr. Wübben: At the University of Bonn, the enaCom Transfer Center and the Transfer Team at the Faculty of Medicine regularly draw attention to relevant funding programs. These institutions also prepared me for various pitch contests, and I took part in Pitch4med and the MIB Future Panel Pitch. I realized early on that my ambitions lay more in the translation of new therapeutic approaches.
Through the BMFTR-funded GO-Bio initial exploratory phase, we examined the medical need, feasibility, and economic viability of our idea for an antiviral product. Together with PROvendis, we conducted a technology field analysis, and with B2B international, we conducted a market analysis in the form of surveys of decision-makers, physicians, and patients. The opportunity to conduct such analyses with the support of GO-Bio initial funding is essential for evaluating potential commercial viability. Our results showed that there is a high level of interest in an antiviral nasal spray to protect at-risk populations from respiratory viruses, which demonstrated the benefits of this funding program.
What happens next? What are the next steps on the road to bringing your invention to market?
Prof. Dr. Hartmann: Of course, simply knowing that our antiviral nasal spray could make an important contribution to protecting against viral respiratory infections is not enough for us. We are now doing everything we can to secure further funding so that we can carry out the costly preclinical trials. We want to advance development to the point where we can start clinical trials. At this stage, we then want to push ahead with further clinical development through a venture capital-financed spin-off until market launch.
(This article was originally published by Provendis, and has been translated and adapted for clarity and relevance.)
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