April 10, 2017
Text: Markus Berninger
FLASH is the most successful patent that Max Planck Innovation has ever marketed. The patent has generated around 155 million euros in licensing revenues for the Max Planck Society, the Max Planck Institute for Biophysical Chemistry and the inventors. In 2016, the physicist Jens Frahm, head of Biomedizinische NMR Forschungs GmbH at the MPI for Biophysical Chemistry and the inventor of FLASH, was inducted into the Hall of Fame of German Research. In doing so, Manager magazine singled out the researcher for his breakthrough developments in magnetic resonance imaging (MRI). Thanks to the FLASH technology he invented, MRI is now the most important imaging method in clinical diagnostics and is used worldwide. A recent development by Frahm (FLASH 2) has made magnetic resonance imaging even faster, allowing videos of the interior of the body to be obtained in real time. The technique is currently being tested for use in hospitals.
“The path from scientific discovery to innovation, from a brainwave to practical applications, is long and requires a wide range of skills. I would therefore like to express my thanks for this extraordinary distinction on behalf of the many colleagues and cooperation partners I’ve been fortunate enough to work with,” Frahm said on the occasion of his induction into the Hall of Fame on 16 November at a ceremony held in the Wiesbaden Kurhaus, which was attended by numerous invited guests from industry, science and politics.
Does a patient have brain tissue abnormalities? Have an accident victim’s internal organs been damaged? Is a patient’s heart function impaired? To answer such questions, radiologists turn to MRI, which quickly produces precise sectional images of the body. The technique is particularly good at imaging soft tissues and organs. Unlike X-ray techniques, such as computed axial tomography (CAT scans), it is also completely safe for patients.
MRI has become an integral part of routine clinical practice thanks to the efforts of Jens Frahm. Between its discovery in 1973 and the mid-1980s, MRI was quite simply too slow for practical use. It took several minutes to obtain a simple slice image. In 1985, Frahm and his coworkers developed the FLASH (Fast Low-Angle Shot) technique, which shortened the imaging time by a factor of 100 and ushered in a breakthrough in the use of MRI in medical diagnostics. Some 100 million MRI procedures are now performed every year. FLASH is therefore the Max Planck Society’s most successful patent ever.
MRI exploits a specific property of hydrogen nuclei, which are ubiquitous in the body: nuclear spin, which makes the nuclei act like tiny magnets. When exposed to a magnetic field, the nuclei align themselves with the magnetic field lines. An MRI scanner generates such a magnetic field as well as short radio pulses in the ultra-shortwave range. The pulses nudge the nuclei briefly from their state of equilibrium. As they return to their original alignment, they emit radio waves, which are detected by highly sensitive coils. The process is repeated many times, and the emitted signals are analyzed by a computer to produce an image.
However, a fundamental obstacle to the widespread use of MRI was its long processing time. This was because a large number of measurements with different site codings were required with waiting times between measurements. Frahm’s FLASH technique uses only part of the available MRI signal – a physical trick that completely eliminates the pauses and radically shortens the time needed to produce an image.
In 2010, Frahm and his team achieved another breakthrough when they also solved the problem of requiring a large number of individual measurements. In FLASH 2, they presented another innovation that uses a new mathematical method for reconstructing images and therefore needs far fewer measurements per image. The procedure significantly shortens MRI scanning times. An image can be produced in as little as one hundredth of a second, making it possible for the first time to capture images of the inside of the body in real time and observe joint movements, speech and swallowing processes or the beating heart live. Now MRI can also be used for examining patients who are unable to hold their breath for long. Moreover, the new technique may serve as an aid in minimally invasive interventions and treatments that until now have been performed under X-ray guidance.
Realtime MRI is already undergoing clinical testing at Göttingen Medical School and other universities, including Oxford University and Johns Hopkins University. “Clinical imaging as an important diagnostic tool would be inconceivable today without MRI. Countless scans are performed around the world every day. This presupposes the possibility of fast analysis. The invention of FLASH technology by Jens Frahm and its systematic implementation by his team has therefore created the basis for a diagnostic tool without which modern medicine would not exist. In terms of innovation, the refinement of the technique to allow realtime imaging of moving organs (for example the beating heart) with the help of FLASH 2 is on a par with the earlier introduction of FLASH technology. Once realtime MRI has been rolled out on a wide scale, it will open up new diagnostic possibilities. In summary, Jens Frahm’s unstinting dedication to MRI has resulted in advances that benefit an untold number of patients every day,” says Professor Heyo K. Kroemer, speaker of Research and Teaching Board and Dean of Göttingen Medical School.
In 2016, a total of 79 exploitation agreements were concluded with industrial partners, including an agreement with Abberior Instruments GmbH, which has licensed the next-generation STED technology. STED microscopy is a Nobel-Prize-winning technology that allows high-resolution fluorescence images to be generated far below the diffraction limit. At the beginning of the year, researchers at the Max Planck Institute for Biophysical Chemistry in Göttingen presented their innovative protected STED concept, which not only improves image contrast but also reduces image fading in STED microscopy by as much as an order of magnitude. This invention is expected to lend impetus to applications in live cell imaging and medical technology.
Max Planck Innovation and Abberior Instruments GmbH have concluded their negotiations on an exclusive licence for the commercial rights to protected STED technology. “Abberior Instruments is thrilled to integrate protected STED technology into its STED microscopes of the next generation,” says Dr Gerald Donnert, CEO of Abberior Instruments. “It fits perfectly into our strategy to offer our customers the most advanced STED microscopes available for live cell imaging.”
Protected STED is an innovation that has recently been introduced into STED microscopy. The technique utilizes fluorescence markers that are activated by light. During the imaging process, the initially non-fluorescing markers are photoactivated in each scanning position, after which they are imaged with STED. Because the markers outside the actual scanning point remain non-fluorescent, they do not contribute to the fluorescence background. This improves image contrast enormously. In addition, the markers do not undergo photobleaching, because in the non-fluorescent state they absorb no stimulating energy or STED light. Protected STED has been shown to reduce photobleaching by an order of magnitude while at the same time dramatically improving image contrast.
“This innovation raises the quality of STED microscopy to a new level. The improved resolution and contrast open up new avenues of scientific research and will usher in new developments in medical research. In Abberior Instruments we have an experienced partner who will help ensure the market success of this innovation,” says Dr Bernd Ctortecka, patent and licence manager at Max Planck Innovation.
A licensing agreement in the field of optogenetics with the American company Photoswitch Biosciences forms the basis for a new platform for the screening and testing of new drug candidates.
Using light-sensitive channelrhodopsin proteins, scientists are able to explore how drug candidates affect critical cardiac and neural functions in a fundamentally new way. The proteins, discovered by Max Planck scientists, are introduced into experimental cells and used in conjunction with a device from Photoswitch Biosciences to control the function of other ion channels. By monitoring tiny voltage changes in cells, scientists are able to search chemical substance databases for new drugs and evaluate their safety for use in humans.
In 2002, Max Planck scientists isolated channelrohodopsins for the first time from Chlamydomonas reiinhardii, a green alga, and successfully carried out tests both in vitro and in living organisms. The discovery allows researchers to control and study many critical bioelectrical systems. Photoswitch Biosciences is now developing a complete testing system for drug discovery and pharmacological safety studies. It allows researchers to exploit the advantages of channelrhodopsin-based optical control. The system analyzes the function of nerve and heart cells much faster and at a lower cost than previous methods.
The new device platform was developed partly on the basis of a non-exclusive licensing agreement with Max Planck Innovation on the use of biological photoreceptors to control light-activated ion channels directly.
In 2016, Max Planck Innovation once again supported numerous spin-off projects of the Max Planck Society in various phases of their corporate establishment – from the initial idea to securing initial funding.
Ambiverse GmbH is one of 11 new companies set up in 2016. It was founded after successful promotion within the framework of EXIST Research Transfer. A spin-off project of the Max Planck Institute for Informatics in Saarbrücken, Ambiverse has developed a new software program for the machine comprehension of texts that allows companies to access more relevant information on the Internet and improves access to information in their own databases.
Another new company is Cardior Pharmaceuticals GmbH, a joint spin-off of Hanover Medical School and the Max Planck Institute for Biophysical Chemistry in Göttingen. The company is working on the development of a drug for the treatment of tissue damage following a heart attack. The technology has already been validated by various preclinical experiments.
Vaxxilon AG was named Science Start-up of 2016. Under the motto “building bridges, transcending borders”, 23 start-up companies presented their research projects at the Falling Walls Venture science competition on 8 November in Berlin. The company nominated by Max Planck Innovation, Vaxxilon, emerged as the winner for its development of carbohydrate-based vaccines. The new vaccines should cut the cost of immunizations against bacterial infections and make them more heat-stable, thereby improving access to vaccines in poorer countries.
Falling Walls is an international conference on pioneering social and scientific developments. A highlight of the programme is the Falling Walls Venture start-up competition. In conferring the award, the jury recognized the technological innovation and beneficial social impact of Vaxxilon’s technology, which is based on a new class of synthetic substances created by Peter Seeberger’s team at the Max Planck Institute of Colloids and Interfaces.
Vaxxilon was founded in 2015 by the Max Planck Society together with the Swiss biotech company Actelion Ltd to promote research, translate research findings into products and market them. For its commercialization, Vaxxilon was granted exclusive rights to a number of preclinical vaccine candidates and methods by Max Planck Innovation. Vaxxilon plans to carry out initial trials with the new vaccines in humans within the next two years.
With the Enabling Innovation programme of the German Ministry of Education and Research (BMBF), Max Planck Innovation helps institutes to creatively analyze and optimize their innovative capacity. Institutes and their employees attend a workshop to discover what innovative capacity they already possess, identify hidden obstacles to innovation and develop more effective innovation strategies that will enable them to drive innovations more efficiently. The programme helps institutes to reliably analyze, evaluate and optimize their innovative capacity. The workshop was highly rated by institute scientists in 2016.
The new Expertise Meets Innovation (EMI) project was successfully launched on 1 March 2016 to promote spin-off projects. This project is based on a continuation of the BMBF promotional initiative Good Practice to Facilitate Spin-off Projects, which ran out in July 2015. The Industry Expert Method it encapsulates, which was found to be a highly effective promotional measure in the Good Practice Initiative, is now also being applied within the EMI project. The use of industry experts provides industry-specific know-how and expertise (market knowledge, industry-specific quality and development standards, etc.) to scientists in founding, licensing and patent projects. In 2016, eight external experts were deployed. They have so far successfully supported five projects.
In recent years, Max Planck Innovation has created several incubators with a view to validating inventions, some of which are derived from basic research carried out by the Max Planck Institutes, in accordance with the requirements of equity investors and therefore in a manner better tuned to the industry and the market. In 2016, the incubators once again produced a raft of positive developments.
Lead Discovery Center GmbH (LDC), which was set up in 2008 in Dortmund, is concerned with pharmaceutical research. It pursues projects based on research by the Max Planck Society and other research institutions right up to the lead-compound phase.
Since 2016, LDC and Boehringer Ingelheim have been working together to develop new approaches to the treatment of schizophrenia. For example, Max Planck Innovation and Boehringer Ingelheim International GmbH have signed an agreement giving Boehringer Ingelheim an exclusive option to license a new drug for the treatment of schizophrenia that is currently being developed at the LDC. The new approach is based on pioneering research findings by Professor Moritz Rossner and his team at the Max Planck Institute for Experimental Medicine in Göttingen. Professor Rossner is working closely with LDC to discover and optimize new therapeutic agents and develop them to the stage of a validated lead compound that is effective in in vivo models.
In addition, LDC has launched a cooperative agreement with UGISense AG for a new class of drugs. The two companies will collaborate to develop innovative compounds using the proprietary UgimerTM antisense platform. LDC has also acquired a minority interest in UGISense AG worth 1.2 million euros as part of an initial financing round via several private investors. The aim of the partnership is to combine the potential of the innovative Ugimer antisense platform with the drug-discovery expertise and target know-how of LDC to fully exploit the synergy effects and to jointly commercialize successful projects.
As part of the first grant project of the Canadian-German Grant Programme (based on a cooperation between the German Ministry for Economics and Energy and the CQDM consortium in Canada), LDC and McGill University in Montreal will receive $ 1 million in funding for joint drug discovery. Together, the teams at the two institutions plan to develop a new technology platform to identify drugs for diseases associated with faulty transport and folding of proteins. The cooperation will initially be funded over a period of three years.
In addition, LDC has entered into an industry partnership to carry out research into innovative drugs with Roche. The focus is on disease entities with an urgent medical need. Project ideas can come either from academic partners of LDC, including leading universities and institutes of the Max Planck Society and Helmholtz Association, or the Roche innovation network. The partners work closely to advance pharmaceutical projects from the idea stage – for example a new target structure – to the identification of a preclinical candidate. In the process, LDC will assume the function of an incubator for Roche, working closely with academic inventors and their institutions to advance new approaches in the field of low-molecular-weight substances.
Life Science Inkubator GmbH (LSI), which has been operating in Bonn since 2009 and in Dresden since 2013, incubates promising spin-off projects in the fields of biotechnology, pharmaceuticals and medical technology, supporting them to the stage of financial viability.
The following projects were in incubation in 2016:
The EPN project group is developing protein nanoparticles that make it possible to transport drugs effectively while minimizing side effects. EPN is currently in the LSI transfer.
The aim of the InfanDx project is to launch a test system for the early diagnosis of oxygen deficiency in newborn infants. It will enable doctors for the first time to unambiguously identify children who can be treated with the help of hypothermia.
A sensor technology under development at VesselSens allows doctors to detect recurrent vascular narrowing in a stent (restenoses) without invasive surgery. This not only minimizes the risk for patients but also reduces the number of surgical interventions required.
The NanoscopiX project group is developing special cooling chambers for fluorescence microscopy and spectroscopic analysis that operate at cryogenic temperatures as low as -263°C.
The team at ProDetekt is developing modern biomarker assays for biomedical research and in vitro medical diagnostics, particularly the highly sensitive and ultra-fast detection of target proteins and the early, reliable diagnoses of specific diseases.
The following companies have been spun off after successful incubation:
A drug delivery system developed by the VLP Group, now Neuway Pharma GmbH, is based on synthetically produced protein capsules that can be filled with specific drugs. The capsule proteins act like a GPS system: they find target cells and deliver their payload to them. In Wellington Partners, a reputable investor has been found not only for the starting and follow-on funding but also for active corporate development.
Bomedus GmbH is now successfully integrating the Small SFMS® technology incubated at LSI into an array of products. Small Fiber Matrix Stimulation® alters pain memory and leads to a lasting reduction in acute and chronic pain, significantly relieving pain associated with osteoarthritis of the knee and meniscus injuries.
EpiVios GmbH is developing a biomarker at LSI for the reliable early detection of prostate cancer.
Photonik Inkubator GmbH was founded in Göttingen in 2014. It offers company founders who have promising ideas an ideal environment for implementing them. Innovative research projects in the fields of photonics, optical technology and plasma mature here to marketable products.
Three projects were in incubation in 2016:
FiberLab: The team is developing a glass fibre that can simultaneously measure the temperature, expansion and three-dimensional shape as well as the refractive index of surrounding fluids. With a diameter of less than a quarter of a millimetre, the fibre has key advantages, particularly on the micro scale, e.g. in brain catheters. The sensors are insensitive to electrical and magnetic influences and, thanks to their high temperature resistance, can be sterilized. The project was successfully completed in December 2016. The spin-off is now being prepared.
SUPERLIGHT Photonics translates micro and nano LED technologies based on gallium nitride into products for sensory, analytical instruments and process technology. The main product for the planned start-up is a fluorescence-stimulating micro-LED platform measuring just a few millimetres across. Thanks to its high spatial and temporal resolution, it will open up new horizons in medical and biotechnology and biophotonics. However, the intelligently controlled structured lighting will also find applications in other fields, for example gas analysis, point-of-care diagnostics and materials analysis.
Patient Safety 4.0: Instances occasionally occur in intensive care medicine where the medications are incorrectly administered. Avoiding such errors by means of instrumental analysis is an important concern. The project aims to develop an automated analyzer to monitor long-term infusions via perfusor injection pumps in intensive care units as an aid for medical staff. The analyzer is being developed as a building block for checking medication in the intensive care setting and will support existing systems to improve quality management.
IT Inkubator GmbH was officially opened in Saarbrücken in March 2015. Ideas and inventions from research projects of the Saarbrücken informaticians and the Max Planck Society will be further developed on the university campus and then marketed for use.
IT incubator had the following projects in 2016:
Uvibo is a new approach from the field of machine learning for displaying dynamic web content that allows intuitive user interactions. Uvibo recognizes and learns users’ preferences and adapts to their specific interests. Content is suggested to users that interest them with the aim of reducing the bounce rate, i.e. the percentage of visitors to a particular website who navigate away from the site after viewing only one page.
HDR Everywhere is a new technology for easily creating high-quality HDR (high-dynamic-range) images with moving objects. High-contrast images that contain large brightness differences used to require special software and were very time-consuming. Particularly when taking photos of moving people, images are often marred by unwanted artefacts. The new technology provides a solution.
The K|Lens project set the stage for founding a new high-tech company by developing a first prototype for the photographic market. The prototype consists of an optomechanical component and the necessary software and is based on an optical technology developed and patented at the Max Planck Institute for Informatics and the University of Saarland. The finished product greatly expands the functions of today’s photographic cameras with interchangeable lenses by introducing three-dimensionality.
The new TripAround travel platform provides shareconomy for round trips. The platform shortens the preparation time for round trips by making user-generated tour reports and package round trips (which can be stored on multimedia) searchable and usable based on personal preferences. By automatically assigning multimedia data to a map, the platform visualizes travel experiences in a time-efficient and inspirational way.
Every year, Max Planck Innovation organizes a series of events with various partners. They are intended to promote links between science and industry and the translation of research findings into products.
The fourth Start-up Days event was held in 2016. The seminar series were organized by Max Planck Innovation GmbH together with the Fraunhofer Society, the Helmholtz Association and the Leibniz Association. They were well attended, attracting around 100 participants. The event, which is aimed at scientists from four non-academic research institutes who are interested in setting up a company, provides practical information and interdisciplinary experience on topics relevant to founding and financing a company. It does so through lectures, interactive workshops and reports by successful entrepreneurs. The Start-up Days also enable participants to exchange information with research institutions and others.
The tenth Biotech NetWorkshop, which was jointly hosted by Max Planck Innovation GmbH and Ascenion GmbH, was held in 2016 under the auspices of Max Planck Innovation at Ringberg Castle on Tegernsee. The workshop was aimed at scientists interested in setting up a company and existing life-science spin-offs from the Max Planck Society, the Helmholtz Association, the Leibniz Association and the University of Hanover. In the past decade, 130 experienced high-calibre, speakers from the life science sector held lectures on a wide range of topics. The key success factors are cross-ideas from speakers, for example Father Anselm Bilgri, the football referee Dr Markus Merk, the scientific journalist Ulrich Schnabel and former minister Dr Heiner Geissler. The programme contains specific networking elements, thanks to which the event has become firmly established over the past decade and is regularly booked out.
In 2016, Max Planck Innovation registered 121 inventions (2015: 139) and concluded 79 exploitation agreements (including agreements on joint inventions/technology transfer agreements) (2015: 71). Exploitation revenues are expected to reach 21.6 million euros (2015: 23.8 million euros). This includes residual proceeds payments of around 1.8 million euros (2015: 1.3 million euros) resulting from the sale of a company in 2015. The final figures for the 2016 financial year will not be available until mid-2017 due to the deferred accounting of a number of licensees.
Two new subsidiaries and a commercial MI profit-sharing company were founded in 2016. Several new subsidiaries and profit-sharing companies are at various advanced stages of negotiation. Three spin-off projects managed to secure funding for their pre-founding phase to the tune of several million euros from Go-Bio, the M4 Award and an EU technology and foundation preparation programme. In addition, a spin-off was launched through order financing. Another spin-off with Max Planck participation secured series B funding. Unfortunately, one company in which the MPG had an interest filed for bankruptcy in 2016. As at 31 December 2016, the MPG portfolio therefore comprised 16 active Max Planck subsidiaries, of which one was a commercial profit-sharing company.