The “Development of a Diagnostic Platform on microRNAs in oncology” project, acronym “SPID” is part of the public tender for the creation of Patent valorization programs through the financing of Proof of Concept (PoC) projects of Italian Universities, of the Italian Public Research Bodies (EPR) and the Scientific Hospitalization and Care Institutes (IRCCS) to be financed as part of the National Recovery and Resilience Plan (PNRR), Mission 1 “Digitalization, innovation, competitiveness, culture and tourism ” - Component 2 “Digitalization, innovation and competitiveness in the production system” – Investment 6 “Industrial property system” financed by the European Union – NextGenerationEU.

Over the last few years, the research activity of the Istituti Fisioterapici Ospitalieri (IFO) has produced numerous and significant contributions in the context of translational research projects involving various tumor pathologies. Projects which, starting from the molecular characterization of the tissues of cancer patients, have as their final target the transfer of the information acquired from the patient's bedside to the laboratory and from the laboratory to the patient's bedside.

Among the fundamental objectives we highlight: the promotion of interdisciplinary projects involving different scientific skills aimed at guaranteeing results with clear clinical implications on cancer patients; a high quality level of scientific publications and access to competitive funding.

Interdisciplinarity in the field of medical-scientific Research is essential to identify the main clinical needs and to develop the best research strategies aimed at identifying new prognostic and/or predictive biomarkers, or new therapeutic associations for personalized tumor therapy.

The innovative diagnostics, based on biomarkers present in biological liquids, in addition to having significant clinical repercussions in a relatively short time, has the great advantage of having a significant impact on the National Health System, since, presenting itself as non-invasive, well tolerated and, therefore, widely usable spectrum in the population, allows us to significantly reduce costs and guarantee the general well-being of citizens.

The focus of this project does not, however, concern only the phase of conception and clinical validation of diagnostic tests but also their transfer to the industrial sector, combining the sector of collaborations with that of Intellectual Property, this allowing the results of the Scientific research at the market.

The Technology Transfer, collaboration and involvement strategy of the entrepreneurial system is developed according to the following trajectories:

1. Identify, on the basis of predefined objective criteria, which are the most important patents present in the institutional portfolio;
2. Monitor the most monitored technological areas and the use of patented technology on products;
3. Update the drivers of the patenting strategy (geographical areas, technological areas);
4. Understand which patents are suitable for licensing;
5. Understand the monetary value of the patent portfolio held.

Given the above, the main objectives of the project are:

• Design a global workflow that is able to start from a discovery of biomarker-pathology correlation (consolidated within a patent) to a diagnostic assay stage that can be proposed to the market;
• Demonstrate the validity and effectiveness of this workflow through the development of 2/3 research studies to be carried from the patenting phases to the CE-IVD assay phases;
• Bring the candidate patents, having a TRL (Technology Readiness Level) equal to 4/5 at project initiation, to a suitable market entry level (TRL 6/7). This path will allow us to achieve better freedom to operate in terms of technologies to be used for analysis, without any violation of previous rights and/or patents.

The operational plan envisages bringing the three candidate patents from the discovery and patenting phase to the market. The proposed pathway will be validated on a larger cohort of patients and implemented with the technologies necessary to create clinical-grade kits suitable for commercial development.

These are the patents selected and nominated in the project:

• Method for the in vitro diagnosis of mucositis in cancer patients undergoing anti-tumor therapy;
• MicroRNAs as biomakers for the in vitro diagnosis of glioma;
• MiRNA for the treatment and in vitro diagnosis of drug-resistant tumors.

c) Analisi di correlazione (AC): corrisponde alla validazione analitica e statistica dei risultati ottenuti dal VC con il calcolo dei vari indicatori di Validazione Analitica del test: Accuratezza, Sensitività Analitica, Specificità Analitica, Precisione.

d) Attività di standardizzazione (ADS): dovrà identificare e formalizzare il protocollo di azioni da svolgere per effettuare la richiesta per l’apposizione della label CE al prodotto per garantire la conformità con tutti i requisiti pertinenti a livello dell'UE.

e) Attività di Industrializzazione (ADI): dovrà identificare:

1. le azioni da compiere per l’implementazione del saggio in un “kit” diagnostico commercializzabile;
2. identificare la società in grado di realizzare il kit;
3. mettere a punto le componenti contrattuali necessarie allo sviluppo di tutte le fasi.

The actions to be undertaken for the valorization of patents are divided into the following operational plan:

a) Standardization of procedures: starting from the results obtained in the discovery phase, the biotechnological analysis technologies are confirmed or modified to guarantee compliance with a pre-identified range of reproducibility, robustness, as well as cost parameters. The result of this phase will be a Standard Operating Protocol (SOP).

b) Clinical Validation (VC) of the patent: has the function of comparing the information on the pathological condition that can be acquired from the test being evaluated which is the subject of the patent, with that obtainable from the diagnostic reference standard for that condition. The actions necessary to carry out this phase are the following:

1. identification of a cohort of patients/controls and evaluation of their “statistical power”;
2. preparation of the documentation to be issued to patients (Informed Consent) and that to be presented for approval by an Ethics Committee;
3. taking a sample of the matrix (blood, urine, or saliva, depending on the test);
4. execution of the procedures required by the SOPs for the analysis of biomarkers from the matrix;
5. acquisition of the reference standard diagnostic data on the patient.

c) Correlation Analysis (AC): corresponds to the analytical and statistical validation of the results obtained from the VC with the calculation of the various Analytical Validation indicators of the test: Accuracy, Analytical Sensitivity, Analytical Specificity, Precision.

d) Standardization activities (ADS): must identify and formalize the protocol of actions to be carried out to make the request for the affixing of the CE label to the product to ensure compliance with all relevant requirements at EU level.

e) Industrialization Activities (ADI): must identify:

1. the actions to be taken for the implementation of the assay in a marketable diagnostic "kit";
2. identify the company capable of producing the kit;
3. develop the contractual components necessary for the development of all phases.