DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 4/7/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Priority
Acknowledgment is made of applicant’s claim for priority. Application is a 371 of PCT/EP2020/070176 and claims the benefit of priority to EP 19186818.1 filed 7/17/2019. As such, the effective filing date of claims 1-15 is 7/17/2019.
Claim Status
Claims 1-15 are pending.
Claims 1-15 are rejected.
Specification
Response to Arguments
In view of applicant’s amendments to the specification, previous objections to the specification are withdrawn.
Drawings
Response to Amendment
In view of applicant’s amendments to the specification, previous objections to the drawings are withdrawn.
Claim Rejections - 35 USC § 112
Response to Amendment
In view of applicant’s amendments to the claims, previous rejections under 35 U.S.C. 112(b) are withdrawn.
Claim Rejections - 35 USC § 101
Response to Amendment
In view of applicant’s amendments to the claims, previous rejections under 35 U.S.C. 101 have been reviewed, updated, and provided below.
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 15 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim does not fall within at least one of the four categories of patent eligible subject matter because tangible is different from a non-transitory CRM, one is directed to the storage device, the other to the instructions, and this still encompass software per se, as this could just be instructions on a piece of paper.
Claims 1-15 are rejected under 35 U.S.C. 101 because the claimed invention is directed to abstract ideas without significantly more. The claims recite a method, system and CRM for determining a treatment for a tumor. The judicial exception is not integrated into a practical application because while claims 1-15 attempt to integrate the exception into a practical application, said application is either generically recited computer elements that do not add a meaningful limitation to the abstract idea, or it is insignificant extra solution activity and simply implementing the abstract idea on a computer. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the computer elements only store and retrieve information in memory as well as perform basic calculations that are known to be well-understood, routine and conventional computer functions as recognized by the decisions listed in MPEP § 2106.05(d).
Framework with which to Analyze Subject Matter Eligibility:
Step 1: Are the claims directed to a category of statutory subject matter (a process, machine, manufacture, or composition of matter)? [see MPEP § 2106.03]
Claims are directed to statutory subject matter, specifically methods (claims 1-12), an apparatus (claim 13), a system (claim 14).
Claim 15 does not recite a statutory category of invention, however in the interest of compact prosecution analysis under 35 U.S.C. 101 is continued below.
Claims 2 and 4 are contingent limitations [See MPEP § 2111.04] – “The broadest reasonable interpretation of a method (or process) claim having contingent limitations requires only those steps that must be performed and does not include steps that are not required to be performed because the condition(s) precedent are not met”. However, in the interest of compact prosecution analysis under 35 U.S.C. 101 is continued below.
Step 2A Prong One: Do the claims recite a judicially recognized exception, i.e., an abstract idea, a law of nature, or a natural phenomenon? [see MPEP § 2106.04(a)]
The claims herein recite abstract ideas, mental processes and mathematical concepts.
With respect to the Step 2A Prong One evaluation, the instant claims are found herein to recite abstract ideas that fall into the grouping of mental processes and mathematical concepts.
Claim 1: Calculating key parameters, predicting key parameters, identifying at least one excipient, suggesting a manufacturing process, predicting product properties, determining whether predicted properties comply with TPP, and identifying a suitable formulation are processes of comparing/contrasting, calculating, transforming, and identifying that can be done via pen and paper or within the human mind and are therefore abstract ideas, specifically mental processes. The mixing rules comprising property specific aggregation of single-component data into blend level properties using weighted combinations based on fractions and metrics is a verbal articulation of a mathematical process and is therefore an abstract idea, specifically a mathematical concept.
Claim 2: Suggesting at least one additional technological measure to optimize the key parameters, suggesting to adjust the user-defined TPP, and suggesting to select a different dosage form are processes of comparing/contrasting, calculating and identifying that can be done via pen and paper or within the human mind and are therefore abstract ideas, specifically mental processes.
Claim 3: The technical measure comprising at least one of milling or micronization, and the addition of and processing with excipients are directed to the data itself, which is an abstract idea, rendering this an abstract idea, specifically a mental process.
Claim 4: Performing steps b to h until a suitable formulation has been identified is a process of comparing/contrasting, calculating, transforming, and identifying that can be done via pen and paper or within the human mind and are therefore abstract ideas, specifically mental processes.
Claim 5: The product development comprising at least one of the specified products in the specified group is directed to the data itself, which is an abstract idea, rendering this an abstract idea, specifically a mental process.
Claim 6: The dosage comprising at least one of those specified in the group provided is directed to the data itself, which is an abstract idea, rendering this an abstract idea, specifically a mental process.
Claim 7: The user-defined TPP comprising at least one of those specified in the specified group is directed to the data itself, which is an abstract idea, rendering this an abstract idea, specifically a mental process.
Claim 8: The user-defined TPP comprising at least one of those specified in the specified group is directed to the data itself, which is an abstract idea, rendering this an abstract idea, specifically a mental process.
Claim 9: The user-defined TPP comprising at least one of those specified in the specified group is directed to the data itself, which is an abstract idea, rendering this an abstract idea, specifically a mental process.
Claim 10: The key physiochemical properties of the AI comprising at least one of those specified in the specified group is directed to the data itself, which is an abstract idea, rendering this an abstract idea, specifically a mental process.
Claim 11: The user-defined TPP comprising a dose of AI per unit and a maximum weight of the dosage is directed to the data itself, which is an abstract idea, rendering this an abstract idea, specifically a mental process. Calculating weight fractions of the AI and the one or more excipients, predicting properties of a combination of the AI and one or more excipients, and selecting at least one promising excipient are processes of comparing/contrasting, calculating and identifying that can be done via pen and paper or within the human mind and are therefore abstract ideas, specifically mental processes.
Claim 12: The dosage form comprising a pharmaceutical dosage form is directed to the data itself, which is an abstract idea, rendering this an abstract idea, specifically a mental process.
Claim 13: Calculating key parameters, predicting key parameters, identifying at least one excipient, suggesting a manufacturing process, predicting product properties, determining whether predicted properties comply with TPP, and identifying a suitable formulation are processes of comparing/contrasting, calculating, transforming, and identifying that can be done via pen and paper or within the human mind and are therefore abstract ideas, specifically mental processes. The mixing rules comprising property specific aggregation of single-component data into blend level properties using weighted combinations based on fractions and metrics is a verbal articulation of a mathematical process and is therefore an abstract idea, specifically a mathematical concept.
Claim 15: Calculating key parameters, predicting key parameters, identifying at least one excipient, suggesting a manufacturing process, predicting product properties, determining whether predicted properties comply with TPP, and identifying a suitable formulation are processes of comparing/contrasting, calculating, transforming, and identifying that can be done via pen and paper or within the human mind and are therefore abstract ideas, specifically mental processes.
Step 2A Prong Two: If the claims recite a judicial exception under prong one, then is the judicial exception integrated into a practical application? [see MPEP § 2106.04(d) and MPEP § 2106.05(a)-(c) & (e)-(h)]
Because the claims do recite judicial exceptions, direction under Step 2A Prong Two provides that the claims must be examined further to determine whether they integrate the abstract ideas into a practical application.
The following claims recite the following additional elements in the form of non-abstract elements:
Claim 1: Receiving a user input of data is an insignificant extra solution activity, specifically necessary data gathering (See Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; OIP Techs., Inc. v. Amazon.com, Inc., 788 F.3d 1359, 1363, 115 USPQ2d 1090, 1092-93 (Fed. Cir. 2015) (presenting offers and gathering statistics amounted to mere data gathering), Performing clinical tests on individuals to obtain input for an equation, In re Grams, 888 F.2d 835, 839-40; 12 USPQ2d 1824, 1827-28 (Fed. Cir. 1989) and Determining the level of a biomarker in blood, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968. See also PerkinElmer, Inc. v. Intema Ltd., 496 Fed. App'x 65, 73, 105 USPQ2d 1960, 1966 (Fed. Cir. 2012) (assessing or measuring data derived from an ultrasound scan, to be used in a diagnosis)) [See MPEP § 2106.05(g)]. A computer is a generic and nonspecific element of a computer that does not improve the functioning of any computer or technology described herein [See MPEP § 2106.04(d)(1) and MPEP § 2106.05(d)].
Claim 4: Receiving a further user input is an insignificant extra solution activity, specifically necessary data gathering (See Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; OIP Techs., Inc. v. Amazon.com, Inc., 788 F.3d 1359, 1363, 115 USPQ2d 1090, 1092-93 (Fed. Cir. 2015) (presenting offers and gathering statistics amounted to mere data gathering), Performing clinical tests on individuals to obtain input for an equation, In re Grams, 888 F.2d 835, 839-40; 12 USPQ2d 1824, 1827-28 (Fed. Cir. 1989) and Determining the level of a biomarker in blood, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968. See also PerkinElmer, Inc. v. Intema Ltd., 496 Fed. App'x 65, 73, 105 USPQ2d 1960, 1966 (Fed. Cir. 2012) (assessing or measuring data derived from an ultrasound scan, to be used in a diagnosis)) [See MPEP § 2106.05(g)].
Claim 13: Receiving a user input of data is an insignificant extra solution activity, specifically necessary data gathering (See Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; OIP Techs., Inc. v. Amazon.com, Inc., 788 F.3d 1359, 1363, 115 USPQ2d 1090, 1092-93 (Fed. Cir. 2015) (presenting offers and gathering statistics amounted to mere data gathering), Performing clinical tests on individuals to obtain input for an equation, In re Grams, 888 F.2d 835, 839-40; 12 USPQ2d 1824, 1827-28 (Fed. Cir. 1989) and Determining the level of a biomarker in blood, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968. See also PerkinElmer, Inc. v. Intema Ltd., 496 Fed. App'x 65, 73, 105 USPQ2d 1960, 1966 (Fed. Cir. 2012) (assessing or measuring data derived from an ultrasound scan, to be used in a diagnosis)) [See MPEP § 2106.05(g)]. An apparatus, input unit, and processing unit are generic and nonspecific elements of computers that do not improve the functioning of any computer or technology described herein [See MPEP § 2106.04(d)(1) and MPEP § 2106.05(d)].
Claim 14: A system, apparatus, web server, web page, application program, input unit, and processing unit are generic and nonspecific elements of computers that do not improve the functioning of any computer or technology described herein [See MPEP § 2106.04(d)(1) and MPEP § 2106.05(d)].
Claim 15: A computer program element, instructions, processor, system, and apparatus are generic and nonspecific elements of computers that do not improve the functioning of any computer or technology described herein [See MPEP § 2106.04(d)(1) and MPEP § 2106.05(d)].
Step 2B: If the claims do not integrate the judicial exception, do the claims provide an inventive
concept? [see MPEP § 2106.05]
Because the additional claim elements do not integrate the abstract idea into a practical application, the claims are further examined under Step 2B, which evaluates whether the additional elements, individually and in combination, amount to significantly more than the judicial exception itself by providing an inventive concept.
The claims do not recite additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite additional elements that are generic, conventional, nonspecific, or insignificant extra solution activity. These additional elements include:
The additional elements of a computer program element, instructions, processor, system, apparatus, web server, web page, application program, input unit, and processing unit are generic and nonspecific elements of a computer that are well-understood, routine and conventional within the art and therefore do not improve the functioning of any computer or technology described therein (See Receiving or transmitting data over a network, e.g., using the Internet to gather data, Symantec, 838 F.3d at 1321, 120 USPQ2d at 1362 (utilizing an intermediary computer to forward information), Performing repetitive calculations, Flook, 437 U.S. at 594, 198 USPQ2d at 199 (recomputing or readjusting alarm limit values), and Storing and retrieving information in memory, Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015)) [See § MPEP 2106.05(d)(II)]. Therefore, taken both individually and as whole, the additional elements do not amount to significantly more than the judicial exception by providing an inventive concept.
The additional elements of receiving a user input of data, and receiving a further user input are insignificant extra solution activities, specifically necessary data gathering (See Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; OIP Techs., Inc. v. Amazon.com, Inc., 788 F.3d 1359, 1363, 115 USPQ2d 1090, 1092-93 (Fed. Cir. 2015) (presenting offers and gathering statistics amounted to mere data gathering), Performing clinical tests on individuals to obtain input for an equation, In re Grams, 888 F.2d 835, 839-40; 12 USPQ2d 1824, 1827-28 (Fed. Cir. 1989) and Determining the level of a biomarker in blood, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968. See also PerkinElmer, Inc. v. Intema Ltd., 496 Fed. App'x 65, 73, 105 USPQ2d 1960, 1966 (Fed. Cir. 2012) (assessing or measuring data derived from an ultrasound scan, to be used in a diagnosis)) [See MPEP § 2106.05(g)]. Therefore, taken both individually and as whole, the additional elements do not amount to significantly more than the judicial exception by providing an inventive concept.
Therefore, claims 1-15, when the limitations are considered individually and as a whole, are rejected
under 35 USC § 101 as being directed to non-statutory subject matter.
Response to Arguments
Applicant asserts on page 12 of the Remarks filed 1/21/2026 that the claims do not recite mental processes that can practically be performed in the human mind or with pen and paper and that specifically the added amendments comprise “specific mathematical equations for predicting particle size distributions, bulk density, tapped density, angle of repose, compressibility profiles, and compactibility profiles of powder blends from single-component data” and that the “specification describes these equations in detail, including volume-weighted arithmetic means, particle-size dependent weighting factors, and least squares fitting operations. Such calculations involving multiple components, multiple parameters, and iterative fitting operations cannot practically be performed in the human mind”. Examiner reminds applicant that according toe MPEP 2106.04(a)(2) subsection (A) - A mathematical relationship is a relationship between variables or numbers. A mathematical relationship may be expressed in words or using mathematical symbols. For example, pressure (p) can be described as the ratio between the magnitude of the normal force (F) and area of the surface on contact (A), or it can be set forth in the form of an equation (B) - A claim that recites a numerical formula or equation will be considered as falling within the "mathematical concepts" grouping. In addition, there are instances where a formula or equation is written in text format that should also be considered as falling within this grouping (C) - A claim that recites a mathematical calculation, when the claim is given its broadest reasonable interpretation in light of the specification, will be considered as falling within the "mathematical concepts" grouping. Therefore, according to the MPEP and the applicant’s own admission the limitation is a mathematical concept which is a judicial exception according to MPEP 2106.05(a) - Mathematical concepts – mathematical relationships, mathematical formulas or equations, mathematical calculations.
Applicant asserts on page 12 of the Remarks filed 1/21/2026 that the claims integrate any abstract ideas into a practical application of reducing the number of laboratory experiments. However, examiner reminds applicant that according to MPEP2106.05(a) - It is important to note, the judicial exception alone cannot provide the improvement. The improvement can be provided by one or more additional elements. Here the additional elements are generically recited computer elements and mere data gathering neither of which the improvement is directed to/facilitates. Rather applicant asserts in the same paragraph that the “claims are directed to a specific technological solution for pharmaceutical product development identifying suitable formulations by predicting blend properties from single-component data using defined mixing rules”, which in the paragraph prior applicant claims those same formulations and mixing rules as mathematical properties which cannot be the basis for the improvement. Therefore, the claims are not directed to an improvement or practical application as the improvement is directed to the judicial exception.
Claim Rejections - 35 USC § 102
Response to Amendment
In view of applicant’s amendments to the claims, previous rejections under 35 U.S.C. 102 have been withdrawn.
Response to Arguments
Applicant’s arguments, see page 13 of the Remarks, filed 1/21/2026, with respect to the rejections of claims 1-15 under 35 U.S.C. 102 have been fully considered and are persuasive. The rejection of claims 1-15 has been withdrawn.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-15 are rejected under 35 U.S.C. 103 as being unpatentable over Ouyang et al. (CN 108984811 A; previously cited) and Ajmani et al. (Journal of Chemical Information and Modeling (2006) 2043-2055; newly cited).
Claim 1 is directed to a method of identifying a suitable formulation for product development using dosage and physiochemical properties of the active compound.
Claim 13 is directed to an apparatus for identifying a suitable formulation for product development using dosage and physiochemical properties of the active compound.
Ouyang et al. teaches in in the abstract “The invention claims a medicine preparation prescription virtual design and assessment method and system. The invention claims a medicine preparation prescription virtual design and evaluating method and system mainly comprises front research module of the pharmaceutical prescription, drug formulary design and optimization module, medicine preparation technique of medicine prescription design and optimization module”, reading on a computer-implemented method for identifying a suitable formulation for product development, comprising. Ouyang et al. teaches in paragraph [0071] “The invention process is similar to the process of present medicine research experiment, firstly input the necessary drug information, and predicting to obtain prescription parameters, drug prescription, preparation technology and in vivo pharmacokinetic behaviour”, reading on receiving, via an input channel, a user input that defines: a dosage form, a target product profile, TPP, comprising a minimum product requirement and key physicochemical properties of an active ingredient, Al. Ouyang et al. teaches in claim 1 “establishing a pharmaceutical prescription before a research module, predicting medicine prescription research basic parameter”, reading on calculating, by a processor, key parameters of the Al relevant for the development of the dosage form based on the key physicochemical properties of the Al. Ouyang et al. teaches in paragraph [0008] “The pharmaceutical prescription database includes serial number information, medicine name, medicine accessories name, CAS number compounds, pharmaceutical/medicinal auxiliary materials information, medical auxiliary function information and drug dosage information” and in the abstract “The invention claims a medicine preparation prescription virtual design and assessment of the method and system, the research front from the drug prescription, prescription design, design, preparation process and in vivo pharmacokinetics prediction aspects of the pharmaceutical prescription process prediction”, reading on predicting, by the processor, the key parameters of the Al when combined with the one or more excipients selected from an excipient database by applying mixing rules. Ouyang et al. teaches is paragraph [0073] “Embodiments of the invention injection development process, the process is a classic case of medicine prescription design and operation of the optimization module, the specific step is as follows…additive type selection range derived from a pharmaceutical prescription database statistical analysis result”, reading on identifying, by the processor, at least one promising excipient from the one or more selected excipients capable of improving the key parameters of the Al. Ouyang et al. teaches in claim 1 “A medicine preparation prescription for virtual design and evaluation method and system, wherein comprising the steps: (1) establishing a pharmaceutical prescription before a research module, predicting medicine prescription research basic parameter; (2) establishing the medicine prescription design and optimization module, according to the parameters obtained by the prediction and specific pharmaceutical dosage form, predicting medicine composition; (3) preparation process of establishing drug design and optimization module, according to the parameter obtained by the prediction, pharmaceutical dosage form and pharmaceutical composition, preparation technique route and parameter prediction; (4) establishing drug formulary forecasting and evaluation module according to the parameter obtained by the prediction, pharmaceutical compositions and preparation process”, reading on suggesting, by the processor, a manufacturing process based on the Al, the at least one selected promising excipient, and the dosage form, and predicting, by the processor, product properties based on the suggested manufacturing process, a combination of the Al and the at least one selected promising excipient, and the dosage form. Ouyang et al. teaches in paragraph [0001] “…combined with the selected solvent or accessories before design prescription, the medicine stably and effectively, meet the requirement of the preparation prescription and preparation technique in the industrial production…”, and in paragraph [0075] “…main simulation method of molecular simulation of quantum mechanics simulation and classical mechanics simulation, the quantum mechanical simulation mainly according to the calculation method from the head, a semi-empirical method, DFT method, and method of classical mechanics simulation mainly by molecular mechanics, molecular dynamics, Monte Carlo simulation, Brownian dynamics, etc. current drug prescription experiment research of molecular simulation mainly comprises the following step: firstly medicinal accessories system modelling, by document reading or the existing experimental data and the actual requirement, selecting the proper medicine/types and proportions of auxiliary material…”, reading on determining, by the processor, whether the predicted product properties comply with the user-defined TPP. As such, the previous limitations being read on by Ouyang et al. would therefore implicitly read on identifying, by the processor, a suitable formulation based on the combination of the Al and the at least one selected promising excipient, the suggested manufacturing process, and the dosage form, if it is determined that the predicted product properties comply with the user- defined TPP, as the step of predicting product properties would be understood, due to the broadness of the phrase “identifying…a suitable formulation”, as the same. Ouyang et al. teaches in the abstract “Compared with the traditional drug formulary screening laboratory in the empirical formula and preparing method, the invention can accelerate development of pharmaceutical product, and does not consume any laboratory equipment, completely via the computer platform”, reading on an apparatus for identifying a suitable formulation for product development, comprising: an input unit, and a processing unit.
Ouyang et al. does not teach the mixing rules comprise property-specific aggregation of single- component data into blend-level properties using weighted combinations with weights dependent on at least the components' volume fractions and particle-size metrics.
Ajmani et al. teaches in the abstract “The QSPR methodology was applied to a data set of experimental measured density of binary liquid mixtures compiled from the literature. The present study is aimed to develop models to predict the “delta” value of a mixture i.e., deviation of the experimental mixture density (MED) from the ideal, mole-weighted calculated mixture density (MCD)”, on page 2043, column 1, paragraph 1 “In principle, the techniques of computer-aided drug design (CADD) such as molecular modeling and quantitative structure-activity relationships (QSAR) can be applied to the optimization of “performance” or “effect” chemicals…Where the chemical to be optimized is used essentially on its own or as the only “active” ingredient of a formulation, then the well-known CADD techniques may be used for the optimization. This circumstance, though, in materials science applications may be unusual, and it is more likely that the subject of optimization will be some form of more or less complicated formulation, in other words a mixture”, on page 2044, column 1, paragraph 2 “The ideal mixture density (referred to here as the calculated mixture densitys MCD) was obtained by adding the product of the experimental density value of each component with its corresponding mole fraction in the mixture where R1 and R2 are the mole fractions of the first and the second components in the mixture, and F1 and F2 are the experimental densities of the first and second components in the mixture”, and on page 2047, column 2, paragraph 2 “the delta (property) of a mixture can be predicted using weighted average delta (eq 1) of the k most similar mixtures in the training set where yi and yˆi are the actual and predicted delta of the ith mixture respectively, and wi are weights calculated using (eq 2)”, reading on wherein the mixing rules comprise property-specific aggregation of single- component data into blend-level properties using weighted combinations with weights dependent on at least the components' volume fractions and particle-size metrics.
It would have been obvious at the time of first filing to have modified the teachings of Ouyang et al. for a virtual design and assessment method/system for chemical mixtures, specifically pharmaceuticals, with the teachings of Ajmani et al. for modeling mixtures based on weighted combinations of single component properties as the latter teaches in the abstract “The study resulted in significant ensemble neural network and k-nearest neighbor models having statistical parameters r2, q2 10cv greater than 0.9, and pred_r2 greater than 0.75. The developed models can be used to predict the delta and hence the density of a new mixture. The QSPR analysis shows the importance of hydrogen bond, polar, shape, and thermodynamic descriptors in determining mixture density, thus aiding in the understanding of molecular interactions important in molecular packing in the mixtures”. One would have had a reasonable expectation of success given that the models of Ajamani et al. are designed for the exact problem for which Ouyang et al. is trying to optimize using the same or similar data. Therefore, it would have been obvious at the time of first filing to have modified the teachings of each and to be successful.
Claim 2 is directed to the method of claim 1 but further specifies that if the properties do not comply with the user-defined TPP that continual optimization continue based on the difference between properties and dosage.
Ouyang et al. teaches in paragraph [0074] “…expert system prediction by oral solution preparation of ritonavir prescription composition is very close to the actual pharmaceutical prescription and have high accuracy and reliability. and the output of the results contained in content and function division of each component, which is good for guiding preparation research staff to further adjust and improve prescription”, reading on if it is determined that the predicted product properties do not comply with the user-defined TPP or if it is determined that an experimental result obtained after preparing and characterizing the identified suitable formulation does not comply with the user defined TPP, performing at least one of the following steps: suggesting at least one additional technological measure to optimize the key parameters of the Al, based on a difference between the predicted product properties and the user-defined TPP or a difference between the experimental result and the user-defined TPP; suggesting to adjust the user-defined TPP based on a difference between the predicted product properties and the user-defined TPP or a difference between the experimental result and the user-defined TPP; and suggesting to select a different dosage form based on a difference between the predicted product properties and the user-defined TPP or a difference between the experimental result and the user-defined TPP.
Claim 3 is directed to the method of claim 2 and thus claim 1, but further specifies that at least one of the additional technical measures listed be used in the method.
Ouyang et al. teaches in paragraph [0073] “Embodiments of the invention injection development process, the process is a classic case of medicine prescription design and operation of the optimization module, the specific step is as follows: (1) based on the pharmaceutical prescription parameters before. medicine prescription design and optimizing module in the pharmaceutical prescription database according to dosage collects relevant prescription record; (2) according to the prescription in the rule module marks the key parameters of the formulation-drug solubility, drug solubility analysis judging, when content of medicine in the medicine solubility > dose. then using conventional solvent-water, the solubility drug contained in < single dose amount, it is necessary to start solubilizing module adding corresponding additive, increasing drug solubility, (3) additive type selection range derived from a pharmaceutical prescription database statistical analysis result. a co-solvent and surfactant, specifically additive type selected is need to prescription by machine learning analysis or molecular simulation interaction analysis for medicine and accessories, recommending a suitable additive”, reading on wherein the at least one additional technical measure comprises at least one of: milling or micronization, and addition of and processing with excipients.
Claim 4 is directed to the method of claim 1 but further specifies that if the predicted product properties do not comply with the user-defined TPP then the method repeatedly receives further user input and steps b-h.
Ouyang et al. teaches in paragraph [0074] “…expert system prediction by oral solution preparation of ritonavir prescription composition is very close to the actual pharmaceutical prescription and have high accuracy and reliability. and the output of the results contained in content and function division of each component, which is good for guiding preparation research staff to further adjust and improve prescription”, reading on further comprising: if the predicted product properties do not comply with the user-defined TPP or if it is determined that the experimental result obtained after preparing and characterizing the identified suitable formulation does not comply with the user defined TPP, repeatedly performing a sequence comprising: receiving a further user input related to a different dosage form, a user- redefined TPP, and/or re-determined key physicochemical properties of the Al; and performing steps b) to h), until a suitable formulation has been identified with the product properties complying with the user-defined or user-redefined TPP.
Claim 5 is directed to the method of claim 1 but further specifies that the product development comprise at least one of the listed products provided in the specified group.
Ouyang et al. teaches in the abstract “The invention claims a medicine preparation prescription virtual design and assessment method and system. The invention claims a medicine preparation prescription virtual design and evaluating method and system mainly comprises front research module of the pharmaceutical prescription, drug formulary design and optimization module, medicine preparation technique of medicine prescription design and optimization module”, reading on herein the product development comprises at least one of the following: development of cleaning agents; development of cosmetic products; development of dietary supplements; development of drug products; development of fungicide formulations; development of herbicide formulations; development of pesticide formulations; and development of washing agents.
Claim 6 is directed to the method of claim 1 but further specifies that the dosage form comprise at least one of those specified in the group provided.
Ouyang et al. teaches in claim 9 “The medicine preparation prescription according to claim 1, said virtual design and evaluation method and system, wherein the medicine prescription comprises tablet, capsule, pill, film, granule, solution agent, aromatic water, syrup, injection, eye drops, nasal drops, mixture, lotion, liniment, suppository, aerosol, spraying agent, jellies, transdermal administration preparation, ointment, paste, slow-release preparation, microsphere preparation, a liposome, a nanoparticle formulation, target formulation, the traditional Chinese medicine preparation. biological medical preparation is one kind or several kinds”, reading on wherein the dosage form comprises at least one of a capsule, a chewing gum, a cream, an emulsion, a foam, a spray, a gel, a stick, granules, gummies, an implant, an ointment, a paste, pellets, a powder, a solution, a suppository, a suspension, a sustained-release form, a tablet, and a therapeutic patch.
Claim 7 is directed to the method of claim 1 but further specifies that the user-defined TPP comprises at least one of the specified measurements/parameters listed in the group provided.
Claim 8 is directed to the method of claim 1 but further specifies that the user-defined TPP comprises at least one of the specified measurements/parameters listed in the group provided.
Claim 9 is directed to the method of claim 1 but further specifies that the user-defined TPP comprises at least one of the specified measurements/parameters listed in the group provided.
Ouyang et al. teaches in paragraph [0074] “The invention process is similar to the process of present medicine research experiment, firstly input the necessary drug information, and predicting to obtain prescription parameters, drug prescription, preparation technology and in vivo pharmacokinetic behaviour…”, it would be inherent to any pharmacokinetic behaviour, prescription parameters, and preparation technology to read on wherein the user-defined TPP comprises at least one of: amount and/or concentration of the active ingredient; size, volume and/or weight of the dosage form; mechanical and/or rheological properties of the dosage form; release profile of the active ingredient; other application-relevant parameters; compatibility and stability; and other manufacturing-relevant properties, and wherein the user-defined TPP comprises at least one of: amount of Al per unit; size and/or weight of the dosage form; mechanical strength of the dosage form; desired release behaviour of the dosage form; disintegration time of the dosage form; dissolution profile of the Al; compatibility of active ingredients and excipients; probability to pass content uniformity criteria; flowability of a powder blend; tabletability of a powder blend; and compatibility and stability of active ingredients and excipients, and wherein the user-defined TPP comprises at least one of: concentration of Al; volume of the dosage form; rheological behaviour and/or viscosity of the dosage form; spreading and/or adherence of the dosage form; dispersity and/or volume fractions of phases; hydrophilicity and/or lipophilicity; release behaviour of the dosage form; melting point of the dosage form; dissolution profile of the Al; and compatibility and stability of active ingredients and excipients.
Claim 10 is directed to the method of claim 1 but further specifies that the physiochemical properties of the AI comprise at least of those specified in the group provided.
Ouyang et al. teaches in paragraph [0074] “The invention process is similar to the process of present medicine research experiment, firstly input the necessary drug information, and predicting to obtain prescription parameters, drug prescription, preparation technology and in vivo pharmacokinetic behaviour…” and in paragraph [0003] “The invention claims a medicine preparation prescription virtual design and evaluation method and system, mainly including but not limited to the following four kinds of technology method: (1) molecular simulation technology from molecular level to simulate the medicine and auxiliary material molecular structure and behavior. the method is mainly based on quantum mechanics or molecular mechanics principle of the interaction of between the molecular conformation and driving, various physical and chemical properties can be directly given…”, which would implicitly contain at least some of the properties listed thereby reading on wherein the key physicochemical properties of the Al comprise at least one of: hydrophilicity and/or lipophilicity (e.g., distribution coefficient); melting point; permeability across biological or artificial lipid membranes; solubility in water, solvents, co-solvents and/or biorelevant media; miscibility with water, solvents, co-solvents and/or biorelevant media; true density; viscosity; wettability; interfacial and/or surface tension; particle size distribution data; particle morphology, shape and/or aspect ratio; bulk and tapped density; flowability; compressibility and compactibility; hygroscopicity; water content; concentration of impurities; other chemical, physicochemical and/or physical properties; and information on compatibility and stability.
Claim 11 is directed to the method of claim 1 but further specifies that the user-defined TPP comprise a dose of AI and maximum weight, calculation of weight fractions, predicting properties and selecting at least one promising excipient.
Ouyang et al. teaches in paragraph [0004] “the medicines with pharmaceutical auxiliary materials database comprising number information, compound name, CAS number compounds, compound molecular weight” and in paragraph [0073] “Embodiments of the invention injection development process, the process is a classic case of medicine prescription design and operation of the optimization module, the specific step is as follows: (1) based on the pharmaceutical prescription parameters before. medicine prescription design and optimizing module in the pharmaceutical prescription database according to dosage collects relevant prescription record; (2) according to the prescription in the rule module marks the key parameters of the formulation-drug solubility, drug solubility analysis judging, when content of medicine in the medicine solubility > dose. then using conventional solvent-water, the solubility drug contained in < single dose amount, it is necessary to start solubilizing module adding corresponding additive, increasing drug solubility, (3) additive type selection range derived from a pharmaceutical prescription database statistical analysis result. a co-solvent and surfactant, specifically additive type selected is need to prescription by machine learning analysis or molecular simulation interaction analysis for medicine and accessories, recommending a suitable additive; (4) additive dosage according to prescription rules and machine learning analysis obtained calculation”, reading on wherein the user-defined TPP comprises a dose of Al per unit and a maximum weight of the dosage form; wherein step c) further comprises: calculating weight fractions of the Al and the one or more excipients selected from the excipient database based on the dose of Al per unit and the maximum weight of the dosage form; predicting properties of a combination of the Al and the one or more excipients; and wherein step d) further comprises selecting at least one promising excipient from the one or more excipients if the properties of a corresponding mixture satisfy a predefined criterion.
Claim 12 is directed to the method of claim 1 but further specifies that the dosage form comprises a pharmaceutical dosage form.
Ouyang et al. teaches in claim 9 “The medicine preparation prescription according to claim 1, said virtual design and evaluation method and system, wherein the medicine prescription comprises tablet, capsule, pill, film, granule, solution agent, aromatic water, syrup, injection, eye drops, nasal drops, mixture, lotion, liniment, suppository, aerosol, spraying agent, jellies, transdermal administration preparation, ointment, paste, slow-release preparation, microsphere preparation, a liposome, a nanoparticle formulation, target formulation, the traditional Chinese medicine preparation. biological medical preparation is one kind or several kinds”, reading on wherein the dosage form comprises a pharmaceutical dosage form.
Claim 14 is directed to the apparatus of claim 13 but further specifies the use of a web server and webpage for the program to display a GUI to a user.
Ouyang et al. teaches in Figure 4 a GUI and webpage for the method, reading on an apparatus according to claim 12, and a web server configured to interface with a user via a webpage and/or an application program served by the web server; wherein the apparatus is configured to provide a graphical user interface, GUI, to a user, by the webpage and/or the application program.
Claim 15 is directed to a computer program element which when executed on a computer performs the method of claim 1.
Ouyang et al. teaches in the abstract “Compared with the traditional drug formulary screening laboratory in the empirical formula and preparing method, the invention can accelerate development of pharmaceutical product, and does not consume any laboratory equipment, completely via the computer platform”, reading on a computer program element comprising sets of instructions, wherein, when the sets of instructions are executed on a processor of an apparatus, the sets of instructions cause the apparatus or the system to perform the method of claim 1.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/K.N.A./ Examiner, Art Unit 1687
/OLIVIA M. WISE/ Supervisory Patent Examiner, Art Unit 1685
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