DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant's response, filed 10/14/2025, has been fully considered. The following rejections and/or objections are either reiterated or newly applied. Herein, "the previous Office action" refers to the Non-Final Rejection of 07/14/2025.
In view of the amendment and remarks from 10/14/2025, the rejection of claims 2-5, 13, 15-18 and 20-22 under 35 USC § 112(b) is hereby withdrawn in view of Applicant's amendments, rendering the ground of rejection moot. The following rejections and/or objections are either maintained or newly applied for claims 1-23. They constitute the complete set applied to the instant application.
Status of the Claims
Claims 1-23 are examined.
Priority
This application is a 371 of PCT/EP2019/061878 (05/08/2019), which claims no further priority herein as reflected in the filing receipt mailed on Apr. 01, 2022. The claims to the benefit of priority are acknowledged and the effective filing date of claims 1-23 is 05/08/2019.
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 1-23 are rejected under 35 USC § 101 because the claimed inventions are directed to an abstract idea without significantly more. "Claims directed to nothing more than abstract ideas (such as a mathematical formula or equation), natural phenomena, and laws of nature are not eligible for patent protection" (MPEP 2106.04 § I). Abstract ideas include mathematical concepts, and procedures for evaluating, analyzing or organizing information, which are a type of mental process (MPEP 2106.04(a)(2)).
101 background
MPEP 2106 organizes JE analysis into Steps 1, 2A (Prong One & Prong Two), and 2B as analyzed below.
Step 1: Are the claims directed to a process, machine, manufacture, or composition of matter (MPEP 2106.03)?
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 (MPEP 2106.04(a-c))?
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
Analysis of instant claims
Step 1: Are the claims directed to a 101 process, machine, manufacture, or composition of matter (MPEP 2106.03)?
The instant claims are directed to a method (claims 1-9), a system (claims 10-11, 14-15 and 20-23), and a CRM (claims 12-13 and 16-19); each of which falls within one of the categories of statutory subject matter. [Step 1: claims 1-23 Yes].
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 (MPEP 2106.04(a-c))?
Background
With respect to Step 2A, Prong One, the claims recite judicial exceptions in the form of abstract ideas. MPEP § 2106.04(a)(2) further explains that abstract ideas are defined as:
• mathematical concepts (mathematical formulas or equations, mathematical relationships
and mathematical calculations) (MPEP 2106.04(a)(2)(I));
• certain methods of organizing human activity (fundamental economic principles or practices, managing personal behavior or relationships or interactions between people) (MPEP 2106.04(a)(2)(II)); and/or
• mental processes (concepts practically performed in the human mind, including observations, evaluations, judgments, and opinions) (MPEP 2106.04(a)(2)(III)).
Analysis of instant claims
Mathematical concepts recited in instant claims 1-6 and 12-23, include the terms:
• "calculating" (claims 3, 5, 16, 18, 20 and 22
• "reducing/reduce the number of and overlaying the elementary flux modes by a trainable matrix H to obtain a reduced matrix Shred of base flux modes" (claims 1, 12 and 14)
• "solving the resulting mass balances of substrates, products and biomass" (claims 1, 12 and 14) --
• "training/train the H matrix and the neural network by the dynamic cultivation data" (claim 1, 12 and 14);
• "applying the trainable matrix H to transform the number of modes Nummodes to a reduced number Nummodes,red …by removing all exchange reactions from both matrices, and including in only the exchange compounds" (claims 2, 13 and 15);
• "solved by a recurrent network model … training the neural network weights W along with their corresponding biases b, where the neurons of the next layer are activated by a sigmoidal activation function" (claim 3, 16 and 20);
• "using … the cultivation data (training set), by minimizing the loss function …" (claims 4, 17 and 21); and
• "evaluating the trained RNN by calculating Loss on the basis of a second subset of the cultivation data (evaluation set), the second subset being different from the first subset" (claims 5, 18 and 22).
Said terms are being identified as actions executed by a group of mathematical steps in a form of a mathematical algorithm; thus mathematical concepts; A mathematical concept need not be expressed in mathematical symbols, because "words used in a claim operating on data to solve a problem can serve the same purpose as a formula." In re Grams, 888 F.2d 835, 837 and n.1, 12 USPQ2d 1824, 1826 and n.1 (Fed. Cir. 1989). MPEP 2106.04(a)(2) pertains.
Dependent claims 2-4, 6, 13, 15-17, 19-21 and 23 further recite mathematical equations related to the "calculating" steps. Dependent claims 6, 19 and 23 recite further details about how the matrix M of elementary flux modes is obtained in order to be inputted into mathematical calculations: "transforming all metabolic fluxes to separate off reversible reactions to obtain all irreversible reactions; - minimizing an objective function and deactivation of inactivate transformers are recurrently applied to obtain elementary flux modes …".
Mental processes, defined as concepts or steps practically performed in the human mind such as steps of observations, evaluations, judgments, analysis, opinions or organizing information include:
• "connecting the base flux modes to extracellular reactions of the cell cultivation process; connecting the base flux modes to inflows and outflows to and from the reactor system of the cell cultivation process" (claims 1, 12 and 14);
• "assigning/assign a neural network for describing the kinetics of the individual base flux modes
S
~
M
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red" (claims 1, 12 and 14);
• "providing a mode matrix M of elementary flux modes, extracted from metabolic fluxes of a real biological cell" (claims 1, 12 and 14);
• "adapting or generating at least one optimized process specification from acquired cultivation data by applying a Digital Twin" (claims 7-8); and
• "adapt or generate process specifications of the reactor system from the acquired cultivation data" (claim 10).
Under the BRI, the recited limitations are mental processes because, said limitations equate to organizing how the base flux modes are connected; deciding to use a particular neural network; writing down a matrix of numbers based on data from a cell; applying that matrix/ neural network to decide on a process based on cultivation data and evaluating data to generate a process.
Hence, the claims explicitly recite numerous elements that, individually and in combination, constitute abstract ideas. The instant claims must therefore be examined further to determine whether they integrate that abstract idea into a practical application (MPEP 2106.04(d)). [Step 2A Prong One: claims 1-23 - Yes]
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Background
MPEP 2106.04(d).I lists the following example considerations for evaluating whether a judicial exception is integrated into a practical application:
An improvement in the functioning of a computer or an improvement to other technology or another technical field, as discussed in MPEP §§ 2106.04(d)(1) and 2106.05(a);
Applying or using a judicial exception to effect a particular treatment or prophylaxis for a disease or medical condition, as discussed in MPEP § 2106.04(d)(2);
Implementing a judicial exception with, or using a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim, as discussed in MPEP § 2106.05(b);
Effecting a transformation or reduction of a particular article to a different state or thing, as discussed in MPEP § 2106.05(c); and
Applying or using the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception, as discussed in MPEP § 2106.05(e).
Analysis of instant claims
Instant claims 1, 5, 7-12, 14-15, 18 and 20-23 recite additional elements that are not abstract ideas: "providing dynamic cultivation data from a real cell cultivation process; "computational system" (claims 14-15 and 20-23); "trained RNN" (claims 5, 18 and 22); "acquiring cultivation data of the cell cultivation process; "cultivating the biological cells in the reactor system; - acquiring cultivation data from the cell culture in the reactor system; "applying the at least one optimized process specification to the reactor system" (claim 8); "executed by a computer/processor" (claims 10, 12 and 14); "acquire cultivation data from the running cell culture in the reactor system" (claim 10); Dependent claims 9 and 11 recite further details about: the "process specification" optimization details (claim 9) and the composition of the "reactor system" (claim 11) which are also identified as additional elements.
Said limitations are being interpreted as requiring the use of a computer. Hence, the claims explicitly recite steps executed by computers and therefore can be described as computer functions; not describing any specific computational steps by which the computer performs or carries out the abstract idea, nor do they provide any details of how specific structures of the computer are used to implement these functions.
Claims directed to the "trained RNN" equates to mere instructions to implement on a generic computer. Claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible. MPEP 2106.05(b) pertains.
Claims directed to: "acquiring cultivation data of the cell cultivation process" (claim 7); "cultivating the biological cells in the reactor system" (claim 8); "acquire/acquiring cultivation data from the cell culture in the reactor system" (claims 8 and 10); "providing dynamic cultivation data from a real cell cultivation process" and "providing a mode matrix M of elementary flux modes, extracted from metabolic fluxes of a real biological cell" (claims 1, 12 and 14) read on data gathering activity; reciting steps performed to gather information that is used as input for the subsequent mathematical calculations, reading on receiving or transmitting data over a network, e.g., using the Internet to gather data, MPEP-cited case law Symantec, 838 F.3d at 1321. MPEP 2106.05(a) pertains
Claims directed to "adapt/adapting or generate/generating at least one optimized process specification from acquired cultivation data" (claims 7-8 and 10) are being interpreted as generic instructions regarding the optimization step and merely recites an optimization idea without any indication of how the judicial exception impacts or influences this step.
Hence, these are mere instructions to apply the abstract idea using a computer and insignificant extra-solution activity, and therefore the claims do not integrate that abstract idea into a practical application (see MPEP 2106.04(d) § I; 2106.05(f); and 2106.05(g)). None of the dependent claims recite any additional non-abstract elements; they are all directed to further aspects of the information being analyzed, the manner in which that analysis is performed, or the mathematical operations performed on the information.
In Step 2A, Prong One above, claim steps and/or elements were identified as part of one or more judicial exceptions (JEs).
In this Step 2A, Prong Two immediately above claim steps and/or elements were identified as part of one or more additional elements. Additional elements are further discussed in Step 2B below.
Here in Step 2A, Prong Two, no additional step or element clearly demonstrates integration of the JE(s) into a practical application.
At this point in examination it is not yet the case that any of the Step 2A, Prong Two considerations enumerated above clearly demonstrates integration of the identified JE(s) into a practical application. Referring to the considerations above, none of 1. an improvement, 2. treatment, 3. a particular machine or 4. a transformation is clear in the record.
For example, regarding the first consideration at MPEP 2106.04(d)(1), the record, including for example the specification, does not yet clearly disclose an explanation of improvement over the previous state of the technology field. The claims do not yet clearly result in such an improvement.
[Step 2A Prong Two: claims 1-23 - No]
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
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 of the 35 USC § 101 analysis determines whether the claims contain additional elements that amount to an inventive concept, and an inventive concept cannot be furnished by an abstract idea itself (MPEP 2106.05).
As discussed above regarding acquiring data cannot integrate a judicial exception as mere data gathering activity; reading on performing a standard computer task, which the courts have identified as a conventional computer function in Symantec, 838 F.3d at 1321, 120 USPQ2d at 1362; OIP Techs., Inc., v. Amazon.com, Inc., 788 F.3d 1359, 1363, 115 USPQ2d 1090, 1093 (Fed. Cir. 2015); and buySAFE, Inc. v. Google, Inc., 765 F.3d 1350, 1355, 112 USPQ2d 1093, 1096 (Fed. Cir. 2014). MPEP 2106.05(d) pertains.
The use of trained artificial neural network algorithms to improve metabolic data and metabolic pathway modeling is known in the art as well-understood, routine and conventional (Cuperlovic-Culf "Machine Learning Methods for Analysis of Metabolic Data and Metabolic Pathway Modeling" Metabolites 8:4 (2018) – pg. 2 Table 1). The use of automated bioreactor systems to cultivate cells in a reactor while applying processes to the reactor is known in the art as well-understood, routine and conventional (Hemmerich et. al. "Microbioreactor Systems for Accelerated Bioprocess Development" Biotechnol. J. 13:1700141 (2018) – pg. 3 Table 1).
When the claims are considered as a whole, they do not integrate the abstract idea into a practical application; they do not confine the use of the abstract idea to a particular technology; they do not solve a problem rooted in or arising from the use of a particular technology; they do not provide details about how to improve a technology by allowing the technology to perform a function that it previously was not capable of performing; and they do not provide any limitations beyond generally linking the use of the abstract idea to a broad technological environment. See MPEP 2106.05(a) and 2106.05(h). [Step 2B: claims 1-23 - No]
Conclusion: Instant claims are directed to non-statutory subject matter
For these reasons, the claims in this instant application, when the limitations are considered individually and as a whole, are directed to an abstract idea and lack an inventive concept. Hence, the claimed invention does not constitute significantly more than the abstract idea, so instant claims 1-23 are rejected under 35 USC § 101 as being directed to non-statutory subject matter.
Response to applicant's remarks in regard to Claim Rejection 35 U.S.C. ~ 101
The Remarks of 10/14/2025 have been fully considered but are not persuasive for the reasons below:
Applicant asserts
"With respect to Prong One, the Office Action contends that the claims recite an abstract idea in the form of mathematical modeling using matrix operations and neural networks. Pursuant to MPEP §2106.04(a)(2)(1), "[a] claim does not recite a mathematical concept (i.e., the claim limitations do not fall within the mathematical concept grouping), if it is only based on or involves a mathematical concept." (Emphasis added.) The "mathematical concepts grouping" is defined as "mathematical relationships, mathematical formulas or equations, and mathematical calculations." Applicant submits that the present claims do not recite any of the foregoing categories of mathematical concepts. First, the subject matter of independent claim 1 does not recite a "mathematical calculation." As explained in MPEP §2106.04(a)(2)(I)(C), a mathematical calculation refers to an operation "to determine a variable or number, e.g., performing an arithmetic operation such as exponentiation." – pg. 15 para. 3-4.
It appears that Applicant's remarks addressees Step 2A, Prong 1. The argument is not yet persuasive because the MPEP §2106.04(a)(2)(1) further describes that "a limitation that is merely based on or involves a mathematical concept described in the specification may not be sufficient to fall into this grouping, provided the mathematical concept itself is not recited in the claim"; and in this instant application both claims and disclosure describe the use of variables and equations equating to mathematical calculations. The instant disclosure discusses the use of variables in the claimed model (pg. 12 line 2) and the use of mathematical symbols/equations to construct the claimed Digital Twin model (such as in pgs. 8 and 10-16); thus characterizing the use of mathematical concepts.
Applicant asserts
"Examples cited therein include performing statistical analyses, determining optimal routes or schedules, or calculating differences between data values (see, SAP America, Inc. v. InvestPic, LLC, 898 F.3d 1161 (Fed. Cir. 2018); In re Maucorps, 609 F.2d 481 (CCPA 1979); In re Abele, 684 F.2d 902 (CCPA 1982))." In contrast, the present claims do not perform any abstract mathematical computation for its own sake. Rather, they define a concrete method of constructing and using a Digital Twin of a real biological cell cultivation process. This method processes dynamic cultivation data obtained from an actual bioreactor, applies mass balance equations for substrates, products, and biomass, and generates a trained hybrid model (combining mechanistic and neural network components) that corresponds directly to a physical process. The mathematical operations (e.g., matrix reduction, neural network computation) are not claimed in the abstract but are expressly tied to the technical modeling of a biological reactor system, namely, computing substrate fluxes, product formation rates, and biomass growth within a real reactor. Thus, the claims involve applied bioprocess engineering and not a mere mathematical formula." – pg. 16 para. 1-2.
It appears that Applicant's remarks addressees Step 2A, Prong 1. The argument is not yet persuasive because, in regard to the described case law, the difference between is that, here, there is no evidence of any application of statistical analysis. As explained above, the instant specification discloses the use of variables in the claimed model and the use of mathematical symbols/equations to construct the claimed Digital Twin model. The described mathematical operations (e.g., matrix reduction, neural network computation) are indeed tied to the make-up of the claimed Digital Twin model and cannot be separated from the claimed recitations to argue that the claims are not directed to a math concept.
Applicant asserts
"Second, the subject matter of independent claim 1 does not recite a "mathematical relationship." According to MPEP §2106.04(a)(2)(I)(A), a mathematical relationship "is a relationship between variables or numbers ... expressed in words or mathematical symbols." Examples include the Arrhenius equation (Diamond v. Diehr, 450 U.S. 175 (1981)), binary conversion (Gottschalk v. Benson, 409 U.S. 63 (1972)), or mathematical correlations for organizing information (Digitech Image Techs., LLC v. Electronics for Imaging, Inc., 758 F.3d 1344 (Fed. Cir. 2014)). By contrast, the relationships described in the instant claims, such as those between substrate inflow, product outflow, and biomass concentration, are physical, process-based relationships governed by mass conservation in a real reactor system. The claimed model ensures that mass is conserved over time and across reaction networks, which is a core physical constraint in biotechnology, not a purely mathematical one." – pg. 16 para. 3-4.
It appears that Applicant's remarks addressees Step 2A, Prong 1. The argument is not yet persuasive because the presence of not purely mathematical relationships such as "the relationships described in the instant claims, such as those between substrate inflow, product outflow, and biomass concentration, are physical, process-based relationships governed by mass conservation in a real reactor system" does not negate the fact that there are purely mathematical relationships such as the ones described above; which is not sufficient to integrate an abstract idea into a practical application. Even if the Applicant is aiming for a "other meaningful limits" consideration, the Examiner still have to look at "do the additional elements provide that meaningful limitation?". Thus, the argument that the JE provides the meaningful limit would not yet be persuasive.
Applicant asserts
"… the claims are patent-eligible under Prong Two of Step 2A because they integrate any such concept into a practical application. MPEP §2106.04(d)(I) sets forth "limitations the courts have found indicative that an additional element ( or combination of elements) may have integrated the exception into a practical application," including where the claim provides an "improvement in the functioning of a computer, or an improvement to other technology or technical field." MPEP §2106.05(a). The Federal Circuit has repeatedly held that claims which apply mathematical relationships to improve the functioning of a physical system are patent-eligible (see, Thales Visionix Inc. v. United States, 850 F.3d 1343 (Fed. Cir. 2017);McRO, Inc. v. Bandai Namco Games Am. Inc., 837 F.3d 1299 (Fed. Cir. 2016); Enfish, LLC v. Microsoft Corp., 822 F.3d 1327 (Fed. Cir. 2016))." – pg. 17 para. 1-3.
It appears that Applicant's remarks addressees Step 2A, Prong 2 – first consideration (improvement). The argument is not yet persuasive because any claimed improvement has to be realized in the additional elements and not in the judicial exceptions. Examiners suggest amending the claims to reflect how the additional elements are related to the claimed improvement to technology.
Applicant asserts
"Applicant's claimed subject matter provides exactly such a technological improvement. The invention addresses the longstanding technical problem of accurately predicting and optimizing biological cell growth dynamics in real time within a bioreactor, where biological variability and sensor noise often impede control performance. (See Application as filed, p. 1, lines 5-16; p.2, lines 1-10.) Specifically, Applicant's application as filed states: … The claimed subject matter constitutes a technological solution to a technological problem, not a mere mathematical exercise. The claimed Digital Twin enhances the performance and controllability of actual cultivation hardware, improving prediction stability, avoiding overflows or oxygen depletion, and optimizing product yield. Accordingly, any abstract mathematical aspect is fully integrated into a practical, real-world application within the field of bioprocess engineering, thereby satisfying Step 2A, Prong Two. With regard to Step 2B, the claimed invention includes "significantly more" than any alleged abstract idea. The claimed Digital Twin architecture employs a hybrid mechanistic-data driven model constrained by physical mass-balance laws and trained on empirical sensor data from biological reactors. The Federal Circuit has confirmed that such integration of mathematical models into technical systems constitutes an inventive concept (Thales, 850 F.3d at 1348-49; DDR Holdings, LLC v. Hotels.com, L.P, 773 F.3d 1245 (Fed. Cir. 2014)). Moreover, the dependent claims ( e.g., claims 7-11) further apply the Digital Twin for automated reactor control, which represents a direct and concrete technical implementation. The combination of features produces a real, measurable improvement in reactor operation, rendering the claims patent-eligible under Alice Step 2B." – pg. 17 para. 4 to pg. 8 para. 2.
It appears that Applicant's remarks addressees Step 2A, Prong 2 – first consideration (improvement). The argument is not yet persuasive because the cited case law instances do not compare to the instant application. The difference between the instant application and the cited cases is that, here, there is no evidence of an asserted improvement realized by an additional element. An improvement is provided by the additional elements either on their own or in combination with the judicial exception. If the improvement is not realized in the additional elements then the improvement is merely in the judicial exception itself, which is not considered an improvement to technology. However, any improvement to technology must be commensurate in scope with the claimed invention and the improvement must be provided by one or more additional elements, either on their own or in combination with the recited judicial exception. In this case, the improvement does not exist since all claims directed to judicial elements.
In summary, when the claims are considered as a whole, they do not integrate the abstract idea into a practical application; they do not confine the use of the abstract idea to a particular technology; they do not solve a problem rooted in or arising from the use of a particular technology; they do not provide details about how to improve a technology by allowing the technology to perform a function that it previously was not capable of performing; and they do not provide any limitations beyond generally linking the use of the abstract idea to a broad technological environment. See MPEP 2106.05(a) and 2106.05(h).
Conclusion
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FRANCINI A FONSECA LOPEZ whose telephone number is (571)270-0899. The examiner can normally be reached Monday - Friday 8AM - 5PM ET.
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/F.F.L./Examiner, Art Unit 1685
/G. STEVEN VANNI/Primary patents examiner, Art Unit 1686