DETAILED ACTION
Applicant’s response filed 06/24/2026 has been fully considered. Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied.
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 .
Status of the Claims
Claims 1, 3-10, 12, and 14-18 are pending and under consideration in this action. Claims 2, 11, 13, and 19 were canceled in the amendment filed 06/24/2026.
Priority
The instant application is a CON of PCT/JP2021/005417, filed 2/15/2021, which claims priority to Japanese Application Number 2020-026428, filed 2/19/2020, as reflected in the filing receipt mailed on 8/26/2022. Acknowledgment is made of Applicant's claim for foreign priority under 35 U.S.C. 119 (a)-(d). Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. The claims to the benefit of priority are acknowledged and the effective filing date of claims 1, 3-10, 12, and 14-18 is 2/19/2020.
Specification
The objection to the Specification is withdrawn in view of Applicant’s amendments to the Specification filed 06/24/2026 (Applicant’s Remarks, Pg. 9).
Claim Objections
Withdrawn Objections
The objection to claim 13 is withdrawn in view of Applicant’s cancelation of claim 13 in the amendment filed 06/24/2026 (Applicant’s Remarks, Pg. 11).
Newly Recited Objections
Claims 1, 3-10, 12, and 14-18 are objected to because of the following informalities:
Claim 1 recites the phrase “a computer-implemented method for improving cell culture process search” in lines 1-2 of the claim, which should be corrected to “a computer-implemented method for improving a cell culture process search” to correct the grammar.
Claims 3-10, 12, and 14-18 recite the phrase “the computer-implemented method for improving cell culture process search”, which should be corrected to “the computer-implemented method for improving the cell culture process search” to correct the grammar.
Claim 6 recites “wherein in generating the plurality of process conditions , a part of items…”, which should be corrected to remove the extra space after conditions, “wherein in generating the plurality of process conditions”.
Claim 16 recites the phrase “wherein the prokaryotic cell is a bacterium including Escherichia coli, Bacillus subtilis, cyanobacteria, or actinomycetes and an archaeon including methanogen, extreme halophile, or hyperthermophile”, which should be corrected to italicize the species of bacteria, “wherein the prokaryotic cell is a bacterium including Escherichia coli, Bacillus subtilis, cyanobacteria, or actinomycetes and an archaeon including methanogen, extreme halophile, or hyperthermophile”.
Appropriate correction is required.
Claim Interpretation
MPEP § 2111.04 recites:
The determination of whether each of these clauses is a limitation in a claim depends on the specific facts of the case. See, e.g., Griffin v. Bertina, 285 F.3d 1029, 1034, 62 USPQ2d 1431 (Fed. Cir. 2002) (finding that a "wherein" clause limited a process claim where the clause gave "meaning and purpose to the manipulative steps"). In In re Giannelli, 739 F.3d 1375, 1378, 109 USPQ2d 1333, 1336 (Fed. Cir. 2014), the court found that an "adapted to" clause limited a machine claim where "the written description makes clear that 'adapted to,' as used in the [patent] application, has a narrower meaning, viz., that the claimed machine is designed or constructed to be used as a rowing machine whereby a pulling force is exerted on the handles." In Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), the court held that when a "‘whereby’ clause states a condition that is material to patentability, it cannot be ignored in order to change the substance of the invention." Id. However, the court noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)).
Claim 1 recites the limitation “thereby reducing the number of trials required to obtain process conditions satisfying the desired cell proliferation amount and the desired bioproduction amount in a cell culture experiment.” The “reducing the number of trials required to obtain process conditions” to “satisfy the desired cell proliferation amount and the desired bioproduction amount in a cell culture experiment” is an intended result, since there are no positive steps whereby the number of trials is reduced when the desired cell proliferation amount and the desired bioproduction are satisfied. Accordingly, since it is unclear what steps result in a reduction of the number of trials to satisfy desired values, this limitation is not given patentable weight.
Claim Rejections - 35 USC § 112(a)
Withdrawn Rejections
The rejection of claims 13 and 19 under 35 U.S.C. 112(a) as failing to comply with the written description requirement is withdrawn in view of Applicant’s cancelation of claims 13 and 19 in the amendment filed 06/24/2026 (Applicant’s Remarks, Pg. 11).
Newly Recited Rejections
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 3-10, 12, and 14-18 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
This rejection is newly recited and necessitated by claim amendment.
Claim 1 recites the limitation “wherein the candidate process conditions are calculated by solving an inverse problem using a deep-learning-based regression model generated using, as training data, the generated process conditions and results of the cell culture simulation”.
MPEP 2161.01(I) recites:
“Original claims may lack written description when the claims define the invention in functional language specifying a desired result but the specification does not sufficiently describe how the function is performed or the result is achieved. For software, this can occur when the algorithm or steps/procedure for performing the computer function are not explained at all or are not explained in sufficient detail (simply restating the function recited in the claim is not necessarily sufficient). In other words, the algorithm or steps/procedure taken to perform the function must be described with sufficient detail so that one of ordinary skill in the art would understand how the inventor intended the function to be performed. … When examining computer-implemented functional claims, examiners should determine whether the specification discloses the computer and the algorithm (e.g., the necessary steps and/or flowcharts) that perform the claimed function in sufficient detail such that one of ordinary skill in the art can reasonably conclude that the inventor possessed the claimed subject matter at the time of filing.”
For these claim elements, the disclosure “does not sufficiently describe how the function is performed or the result is achieved”. The instant Specification (see Para. [0023]) recites the creation of a learned model by machine learning with the process condition and the culture prediction result as input; and calculating an optimal process by solving an inverse problem using the learned model. The instant Specification (see Para. [0073]) further recites an example where in a case where the machine learning is performed, the plurality of process conditions generated in the process condition generation step and the culture prediction results acquired in the culture result prediction step are input to an input side (input step). Next, with the process conditions and the culture prediction results, which are input in the input step, as learning data, a regression model (learned model) is created by the machine learning (creation step). An inverse problem is solved by using the regression model created as a result of learning to calculate the optimal process condition (calculation step). In a case where the inverse problem is solved, the desired cell proliferation amount, the culture medium composition which is the desired calculated amount of antibody, or the culture condition are calculated. However, the Specification is silent on the specific type and/or architecture of regression model, machine learning model, or deep learning model used to carry out the claimed method. Additionally, the Specification is silent on any steps for training, or any training data, used to carry out the claimed method. Accordingly, the disclosure is not commensurate with the written description scope of the claim.
Claim Rejections - 35 USC § 112(b)
Newly Recited Rejections
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 3-10, 12, and 14-18 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
This rejection is newly recited and necessitated by claim amendment.
Claim 1 recites the phrase “thereby reducing the number of trials required to obtain process conditions satisfying the desired cell proliferation amount and the desired bioproduction amount in a cell culture experiment” in lines 22-24 of the claim. There is insufficient antecedent basis for the number of trials in the claim, as there is no prior mention of this phrase earlier in claim 1. This rejection can be overcome by amendment of claim 1 to recite “thereby reducing a number of trials required to obtain process conditions satisfying the desired cell proliferation amount and the desired bioproduction amount in a cell culture experiment”. Claims 3-10, 12, and 14-18 are also rejected due to their dependency on claim 1.
Claim 10 recites the phrase “wherein in the method by the random number generation…” in line 3 of the claim. The metes and bounds of the claim are rendered indefinite due to the lack of clarity. It is unclear what the method by the random number generation means. Based on the Specification (see Para. [0050-[0054]), it appears the method is using a random number generator to generate the process condition values. Examiner suggests amendment of claim 10 to recite “wherein in the method of ”.
Claim 17 recites “a non-transitory, computer-readable tangible recording medium on which a program for causing, when read by a computer, the computer to perform the computer-implemented method for improving cell culture process search according to claim 1 is recorded”. The metes and bounds of the claim are rendered indefinite due to the lack of clarity. It is unclear what else is being recorded in the phrase “is recorded” at the end of claim 17, because the non-transitory-computer readable medium already recorded the steps for improving the cell culture process search according to claim 1. Examiner suggests amendment of claim 17 to recite “a non-transitory computer-readable recording medium with instructions stored thereon to cause a computer to perform the computer-implemented method for improving the cell culture process search of claim 1”, or similar.
Claim Rejections - 35 USC § 101
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.
Claims 1, 3-10, 12, and 14-18 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claims recite both (1) mathematical concepts (mathematical relationships, formulas or equations, or mathematical calculations) and (2) mental processes, i.e., concepts performed in the human mind (including observations, evaluations, judgements or opinions) (see MPEP § 2106.04(a)).
Any newly recited portion is necessitated by claim amendment.
Framework with which to evaluate Subject Matter Eligibility as outlined in MPEP § 2106:
Step 1: Are the claims directed to a process, machine, manufacture or composition of matter;
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of nature, a natural phenomenon, or an abstract idea;
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application (Prong Two); and
Step 2B: If the claims do not integrate the judicial exception, do the claims provide an inventive concept.
Framework as it pertains to the instant claims:
Step 1:
In the instant application, claims 1, 3-10, 12, and 14-16 are directed towards a method, claim 17 is directed towards a manufacture, and claim 18 is directed toward a machine, which falls into one of the categories of statutory subject matter (Step 1: YES).
Step 2A, Prong One:
In accordance with MPEP § 2106, claims found to recite statutory subject matter (Step 1: YES) are then analyzed to determine if the claims recite any concepts that equate to an abstract idea, law of nature or natural phenomenon (Step 2A, Prong One). The following instant claims recite limitations that equate to one or more categories of judicial exceptions:
Claims 1, 17, and 18 recite a mental process (i.e., an evaluation of process conditions) in “varying the process condition within a predetermined range”; a mental process (i.e., an evaluation of candidate culture mediums for process conditions) in “acquiring a culture prediction result of the cells for each of the plurality of process conditions, by generating a candidate culture medium for each of the plurality of process conditions”; a mathematical concept (i.e., estimating a metabolic flux, see Specification Para. [0063]) in “estimating a metabolic flux in a constrained metabolic flux space of a metabolic reaction network defined based on at least one of stoichiometric constraints and flux constraints”; a mathematical concept (i.e., performing a cell culture simulation using a model or flux balance analysis, see Specification Para. [0057]) in “performing a cell culture simulation for the generated candidate culture medium”; a mathematical concept (i.e., solving an inverse problem based on a regression model) in “calculating candidate process conditions that satisfy the desired cell proliferation amount and the desired bioproduction amount based on the culture prediction result for each of the plurality of process conditions obtained by the cell cultured simulation, wherein the candidate process conditions are calculated by solving an inverse problem using a deep-learning-based regression model generated using, as training data, the generated process conditions and results of the cell culture simulation”; and a mental process (i.e., an evaluation of the number of reduced trials) in “thereby reducing the number of trials required to obtain process conditions satisfying the desired cell proliferation amount and the desired bioproduction amount in a cell culture experiment”.
Claim 5 recites a mathematical concept (i.e., matrix generation) in “wherein the plurality of process conditions are acquired as a matrix”.
Claim 6 recites a mental process (i.e., selecting a portion of the data with a corresponding numerical value) in "wherein in generating the plurality of process conditions, a part of items of the process condition is selected and a numerical value for the selected item is determined”.
Claim 7 recites a mental process (i.e., comparison to a predetermined numerical value, experimental result, or expansion culture medium mixing strategy result) and a mathematical concept (i.e., random number generation) in “wherein the plurality of process conditions are generated by a method including at least any one of a method of determining a numerical value for an item of the process condition based on a predetermined numerical value, a method of performing the determination by random number generation in a predetermined range, a method of performing the determination by a numerical value obtained by an experiment, or a method of performing the determination based on an expansion culture medium mixing strategy”.
Claim 8 recites a mathematical concept (i.e., setting the range using a mechanistic equation) in “wherein the predetermined range is set by using a mathematically modeled equation of a mechanism by which an organism takes in a culture medium component”.
Claim 9 recites a mathematical concept (i.e., modeling the equation using Michaelis-Menten kinetics or Fick's law) in “wherein the mathematically modeled equation is Michaelis-Menten kinetics or Fick's law”.
Claim 10 recites a mathematical concept (i.e., random number generation) in “wherein in the method by the random number generation, the numerical value for the item of the process condition is determined by using a numerical value generated by a continuous uniform random number, a continuous normal random number, a discrete random number, or a binary random number”.
Claim 12 recites a mathematical concept (i.e., performing metabolic flux analysis; see Specification Para. [0063]) in “wherein the cell culture simulation method includes a modeling approach including metabolic flux analysis using a genome-scale metabolic model or flux balance analysis”.
These recitations are similar to the concepts of collecting information, and displaying certain results of the collection and analysis in Electric Power Group, LLC, v. Alstom (830 F.3d 1350, 119 USPQ2d 1739 (Fed. Cir. 2016)), comparing information regarding a sample or test to a control or target data in Univ. of Utah Research Found. v. Ambry Genetics Corp. (774 F.3d 755, 113 U.S.P.Q.2d 1241 (Fed. Cir. 2014)) and Association for Molecular Pathology v. USPTO (689 F.3d 1303, 103 U.S.P.Q.2d 1681 (Fed. Cir. 2012)), and organizing and manipulating information through mathematical correlations in Digitech Image Techs., LLC v Electronics for Imaging, Inc. (758 F.3d 1344, 111 U.S.P.Q.2d 1717 (Fed. Cir. 2014)) that the courts have identified as concepts that can be practically performed in the human mind or mathematical relationships.
The abstract ideas recited in the claims are evaluated under the broadest reasonable interpretation (BRI) of the claim limitations when read in light of and consistent with the specification, and are determined to be directed to mental processes that in the simplest embodiments are not too complex to practically perform in the human mind. Additionally, the recited limitations that are identified as judicial exceptions from the mathematical concepts grouping of abstract ideas are abstract ideas irrespective of whether or not the limitations are practical to perform in the human mind.
Specifically, claims 1, 17 and 18 involve nothing more than varying process conditions, generating candidate culture mediums, estimating metabolic flux and performing a cell culture simulation, calculating candidate process conditions by solving an inverse problem using a regression model, and reducing the number of trials required to obtain process conditions satisfying the desired cell proliferation amount and the desired bioproduction amount. The steps reciting estimating metabolic flux and performing a cell culture simulation; and calculating candidate process conditions by solving an inverse problem using a regression model are, under the BRI, performed using mathematical operations. The instant Specification (see Para. [0063]) recites that the metabolic flux is calculated by using a mathematical model for cell metabolism. Specifically, the objective function F11 is maximized within a constraint condition range for each time point. The instant Specification (see Para. [0057]) also recites that the cell culture simulation method can be performed by a method including a modeling approach including metabolic flux analysis (MFA) using a genome-scale metabolic model or flux balance analysis (FBA). Additionally, since there are no specifics in the methodology, the steps reciting varying process conditions, generating candidate culture mediums and reducing the number of trials required to obtain process conditions satisfying the desired cell proliferation amount and the desired bioproduction amount, are something that under BRI, one could perform mentally. Therefore, the claimed steps are not further defined beyond something that reads on performing a calculation using a computer as a tool, and merely looking at data and making a determination. As such, said steps are directed to judicial exceptions. The instant claims must therefore be examined further to determine whether they integrate the abstract idea into a practical application (Step 2A, Prong One: YES).
Step 2A, Prong Two:
In determining whether a claim is directed to a judicial exception, further examination is performed that analyzes if the claim recites additional elements that when examined as a whole integrates the judicial exception(s) into a practical application (MPEP § 2106.04(d)). A claim that integrates a judicial exception into a practical application will apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception. The claimed additional elements are analyzed to determine if the abstract idea is integrated into a practical application (MPEP § 2106.04(d)(I)). If the claim contains no additional elements beyond the abstract idea, the claim fails to integrate the abstract idea into a practical application (MPEP § 2106.04(d)(III)). The following independent claims recite limitations that equate to additional elements:
Claims 1, 17, and 18 recite “a computer-implemented method”; “obtaining a desired cell proliferation amount and a desired bioproduction amount”; and “generating a plurality of process conditions by obtaining, as a process condition, at least one of a culture medium composition and a culture condition for culturing cells”.
Claim 17 further recites “a non-transitory, computer-readable tangible recording medium on which a program for causing, when read by a computer, the computer to perform steps”.
Claim 18 further recites “a memory storing instructions”; and “a processor configured to execute the instructions to perform the computer-implemented method for improving cell culture process search”.
Regarding the above cited limitations in claims 1, 17, and 18 of (i) obtaining a desired cell proliferation amount and a desired bioproduction amount; and (ii) generating a plurality of process conditions by obtaining, as a process condition, at least one of a culture medium composition and a culture condition for culturing cells. These limitations equate to insignificant, extra-solution activity of mere data gathering because these limitations gather data before or after the recited judicial exceptions of varying process conditions, generating candidate culture mediums, estimating metabolic flux and performing a cell culture simulation, calculating candidate process conditions by solving an inverse problem using a regression model, and reducing the number of trials required to obtain process conditions satisfying the desired cell proliferation amount and the desired bioproduction amount (see MPEP § 2106.04(d)).
Regarding the above cited limitations in claims 1, 17, and 18 of (iii) a computer-implemented method (claim 1); (iv) a non-transitory, computer-readable tangible recording medium on which a program for causing, when read by a computer, the computer to perform the cell culture process search method (claim 17); (v) a memory storing instructions (claim 18); and (vi) a processor configured to execute the instructions to perform the computer-implemented method for improving cell culture process search (claim 18). These limitations require only a generic computer component, which does not improve computer technology. Therefore, these limitations equate to mere instructions to implement an abstract idea on a generic computer, which the courts have established does not render an abstract idea eligible in Alice Corp. 573 U.S. at 223, 110 USPQ2d at 1983.
Additionally, none of the recited dependent claims recite additional elements which would integrate the judicial exception into a practical application. Specifically, claims 3-4 further limit the types of process conditions or culture conditions, and claims 14-16 further limit the type of cells. As such, claims 1, 3-10, 12, and 14-18 are directed to an abstract idea (Step 2A, Prong Two: NO).
Step 2B:
Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself (Step 2B). The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. The instant independent claims recite the same additional elements described in Step 2A, Prong Two above.
Regarding the above cited limitations in claims 1, 17, and 18 of (i) obtaining a desired cell proliferation amount and a desired bioproduction amount; and (ii) generating a plurality of process conditions by obtaining, as a process condition, at least one of a culture medium composition and a culture condition for culturing cells. These limitations do not include any specific steps for obtaining desired cell proliferation amount and desired bioproduction amount or for obtaining culture medium composition and culture conditions. Under the BRI, these limitations are merely receiving data for subsequent steps of varying process conditions, generating candidate culture mediums, estimating metabolic flux and performing a cell culture simulation, calculating candidate process conditions by solving an inverse problem using a regression model, and reducing the number of trials required to obtain process conditions satisfying the desired cell proliferation amount and the desired bioproduction amount. Therefore, these limitations equate to receiving/transmitting data over a network, which the courts have established as a WURC limitation of a generic computer in buySAFE, Inc. v. Google, Inc., 765 F.3d 1350, 1355, 112 USPQ2d 1093, 1096 (Fed. Cir. 2014).
Regarding the above cited limitations in claims 1, 17, and 18 of (iii) a computer-implemented method (claim 1); (iv) a non-transitory, computer-readable tangible recording medium on which a program for causing, when read by a computer, the computer to perform the cell culture process search method (claim 17); (v) a memory storing instructions (claim 18); and (vi) a processor configured to execute the instructions to perform the computer-implemented method for improving cell culture process search (claim 18). These limitations equate to instructions to implement an abstract idea on a generic computing environment, which the courts have established does not provide an inventive concept (see MPEP § 2106.05(d) and MPEP § 2106.05(f)).
These additional elements do not comprise an inventive concept when considered individually or as an ordered combination that transforms the claimed judicial exception into a patent-eligible application of the judicial exception. Therefore, the instant claims do not amount to significantly more than the judicial exception itself (Step 2B: NO). As such, claims 1, 3-10, 12, and 14-18 are not patent eligible.
Response to Arguments under 35 U.S.C. 101
Applicant’s arguments filed 06/24/2026 have been fully considered but they are not persuasive.
1. Applicant argues that the claimed invention does not perform generic data processing. Instead, it performs simulation in a constrained metabolic flux space of a metabolic reaction network defined by stoichiometric constraints and flux constraints. Accordingly, the claimed invention is not directed merely to abstract decision-making or mathematical optimization (Applicant’s Remarks, Pg. 13).
It is respectfully submitted that this is not persuasive for the following reasons:
MPEP § 2106.04(d)(II) recites:
The analysis under Step 2A Prong Two is the same for all claims reciting a judicial exception, whether the exception is an abstract idea, a law of nature, or a natural phenomenon (including products of nature). Examiners evaluate integration into a practical application by: (1) identifying whether there are any additional elements recited in the claim beyond the judicial exception(s); and (2) evaluating those additional elements individually and in combination to determine whether they integrate the exception into a practical application, using one or more of the considerations introduced in subsection I supra, and discussed in more detail in MPEP §§ 2106.04(d)(1), 2106.04(d)(2), 2106.05(a) through (c) and 2106.05(e) through (h).
The limitation in claim 1, as indicated by Applicant, of “estimating a metabolic flux in a constrained metabolic flux space of a metabolic reaction network defined based on at least one of stoichiometric constraints and flux constraints” has been identified as a judicial exception (a mathematical concept) in Step 2A, Prong One above. The integration of a judicial exception into a practical application can only be achieved by additional elements, not by a limitation that recites a judicial exception. Thus, the recited limitation is not considered as an improvement in computer-implemented cell culture simulation technology. This argument is thus not persuasive.
2. Applicant also argues that the present invention solves an inverse problem using a deep-learning-based regression model. By employing a regression model and solving the problem as an inverse problem, the claimed invention efficiently determines candidate process conditions satisfying the desired cell proliferation amount and desired bioproduction amount. As a result, the claimed invention improves computational efficiency in the practical application of computer-implemented cell culture simulation. In other words, the claimed invention provides a technical improvement in computer-implemented cell culture simulation technology (Applicant’s Remarks, Pg. 13).
It is respectfully submitted that this is not persuasive for the following reasons:
Analogous to argument (1) above, and following MPEP § 2106.04(d)(II), the following limitations in claim 1, as indicated by Applicant above, recite judicial exceptions: (a) “calculating candidate process conditions that satisfy the desired cell proliferation amount and the desired bioproduction amount based on the culture prediction result for each of the plurality of process conditions obtained by the cell cultured simulation, wherein the candidate process conditions are calculated by solving an inverse problem using a deep-learning-based regression model generated using, as training data, the generated process conditions and results of the cell culture simulation” and (b) “thereby reducing the number of trials required to obtain process conditions satisfying the desired cell proliferation amount and the desired bioproduction amount in a cell culture experiment”. As described in Step 2A, Prong One above, limitation (a) recites a mathematical concept and limitation (b) recites a mental process. Additionally, as described in the Claim Interpretation section above, it is noted that limitation (b) is not given patentable weight as the limitation recites an intended use, rather than any positive steps which result in a reduction of the number of trials to satisfy desired values.
The integration of a judicial exception into a practical application can only be achieved by additional elements, not by limitations that recite judicial exceptions. Thus, the recited limitations are not considered as a technical improvement in computer-implemented cell culture simulation technology. This argument is thus not persuasive.
Claim Rejections - 35 USC § 102
Withdrawn Rejections
The rejection of claims 1-4, 13-16, and 18-19 under 35 U.S.C. 102(a)(1) as being anticipated by Downey et al. is withdrawn in view of Applicant’s amendments to the claims filed 06/24/2026 (Applicant’s Remarks, Pg. 12-13). Specifically, Downey et al. does not teach the estimation of a metabolic flux in a constrained metabolic flux space of a metabolic reaction network or performing a cell culture simulation as disclosed in amended claim 1.
Claim Rejections - 35 USC § 103
Withdrawn Rejections
The rejection of claims 5-6 and 11-12 under 35 U.S.C. 103 as being unpatentable over Downey et al. in view of Zampieri et al. is withdrawn in view of Applicant’s amendments to the claims filed 06/24/2026 (Applicant’s Remarks, Pg. 12-13). Specifically, Zampieri et al. teaches that the model optimizes conditions based on flux distributions for the production of lactate (i.e., a bioproduction amount), but does not teach the calculation of candidate process conditions that also satisfy the desired cell proliferation amount, as disclosed in amended claim 1.
The rejection of claims 7-9 under 35 U.S.C. 103 as being unpatentable over Downey et al. in view of Mehta et al. is withdrawn in view of Applicant’s amendments to the claims filed 06/24/2026 (Applicant’s Remarks, Pg. 12-13). Specifically, Mehta et al. teaches a mathematical model for cellular uptake of oxygen based in cell culture systems based on the Michaelis-Menten equation. However, Mehta et al. also does not teach the calculation of candidate process conditions that satisfy the desired cell proliferation amount, as disclosed in amended claim 1.
The rejection of claim 10 under 35 U.S.C. 103 as being unpatentable over Downey et al. in view of Mehta et al. and Schellenberger et al. is withdrawn in view of Applicant’s amendments to the claims filed 06/24/2026 (Applicant’s Remarks, Pg. 12-13). Schellenberger et al. teaches the use of randomized sampling in the analysis of metabolic flux networks. However, Schellenberger et al. also does not teach the calculation of candidate process conditions that satisfy the desired cell proliferation amount, as disclosed in amended claim 1.
The rejection of claim 17 under 35 U.S.C. 103 as being unpatentable over Downey et al. is withdrawn in view of Applicant’s amendments to the claims filed 06/24/2026 (Applicant’s Remarks, Pg. 12-13). Downey et al. does not teach all the limitations of amended claim 1, as disclosed in the Claim Rejections - 35 USC § 102 section above.
Conclusion
No claims allowed.
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.
Claims 1, 3-10, 12, and 14-18 appear to be free from the prior art because the prior art does not fairly suggest or teach the calculation of candidate process conditions that satisfy both the desired cell proliferation amount and the desired bioproduction amount, as disclosed in amended claim 1. The closest prior art is Zampieri et al. (A poly-omics machine-learning method to predict metabolite production in CHO cells, in Proceedings of the 2nd International Electronic Conference on Metabolomics, 20-27 November 2017, MDPI: Basel, Switzerland; published 11/20/2017; previously cited). Zampieri et al. discloses a method that combines machine learning techniques with metabolic modelling to estimate lactate production (i.e., a desired bioproduction amount) in CHO cell cultures (Abstract). Zampieri et al. further discloses the generation of data with varying cell culture conditions (Pg. 3, Para. 1), and a model for the computation of flux distributions using flux balance analysis (FBA) for several conditions (Pg. 3, Para. 3 – Pg. 4, Para. 2). However, Zampieri et al. does not teach calculating candidate process conditions that satisfy the desired cell proliferation amount and the desired bioproduction amount based on the culture prediction result for each of the plurality of process conditions obtained by the cell culture simulation, as disclosed in instant claim 1. Claims 3-10, 12, and 14-18 appear to be free from the prior art due to their dependency on claim 1.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DIANA P SANFORD whose telephone number is (571)272-6504. The examiner can normally be reached Mon-Fri 8am-5pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Karlheinz Skowronek can be reached at (571)272-9047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/D.P.S./Examiner, Art Unit 1687
/Lori A. Clow/Primary Examiner, Art Unit 1687
Prosecution Insights