Method and system for computational modeling and simulation applied to drug characterization and / or optimization

Abstract

To disclose a computational modeling and a simulation method applied to drug characterization and optimization.SOLUTION: A system (10) comprises a step of storing, on a computation platform 1: digital data D1 for modeling individual characteristics; digital data D2 for modeling animal characteristics; digital data D3 for modeling characteristics of a chemical and / or biological compound and / or drug; digital modeling data D4 of a biological object; and digital modeling data D5 of disease characteristics and / or a therapeutic area towards which the drug is directed.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates generally to the technical field of computational modeling and simulation by electronic processors / computers in the area broadly defined as "in silico clinical trials" or simply "in silico trials". [Background technology]

[0002] In particular, the present invention relates to methods and systems for computational modeling and simulation applied to drug research and development.

[0003] More particularly, the present invention relates to methods and systems for computational modeling and simulation applied to drug characterization and / or optimization.

[0004] The technical field of "in silico testing" relates to computational modeling and simulations carried out in the fields of pharmacology, medicine, or biology. The use of "in silico testing" is becoming more and more common as it is advantageous to complement, complete, or even replace experimental testing and evaluation.

[0005] The terms "drug characterization" and "drug optimization" refer to several aspects and / or stages of the drug research and development process, including, for example, testing of chemical and / or biological compound selection (or deselection), and preclinical and / or clinical testing.

[0006] Typically, these stages are sequential and distinct from the early stages of "discovery" (especially "high-throughput discovery"), although "discovery" as used herein is outside the primary application of the present invention.

[0007] In the more specific case of "in silico testing" for drug characterization and / or optimization, many complex aspects have to be taken into account, especially biological, pharmacological, physiological properties, etc. Evaluation of the basic properties of the chemical or biological compound, the mechanism of action, the biological target and / or the effect on physiological and organic responses in preclinical species and / or humans, characterization of the disease and / or therapeutic area, evaluation of the risk / benefit balance considering the disease to be treated, identification of adverse side effects, etc. are only some of the aspects that have to be deeply considered in drug characterization and / or optimization.

[0008] Computational modeling and simulation currently provide necessary and most important ongoing experimental support in drug characterization and / or optimization, lending help to single property aspects of the above.

[0009] Furthermore, known computational simulation software packages or programs are typically very complex and expensive, as well as very specific and purpose-specific, and their use also requires a combination of specialized medical science and IT skills (e.g., the operations controlling the numerous computational parameter settings are often related to clinical aspects).

[0010] In view of this, there is a need for computational modelling and simulation tools that are able to address drug research and development in a broader and more integrated way, in order to replace as far as possible and to support more widely and better experimental activities in the technical field of "in silico testing" for drug characterisation and / or optimisation.

[0011] At the same time, these computational modeling and simulation systems and methods need to be as simple as possible, usable, and easily accessible to all entities that may need them (not just large entities such as large clinical institutions or large pharmaceutical companies), and need to be adaptable to most likely cases.

[0012] In light of these considerations, there is an urgent need for a computing platform that allows for the creation of a sharing and collaborative working environment between different entities that may access the platform as providers of data and / or models and as consumers of modeling and / or simulation services, and this methodology is also useful in the aspects related to the present application.

[0013] No computational simulation solution known so far fully meets all the above-mentioned requirements needed for "in silico testing" for drug characterization and / or optimization. Summary of the Invention [Problem to be solved by the invention]

[0014] In view of the above considerations, the object of the present invention is to provide a method for computational modelling and simulation applied to the characterisation and / or optimisation of drugs, which makes it possible to at least partially avoid the drawbacks mentioned with reference to the prior art and which meets the above mentioned requirements, which are particularly felt in the technical field considered. [Means for solving the problem]

[0015] This object is achieved by the method according to claim 1.

[0016] Further embodiments of such a method are defined by claims 2-12.

[0017] The invention also relates to a computational modelling and simulation system applied to drug characterisation and / or optimisation, said system being defined in claim 13.

[0018] Further embodiments of the system are defined in claims 14-16.

[0019] Further characteristics and advantages of such a system and method according to the invention will become apparent from the following description of preferred exemplary embodiments, given as non-limiting examples with reference to the accompanying drawings, in which: [Brief description of the drawings]

[0020] [Figure 1] FIG. 1 is a simplified block diagram of a system for computational modeling and simulation applied to drug characterization and / or optimization according to an embodiment of the present invention; DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0021] With reference to FIG. 1, a method for computational modeling and simulation applied to the characterization and / or optimization (in individuals and / or animals) of at least one drug is described.

[0022] First, the method includes storing a first set of digital modeling data D1, a second set of digital modeling data D2, a third set of digital modeling data D3, a fourth set of digital modeling data D4, and a fifth set of digital modeling data D5 on a computing platform 1.

[0023] The first set D1 of digital modeling data includes data indicative of chemical, chemical-physical, biological, pharmacological, physiological, genetic, pharmacokinetic, pharmacodynamic and clinical characteristics of real and / or virtual individuals referring to one or more biological and / or organic and / or functional parts of the individual with which at least one drug is intended to interact, and / or data referring to one or more effects resulting from said interaction.

[0024] For example, the first set D1 of digital modeling data may include chemical and / or chemical-physical and / or biological and / or pharmacological and / or physiological and / or genetic and / or pharmacokinetic and / or pharmacodynamic and / or clinical data of a real and / or virtual individual referring to one or more biological and / or organic and / or functional parts of the individual with which at least one drug is intended to interact, and / or data referring to one or more effects resulting from such interaction.

[0025] Such data (also called "modal data") may be obtained, for example, as a result of the interaction between one or more molecules of a drug and an individual.

[0026] According to various possible embodiments of the method, the biological modal data may include, for example, data on the inhibition of the interleukin-6 protein on inflammatory processes or kinetic processes of antibodies acting against a vaccine. The pharmacological modal data may include data on the repulsive or inhibitory affinity of a chemical or biological compound to a biological object, or on drug-drug interaction data or on dose-response relationship data in a specific population. The physiological modal data may include blood pressure or creatinine levels or electrocardiogram data after drug administration. The genetic modal data may include data on effects caused by genetic polymorphisms of the enzyme CYP450 2D6, or by the P-glycoprotein efflux pump, or by specific mononucleotides. The pharmacodynamic modal data may include concentration data of chemicals or biological compounds in the systemic circulation or in tissues or organs. The pharmacodynamic and clinical modal data may include HERG2 (Human Epidermal Growth Factor Receptor 2) disease biomarker data, or NPS (Neuropathic Pain Scale) score data, or ADAS-Cog (Alzheimer's Disease Assessment Scale - Cognitive) score data.

[0027] The second set of digital modeling data D2 includes data indicative of chemical, chemical-physical, biological, pharmacological, physiological, genetic, pharmacokinetic, pharmacodynamic characteristics of one or more real and / or virtual animals referring to one or more biological and / or organic and / or functional parts of the animal on which at least one drug is intended to be tested, and / or data referring to one or more effects resulting from such interactions.

[0028] For example, the second set D2 of digital modeling data may include biological, pharmacological, physiological, genetic, pharmacokinetic, pharmacodynamic data of one or more real and / or virtual animals referring to one or more biological and / or organic and / or functional parts of the animal on which at least one drug is intended to be tested, and / or data referring to one or more effects resulting from such interactions.

[0029] Such data (also called "modal data") is obtained, for example, as a result of the interaction between one or more molecules of a drug and an animal.

[0030] The above mentioned examples of individuals also provide examples of biological, pharmacological, physiological, genetic and pharmacokinetic modal data that can be obtained for the characterization and optimization of drugs in animals.

[0031] With respect to the pharmacodynamic modal data in animals mentioned above, this may include, for example, survival data on the progression of mammary cancer in human epidermal growth factor receptor 2 (HER-2 / neu) transgenic mice, efficacy data of a drug on pain as assessed in the flick tail test, or QT prolongation data in dogs due to ion channel blockade by administration of a chemical or biological compound.

[0032] The third set of digital modeling data D3 includes data indicative of the chemical-physical properties and / or function and / or structure and / or behavior of chemical compounds and / or biological compounds and / or drugs selected for at least one drug research and development.

[0033] The fourth set of digital modeling data D4 includes data indicative of the chemical-physical properties and / or function and / or structure and / or behavior of a biological object selected for the development of at least one drug.

[0034] The fifth set of digital modeling data D5 includes data indicative of chemical, chemical-physical, biological, genetic, physiological, clinical, pharmacological, pharmacodynamic, and pharmacokinetic data related to one or more diseases and / or therapeutic areas for which the drug is intended.

[0035] According to different possible embodiments of the method, with reference to the above mentioned data of the fifth set of data D5, the chemical data may for example comprise data of molecular functional groups with specific mutagenic or genotoxic properties. The chemical-physical data may comprise data of vascular permeability in acute inflammatory conditions or data of gastric acidity in gastrointestinal disorders. The biological data may comprise data on the interrelationship between the mammary microbiome and malaria or data on the role of tumor necrosis factor alpha (TNF-α) in the pathology of psoriasis. The genetic data may comprise data on specific mutations of the BRCA1 and BRCA2 genes for forms of cancer of organs other than the ovary and breast. The physiological data may comprise data on environmental components leading to obesity. The pharmacological data may comprise data from xenograft studies involving liver cancer patients. The pharmacodynamic data may comprise data of lean muscle obtained from segmentation of CT images in sarcopenic patients. The pharmacokinetic data may comprise data on blood and urinary cortisol levels in rheumatic diseases or data on the conversion rate of the neurotransmitter serotonin in depressive disorders.

[0036] The method then includes a step of providing, by the computing platform 1, a user interface 4 connectable to the Internet and configured to enable a user to connect to and interact with the computing platform 1 and one or more software programs contained therein, and a step of receiving selection and / or definition and / or setting information I inputtable by the user via the user interface 4.

[0037] Such selection and / or configuration information I comprises information regarding the selection and / or definition and / or configuration of a pharmacological and / or physiological model, such as an individual pharmacological and / or physiological model based on said first stored set D1 of digital data and / or an animal pharmacological and / or physiological model based on said second stored set D2 of digital data.

[0038] The selection and / or configuration information includes information I2 regarding the selection and / or definition and / or configuration of a chemical and / or pharmacological and / or biological and / or therapeutic system model. Such a chemical and / or pharmacological and / or biological and / or therapeutic system may include both the pharmacokinetic and / or pharmacological and / or physiological and / or clinical data mentioned above, and chemical and / or biological compounds and / or drugs, and biological subjects and / or diseases. Thereby, the model of the chemical and / or pharmaceutical and / or biological and / or therapeutic system is based on the first stored set D1 and / or the second stored set D2 and / or the third stored set D3 and / or the fourth stored set D4 and / or the fifth stored set D5 of the digital modeling data mentioned above, and can thus be considered as an indication of the chemical, physical, pharmacological, biological, genetic, pharmacological, physiological, clinical characteristics of the chemical and / or therapeutic system.

[0039] The selection and / or setting information further includes information I3 regarding the selection and / or definition and / or setting of a screening and / or optimization model based on the third stored set D3 and / or the fourth stored set D4 and / or the fifth stored set of digital modeling data, and also includes selection and setting information I4 of a simulation type, and / or selection and setting information I5 of one or more input simulation parameters, and selection and setting information I6 of one or more output simulation parameters.

[0040] The method then includes a step of processing, using the computational platform 1, information I1 relating to the selection and / or definition and / or setting of a pharmacological and / or physiological model to develop a pharmacological and / or physiological model M1 based on the above-mentioned first stored set D1 and / or second stored set D2 of digital modeling data.

[0041] According to some possible embodiment methods, the pharmaceutical model M1 may consist of a model describing the distribution and clearance of a drug whose pattern is target-mediated, or may consist of a model identifying the relationship between the levels of analgesics in the systemic circulation and their effect on reducing chronic pain in a population of cancer patients.

[0042] According to some possible embodiment options of the method, the physiological model M1 may consist of a model describing the concentration of a drug in the systemic circulation as a function of the expression level of metabolic enzymes and organ development to calculate the dosage of such a drug to be administered to a pediatric patient having specific characteristics of age, weight and sex, or a model describing the pharmacological effect of blocking the P-glycoprotein transporter on the distribution and pattern of a particular drug.

[0043] The method then includes a step of processing, by the computational platform 1, information I3 relating to the selection and / or definition and / or configuration of a chemical and / or pharmacological and / or biological and / or therapeutic system model to develop a chemical and / or pharmacological and / or biological and / or therapeutic system model M2 based on the first stored set D1 and / or the second stored set D2 and / or the third stored set D3 and / or the fourth stored set D4 and / or the fifth stored set D5 of digital modeling data as mentioned above.

[0044] According to different possible embodiment options of the method, the above-mentioned model M2 of a chemical and / or pharmaceutical and / or biological and / or therapeutic system may refer to a chemical system that assigns the absolute configuration of a chiral compound based on the analysis of molecular vibrational circular dichroism spectra, and / or to a pharmacological system that describes the distribution of a drug between blood and / or plasma, cerebrospinal fluid and the central nervous system, and / or to a biological system that represents the immune system (B cells and plasma cells, cytotoxic T cells, dendritic cells, macrophages, antibodies, cytokines) and possible interactions with tumor cells and / or vaccines, and / or to a therapeutic system regarding the nutritional status of a patient integrating lean muscle mass, medical history, results of a QoL questionnaire and nutritional recommendations.

[0045] The method then includes processing, using a computing platform, information I3 relating to the selection and / or definition and / or configuration of a screening and / or optimization model to develop a screening and / or optimization model M3 based on the above-mentioned fifth stored set D5 of digital modeling data and based on the above-mentioned third set D3 and / or fourth set D4 of digital data.

[0046] According to different possible embodiment options of the method, the above-mentioned screening and / or optimization model M3 may be a model adapted to identify patients with a genetic profile of interest for a particular clinical trial, or a model adapted to identify possible relationships between adverse and / or toxic side effects of compounds and / or biological compounds of interest and biological targets that constitute part of their mechanism of action.

[0047] The screening and / or optimization model M3 may include search algorithms and / or artificial intelligence algorithms adapted to identify and connect the functions and / or structures and / or behaviors of chemical compounds and / or biological compounds and / or drugs and / or biological targets and / or diseases relevant to the development of at least one drug.

[0048] The method then includes processing, using the computing platform 1, the selection and / or configuration information I entered by the user to define input configuration data Din (dependent on I4, I5) for one or more computational modeling and simulation software programs included in the computing platform.

[0049] The method then includes a step of performing computational modeling and simulation using one or more computational modeling and / or simulation software programs based on the above-mentioned input setting data Din, the above-mentioned pharmacological and / or physiological model M1, the chemical and / or pharmacological and / or biological and / or therapeutic system model M2, and the screening and / or optimization model M3, to obtain computational simulation output data Dout.

[0050] Finally, the method includes a step of processing the output data Dout of the computational simulation based on information I6 relating to the selection and setting of one or more output simulation parameters, to represent the requested simulation results R in a format selected by the user, and a step of providing such requested simulation results by means of a user interface 4.

[0051] The simulation results R include information suitable for identifying and / or connecting the functions and / or structures and / or behaviors of chemical compounds and / or biological compounds and / or drugs and / or biological targets and / or diseases relevant to the development of at least one drug.

[0052] The above-mentioned "digital models" M1, M2, M3 may, for example, comprise structured digital data sets suitable for digitally representing each of the above-mentioned entities, which may be manipulated or processed by a computational simulation software program or package.

[0053] The method may be run on a computational simulation software program or package known per se, such as, for example, NONMEM®, Monolix, PK-SIM, MATLAB®, etc.

[0054] According to an embodiment of the method, the step of providing a user interface includes providing a plurality of user-selectable templates associated with each type of simulation, each of which includes a plurality of selectable input parameters for the simulation, each parameter associated with a respective range of acceptable values ​​suitable for the feasibility of the simulation within which the parameter value can be set, a plurality of selectable output parameters including quantities requested as output results, and a plurality of user-selectable display and reporting options for choosing a format of the results.

[0055] The input and output parameters mentioned above depend on the requirements and type of simulation being performed.

[0056] In this embodiment, templates can be defined in the most versatile ways, with regard to the selection of input and output parameters of the simulation and their relative tolerance intervals, and with regard to the display and reporting of the results, which allows easier management of the simulation by the user.

[0057] According to one embodiment of the method, the user-enterable selection and / or setting information I further comprises parameters for the definition and refinement (i.e. for the definition and / or refinement) of the pharmacological and / or physiological model M1, parameters for the definition and refinement (i.e. for the definition and / or refinement) of the chemical and / or pharmacological and / or biological and / or therapeutic system model M2, and / or parameters for the definition and customization (i.e. for the definition and customization) of the algorithm of the optimization model M3 using artificial intelligence. The user-enterable selection and / or setting information I further comprises parameters for the selection and / or definition (i.e. for the selection and definition) of a real or virtual patient or a population of real or virtual patients, and / or parameters for the configuration of the computational aspects of the simulation (i.e. for the configuration).

[0058] According to various possible embodiment options, the user-enterable selection and / or configuration information I includes initial and boundary conditions for the simulation and / or parameters related to numerical and / or analytical methods used by the modeling and / or computational simulation software.

[0059] According to an embodiment, the method further comprises obtaining digital modeling data of pharmacological and / or physiological models and / or digital modeling data of chemical and / or pharmacological and / or biological and / or therapeutic and / or screening and / or optimization models by selecting from a plurality of pharmacological and / or physiological digital models and / or chemical and / or pharmacological and / or biological and / or therapeutic and / or screening and / or optimization models stored in the digital library 2 of the computing platform 1 and / or preloaded on the computing platform by a user. The method also comprises obtaining digital modeling data D1 comprising biological, pharmacological, physiological, genetic, pharmacokinetic, pharmacodynamic and clinical data of real and / or virtual individuals by selecting from a plurality of digital models of real or virtual patients stored in the digital library 2 of the computing platform 1 and / or preloaded on the computing platform by a user.

[0060] In this embodiment, the method is applied to a large number of models that may be stored or preloaded in a digital library and thus may be known per se.

[0061] In certain embodiments of the method, the digital modeling data of the real individual is anonymized and / or de-identified and / or pseudonymized.

[0062] According to some possible embodiment options of the method, the computational modeling and simulation includes modeling and simulation of biological objects, and / or chemical compounds, and / or biological compounds, and / or drugs.

[0063] The method can be applied in combination with a number of computational simulations (belonging to the above mentioned categories), characterized by the most diverse complexity, procedures, number of iterations, number and type of computational modeling and simulation programs, etc. Below, we explicitly present some important examples of computational modeling and simulations included in the method of the invention.

[0064] According to one embodiment of the method, the modeling and computational simulation includes modeling and simulation for characterization and / or optimization of the at least one drug as described above, and / or simulation for analysis and prediction of the behavior of the at least one drug in a population of real or virtual patients, and / or simulation for individualized evaluation of the effect of the at least one drug in a particular real or virtual patient, and / or simulation for evaluation of safety, efficacy, and / or compliance with current safety and / or efficacy regulations.

[0065] According to one embodiment of the method, the computational modeling and / or simulation further includes simulation for analysis and prediction of the behavior of one or more drugs on a population of real or virtual animals, and / or simulation for customized assessment of the effect of one or more drugs on a particular real or virtual animal.

[0066] According to another embodiment of the method, the modeling and computational simulation includes modeling and simulation for the design and / or development of chemo-physical and / or pharmacological and / or biological properties of one or more chemical compounds, and / or for evaluation of safety and / or efficacy and / or compliance with existing safety and / or efficacy regulations.

[0067] According to further embodiments of the method, the computational modeling and simulation includes modeling and simulation for the analysis and / or identification and / or characterization of biological objects for research and / or evaluation of safety and / or efficacy.

[0068] According to another embodiment of the method, the modeling and computational simulation includes a search algorithm operating on the digital modeling data.

[0069] According to an embodiment of the method, the software simulation programs or packages used to perform some of the above-mentioned simulations may include a set of artificial intelligence-based processing solutions known per se, provided by major suppliers of this type of software solutions (e.g., Microsoft, Google, Amazon, etc.).

[0070] Referring again to FIG. 1, a system 10 for computational modeling and simulation applied to the characterization and / or optimization of at least one drug is described, comprising a computational platform 1.

[0071] The computing platform includes at least one digital library 2 and one or more electronic processing components 3 on which one or more software programs or applications (S1-S7) are stored and executable.

[0072] Digital library 2 stores a first set of digital modeling data D1, a second set of digital modeling data D2, a third set of digital modeling data D3, a fourth set of digital modeling data D4, and a fifth set of digital modeling data D5.

[0073] The first set D1 of digital modeling data includes biological, pharmacological, physiological, genetic, physiological, pharmacokinetic, pharmacodynamic, and clinical data (also referred to as "modal data") of real and / or virtual individuals referring to one or more biological and / or organic and / or functional parts of the individual with which at least one drug is intended to interact, and / or data referring to one or more effects resulting from the aforementioned interactions.

[0074] The second set of digital modeling data D2 includes biological, pharmacological, genetic, physiological, pharmacokinetic, pharmacodynamic data (also referred to as "modal data") of one or more real and / or virtual animals referring to one or more biological and / or organic and / or functional parts of the animal on which at least one drug is intended to be tested, and / or data referring to one or more effects resulting from such interactions.

[0075] The third set of digital modeling data D3 includes data indicative of the chemical-physical properties and / or function and / or structure and / or behavior of chemical compounds and / or biological compounds and / or drugs selected for at least one drug research and development.

[0076] The fourth set of digital modeling data D4 includes data indicative of the chemical-physical properties and / or function and / or structure and / or behavior of a biological object selected for drug development.

[0077] The fifth set of digital modeling data D5 includes data indicative of chemical, chemical-physical, biological, physiological, clinical, pharmacological, genetic, pharmacodynamic, and pharmacokinetic data related to one or more diseases and / or therapeutic areas for which the drug is intended.

[0078] The one or more electronic processing components 3 mentioned above are configured by one or more software programs or applications (S1-S7) stored and executed on the one or more electronic processing components 3 to perform the following operations: providing a user interface 4 connectable to the Internet and configured to allow a user to connect to and interact with the digital data processing platform 1 and the one or more software programs contained therein, and then receiving selection and / or setting information I that can be input by the user via the user interface 4. Such selection and / or setting information includes information I1 on the selection and / or definition and / or setting of pharmaceutical and / or physiological models, information I2 on the selection and / or definition and / or setting of chemical and / or pharmacological and / or biological and / or therapeutic system models, information I3 on ​​the selection and / or definition and / or setting of screening and / or optimization models, information I4 on the selection and / or setting of a simulation type, and / or information I5 on the selection and setting of one or more simulation input parameters, and information I6 on the selection and setting of one or more simulation output parameters. Further details of such selection and / or setting information are exemplified above in the context of the description of the method according to the invention.

[0079] One or more electronic processing components 3, by means of one or more software programs or applications (S1-S7), carry out further processing aimed at preparing a number of digital models, namely: processing information I1 relating to the selection and / or definition and / or configuration of a pharmacological and / or physiological model to develop a pharmacological and / or physiological model M1 based on said first and second sets D1, D2 of digital modeling data; and processing information I2 related to the selection and / or definition and / or configuration of a chemical and / or pharmacological and / or biological and / or therapeutic system model M2 for developing a chemical and / or pharmacological model M2 based on the first stored set D1 and / or the second stored set D2 and / or the third stored set D3 and / or the fourth stored set D4 and / or the fifth stored set D5 of digital modeling data. Additionally, processing information I3 relating to the selection and / or definition and / or configuration of the screening and / or optimization model based on the fifth stored set D5 of digital modeling data and based on the third stored set D3 and / or the fourth stored set D4 of digital data to generate a screening and / or optimization model M3; wherein such screening and / or optimization model M3 may comprise search algorithms and / or artificial intelligence algorithms suitable for identifying and connecting functions and / or structures and / or behaviors of chemical compounds and / or biological compounds and / or drugs and / or biological objects and / or diseases relevant for the development of at least one drug.

[0080] The one or more electronic processing components 3 mentioned above, by means of one or more software programs or applications S1-S7, perform the following operations: processing the selection and / or configuration information I entered by the user to prepare input configuration data Din (depending on I4, I5) for one or more computational simulation and modeling software programs S5 included in the computational platform 1; Thereafter, obtaining modeling and / or computational simulation output data Dout using one or more computational simulation software programs S5 based on the input configuration data Din, based on the pharmaceutical and / or physiological model M1, and based on the chemical and / or pharmacological and / or biological and / or therapeutic system model M2; Finally, processing the modeling and / or computational simulation output data Dout based on the information I6 regarding the selection and configuration of one or more modeling and / or simulation output parameters to report the requested simulation results R in a format selected by the user; and providing the requested modelling and / or simulation results by means of a user interface 4; The simulation results R include information suitable for identifying and / or characterizing and / or relating functions and / or structures and / or behaviors of chemical compounds and / or biological compounds and / or drugs and / or biological objects and / or diseases relevant to drug development.

[0081] According to one embodiment of the system 10, the one or more software programs or applications (S1-S7) of the computing platform described above include: one or more user interface management software programs S4; one or more computational modeling and / or simulation software programs S5 configured to perform modeling and computational simulations when executed by a computer; The following steps (1)-(5) (1) processing information relating to the selection and / or definition and / or configuration of a pharmacological and / or physiological model; (2) processing information relating to the selection and / or definition and / or configuration of a chemical and / or pharmacological and / or biological and / or therapeutic system model; (3) processing information regarding the selection and / or definition and / or configuration of a screening and / or optimization model; (4) processing the selection and / or setting information entered by the user to generate input setting data Din (depending on I4, I5) for the computational model and / or simulation software program; and (5) Processing the output data Dout of the computational model and / or simulation to report the requested simulation results R in a format selected by the user. one or more processing software programs (S1, S2, S3, S4, S6) configured to execute Includes.

[0082] According to an embodiment option, the computing platform 1 further comprises a software program S7 of the PIDO type (Process Integration and Design Optimization) configured to manage the flow processes of the software programs contained in the computing platform and to optimize the computational modeling and / or simulation.

[0083] With reference to the above-mentioned software programs included in the system, the most diverse options known per se can be considered for the implementation, partitioning, storage and execution of such software programs, either as individual programs or as a package of programs and / or software modules interacting with each other.

[0084] From an infrastructure point of view, several options are possible for the practical implementation of the system: Among these, centralized or distributed platforms based on one or more interacting servers and computers are conceivable.

[0085] For example, the system may be implemented using a distributed cloud computing platform.

[0086] According to a further embodiment, the system is configured to perform a method according to any one of the method embodiments described above.

[0087] According to an embodiment, one or more software programs S1, S4, S5 may be configured to perform steps of processing information relating to the definition and establishment of a pharmacological model in a particular animal species.

[0088] As is apparent from the description, the objects of the present invention are fully achieved by the above-mentioned method and system by virtue of their functional and structural features.

[0089] Indeed, due to the above-mentioned features, the computational modeling and simulation methods of the present invention may support clinical trial / testing activities in the field of pharmaceutical research and development in a more effective and integrated manner, increasing and expanding the role of computational modeling and simulation in this field (which may thus provide advantages in terms of time and cost reduction and performance improvement in pharmaceutical development).

[0090] Furthermore, due to the processing performed by the provided computing platform and user interface (as detailed above), the computational simulation method can be used in a simple manner and is easily accessible to anyone who has access to the platform (if appropriately authorized). The user interface offers a wide range of possibilities for personalization and adaptation of the modeling and / or simulation, while at the same time providing guidance and facilitating the set-up of the modeling and / or simulation.

[0091] Furthermore, the above mentioned features make it possible to create a shared and collaborative working environment between different entities having access to the platform, acting as digital data and / or model providers and / or requesting modelling and / or simulation services, thereby making the methodology effective in application aspects as well.

[0092] Similar advantages can be seen with reference to the above-mentioned systems capable of carrying out the methods of the invention.

[0093] In order to satisfy the attendant needs, those skilled in the art can make several modifications, adjustments and adaptations to the embodiments of the system and method according to the invention and can replace the elements with functionally equivalent alternatives without departing from the scope of protection of the following claims. Each of the features described as belonging to a possible embodiment can be achieved independently of the other embodiments described.

Claims

1. 1. A method for computational modeling and simulation applied to the characterization and optimization of at least one drug, comprising the steps of: storing on a computer platform (1) a first set of digital modeling data (D1) comprising chemical, chemical-physical, biological, pharmacological, physiological, genetic, pharmacokinetic, pharmacodynamic, and clinical data of real and / or virtual individuals referring to one or more biological and / or organic and / or functional parts of the individuals with whom at least one drug is intended to interact, and / or data referring to one or more effects resulting from such interactions; storing on said computer platform (1) a second set of digital modeling data (D2) comprising biological, pharmacological, genetic, physiological, pharmacokinetic, pharmacodynamic data of one or more real and / or virtual animals referring to one or more biological and / or organic and / or functional parts of the animal in which said at least one drug is intended to be tested, and / or data referring to one or more effects resulting from the test interaction; storing on said computer platform (1) a third set of digital modeling data (D3) indicative of the chemico-physical properties and / or function and / or structure and / or behavior of said at least one chemical compound and / or biological compound and / or drug selected for drug research and development; storing on said computer platform (1) a fourth set (D4) of digital modeling data indicative of the chemophysical properties and / or function and / or structure and / or behavior of said at least one biological object selected for drug research and development; storing on said computer platform (1) a fifth set of digital modeling data (D5) indicative of chemical, chemical-physical, biological, genetic, physiological, clinical, pharmacological, pharmacodynamic, and pharmacokinetic data related to one or more diseases and / or therapeutic areas for which said at least one drug is intended; providing, by said computer platform (1), a user interface (4) connectable to the Internet and configured to allow a user to connect to and interact with the computing platform (1) and one or more software programs contained therein; A step of receiving user-inputtable selection and / or definition and / or setting information (I) using the user interface (4), wherein the selection and / or setting information includes the following (A) to (D): (A) information (I1) relating to the selection and / or definition and / or setting of a pharmacological and / or physiological model, comprising parameters for the refinement of said pharmacological and / or physiological model, said pharmacological and / or physiological model comprising an individual pharmacological and / or physiological model based on said first stored set of digital modeling data (D1) and / or an animal pharmacological and / or physiological model based on said second stored set of digital modeling data (D2); (i) information (I2) regarding the selection and / or definition and / or configuration of a chemical and / or pharmacological and / or biological system model based on the first stored set (D1), and / or based on the second stored set (D2), and / or based on the third stored set (D3), and / or based on the fourth stored set (D4), and / or based on the fifth stored set (D5) of digital modeling data, the information being indicative of chemical, chemo-physical, pharmacological, biological, genetic, physiological properties of the chemical and / or pharmacological and / or biological system, the information regarding the selection and / or definition and / or configuration of the chemical and / or pharmacological and / or biological system model including parameters for the refinement of the chemical and / or pharmacological and / or biological system model; (c) Information regarding the selection and / or definition and / or configuration of a screening and / or optimization model, including parameters for customizing a computational model algorithm using artificial intelligence (I3); and (d) Information regarding the selection and setting of a simulation type (I4), and / or information regarding the selection and setting of one or more input simulation parameters (I5), and information regarding one or more output simulation parameters (I6). and - using said computing platform (1) to process information relating to the selection and / or definition and / or configuration of said pharmacological and / or physiological model, including said parameters for the refinement of said pharmacological and / or physiological model, to develop a pharmacological and / or physiological model (M1) based on said first stored set of digital modeling data (D1) and / or said second stored set of digital modeling data (D2); using the computing platform (1) to process information (I2) related to the selection and / or definition and / or configuration of the chemical and / or pharmacological and / or biological system model, including the parameters for the refinement of the chemical and / or pharmacological and / or biological system model, to develop a chemical and / or pharmacological and / or biological system model (M2) based on the first stored set of digital modeling data (D1), and / or based on the second stored set of digital modeling data (D2), and / or based on the third stored set of digital modeling data (D3), and / or based on the fourth stored set of digital modeling data (D4), and / or based on the fifth stored set of digital modeling data (D5); using said computing platform (1) to process information (I3) related to the selection and / or definition and / or configuration of said screening and / or optimization model, including said parameters for customizing a computational model algorithm using artificial intelligence, to develop a screening and / or optimization model (M3) based on said fifth stored set (D5) of digital modeling data and / or based on said third stored set (D3) of digital modeling data and / or based on said fourth stored set (D4) of digital modeling data, said screening and / or optimization model (M3) comprising search algorithms and / or artificial intelligence algorithms suitable for identifying and connecting functions and / or structures and / or behaviors of chemical compounds and / or biological compounds and / or drugs and / or biological objects and / or diseases relevant to said development of said at least one drug; processing, using said computing platform (1), said user input selections and / or configuration information (I) to define input configuration data (Din) for one or more computational simulation software programs included in said computing platform (1); using the one or more computational simulation software programs (S5) to perform one or more simulations based on the input configuration data (Din), based on the pharmacological and / or physiological model (M1), based on the chemical and / or pharmacological and / or biological system model (M2), and based on the screening and / or optimization model (M3), to obtain output data (Dout) of the computational modeling and / or simulation; - processing the output data (Dout) of the computational modeling and / or simulation based on information (I6) relating to the selection and configuration of one or more output modeling and / or simulation parameters to report requested modeling and / or simulation results (R) in a format selected by the user, the simulation results (R) including information tending to identify and / or characterize and / or connect the function and / or structure and / or behavior of chemical compounds and / or biological compounds and / or drugs and / or biological objects and / or diseases relevant to the development of the at least one drug; providing said requested modeling and / or simulation results using said user interface (4); Including, method.

2. The step of providing a user interface includes presenting a plurality of user-selectable templates associated with respective simulation types, each template comprising: a plurality of selectable input parameters for the simulation, each parameter associated with a respective range of acceptable values ​​suitable for the feasibility of the simulation, within which a parameter value can be set; a plurality of selectable output parameters containing quantities requested as output results; a plurality of user-selectable display and reporting options for selecting a format for the results. The method of claim 1.

3. The user-enterable selection and / or setting information (I) includes: parameters for the purpose of selecting and / or defining a real or virtual patient or a population of real or virtual patients; and / or parameters aimed at setting up the computational aspects of the simulation, and / or initial and boundary conditions for performing computational modeling and simulation; and / or Parameters related to the numerical methods used by the computational simulation software further comprising:

3. The method according to claim 1 or 2.

4. obtaining digital modeling data of pharmacological and / or physiological models, and / or digital modeling data of chemical and / or pharmacological and / or biological and / or therapeutic systems, and / or digital modeling data of screening or optimization models by selecting from a plurality of pharmacological and / or physiological digital models, and / or chemical and / or pharmacological and / or biological systems, and / or screening or optimization models stored in a digital library (2) of said computing platform (1) and / or preloaded on said computing platform (1) by said user; obtaining digital modeling data (D1) comprising biological, pharmacological, genetic, physiological, pharmacokinetic, pharmacodynamic, and clinical data of real and / or virtual individuals by selecting from a plurality of digital models of real or virtual patients stored in a digital library (2) of said computing platform (1) and / or preloaded on said computing platform (1) by said user, The method according to any one of claims 1-3.

5. the digital modeling data of real individuals is anonymized and / or de-identified and / or pseudonymized; The method according to any one of claims 1 to 4.

6. The computational modeling and / or simulation includes modeling and / or simulation of biological objects, chemical compounds, biological compounds, and / or drugs. The method according to any one of claims 1 to 5.

7. The computational modeling and simulation modelling and / or simulation for the characterisation and / or optimisation of said at least one drug; and / or Modeling and / or simulation for the analysis and prediction of the behavior of at least one drug in a real or virtual patient population; and / or modeling and / or simulation for the individualized assessment of the effect of said at least one drug in a particular real or virtual patient; and / or including modeling and / or simulation for the assessment of safety, effectiveness, and / or compliance with current safety and / or effectiveness regulations; The method according to any one of claims 1 to 6.

8. The computational modeling and simulation further includes modeling and / or simulation for analyzing and predicting the behavior of one or more drugs in a population of real or virtual animals and / or for customized assessment of the effects of one or more drugs in a particular real or virtual animal. The method of claim 7.

9. said computational modelling and / or simulation including modelling and / or simulation for the design and / or development of one or more chemical compounds, and / or for the analysis and prediction of the chemo-physical and / or pharmacological and / or biological properties of one or more chemical compounds, and / or for the assessment of safety and / or efficacy and / or compliance with existing safety and / or efficacy regulations; The method according to any one of claims 1 to 8.

10. The computational modeling and / or simulation includes modeling and / or simulation for the analysis and / or identification and / or characterization of biological objects for research and / or safety and / or efficacy assessment; and / or the computational modeling and / or simulation includes a search algorithm operating on the digital modeling data; The method according to any one of claims 1 to 9.

11. A system (10) for computational modeling and simulation applied to the characterization and optimization of at least one drug, comprising a computing platform (1) and one or more electronic processing components (3), said computing platform comprising: a first set of digital modeling data (D1) including chemical, chemical-physical, biological, pharmacological, physiological, genetic, pharmacokinetic, pharmacodynamic, and clinical data of a real and / or virtual individual that refers to one or more biological and / or organic and / or functional parts of the individual with which at least one drug is intended to interact, and / or data that refers to one or more effects resulting from such an interaction; a second set of digital modeling data (D2) comprising biological, pharmacological, genetic, physiological, pharmacokinetic, pharmacodynamic data of one or more real and / or virtual animals referring to one or more biological and / or organic and / or functional parts of the animal on which the at least one drug is intended to be tested, and / or data referring to one or more effects resulting from the test interaction; a third set of digital modeling data (D3) indicative of the chemico-physical properties and / or function and / or structure and / or behavior of the chemical and / or biological compounds and / or drugs selected for the at least one drug research and development; a fourth set of digital modeling data (D4) indicative of the chemophysical properties and / or function and / or structure and / or behavior of the at least one biological object selected for drug development; a fifth set of digital modeling data (D5) indicative of chemical, chemical-physical, biological, physiological, clinical, pharmacological, genetic, pharmacodynamic, and pharmacokinetic data related to one or more diseases and / or therapeutic areas for which the at least one drug is intended; and a digital library (2) storing The one or more electronic processing components (3) perform the following operations by means of one or more software programs or applications (S1-S6) stored and executed on the one or more electronic processing components (3), namely: providing, by said computer platform (1), a user interface (4) connectable to the Internet and configured to allow a user to connect to and interact with the digital data computing platform (1) and one or more software programs contained therein; A step of receiving selection and / or setting information (I) that can be input by the user using the user interface (4), the selection and / or setting information including the following (A) to (D): (A) information (I1) relating to the selection and / or definition and / or setting of a pharmacological and / or physiological model, comprising parameters for the refinement of said pharmacological and / or physiological model, said pharmacological and / or physiological model comprising an individual pharmacological and / or physiological model based on said first stored set of digital modeling data (D1) and / or an animal pharmacological and / or physiological model based on said second stored set of digital modeling data (D2); (i) information (I2) regarding the selection and / or definition and / or configuration of a chemical and / or pharmacological and / or biological system model based on the first stored set (D1), and / or based on the second stored set (D2), and / or based on the third stored set (D3), and / or based on the fourth stored set (D4), and / or based on the fifth stored set (D5) of digital modeling data, the information being indicative of chemical, chemo-physical, pharmacological, biological, genetic, physiological properties of the chemical and / or pharmacological and / or biological system, the information regarding the selection and / or definition and / or configuration of the chemical and / or pharmacological and / or biological system model including parameters for the refinement of the chemical and / or pharmacological and / or biological system model; (c) Information regarding the selection and / or definition and / or configuration of a screening and / or optimization model, including parameters for customizing a computational model algorithm using artificial intelligence (I3); and (D) Information regarding the selection and configuration of a modeling and / or simulation type (I4), and / or information regarding the selection and configuration of one or more input modeling and / or simulation parameters (I5), and information regarding the selection and configuration of one or more output modeling and / or simulation parameters (I6). and - processing information relating to the selection and / or definition and / or configuration of said pharmacological and / or physiological model, including said parameters for the refinement of said pharmacological and / or physiological model, to develop a pharmacological and / or physiological model (M1) based on said first stored set of digital modeling data (D1) and / or said second stored set of digital modeling data (D2); processing information (I2) related to the selection and / or definition and / or configuration of the chemical and / or pharmacological and / or biological system model, including the parameters for the refinement of the chemical and / or pharmacological and / or biological system model, to develop a chemical and / or pharmacological and / or biological system model (M2) based on the first stored set of digital modeling data (D1), and / or based on the second stored set of digital modeling data (D2), and / or based on the third stored set of digital modeling data (D3), and / or based on the fourth stored set of digital modeling data (D4), and / or based on the fifth stored set of digital modeling data (D5); processing information (I3) related to the selection and / or definition and / or configuration of said screening and / or optimization model, including the parameters for customizing a computational model algorithm using artificial intelligence, to develop a screening and / or optimization model (M3) based on said fifth stored set of digital modeling data (D5) and / or based on said third stored set of digital modeling data (D3) and / or based on said fourth stored set of digital modeling data (D4), wherein said screening and / or optimization model (M3) includes search algorithms and / or artificial intelligence algorithms that tend to identify and connect function and / or structure and / or behavior of chemical compounds and / or biological compounds and / or drugs and / or biological objects and / or diseases relevant to said development of said at least one drug; processing the selection and / or configuration information (I) entered by the user to prepare input configuration data (Din) for one or more computational modeling and / or simulation software programs included in the computing platform (1); performing one or more modeling and simulations using the one or more computational modeling and / or simulation software programs (S5) based on the input configuration data (Din), based on the pharmacological and / or physiological model (M1), based on the chemical and / or pharmacological and / or biological systems model (M2), and based on the screening and / or optimization model (M3) to obtain output data (Dout) of the computational modeling and / or simulation; - processing the output data (Dout) of the computational modeling and / or simulation based on information (I6) regarding the selection and configuration of one or more output modeling and / or simulation parameters to report requested simulation results (R) in a format selected by the user, the simulation results (R) including information tending to identify and / or characterize and / or connect functions and / or structures and / or behaviors of chemical compounds and / or biological compounds and / or drugs and / or biological objects and / or diseases relevant to the development of the at least one drug; providing said requested modeling and / or simulation results using said user interface (4); Including, system.

12. The one or more software programs or applications (S1-S7) of the computing platform (1) one or more user interface management software programs (S4); one or more computational modeling and / or simulation software programs (S5) configured, when executed by a computer, to perform said computational modeling and / or simulation; one or more software processing programs (S1, S2, S3, S4, S6), - processing information (I1) relating to the selection and / or definition and / or setting of said pharmacological and / or physiological model; processing information (I2) relating to the selection and / or definition and / or configuration of said chemical and / or pharmacological and / or biological model; - processing information (I3) relating to the selection and / or definition and / or configuration of the screening and / or optimization model; processing the user-entered selection and / or configuration information (I) to prepare input configuration data (Din) for the computational modeling and / or simulation software program; and processing the output data (Dout) of the computational modeling and / or simulation to report requested modeling and / or simulation results (R) in a format selected by the user; and a software processing program (S1, S2, S3, S4, S6) configured to execute the The system (10) according to claim 11.

13. the computing platform (1) comprises a software program (S7) of the PIDO (Process Integration and Design Optimization) type, configured to manage the flow processes of the software programs contained in the computing platform (1) and to optimize the computational simulations; and / or The system is implemented by a distributed cloud computing platform. The system of claim 12.

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