Activity-based enzyme inventory management

Abstract

The present invention relates to a computer-implemented method for activity-based enzyme preparation management of an enzyme preparation, comprising (i) receiving input data of at least one storage segment data defined by at least the temperature and storage duration of the enzyme preparation and an initial enzyme activity value, preferably via an input unit (10); (ii) determining, in particular calculating, a residual activity value of the enzyme preparation based on the storage segment data and the initial enzyme activity value, via a processing unit (20); (iii) providing the residual activity value of the enzyme preparation, preferably via an output unit (30), and (iv) managing the enzyme preparation based on the residual activity value of step (iii), the management preferably comprising at least one of the following: - providing a dosage recommendation based on the residual activity value of the enzyme preparation, preferably via the output unit (30); - providing an indicator of the remaining shelf life of the enzyme preparation based on the residual activity value of the enzyme preparation; - automatically adjusting the dosage of the enzyme preparation by controlling an application device; and / or - placing an order for a batch of the enzyme preparation if the residual activity value indicates that the total enzyme activity in the enzyme preparation is below a predetermined threshold value. The present invention also relates to a device for activity-based enzyme preparation management of an enzyme preparation, comprising: an input unit (10) configured to receive data input, the input unit is preferably a user interface, wherein the data input includes storage segment data defined by at least the temperature and duration of the enzyme preparation and an initial enzyme activity value; a processing unit (20), preferably a processing unit comprising at least one processor, the processing unit being configured to determine, specifically calculate the residual activity value of the enzyme preparation based on the storage segment data and the initial enzyme activity value, specifically by programming; and an output unit (30), which is configured to output the residual activity value of the enzyme preparation to a user and / or a data interface; and a system comprising the device. The present invention further relates to methods, computer programs, data carriers and uses related to the above-mentioned methods, devices and systems.

Description

Technical Field

[0001] The present invention relates to a computer-implemented method for activity-based enzyme preparation management of an enzyme preparation, comprising (i) preferably receiving input data of at least one storage segment data defined by at least the temperature and storage duration of the enzyme preparation and an initial enzyme activity value via an input unit; (ii) determining, specifically calculating, a residual activity value of the enzyme preparation based on the storage segment data and the initial enzyme activity value via a processing unit; (iii) preferably providing the residual activity value of the enzyme preparation via an output unit, and (iv) managing the enzyme preparation based on the residual activity value of step (iii), the management preferably comprising at least one of the following: - preferably providing a dosage recommendation based on the residual activity value of the enzyme preparation via the output unit; - providing a remaining shelf life indicator of the enzyme preparation based on the residual activity value of the enzyme preparation; - automatically adjusting the dosage of the enzyme preparation by controlling a dosing device; and / or - placing an order for a batch of the enzyme preparation if the residual activity value indicates that the total enzyme activity in the enzyme preparation is below a predetermined threshold. The present invention also relates to a device for activity-based enzyme preparation management of an enzyme preparation, comprising: - an input unit, which is configured to receive data input, the input unit is preferably a user interface, wherein the data input includes storage segment data defined by at least the temperature and duration of the enzyme preparation and the initial enzyme activity value; - a processing unit, preferably including at least one processor, the processing unit is configured to determine, specifically calculate the residual activity value of the enzyme preparation based on the storage segment data and the initial enzyme activity value by programming; and - an output unit, which is configured to output the residual activity value of the enzyme preparation to a user and / or a data interface; and to a system comprising the device. The present invention further relates to methods, computer programs, data carriers and uses related to the above-mentioned methods, devices and systems. Background Art

[0002] Inactivation of enzymes, particularly heat inactivation, may be caused by a variety of mechanisms, such as denaturation, aggregation or dissociation into subunits. For this reason, several enzyme stability models have been established in the art, such as in Sant'Anna et al. (2013) Bioprocess Biosyst Eng 36:993, Martinus & Boekel (2002), Int J Food Microbiol 74 (1-2): 139; Brown 1987), Australian J Botany 35 (5): 581, and as discussed in EPSchokker, PhD, Thesis, University of Wageningen, 1997.

[0003] Nevertheless, enzymes degrade when stored, especially at temperatures above the recommended storage temperature. In addition, especially on an industrial scale, enzyme products may be exposed to unfavorable storage conditions during transport and / or storage (e.g. unplanned lengthy customs processes, failures in cooling technology, unplanned interruptions in the logistics chain). In all these cases, the only way to determine whether the product is still saleable or usable is to retest the activity. However, a problem associated with this is that warehouses are usually not equipped and employees are not qualified to carry out sample testing. Since the product can still be used even when the initially specified minimum activity is not reached, it is desirable that the residual activity of the enzyme preparation (depending on the storage conditions) is known or foreseeable if a defined overdose compared to the original formulation can be applied. Summary of the invention

[0004] Therefore, there is a need in the art to provide reliable means and methods for the activity-based management of enzyme preparations. In particular, there is a need to provide means and methods that at least partially avoid the disadvantages of the prior art as described above.

[0005] This problem is solved by a method, a device, a system and a use having the features of the independent claims. Preferred embodiments are listed in the dependent claims, which can be realized in isolation or in any combination.

[0006] Therefore, the present invention relates to a computer-implemented method for activity-based enzyme preparation management of an enzyme preparation, comprising

[0007] (i) receiving input via an input unit of at least one storage section data defined by at least the temperature and storage duration of the enzyme preparation and an initial enzyme activity value;

[0008] (ii) determining, specifically calculating, a residual activity value of the enzyme preparation based on the storage segment data and the initial enzyme activity value via a processing unit;

[0009] (iii) providing a residual activity value of the enzyme preparation, preferably via an output unit; and

[0010] (iv) managing the enzyme preparation based on the residual activity value of step (iii).

[0011] The method of the present invention may include steps other than those steps explicitly mentioned above. For example, further steps may relate to, for example, specific steps for managing enzyme preparations or combinations of such steps, preferably as indicated in the claims and / or embodiments herein. Preferably, the method preferably includes an automatic comparison step before performing steps (ii) and (iii), wherein the comparison step includes comparing the temperature and / or storage duration value with the corresponding predefined values, wherein steps (ii) and (iii) are performed according to the result of the comparison step, preferably, wherein steps (ii) and (iii) are performed only when the temperature and / or storage duration exceed the corresponding predefined values. Preferably, the method is used for any process using a specific enzyme activity (e.g., for enzyme application), such as a laundry process, such as in a washing machine, a dishwasher or an industrial washing machine, in food (e.g., milk or meat) processing, animal feed processing, biofuel production, leather production, textile production, pulp and paper industry, beverage production, enzyme chemical production processes, particularly in the "white" chemical industry.

[0012] In addition, the method can be carried out before the step of establishing the enzyme stability model, for example by providing a method for the stability model for the enzyme preparation, the method comprising the steps of (I) storing aliquots of the enzyme solution at at least three different values ​​of at least one storage parameter, preferably storage temperature, (II) determining the residual enzyme activity in the aliquots at at least two different time points after the start of storage, (III) preferably as described below, preferably based on the Arrhenius equation and / or based on the Weibull model, modeling the values ​​of the different time points and storage parameters into a stability model, and thus (IV) providing the stability model. In addition, the data from the stability model can be provided in a database, preferably tangibly embedded in a data carrier, including an identification code for at least one enzyme preparation and the parameters assigned thereto at least required for determining the residual activity value of the enzyme preparation. As will be appreciated by those skilled in the art, the above-mentioned method for providing the stability model preferably precedes the computer-implemented method for the management of enzyme preparations based on activity, and is also preferably performed only once to establish the model, and preferably, includes the required parameters stored in the above-mentioned database.

[0013] With reference to computer-implemented aspects of the present invention, one or more method steps, preferably all method steps, can be performed according to the method for one or more embodiments disclosed herein by using a computer or a computer network. Therefore, any method step that generally includes providing and / or manipulating data can be performed by using a computer or a computer network. Generally, these method steps can include any method step, generally except the method step that needs manual work, such as providing sample and / or performing some aspect of the actual measurement of enzyme activity.

[0014] Specifically, it is further disclosed herein that:

[0015] A computer or a computer network comprising at least one processor, wherein the processor is adapted to execute the method according to one of the embodiments described in this specification,

[0016] A computer-loadable data structure adapted to execute a method according to one of the embodiments described in this specification while the data structure is executed on the computer,

[0017] A computer program, wherein the computer program is adapted to perform a method according to one of the embodiments described in this specification when the program is executed on a computer,

[0018] A computer program comprising program means for executing a method according to one of the embodiments described in this specification while the computer program is executed on a computer or a computer network,

[0019] A computer program comprising a program component according to the aforementioned embodiment, wherein the program component is stored on a computer-readable storage medium,

[0020] A storage medium, wherein a data structure is stored on the storage medium, and wherein the data structure is suitable for executing a method according to one of the embodiments described in the present description after having been loaded into a main storage device and / or a working storage device of a computer or a computer network, and

[0021] A computer program product with program code means, wherein the program code means can be stored or stored on a storage medium for executing a method according to one of the embodiments described in this description, if the program code means is executed on a computer or on a computer network.

[0022] The apparatus and method according to the invention have several advantages over known methods of enzyme preparation management based on activity. Using a computer-implemented method, preferably automatically obtaining storage segment data, such as via a network, can allow analysis of large amounts of complex input data and can provide fast, reliable and accurate results.

[0023] As used hereinafter, the terms "having", "comprising" or "including" or any of their arbitrary grammatical variations are used in a non-exclusive manner. Therefore, these terms can refer to the situation where, in addition to the features introduced by these terms, there are no other features in the entity described in the present context, and can also refer to the situation where one or more other features are present. As an example, the expressions "A has B", "A contains B" and "A includes B" can all refer to the situation where, in addition to B, there are no other elements in A (i.e., the situation where A is composed solely and only of B), and the situation where, in addition to B, there are one or more other elements in the entity A (such as element C, element C and D or even other elements).

[0024] Furthermore, as used hereinafter, the terms "preferably", "more preferably", "most preferably", "particularly", "more particularly", "specifically", "more specifically" or similar terms are used in conjunction with optional features without limiting further possibilities. Therefore, the features introduced by these terms are optional features and are not intended to limit the scope of the claims in any way. As will be appreciated by those skilled in the art, the present invention may be implemented by the use of alternative features. Similarly, the features introduced by "in an embodiment" or similar expressions are intended to be optional features, without any limitation on further embodiments of the invention, without any limitation on the scope of the invention, and without any limitation on the possibility of combining the features introduced in this manner with other optional or non-optional features of the invention.

[0025] As used herein, unless otherwise specified, the term "about" refers to an indicated value with a technical accuracy generally accepted in the relevant field, preferably involving an indicated value of ±20%, more preferably ±10%, and most preferably ±5%. In addition, the term "substantially" indicates that there is no deviation that has an impact on the indicated result or use, that is, the potential deviation will not cause the indicated result to deviate by more than ±20%, more preferably ±10%, and most preferably ±5%. Therefore, "substantially consisting of..." means including the specified components, but not including other components, except for materials present as impurities, unavoidable materials present due to the process for providing these components, and components added for purposes other than achieving the technical effects of the present invention. For example, a composition defined using the phrase "substantially consisting of..." includes any known acceptable additives, excipients, diluents, carriers, etc. Preferably, a composition consisting essentially of a group of components will contain less than 5% by weight of non-specific components, more preferably less than 3% by weight, even more preferably less than 1%, and most preferably less than 0.1% by weight.

[0026] As used herein, the term "enzyme" includes, but is not limited to, any type of biomacromolecule having an activity as specified below. The enzyme is preferably a polypeptide or a nucleic acid, preferably RNA or DNA. More preferably, the enzyme is a polypeptide. Preferably, the enzyme is non-thermostable.

[0027] In particular embodiments, the enzyme is an oxidoreductase (EC 1), a transferase (EC 2), a hydrolase (EC 3), a lyase (EC 4), an isomerase (EC 5), or a ligase (EC 6) (EC numbering according to the Enzyme Nomenclature, Recommendations of the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (1992), including supplements thereto published from 1993 to 1999).

[0028] More preferably, the enzyme is a hydrolase (EC 3), preferably a glycosidase (EC 3.2) or a peptidase (EC 3.4). Particularly preferred enzymes are selected from the group consisting of amylases (particularly α-amylases (EC 3.2.1.1)), cellulases (EC 3.2.1.4), lactases (EC 3.2.1.108), mannanases (EC 3.2.1.25), lipases (EC 3.1.1.3), phytases (EC 3.1.3.8), nucleases (EC 3.1.11 to EC 3.1.31) and proteases (EC 3.4); in particular enzymes selected from the group consisting of amylases, proteases, lipases, mannanases, phytases, xylanases, phosphatases, glucoamylases, nucleases and cellulases, preferably amylases or proteases, preferably proteases. Most preferred are serine proteases (EC 3.4.21), preferably subtilisin.

[0029] In particularly preferred embodiments, the following proteins of interest are preferred:

[0030] Protease

[0031] Enzymes with proteolytic activity are called "proteases" or "peptidases". Proteases are active proteins that exert "protease activity" or "proteolytic activity". Proteases are members of the EC 3.4 class. Proteases include aminopeptidases (EC 3.4.11), dipeptidases (EC 3.4.13), dipeptidyl peptidases and tripeptidyl peptidases (EC 3.4.14), peptidyl dipeptidases (EC 3.4.15), serine carboxypeptidases (EC 3.4.16), metallocarboxypeptidases (EC 3.4.17), cysteine ​​carboxypeptidases (EC 3.4.18), omega peptidases (EC 3.4.19), serine endopeptidases (EC 3.4.21), cysteine ​​endopeptidases (EC 3.4.22), aspartate endopeptidases (EC 3.4.23), metalloendopeptidases (EC 3.4.24), threonine endopeptidases (EC 3.4.25), endopeptidases of unknown catalytic mechanism (EC 3.4.99). Commercially available proteases include, but are not limited to, Lavergy TM Pro (BASF); Duralase TM 、Durazym TM , Ultra, Ultra, Ultra, Ultra, and (Novozymes A / S), under the trade name Prime, Purafect Purafect Purafect and (Danisco / DuPont), Axapem TM Products sold include Protease® (Gist-Brocases NV), Bacillus lentus alkaline protease, and KAP (alkaliphilic Bacillus subtilisin) from Kao.

[0032] At least one subtilisin may have SEQ ID NO: 22 as described in EP 1921147, or a variant thereof which is at least 80%, at least 90%, at least 95% or at least 98% identical to SEQ ID NO: 22 as described in EP 1921147 and has proteolytic activity. In one embodiment, the subtilisin is at least 80%, at least 90%, at least 95% or at least 98% identical to SEQ ID NO: 22 as described in EP 1921147 and is characterized in having an amino acid glutamic acid (E), or aspartic acid (D), or asparagine (N), or glutamine (Q), or alanine (A), or glycine (G), or serine (S) at position 101 (according to BPN' numbering) and has proteolytic activity. In one embodiment, the subtilisin is at least 80%, at least 90%, at least 95% or at least 98% identical to SEQ ID NO:22 described in EP 1921147 and is characterized in that it has the amino acid glutamic acid (E) or aspartic acid (D), preferably glutamic acid (E), at position 101 (according to BPN' numbering) and has proteolytic activity.

[0033] Methods for determining proteolytic activity are well known in the literature (see, e.g., Gupta et al. (2002), Appl. Microbiol. Biotechnol. 60: 381-395). Proteolytic activity can be determined by using succinyl-Ala-Ala-Pro-Phe-p-nitroanilide (Suc-AAPF-pNA, referred to as AAPF; see, e.g., DelMar et al. (1979), Analytical Biochem 99, 316-320) as a substrate. pNA is cleaved from the substrate molecule by proteolytic cleavage, resulting in the release of yellow free pNA, which can be quantified by measuring OD405.

[0034] Amylase

[0035] α-Amylase (EC 3.2.1.1) enzymes can endohydrolyze (1->4)-α-D-glycosidic bonds in polysaccharides containing three or more (1->4)-α-linked D-glucose units. Other examples of amylases include: β-amylase (EC 3.2.1.2), glucan 1,4-α-maltotetraose hydrolase (EC 3.2.1.60), isoamylase (EC 3.2.1.68), glucan 1,4-α-maltohexaosidase (EC 3.2.1.98), and glucan 1,4-α-maltohydrolase (EC 3.2.1.133). Commercially available amylases include: Duramyl TM TermamylTM 、Fungamyl TM 、Stainzyme TM 、Stainzyme Plus TM 、Natalase TM , Liquozyme X and BAN TM (from Novozymes A / S) and Rapidase TM 、Purastar TM 、Powerase TM 、Effectenz TM (M100 from DuPont), Preferenz TM (S1000, S110 and F1000; from DuPont), PrimaGreen TM (ALL; DuPont), Optisize TM (DuPont).

[0036] Lipase

[0037] "Lipase", "lipolytic enzyme", "lipid esterase" all refer to enzymes of EC class 3.1.1 ("carboxylic ester hydrolase"). Lipases (EC 3.1.1.3, triacylglycerol lipases) can hydrolyze triglycerides into more hydrophilic mono- and diglycerides, free fatty acids, and glycerol. Lipases generally also include enzymes that have activity on substrates other than triglycerides or cleave specific fatty acids, such as phospholipase A (EC 3.1.1.4), galactolipase (EC 3.1.1.26), cutinase (EC 3.1.1.74), and enzymes with sterol esterase activity (EC 3.1.1.13) and / or wax ester hydrolase activity (EC 3.1.1.50).

[0038] Commercially available lipases include, but are not limited to: Lipolase TM 、Lipex TM 、Lipolex TM and Lipoclean TM (Novozymes A / S), Lumafast (originally from Genencor), and Lipomax (Gist-Brocades / now DSM).

[0039] Methods for determining lipolytic activity are well known in the literature (see, e.g., Gupta et al. (2003), Biotechnol. Appl. Biochem. 37, p. 63-71). For example, lipase activity can be measured by hydrolysis of the ester bond in the substrate p-nitrophenyl palmitate (pNP-palmitate, C:16), releasing pNP, which is yellow and detectable at 405 nm.

[0040] Cellulase

[0041] "Cellulase", "cellulase enzyme" or "cellulolytic enzyme" is an enzyme involved in the hydrolysis of cellulose. Three main types of cellulases are known, namely endo-ss-1,4-glucanases (endo-1,4-PD-glucan 4-glucanohydrolase, EC 3.2.1.4; hydrolyzes β-1,4-glycosidic bonds in cellulose), cellobiohydrolases (1,4-PD-glucan cellobiohydrolase, EC 3.2.1.91) and ss-glucosidases (EC 3.2.1.21). Commercially available cellulases include Celluzyme TM 、Endolase TM 、Carezyme TM 、Cellusoft TM 、Renozyme TM , CellucleanTM (from Novozymes A / S), Ecostone TM 、Biotouch TM 、Econase TM 、Ecopulp TM (from AB Enzymes Finland), Clazinase TM and Puradax HA TM 、Genencor Detergent Cellulase L, IndiAge TM Neutra (from Genencor International Inc. / DuPont), Revitalenz TM (2000 from DuPont), Primafast TM (DuPont) and KAC-500 TM (From Kao Company).

[0042] The cellulase according to the invention has "cellulolytic activity" or "cellulase activity". Assays for measuring cellulolytic activity are known to those skilled in the art. For example, according to Hoffman, WS, J. Biol. Chem. 120, 51 (1937), cellulolytic activity can be determined by the fact that the cellulase hydrolyzes carboxymethyl cellulose to reducing carbohydrates, the reducing power of which is determined colorimetrically by means of the ferrocyanide reaction.

[0043] Mannanase

[0044] Mannanase (EC 3.2.1.78) enzymes hydrolyze internal β-1,4 bonds in mannose polymers. A "mannanase" may be an alkaline mannanase of family 5 or 26. Mannanases are known to be derived from wild-types from Bacillus or Humicola, in particular B. agaradhaerens, B. licheniformis, B. halodurans, B. clausii or H. insolens.

[0045] Commercially available mannanases include: (Novozymes AIS).

[0046] Pectin lyase

[0047] Pectate lyase (EC 4.2.2.2) enzymes eliminate the cleavage of (1->4)-α-D-galacturonic acid to produce an oligosaccharide with a 4-deoxy-α-D-galactose-4-ribonucleoside group at its non-reducing end. Commercially available pectate lyases include: Xpect TM 、Pectawash TM and Pectaway TM (Novozymes A / S); PrimaGreen TM , EcoScour (DuPont).

[0048] Nuclease

[0049] Nuclease (EC 3.1.21.1), also known as deoxyribonuclease I or DNase, cleaves nucleic acids into 5'-phosphodinucleotide and 5'-phosphotoligonucleotide end products.

[0050] The "activity" of an enzyme as referred to herein is catalytic activity, preferably as specified above for various types of enzymes. More preferably, the activity is a hydrolase activity, an oxidoreductase activity, a transferase activity, a lyase activity, an isomerase activity, a ligase activity or a translocation activity, more preferably a hydrolase activity, more preferably a proteolytic enzyme, a lipolytic enzyme, an amylolytic activity, a cellulolytic activity, a mannitol decomposition activity or a saccharolytic activity. More preferably, the enzyme is a protease and has proteolytic activity. As will be understood by those skilled in the art, the term activity can relate to a specific activity, i.e., activity per mass unit, such as units per milligram of protein. However, the activity can be a volumetric activity, i.e., activity per volume of enzyme solution, such as units per milliliter of solution; in addition, the activity can also be an absolute activity, i.e., activity contained in a given preparation, such as units. As will be understood by those skilled in the art, the activity decreases, preferably the specific activity decreases; preferably, in the case of a constant dosage of the preparation, this will be associated with a decrease in absolute activity; and, in the case of a constant dilution, it will also be associated with a decrease in volumetric activity. Therefore, if the total amount of preparation and / or dilution does not change, the reduction of activity can be determined as total activity, volume activity or specific activity. Preferably, activity is determined as specific activity and / or absolute activity, more preferably as specific activity. Therefore, "initial enzyme activity value" is the activity value of the enzyme preparation determined at or before the beginning of storage, preferably before the first storage section; more preferably determined shortly before the beginning of storage, such as at most 10 days before the beginning of storage, preferably at most 5 days before the beginning of storage, more preferably at most 2 days before the beginning of storage, most preferably at most 1 day before the beginning of storage. Means and methods for determining the initial enzyme activity value are known to those skilled in the art. Preferably, the initial enzyme activity value is determined by an enzyme assay that tests enzyme activity. Likewise therefore, as used herein, the term "residual activity value" relates to the activity value of the enzyme preparation determined at or after the end of storage, preferably after the last storage period; more preferably, the residual activity value is determined shortly before deciding and / or applying at least one management measure specified elsewhere herein, for example at most 10 days, preferably at most 5 days, more preferably at most 2 days, most preferably at most 1 day before deciding and / or applying at least one management measure. Means and methods for determining the residual activity value are described below and in the Examples.

[0051] As used herein, the term "enzyme preparation" includes, but is not limited to, any type of preparation comprising at least one active enzyme. Thus, the preparation may be liquid or solid, and may be a solution, emulsion, suspension, sol, gel or solid. Preferably, the preparation is a solution, emulsion or suspension, more preferably a solution. Preferably, the preparation comprises additional compounds other than the enzyme, in particular buffer compounds, salts, stabilizers, solvents, etc. Also preferably, the enzyme preparation is an enzyme solution, preferably an aqueous solution, more preferably a buffer solution. Thus, preferably, the enzyme preparation further comprises water. The enzyme preparation may comprise more than one enzyme and / or more than one activity, i.e., may comprise a plurality of enzymes and / or activities that may be affected differently by the storage segment. Preferably, in this case, the management measures are based on the enzyme and / or activity showing the strongest activity reduction; more preferably, the management measures are based on the activity showing the strongest reduction in this case. However, the preparation may be a culture medium, preferably a culture supernatant from which cells are removed, more preferably a fermentation broth, and even more preferably a cell-free fermentation broth. The enzyme may be partially or completely purified from the culture medium, more preferably purified from the fermentation broth.

[0052] As used herein, the term "enzyme preparation management" relates to any measures relevant to the further use of the enzyme preparation, and the term "activity-based" indicates that the decision of further measures takes into account the activity of the enzyme preparation, particularly the residual activity as described below.Depending on the residual activity, the management of the enzyme preparation may include use as planned, use with modified dosage (e.g., with higher volume to compensate for the loss of volumetric activity) or recommending this use with higher dosage, the purposes of different purposes (e.g., allowing the purpose of lower specific activity and / or volumetric activity), readjusting the remaining shelf life index (e.g., expiration date or optimal use date) or even possibly discarding and / or returning the enzyme preparation to the manufacturer.In addition, management may include ordering additional and / or fresh batches of enzyme preparation, for example, when determining that the absolute activity of the batch received is too low for the planned purpose.In addition, management may include initiating quality control measures, which are suitable for avoiding further batches of activity reductions, such as improvements in transportation conditions, particularly transportation duration and / or transportation temperature, and also including improvements in packaging or including pre-purification steps and / or protective measures before the transportation. In a preferred embodiment, the enzyme preparation management is the management of an enzyme preparation that has been exposed to a plurality, ie preferably at least two, more preferably at least three, even more preferably at least five different storage sections that differ at least in temperature.

[0053] As used herein, the term "storage section" relates to any sub-portion of the storage history of the enzyme preparation. Preferably, the storage section is a transportation section, for example, a section can be a storage at the manufacturer's location, via ships, ships and / or aircraft transportation, a section of any storage in the storage of the customs and / or the storage at the recipient's location. However, the storage section can also be a temperature section, i.e. preferably, a section of a substantially constant temperature that affects the enzyme preparation over a period of time. Preferably, the transportation section is related to the temperature section. In a preferred embodiment, the storage section is not temperature-controlled, is temperature-controlled within a specific target range, or is controlled to such as not exceeding a predetermined reference value. Therefore, preferably, in at least one storage section, the temperature that affects the enzyme preparation over the time period is uncontrolled. More preferably, in at least two, more preferably at least three, even more preferably at least five, most preferably all storage sections, the temperature of the enzyme preparation that affects the time period is not adjusted. Even more preferably, the enzyme preparation is not cooled and / or heated during at least one, preferably at least two, even more preferably at least three, even more preferably at least five, most preferably all storage sections.

[0054] Therefore, the term "storage segment data" as used herein is data assigned to a specific storage segment. Preferably, the storage segment data at least includes data about the duration and temperature of the storage segment. Measures and equipment for determining the temperature and duration thereof acting on a specific object (such as an enzyme preparation), particularly suitable sensors, are known in the art. Therefore, preferably, the storage segment data is determined based on sensor data. Preferably, during at least one storage segment, preferably during the entire storage period, sensor data is recorded using a sensor adjacent to or in the enzyme preparation. Also preferably, the sensor is located in the same storage space as the enzyme preparation and / or attached to the outer shell of the packaging, tray or container of the enzyme preparation; preferably, in this case, by calculating the temperature in the enzyme preparation, preferably by considering thermal conductivity, particularly based on the mass and heat capacity of the enzyme preparation, specifically by one or both of the receiving unit and the processing unit described below to correct the sensor data. More preferably, the sensor data is received from at least one sensor located in the enzyme preparation, specifically by one or both of the receiving unit and the processing unit. Preferably, the storage segment data is semi-quantitatively or quantitatively determined and provided, more preferably quantitatively determined and provided. Semi-quantitative determination and provision of storage segment data may include reporting temperature and / or duration as categories, such as low (e.g. <15°C), medium (15°C≤temperature≤35°C) and high (>35°C) temperatures, and durations such as short (<1 hour), medium (1 hour≤duration≤1 day) and long (>1 day). Quantitative determination and provision of storage segment data preferably includes reporting temperature and / or duration in an appropriate scale, such as preferably a temperature scale of 1°C, and a duration scale of 1 minute or 1 hour. As will be appreciated by those skilled in the art, for long (preferably >5 minutes, >15 minutes or >30 minutes) storage segments, an average temperature is preferably determined and reported. Preferably, storage segment data may also be determined by determining a surrogate marker associated with the temperature and duration of the storage segment, such as using a temperature sensitive dye that changes color with increasing temperature and / or duration, or, in the case where the enzyme preparation comprises more than one activity, using one activity as a surrogate marker for one or more activities contained in the preparation.

[0055] The term "input data" as used herein is a broad term and is given to those of ordinary skill in the art in its common and customary meaning and is not limited to a special or customized meaning. The term preferably refers to at least the storage segment data and the initial enzyme activity value as specified above. Preferably, the input data includes further data, which are preferably identifiers of the enzyme preparation and / or data providing basic parameters and a stability model suitable for the enzyme preparation in question. Therefore, in the case where the Arrhenius equation specified hereinafter should be used as an enzyme stability model, the parameters A0, k0 and E0 are preferably provided. a'As input data; or preferably, in the case where the Weibull model is used as the enzyme stability model, preferably the parameters A0, k0 and E a' And n as input parameters.As will be appreciated by those skilled in the art, input data can also include the equation of the stability model itself, preferably including all basic parameters.However, it is also envisioned that the stability model preferably including enzyme preparation specific parameters is included in the equipment realizing the method, for example in a memory unit operably connected to a processing unit; As will be appreciated by those skilled in the art, in the case where the equipment includes more than one model and / or parameter of enzyme preparation, the input data preferably includes the identifier of enzyme preparation so that the processing unit can use correct stability model and parameter.In a preferred embodiment, the input data further include a temperature parameter that varies over time.Therefore, in a preferred embodiment, the input data include storage segment data from a plurality of, preferably at least two, more preferably at least three, even more preferably at least five storage segments of different storage temperatures, and more preferably, the storage segment data from the different storage segments include a temperature parameter that varies over time.

[0056] The term "input unit" as used herein includes, but is not limited to, any item or element forming a boundary configured for transmitting information. In particular, the input unit can be configured to transmit information to a computing device such as a computer that receives information. The input unit is preferably a separate unit configured to receive information or transmit information to a computing device, such as one or more of the following: an interface, in particular a network interface and / or a data interface; a keyboard; a terminal; a touch screen or any other input device deemed suitable by a person skilled in the art. More preferably, the input unit includes or is configured to transmit or exchange information as specified below. The data interface.

[0057] The term "output unit" as used herein includes, but is not limited to, any item or element forming a boundary configured for transmitting information. In particular, the output unit can be configured to transmit information from a computing device (e.g., a computer), such as sending or outputting information, for example to another device or user. The output unit is preferably a separate unit configured to output or transmit information from a computing device, such as one or more of the following: an interface, in particular a network interface and / or a data interface; a screen, a printer or a touch screen, or any other output device deemed suitable by the skilled person. More preferably, the output unit includes or is configured to transmit or exchange a data interface of information as specified below.

[0058] Preferably, the input unit and the output unit are configured as at least one or at least two separate data interfaces; that is, preferably a data transmission connection is provided, such as wireless transmission, Internet transmission, Bluetooth, NFC, inductive coupling, etc. As an example, the data transmission connection can be or can include at least one port, which includes one or more of a network or Internet port, a USB port and a disk drive. The input unit and / or the output unit can also be at least one network interface.

[0059] The term "processing unit" as used herein is a broad term and will be given a common and customary meaning for a person of ordinary skill in the art, and is not limited to a special or customized meaning. The term may specifically refer to, but is not limited to, any logic circuit configured to perform the operation of a computer or system, and / or generally refers to a device or unit thereof configured to perform a calculation or logic operation. The processing unit may include at least one processor. In particular, the processing unit may be configured to process basic instructions that drive the computer or system. As an example, the processing unit may include at least one arithmetic logic unit (ALU), at least one floating point unit (FPU), such as a mathematical coprocessor or a digital coprocessor, a plurality of registers and memories, such as a cache. In particular, the processing unit may be a multi-core processor. The processing unit may include a central processing unit (CPU) and / or one or more graphics processing units (GPUs) and / or one or more application specific integrated circuits (ASICs) and / or one or more tensor processing units (TPUs) and / or one or more field programmable gate arrays (FPGAs), etc. The processing unit may be configured to preprocess input data. Preprocessing may include at least one filtering process for input data that meets at least one quality standard. For example, the input data may be filtered to remove missing variables. Preferably, the input data can be compared with at least one predefined threshold value (such as threshold temperature) to determine whether the method step (ii) needs to be fully performed. Preferably, the processing unit is configured to perform the determination of the residual enzyme activity specified in other positions as herein, preferably calculation. The method for determining the residual activity value of enzyme preparation based on storage segment data and initial enzyme activity value is known in the art in principle. Preferably, the determination is based on the experimental data previously established that the activity of the enzyme preparation in question decreases with temperature and / or time. Preferably, the experimental data are condensed into an enzyme stability model. More preferably, the experimental data are modeled into at least two enzyme stability models, the prediction accuracy of the two models is compared, and the model for selecting the accuracy prediction of the enzyme preparation stability in question is provided for the determination step of the computer-implemented method for the management of the enzyme preparation based on activity, i.e., the step (ii) of the preferred method.

[0060] Preferably, the enzyme stability model comprises, more preferably, the Arrhenius equation; thus, the stability model preferably comprises equation (I)

[0061]

[0062] With the following definition:

[0063] - A(t,T) = remaining enzyme activity after storage time t at temperature T;

[0064] - A0 = initial enzyme activity;

[0065] -t = time, i.e. storage time at temperature T;

[0066] - T = storage temperature (in Kelvin);

[0067] - R = 8.314 J / (K mol), the universal gas constant;

[0068] -E a =Activation energy

[0069] -k0 = frequency factor

[0070] -T ref =reference temperature of frequency factor k0.

[0071] Preferably, T ref For example, it is arbitrarily set to a value of 318.15 K (45 ° C) and has no effect on the fit or prediction. Also preferably, the parameters indicated in bold in formula (I) (i.e., A0, k0, and E a ) indicates the fitting parameters. Also preferably, if only experimental data for a single temperature are provided, the activation energy E cannot be estimated. a ; In this case, E can be formally defined a =0, so that the obtained A(t,T) is independent of T.

[0072] In the case of a storage scenario with a non-constant temperature T, i.e., a time-varying temperature T, the model equation (I) is generalized to

[0073]

[0074] More preferably, the enzyme stability model comprises, more preferably, at least one Weibull type equation, and even more preferably at least one temperature-dependent Weibull type equation. Even more preferably, the stability model comprises, more preferably, a Weibull model, and even more preferably, a temperature-dependent Weibull model.

[0075] In a preferred embodiment, the stability model comprises a time-varying temperature parameter T(τ), preferably incorporating the effect of time-varying temperature into the model. Thus, the stability model preferably (i) is capable of predicting degradation under time-varying storage temperatures, preferably when at least one storage section is a storage section in which the storage temperature is not controlled; (ii) uses only a single set of parameter values ​​for all temperatures in all storage sections; and / or (iii) is capable of using experimental data with non-constant temperature profiles to establish a stability model for the enzyme of interest.

[0076] Therefore, the stability model preferably includes equation (II)

[0077]

[0078] It has the same definitions as above formula (I) and additional definitions:

[0079] n = Weibull parameter.

[0080] Preferably, T ref is arbitrarily set to a value of 318.15 K (45° C.), for example, and has no effect on the fit or prediction. It is also preferred that the parameters indicated in bold in formula (II) (i.e., A0, k0, E a' and n) indicate the fitting parameters. Also preferably, if only experimental data for a single temperature are provided, the activation energy E cannot be estimated. a ; In this case, E can be formally defined a =0, so that the obtained A(t,T) is independent of T.

[0081] In the case of a storage scenario with a non-constant temperature T, i.e., a time-varying temperature T, the model equation (II) is generalized to

[0082]

[0083] As will be appreciated by those skilled in the art, other enzyme stability models may be used, such as first-order kinetic models, different isozyme models, two-fraction models, and / or fractional dialogue models (see, e.g., Sant'Anna et al. (2013); Bioprocess Biosyst Eng 36:993).

[0084] Advantageously, it was found in the basic work that by using enzyme stability models, the residual activity of enzyme preparations after storage can be accurately predicted and the management of enzyme preparations can be adjusted accordingly. Preferably, it was found that all Weibull-type degradation models in the literature only involve fixed temperatures, and the advantages of using a temperature-dependent extension are that (i) the temperature-dependent model allows prediction of degradation in the case of storage temperatures that vary over time, which is particularly advantageous in transportation scenarios without strict temperature control; (ii) the above model is advantageous even in the case of time-constant temperatures, as it only requires a single set of parameter values ​​for all temperatures, in contrast to temperature-independent models, which require a separate set of parameters for each temperature value of interest; therefore, the temperature-dependent model requires fewer experimental data points to reliably fit the model parameters for use in scenarios with time-constant (but variable) temperatures; (iii) experiments with non-constant temperature profiles can be used for parameter identification.

[0085] The above definitions apply mutatis mutandis to the following. The additional definitions and explanations further provided below also apply to all embodiments described in this specification with necessary modifications.

[0086] The present invention further relates to a device for activity-based enzyme preparation management of an enzyme preparation, comprising:

[0087] - an input unit configured to receive data input, the input unit preferably being a user interface, wherein the data input comprises storage segment data defined by at least the temperature and duration of said enzyme preparation and an initial enzyme activity value;

[0088] a processing unit, preferably a processing unit comprising at least one processor, which is configured to determine, in particular calculate, a residual activity value of the enzyme preparation based on the storage segment data and the initial enzyme activity value, in particular by programming; and

[0089] - an output unit configured to output the residual activity value of the enzyme preparation to a user and / or a data interface.

[0090] The term "device" as used herein relates to a system of components, which at least includes the above-mentioned components that are operably linked to each other to allow determination. The above discloses typical input and output units and components, particularly processing units, for performing determination in conjunction with the method of the present invention. How to link the components in an operational manner will depend on the type of components contained in the device. Those skilled in the art will be aware of how to link the components without any trouble. Preferably, the component consists of a single device. A typical device is a device that can be applied without the specific knowledge of a professional and technical personnel, particularly a handheld device including an executable code (particularly an application), performing determinations as specified elsewhere herein. The result can be given as the output of raw data that, for example, needs to be explained by a technician. However, more preferably, the output of the device processed, i.e., evaluated, is raw data, and its explanation does not require a technician. Also preferably, some functions of enzyme preparation management based on activity can be automatically performed, i.e., preferably without user interaction, such as if the remaining activity value indicates that the total enzyme activity in the enzyme preparation is lower than a predetermined threshold, then the dosage of the enzyme preparation is adjusted, or an order for a batch of enzyme preparation is drawn. Further typical equipment includes the above-mentioned units according to the method of the present invention, particularly input units, processing units and output units.

[0091] The input unit of the device can be configured to obtain input data from a local storage device (e.g., a USB storage device) or a sensor that stores the storage segment data during storage and / or transmission. However, the input device can also receive input data from an external data storage component or directly from a sensor, for example, via a data connection such as the Internet.

[0092] The device is preferably a handheld device or any type of computing device with specified features. However, the device may also be a device configured to utilize an enzyme preparation, more preferably a washing machine, a dishwasher, an industrial washing machine, a food (e.g. milk or meat) processing machine, an animal feed processing machine, a biofuel production machine, a leather production machine, a textile production machine, a pulp and paper production machine, a beverage production machine or a chemical production machine, in particular in the "white" chemical industry. Preferably, the device configured to utilize an enzyme preparation further comprises a container unit: it is configured to store the enzyme preparation; and a dosage unit, which is configured to apply the amount of the enzyme preparation contained in the container unit based on the residual activity value determined by the processing unit during the wash cycle.

[0093] In addition to the enzyme preparation management measures as described above, the device is preferably configured to further perform at least one of the following:

[0094] - Download relevant information, including quality information, regulatory information, safety data and / or technical documents;

[0095] - order enzyme preparations; and / or

[0096] - Provide user feedback including usability, information content and / or enzyme preparation results.

[0097] The present invention also relates to a system for providing activity-based enzyme inventory management of an enzyme preparation, comprising:

[0098] - a device according to the invention; and

[0099] - a web server configured to interact with a user via web pages served by the web server and / or application;

[0100] The system is configured to provide a graphical user interface (GUI) to the user via a web page and / or an application.

[0101] The term "system" as used herein is a broad term and will be given its ordinary and customary meaning to those of ordinary skill in the art and is not limited to a special or customized meaning. The term includes, but is not limited to, any arrangement having at least two interacting components. In particular, the term may include any type of system comprising the specified components. Preferably, the device included in the system is a device as specified above. Preferably, the device is a computing device comprising a data interface as an input unit and as an output unit. Therefore, preferably, the device included in the system is preferably configured to receive input data from an external data storage component or directly from a sensor, for example via a data connection such as the Internet.

[0102] The system is configured to output the remaining enzyme activity value to an external data storage component and / or a processing device via a network server, preferably a handheld device or a remote computing device, and the network server is configured to interact with a user via a web page provided by the network server and / or via an application program, wherein the system is configured to provide a graphical user interface (GUI) to the user by a web page and / or an application program. Therefore, preferably, the server is configured to provide a graphical user interface (GUI) to the user by a web page and / or an application program. The term "graphical user interface" is known to those skilled in the art, and relates to a user interface that allows a user to interact with an electronic device (particularly a device or other computing device) by visual indicators rather than text-based user interactions (such as typed commands or text navigation). In addition, the term "application program" abbreviated as "application" or "App" is also referred to as a computer executable code by a technician, particularly providing a software program for a graphical user interface for a computing device function or a specific application of a computing device. Preferably, an application program is an executable code that opens a web page served by a device specified as other locations herein (preferably on a handheld device).

[0103] As those skilled in the art will understand according to this specification, the network server can therefore serve the residual activity value of the enzyme preparation. However, the network server can also provide all parameters required for determining the residual enzyme activity. Therefore, the network server preferably provides the user with at least one of the following services:

[0104] - storage segment data defined by at least the temperature and duration of said enzyme preparation and an initial enzyme activity value;

[0105] - parameters required for determining the residual activity value of an enzyme preparation and the initial enzyme activity value of said enzyme preparation, preferably according to the stability model specified herein; and

[0106] - The residual activity value of the enzyme preparation, preferably determined according to the method of the invention.

[0107] The invention also relates to a computer program comprising instructions which, when executed by the device of the invention (particularly by the processor of the device) and / or by the system of the invention, cause the device and / or the system to perform the method of the invention.

[0108] The present invention also relates to a computer-readable storage medium comprising instructions, which, when executed by the apparatus of any one of the present inventions and / or the system of any one of the present inventions, cause the apparatus and / or the system to perform the method of the present invention.

[0109] As used herein, the terms "computer-readable data carrier" and "computer-readable storage medium" may specifically refer to non-transitory data storage components, such as hardware storage media, on which computer-executable instructions are stored. A computer-readable data carrier or storage medium may specifically be or may include storage media such as a random access memory (RAM) and / or a read-only memory (ROM).

[0110] The present invention also relates to the use of the computer-implemented method according to the invention and / or the residual activity value of an enzyme preparation in a washing machine determined according to the method according to the invention in a washing machine, preferably for determining the use of the enzyme preparation; and to the use of the computer-implemented method according to the invention in industrial cleaning applications.

[0111] The invention further relates to a method for manufacturing a product comprising an enzyme preparation having a predetermined activity, comprising the steps of the activity-based enzyme preparation management method of the invention and the further step of automatically adjusting the application of said enzyme preparation based on the residual activity value of the enzyme preparation.

[0112] As used herein, the term "product comprising an enzyme preparation" is a broad term and will be given its ordinary and customary meaning to those of ordinary skill in the art, and is not limited to a special or customary meaning. In particular, the term includes any type of product comprising an enzyme preparation, preferably comprising a predefined enzyme activity. Preferably, the product is a product for household or industrial cleaning applications, more preferably a cleaning agent or a component thereof.

[0113] In view of the above, the following embodiments are particularly contemplated:

[0114] Example 1. A computer-implemented method for activity-based enzyme preparation management of an enzyme preparation, comprising

[0115] (i) receiving input data of at least one storage segment data defined by at least the temperature and storage duration of the enzyme preparation and an initial enzyme activity value, preferably via an input unit;

[0116] (ii) determining, specifically calculating, a residual activity value of the enzyme preparation based on the storage segment data and the initial enzyme activity value via a processing unit;

[0117] (iii) providing a residual activity value of the enzyme preparation, preferably via an output unit, and

[0118] (iv) managing the enzyme preparation based on the residual activity value of step (iii).

[0119] Embodiment 2: The computer-implemented method according to embodiment 1, wherein step (iv) comprises providing a dosage recommendation based on the residual activity value of the enzyme preparation, preferably via an output unit.

[0120] Embodiment 3. A computer-implemented method according to embodiment 1 or 2, wherein step (iv) comprises providing a remaining shelf life indicator of the enzyme preparation based on the remaining activity value of the enzyme preparation.

[0121] Embodiment 4. The computer-implemented method according to any one of embodiments 1 to 3, wherein step (iv) comprises automatically adjusting the dosage of the enzyme preparation by controlling the administration device.

[0122] Embodiment 5. A computer-implemented method according to any one of embodiments 1 to 4, wherein step (iv) comprises triggering an order for a batch of the enzyme preparation if the remaining activity value indicates that the total enzyme activity in the enzyme preparation is below a predetermined threshold.

[0123] Embodiment 6. A computer-implemented method according to any one of embodiments 1 to 5, wherein at least one storage segment data is determined based on sensor data.

[0124] Embodiment 7. A computer-implemented method according to embodiment 6, wherein sensor data is received from a sensor in close proximity to or within the enzyme preparation during at least one storage period, preferably during the entire storage period.

[0125] Embodiment 8. A computer-implemented method according to embodiment 7, wherein the sensor is located in the same storage space as the enzyme preparation and / or is attached to the housing of the packaging, tray or container of the enzyme preparation.

[0126] Embodiment 9. A computer-implemented method according to any one of embodiments 6 to 8, wherein the sensor data is corrected by calculating the temperature within the enzyme preparation, preferably by taking into account the thermal conductivity, in particular based on the mass and heat capacity of the enzyme preparation, specifically by one or both of the receiving unit and the processing unit.

[0127] Embodiment 10. The computer-implemented method according to any one of embodiments 6 to 9, wherein the sensor data is received from at least one sensor located within the enzyme preparation, specifically by one or both of the receiving unit and the processing unit.

[0128] Embodiment 11. A computer-implemented method according to any one of embodiments 6 to 10, wherein the method preferably includes an automatic comparison step before performing steps (ii) and (iii), wherein the comparison step includes comparing the temperature and / or storage duration value with the corresponding predefined value, wherein steps (ii) and (iii) are performed based on the result of the comparison step, preferably wherein steps (ii) and (iii) are only performed when the temperature and / or storage duration exceeds the corresponding predefined value.

[0129] Embodiment 12. A device for activity-based enzyme management of an enzyme preparation, comprising:

[0130] - an input unit configured to receive data input, the input unit preferably being a user interface, wherein the data input comprises storage segment data defined by at least the temperature and duration of said enzyme preparation and an initial enzyme activity value;

[0131] a processing unit, preferably a processing unit comprising at least one processor, which is configured to determine, in particular calculate, a residual activity value of the enzyme preparation based on the storage segment data and the initial enzyme activity value, in particular by programming, preferably according to the computer-implemented method of any one of embodiments 1 to 11 or 22 to 25; and

[0132] - an output unit configured to output the residual activity value of the enzyme preparation to a user and / or a data interface.

[0133] Embodiment 13. The apparatus according to embodiment 12 is further configured to perform at least one of the following:

[0134] - outputting, preferably printing, the value of the residual activity value of the enzyme preparation via an output unit;

[0135] - determining the remaining shelf life value of the enzyme preparation by the processing unit and outputting it via the output unit;

[0136] - determination of dosage instructions for the enzyme preparation by the processing unit and outputting via the output unit; and / or

[0137] - If the remaining activity value indicates that the total enzyme activity in the enzyme preparation is below a predetermined threshold, an order for an additional batch of the enzyme preparation is automatically placed.

[0138] Embodiment 14. The apparatus according to embodiment 13 is further configured to:

[0139] - Download relevant information, including quality information, regulatory information, safety data and / or technical documents;

[0140] - order enzyme preparations; and / or

[0141] - Provide user feedback including usability, information content and / or enzyme preparation results.

[0142] Embodiment 15. The device of any one of embodiments 12 to 14, wherein the device is a washing machine and further comprises

[0143] - a container unit configured to store an enzyme preparation; and

[0144] - a dosing unit configured to administer during a wash cycle an amount of the enzyme preparation contained in the container unit based on the residual activity value determined by the treatment unit.

[0145] Example 16. A system for providing activity-based enzyme inventory management of an enzyme preparation, comprising:

[0146] - a device according to any one of embodiments 12 to 15; and

[0147] - a web server configured to interact with a user via a web page served by the web server and / or via an application;

[0148] The system is configured to provide a graphical user interface (GUI) to the user via a web page and / or an application.

[0149] Embodiment 17. The system of embodiment 16, wherein the network server provides at least one of the following services to the user:

[0150] - storage segment data defined by at least the temperature and duration of said enzyme preparation and an initial enzyme activity value;

[0151] - parameters required for determining the residual activity value of the enzyme preparation and the initial enzyme activity value of said enzyme preparation; and

[0152] - a residual activity value of the enzyme preparation, which is preferably determined according to the method of any one of Examples 1 to 11 or 22 to 25.

[0153] Embodiment 18. A computer program comprising instructions, when the program is executed by the device described in any one of Embodiments 12 to 15 (specifically by the processor of the device) and / or by the system described in any one of Embodiments 16 or 17, causes the device and / or system to execute the method described in any one of Embodiments 1 to 11 or 22 to 25.

[0154] Embodiment 19. A computer-readable storage medium comprising instructions, which, when executed by the device described in any one of Embodiments 12 to 15 and / or the system described in any one of Embodiments 16 or 17, causes the device and / or system to execute the method described in any one of Embodiments 1 to 11 or 22 to 25.

[0155] Embodiment 20. Use of the residual activity value of an enzyme preparation determined by the computer-implemented method according to any one of embodiments 1 to 11 and / or the method according to any one of embodiments 1 to 11 or 22 to 25 in a washing machine, preferably for determining the application of the enzyme preparation.

[0156] Embodiment 21. Use of the computer-implemented method according to any one of embodiments 1 to 11 or 22 to 25 in industrial applications, preferably in laundry processes, food processing, animal feed processing, biofuel production, leather production, textile production, pulp and paper industry, beverage production and / or enzymatic chemical production processes.

[0157] Embodiment 21. A method for manufacturing a product comprising an enzyme preparation having a predefined activity, comprising the steps of the method of any one of embodiments 1 to 11 or 22 to 25 and the further step of automatically adjusting the application of the enzyme preparation based on the residual activity value of the enzyme preparation.

[0158] Embodiment 22: The computer-implemented method of any one of Embodiments 1 to 11, wherein the enzyme preparation is exposed to a plurality of different storage sections that differ at least in temperature.

[0159] Embodiment 23. A computer-implemented method according to any one of Embodiments 1 to 11 or 22, wherein the temperature of at least one storage section is not controlled.

[0160] Embodiment 24. A computer-implemented method according to any one of embodiments 1 to 11, 22 or 23, wherein, in step (ii), the residual activity value of the enzyme preparation is calculated based on a model including a temperature parameter that varies with time.

[0161] Embodiment 25. A computer-implemented method according to any one of embodiments 1 to 11 or 22 to 24, wherein the model includes at least one Weibull-type equation that is temperature dependent.

[0162] The entire disclosures of all references cited in this specification and the disclosures specifically mentioned in this specification are incorporated herein by reference. BRIEF DESCRIPTION OF THE DRAWINGS

[0163] Figure 1 :Device / System

[0164] Figure 2 : Fitting of enzyme activity data to the Weibull model; x-axis: time; y-axis: storage temperature; residual activity is shown in grayscale shading.

[0165] Figure 3 : An exemplary embodiment of a web-based user interface for predicting residual enzyme activity.

[0166] Figure 4 : Exemplary storage / transportation process with assigned residual enzyme activity values. DETAILED DESCRIPTION

[0167] The following examples are only used to illustrate the present invention. In any case, they should not be interpreted as limiting the scope of the present invention.

[0168] Example 1:

[0169] like Figure 1 As shown in, a system 100 for providing enzyme inventory management based on activity of enzyme preparation is disclosed. System 100 includes a device 110 for enzyme preparation to be carried out based on activity of enzyme preparation management, and further includes a network server 140, which is configured to interact with a user via a web page served by the network server and / or via an application program. Device 110 includes an input unit 10, a processing unit 20 and an output unit 30. In system 100, network server 140 can communicate with input unit 10 and / or output unit 30.

[0170] The device 110 includes at least one processing unit 20, such as a processor, a microprocessor or a computer system, in particular for executing the logic in a given algorithm. The device 110 may be configured to implement and / or execute at least one computer program of the present specification. The processing unit 30 may include at least one processor. In particular, the processing unit 30 may be configured to process basic instructions that drive a computer or system. As an example, the processing unit 30 may include at least one arithmetic logic unit (ALU), at least one floating point unit (FPU), such as a math coprocessor or a digital coprocessor, a plurality of registers and memories, such as a cache. In particular, the processing unit 30 may be a multi-core processor. The processing unit 30 may be configured for machine learning. The processing unit 30 may include a central processing unit (CPU) and / or one or more graphics processing units (GPUs) and / or one or more application specific integrated circuits (ASICs) and / or one or more tensor processing units (TPUs) and / or one or more field programmable gate arrays (FPGAs), etc.

[0171] The apparatus comprises at least one communication interface, preferably an output unit 30, configured to output data. The communication interface may be configured to transfer information from a computing device (e.g., a computer), such as to send or output information, for example, to another device. Additionally or alternatively, the communication interface may be configured to transfer information to a computing device (e.g., a computer), such as to receive information, i.e., it may be an input unit 10. The communication interface may specifically provide a component for transmitting or exchanging information. In particular, the communication interface may provide a data transmission connection, such as Bluetooth, NFC, inductive coupling, etc. As an example, the communication interface may be or may include at least one port, including one or more of a network or Internet port, a USB port, and a disk drive. The communication interface may be at least one network interface. The input data includes storage segment data as specified above.

[0172] The processing unit 20 may be configured to pre-process the input data. The pre-processing unit 20 may include at least one filtering process for the input data meeting at least one quality standard. The processing unit 20 is configured to determine at least one residual enzyme activity, preferably as specified above and in further examples below.

[0173] The web server 140 is configured to provide a GUI to the device 110. Thus, the web server can exchange data with the output unit 30, for example for displaying the data on the GUI. However, the web server 140 can also exchange data with the input unit of the device, for example information about the enzyme stability model used and / or input of the initial enzyme activity value.

[0174] Example 2:

[0175] Protease preparations for washing purposes were stored at different temperatures for different periods of time. The residual activity values ​​were fitted to a Weibull model ( Figure 2 ). The specific parameters of the model obtained for a specific enzyme preparation are:

[0176] A0=99.5%

[0177] k0=0.0376 days -1

[0178] E a =182.1 kJ / mol

[0179] n=1.15

[0180] T ref =318.15K(45℃)

[0181] Example 3:

[0182] The network interface for user interaction can be configured as Figure 3 . The web page allows selection between enzyme stability models, shows the fit of the residual activity data to the model, and may allow selection of storage temperature and storage duration. As will be appreciated, multiple storage segments may also be included in such a web interface.

[0183] Example 4:

[0184] Figure 4 An exemplary storage curve for the enzyme preparation of Example 1 is shown, along with the residual enzyme activity values ​​calculated using the Weibul model based on the data of Example 2. High temperature segments or segments with long durations drop more than short and / or cold storage segments.

[0185] Reference Symbols:

[0186] 10 Input unit

[0187] 20 Processing Units

[0188] 30 Output Units

[0189] 100 Systems

[0190] 110 Devices

[0191] 140 Network Server

[0192] References:

[0193] -Brown 1987),Australian J Botany 35(5):581

[0194] -EP 1921147

[0195] -DelMar et al.(1979),Analytical Biochem 99,316-320

[0196] -Gupta et al.(2002),Appl.Microbiol.Biotechnol.60:381-395

[0197] -Gupta et al.(2003),Biotechnol.Appl.Biochem.37,p.63-71

[0198] -Martinus&Boekel(2002),Int J Food Microbiol 74(1-2):139

[0199] -Sant'Anna et al.(2013);Bioprocess Biosyst Eng 36:993

[0200] -E.P.Schokker,Ph.D.Thesis,University of Wageningen,1997

Claims

1. A computer-implemented method for activity-based enzyme preparation management of an enzyme preparation, comprising: (i) receiving input data of at least one storage segment data defined by at least the temperature and storage duration of the enzyme preparation and an initial enzyme activity value; (ii) determining, via a processing unit (20), a residual activity value of the enzyme preparation based on the storage section data and the initial enzyme activity value; (iii) providing a residual activity value of the enzyme preparation, and (iv) managing the enzyme preparation based on the residual activity value of step (iii), the management comprising at least one of the following: - providing a dosage recommendation based on said residual activity value of said enzyme preparation; - automatically regulating the dosage of the enzyme preparation by controlling the administration device; and / or - placing an order for a batch of enzyme preparation if said residual activity value indicates that the total enzyme activity in said enzyme preparation is below a predetermined threshold value.

2. The computer-implemented method of claim 1 , wherein: The input data are received via the input unit (10), and / or the remaining activity value of the enzyme preparation and / or the dosage recommendation are provided via the output unit (30).

3. The computer-implemented method of claim 1 , wherein: The remaining activity value of the enzyme preparation is calculated based on the storage section data and the initial enzyme activity value via a processing unit (20).

4. The computer-implemented method of claim 1 , wherein: The at least one storage segment data is determined based on the sensor data.

5. The computer-implemented method of claim 4, wherein: The sensor data is received from a sensor proximate to or within the enzyme preparation during at least one storage period.

6. The computer-implemented method of claim 5, wherein: The at least one storage segment includes the entire storage period.

7. The computer-implemented method of claim 5, wherein: The sensor is located in the same storage space as the enzyme preparation and / or is attached to the housing of the package, tray or container of the enzyme preparation.

8. The computer-implemented method of claim 4, wherein: correcting said sensor data by calculating said temperature within said enzyme preparation; Or wherein said sensor data is received from at least one sensor located within said enzyme preparation.

9. The computer-implemented method of claim 8, wherein: The sensor data is corrected by taking thermal conductivity into account.

10. The computer-implemented method of claim 9, wherein: The sensor data was corrected based on the mass and heat capacity of the enzyme preparation.

11. The computer-implemented method of claim 8, wherein: The sensor data is corrected by one or both of the input unit and the processing unit, and / or the sensor data is received by one or both of the receiving unit and the processing unit.

12. The computer-implemented method of claim 1, wherein: The enzyme preparation is exposed to a plurality of different storage sections that differ at least in temperature.

13. The computer-implemented method of claim 1, wherein: The temperature of at least one storage section is not controlled.

14. The computer-implemented method of claim 1, wherein: In step (ii), the residual activity value of the enzyme preparation is calculated based on a model including a temperature parameter that varies with time.

15. The computer-implemented method of claim 14, wherein: The model includes at least one Weibull-type equation that is temperature dependent.

16. An apparatus (110) for activity-based enzyme management of an enzyme preparation, comprising: - an input unit (10) configured to receive data input, wherein the data input comprises storage segment data defined by at least the temperature and duration of the enzyme preparation and an initial enzyme activity value; - a processing unit (20) configured to determine a residual activity value of the enzyme preparation based on the storage segment data and the initial enzyme activity value; and - an output unit (30) configured to output the residual activity value of the enzyme preparation to a user and / or a data interface; The apparatus is further configured to perform at least one of the following: - dosage instructions for the enzyme preparation are determined by the processing unit and outputted via the output unit; and / or - automatically placing an order for an additional batch of enzyme preparation if said remaining activity value indicates that the total enzyme activity in said enzyme preparation is below a predetermined threshold value.

17. The device according to claim 16, wherein: The input unit is a user interface, and / or the processing unit includes at least one processor.

18. The device according to claim 16, wherein: The processing unit is configured to determine the remaining activity value according to the computer-implemented method of any one of claims 1 to 15.

19. The device according to claim 16, wherein: The processing unit is configured to calculate a remaining activity value of the enzyme preparation based on the storage segment data and the initial enzyme activity value.

20. The apparatus according to claim 16, further configured to: - Download relevant information, including quality information, regulatory information, safety data and / or technical documents; - order enzyme preparations; and / or - Provide user feedback including usability, information content and / or enzyme preparation results.

21. The device according to any one of claims 16 to 20, wherein: The device is a washing machine and further comprises - a container unit configured to store an enzyme preparation; as well as - a dosing unit configured to administer during a wash cycle an amount of said enzyme preparation contained in said container unit based on said residual activity value determined by said treatment unit.

22. A system (100) for providing activity-based enzyme inventory management of an enzyme preparation, comprising: - a device (110) according to any one of claims 16 to 21; as well as - a web server (140) configured to interact with a user via a web page served by said web server and / or via an application; The system is configured to provide a graphical user interface (GUI) to the user through the web page and / or the application.

23. The system of claim 22, wherein: The network server provides at least one of the following services to the user: - storage segment data defined by at least the temperature and duration of said enzyme preparation and an initial enzyme activity value; - parameters required for determining the residual activity value of the enzyme preparation and the initial enzyme activity value of said enzyme preparation; as well as - The residual activity value of the enzyme preparation.

24. The system of claim 22, wherein: The residual activity value of the enzyme preparation is determined according to the computer-implemented method of any one of claims 1 to 15.

25. A computer program product having a computer program comprising instructions, when the computer program is executed by an apparatus according to any one of claims 16 to 21, and / or by a system according to any one of claims 22 or 24, the instructions cause the apparatus and / or the system to perform a computer-implemented method according to any one of claims 1 to 15.

26. The computer program product of claim 25, wherein: The apparatus includes a processor.

27. A computer-readable storage medium comprising instructions which, when executed by an apparatus according to any one of claims 16 to 21 and / or a system according to any one of claims 22 to 24, cause the apparatus and / or the system to perform a computer-implemented method according to any one of claims 1 to 15.

28. Use of the computer-implemented method according to any one of claims 1 to 15 and / or of the residual activity value of an enzyme preparation determined according to the computer-implemented method according to any one of claims 1 to 15 in a washing machine.

29. The use according to claim 28, wherein the residual activity value of the enzyme preparation is used to determine the administration of the enzyme preparation.

30. Use of the computer-implemented method according to any one of claims 1 to 15 in industrial applications.

31. The use according to claim 30, wherein Said industrial applications include laundry processes, food processing, animal feed processing, biofuel production, leather production, textile production, pulp and paper industry, beverage production and / or enzyme chemical production processes.

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