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Definition of Translational Medicine
Translational medicine aims at bringing together different disciplines, resources, expertise and technical know-how. In this way it facilitates the development and improvement of health promotion, prevention, diagnosis, therapy and rehabilitation. Essential elements of translational medicine are the combination of basic research with the practical application of research results in patient care. A much used definition of translational medicine explains its purpose as “an interdisciplinary branch of the biomedical field supported by three main pillars: benchside, bedside, and community” [1].ù
Establishing a Close Integration of Stakeholders from Industries, Clinics, and Academia as well as the Involvement of Relevant Legal Bodies and Normative Authorities
Moving new drug candidates from preclinical research into human studies and the approved drug is only approximately 0.1% [2], and major causes are the lack of effectiveness and poor safety profiles unpredicted in preclinical and animal studies. Translating a basic discovery into a potential drug candidate or biomarker that is ready to be tested in humans is a complicated, time-consuming process that requires collaboration between the academic scientists who make discoveries and clinicians. Translational research thus aims to apply fundamental knowledge gained from basic research activities to the human condition. However, translational research is more challenging and costlier to conduct than basic research since with animals and humans it involves complex organisms [3].
Yet this collaboration can make it difficult for universities to engage in translational projects, taking into account that such projects can often be significantly harder to plan than more traditional research projects. Transformative research may require more flexible timeframes and resources. Budgeting and timetabling may be done robustly when there is substantial existing knowledge about the chosen methods and fields of application, but in the absence of such knowledge, parameters are harder to set [4]. It appears that an efficient collaboration between the different stakeholders in a research project of translational medicine is essential.
The WHO’s Best Practices in Clinical Trial Transparency and the Dichotomy of Traditional Practice: Publish and Patent an Invention or Exploit it Under the Regime of Secrecy
States grant patents and the exclusivity in the exploitation in the patented invention in return for the publication of the invention. The inventor, in turn, has the possibility to apply for a patent or – if he prefers to keep his invention secret – to exploit the invention under the regime of secrecy. The latter does not give him exclusivity. This means that, for example, if another person makes an identical invention, he cannot prevent that person from exploiting the invention. However, the public interest in medical research seems to limit the inventor’s possibility to keep his research, which may lead to the invention, in another important manner.
The WHO found that a significant proportion of operators of clinical trials never make their results public. The WHO found that the non-publication results to a waste of research, leading to a duplication of research [5]. Thus European medical research funders should require grantees to register and report clinical trials in line with WHO best practices. It was found that the prospective registration and publication of outcomes of all clinical trials constitute a global ethics requirement set out by the World Medical Association Declaration of Helsinki [6]. Accordingly, it would become necessary to design laws and regulations to ensure the existence of public health programs and the need to train data scientists and the need to access both data and new knowledge [7].
Yet the publication of the outcome of clinical trials has not only positive effects. I will make everybody aware of the subjects of research and testing which is done at research institutions – at least at those receiving support from research funders applying WHO best practices which oblige research institutions in their programs and agreements to apply these practices.
But the high costs of the financing of research in the medical fields may have a disciplinary effect: New innovation models for drug discovery are emerging in response to high costs, duplication of efforts, and diminishing levels of product development. Many of these new models emphasize collaboration between academia, government, industry, nongovernmental organizations, and patient organizations on the basis of the principle that no one entity can itself do most of the R&D needed to develop a new drug or therapy [8].
An Open Innovative Model for Translational Medicine
ince 2000 there are successful types of cooperation developed in the field of translational medicine as so-called PPP (public private partnerships), funded largely by government, philanthropic foundations, and large multinaional companies [9]. For example, the Sitem-Insel, set up in 2019 in the Swiss capital Bern as a national competence centre for translational medicine may qualify as an exemplary PPP. Its task is to bring research to patients quickly and at the highest quality. Doctors, engineers and regulatory experts for medical devices work closely together. From 2019 to 2022 projects supported by the Sitem-Insel led to 28 patent applications, more than 980 scientific articles and the award of some 190 educational diplomas. The Sitem-Insel has some 450 employees [10]. With its research at the interface of medicine, economics and law, the professorship for regulatory issues in healthcare, located at sitem-insel, builds important competencies and contributes to the creation of effective and lean structures for translation.
Importance of Patents in Translational Research
The relevance of the patent system attaches at different stages of the process of translational research and the development of innovations for clinical use. At the research stage it may be useful to undertake a patent search in oder to identify inventions which are patented and therefore excluded from an exploiting use. Additionally, a global patent search can be useful to identify the state of the art in the field the researcher aims to work in. If the field is already covered by patents it is unlikely that the researcher can find sufficient finance for his research. In fact, this approach does not differ much from research in other fields which may have an outcome of patentable inventions. Thus the patent search will provide information on published inventions already in use and on inventions actually protected by patents. From the fields to which publications relate it may also be inferred the level which level of research which competitors achieved.
Patented inventions may create difficulties for translational researchers. It is difficult to decide when it is appropriate and necessary to investigate intellectual property issues and to establish which patents apply and with whom to negotiate licenses, given that this requires a significant investment. Although it may not be necessary to actually negotiate licenses with patent holders until innovative research reaches clinical use, it may then be too late for the investigation of the existing patents impinging on the provision of a clinical service or the commercialization of an invention. Significant effort will have been invested in the research and it is inappropriate, if at this point, it is discovered that appropriate license arrangements cannot be negotiated, or if there is significant delay. Also, a researcher who has not obtained a patent license at this stage will not be in a strong bargaining position to negotiate a competitive license fee [11].
Translational research projects may therefore familiarize researchers with patent law. European research programs may envisage services covering different aspects such as regulation, commercialisation, drug development, intellectual property, patenting and industrial collaborations. Funded projects may include the development of decision making regarding strategic aspects of projects’ organizational tasks such as patenting and the protection by intellectual property [12].
Health related partnerships may have difficulties, even when successful, in accessing resources to further advance innovations. These hurdles consist also in searching a way to market through patenting and licensing spin-offs in collaboration with firms [13]. Therefore a close collaboration between researchers and those familiar with legal issues relating to IP and patenting as well as licensing is important. This could establish a fundamental contribution of translational research for the implementation of public policies and institutional models that produce fertile conditions for the generation and diffusion of innovations in health [14]. Thus safeguarding intellectual property and licensing terms of patent rights are critical for the success of an open innovation model which may involve different players such as public institutions, foundations, universities and pharmaceutical companies [15].
Avoiding the Infringement of Existing Patents During the Research Stage
At the research stage patents become relevant when the invention created by translational research enters the stage of commercialization and when diagnostic testing is done at clinics [16]. Researchers should be aware that the use of technologies can lead to infringements of existing patents and the risk of patent litigation. Researchers and their employers risk not only the payment of damages for patent infringement, additionally, media reports may cause damage to the career of researchers.
Yet at the research stage this risk is relatively low due to the fact that national patent laws generally provide for the so-called experimental use exception from the exclusivity of the patent right. For example, Article 68 of the Italian Code of Industrial Property provides that the exclusive right granted by a patent does not extend to acts carried out in an experimental manner; to studies and experiments aimed at obtaining, also in foreign countries, an authorization for the placing on the market of a drug; or to the consequent practical fulfillments thereof, including the preparation and use of pharmacologically active raw materials strictly necessary for such purpose.
According to this experimental use exemption, it is allowed to use patented inventions to the extent that the research work is finalized. The mere application of a patented product is instead not permitted, but research and its use for improving the invention is permissible [17]. The difference between improving and applying a patented product is determined by observing objectively the type of experiments actually performed by the unauthorized patent user. With this regard the purpose which the researcher aims at with the use, remains irrelevant. Thus clear definitions and awareness of when, and how, the research exemptions apply, are necessary.
If the intended use of the patented invention does not fall within the research exemption, patent licenses may have to be negotiated. Still the risk for researchers to be pursued for patent infringement remains relatively low. This is because patentees may fear a bad press and a bad publicity if they act against researchers. But another factor may be more relevant: even if a patentee may be able to obtain an injunction to stop the use of the patented invention against the researcher, it is unlikely that he will obtain a substantial amount of damages. The infringing use is limited to the research stage and therefore the use of the patented invention will not have caused profits or gains affecting the patent holder’s property.
Patenting Inventions and Exploitation Strategies as Creative Strategies
Concerning their own inventions resarchers in translational medicine should be aware of the commercial value which the patenting of their inventions may assume. This issue is not particularly typical of translational research. Since there are different academic fields involved, it may be necessary to institutionalise joint discussions. Within this context a creative management of patent rights facilitates the development of malleable structures responsive to the pace of change in industry, including the downsizing of research and development in large pharmaceutical companies and increasing translational activity in academia [18]. What is required is a recalibration of how intellectual property rights are used, supported by evidence based on measures that capture the complexity of a networked research and development environment.
Some Italian Projects Concerning Translational Medicine
There are numerous projects in Italy which promote translational medicine and which foster the use of intellectual property.
CITT (Milan)
In October 2023 the foundation Human Technopole’s Centre for Innovation and Technology Transfer (CITT), Milan, and Nature Italy hosted a conference on Future Trends in Translational Medicine [19]. Flight Science Communications reported on the conference [20]: Efficient collaboration among researchers, clinicians, and industry partners is crucial to rapidly translate discoveries into clinical applications. “We are very good at doing research and publishing papers, but we need to motivate and raise awareness in young researchers of the importance of transferring scientific results from laboratories to market and society,” said Fabio Terragni, member of the management committee delegate for technology transfer at Human Technopole.
Set up by the Italian government in 2018, Human Technopole is a research foundation located in Milan, Italy. Its mission is to conduct basic research in the life sciences, promoting people’s health and well-being. The Human Technopole’s Centre for Innovation and Technology Transfer, set up in 2020, is providing entrepreneurial training to Italian scientists and hosting national and international networking events involving academic organizations, public bodies and industry, to capture the value of Italian research. The massive data collections applied by AI supports projects of translational medicine in particular concerning the identification of the state of available technologies, whether patented or not, but also with regard to extract useful information from complex multidimensional data.
DiMET (Novara)
The Dipartimento di Medicina Traslazionale (DiMET) at Novara was set up in 2012. Its research activities relate to “translate” new knowledge from basic sciences to biomedical science, in order to generate advanced diagnostic or therapeutic applications, also offering new investigative tools. Technology transfer belongs to its missions [21].
DISMET (Napoli)
The DISMET (Department of Translational Medical Science) was founded by professors from the Departments of Internal Medicine, Pediatrics and Pediatric Surgery and Clinical Pathology of the University “Federico II”. The Department aims at promoting the transfer of knowledge from basic science to clinical practice for patients of all ages. The Department provides answers to the new requests from the scientific community interested in the translational research and in the technology transfer and applications in the biomedical field. The main feature of the research is a multidisciplinary approach to the study of the molecular basis of hereditary, metabolic, endocrine, cardiovascular, gastroenterological, rheumatologic, pneumological, neurological, oncologic, infectious and immunologic diseases [22].
The Department coordinates the PhD course in Clinical and Experimental Medicine. The training activities promote the application of biotechnology and molecular technologies in medicine. Within the Department operate the Interdepartmental Centre for Research in Basic and Clinical Immunological Sciences (CISI) and the Inter-University Center “European Laboratory for the Investigation of Food Induced Diseases” (ELFID).
IFT (Rome)
The Italian National Research Council’s (CNR) Institute of Translational Pharmacology aims at accelerating the translation of basic research discoveries in biology and medicine into novel therapeutics and diagnostics tools [23]. It is the mission of scientists working at the IFT to contribute to the process of accelerating the translation of basic research discoveries in biology and medicine into novel therapeutics and diagnostics tools.
The IFT serves as a territorial strategic resource for the development of advanced biomedical research and particularly for the development of the pharmaceuticals sector on the regional and national territory. This propensity is documented by a high number of active patents in which researchers of IFT act as inventors. Thus 44 international patents in different countries were active in the 2011-2014 period. Most of them refer to new drug candidates, but some refer to innovative methods for differentiation/maturation of progenitor cells, to new uses of already approved drugs or to the use of new biologically active therapeutics. Activities of technology transfer has been also achieved by past and present participation of IFT to spin-off companies.
INF-ACT(Pavia)
The INF-ACT consortium is composed of 25 research Institutions from the public and the private sector from all over Italy: One Health Basic and Translational Actions Addressing Unmet Needs on Emerging Infectious Diseases (INF-ACT). The INF-ACT research program addresses pressing unmet needs of human emerging infectious diseases in both fundamental as well as in translational aspects [24].
Education and Translational Medicine
Many universities offer courses in translational medicine, for example, the Sant’Anna School of Advanced Studies in Pisa [25], the University of Insubria [26], the University of Milan, the University of Pavia [27], the University of Bologna [28], the University of Padova [29], the University of Verona [30], or the University Sapienza of Rome [31].
