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 .
Applicant Response
Applicant's response, filed 02/02/2026, 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 Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn.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. They constitute the complete set presently being applied to the instant application.
Claim Status
Claim 3 is canceled.
Claims 1-2 and 4-21 are pending and under examination herein.
Claims 1-2 and 4-21 are rejected.
Priority
The instant claim filed 04/14/2021 is a National Stage entry of PCT/EP2019/077040 , International Filing Date: 10/07/2019, which claims foreign priority to EP 18200386.3, filed 10/15/2018. As such, the effective filing date assigned to each of claims 1-2 and 4-21 is 10/15/2018. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Rejections - 35 USC § 112
The rejections of claim 14 under 35 U.S.C. 112(b) is withdrawn in view of claim amendments filed 02/02/2026.
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 1-2 and 4-21 remain rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea/law of nature/natural phenomenon without significantly more. 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 1). Newly recited portions are necessitated by claim amendments.
In the instant application, the claims recite the following limitations that equate to an abstract idea:
Claims 1, 14 and 15 recite correlate the received data; calculating via a multivariate selection function, scores for each one of the sets of candidate cells from the correlated time series data according to the multivariate evaluation criteria, wherein the multivariate selection function includes an objective function, wherein the objective function quantifies a distance from a prioritization range or target, and wherein the prioritization range or target is a set of reference cells having a biosimilar definition in comparison to the sets of candidate cells ; ranking the sets of candidate cells according to the scores; and selecting at least one of the sets of candidate cells as the target cells using the ranking.
Claim 5 recites further comprising: identifying whether the received data for any of the processes is incomplete, wherein one of the processes is identified as having incomplete data when data is not collected during a portion of the process; when any of the processes has incomplete data, predicting values for the incomplete data using at least one multivariate technique, wherein the multivariate technique may include partial least squares regression or interpolation.
Claim 6 recites wherein the correlating includes verifying and correcting values of the data, wherein the correcting comprises revising or excluding values that violate one or more known metabolic dependencies.
Claim 7 recites further comprising: applying mechanistic modelling to the received data to obtain additional values of the process parameters and/or additional process outputs; supplementing the received data with the additional values of the process parameters and/or the additional process outputs.
Claim 8 recites excluding, from the correlated data, data received from the plurality of processes according to exclusion criteria; if at least one of the selected process outputs has a corresponding acceptability range, then the exclusion criteria include the corresponding acceptability range for the at least one of the selected process outputs.
Claim 11 recites wherein the selection function includes a cost function.
Claim 12 recites wherein the selection function includes at least one magnifying function, wherein the at least one magnifying function magnifies a distance between values, wherein each of the prioritization ranges and/or targets has an associated magnifying function, and wherein the at least one magnifying function is non-linear.
These recitations equate to steps of collecting information, analyzing data and making observations, evaluations and judgements that can be carried out in the human mind. Specifically, correlating the received data, calculating scores for each of the sets of candidate cells using a multivariate selection function with an objective function that quantifies a distance from a prioritization range or target, ranking the sets of candidate cells according to the scores, selecting a set of candidate cells based on the ranking, identifying whether the received data is incomplete, predicting values for the incomplete data using a multivariate technique, verifying and correcting values of the data, applying mechanistic modelling to the received data to obtain additional values, supplementing the received data with the additional values, excluding data according to exclusion criteria can be practically performing the human mind as claimed and are similar to the concepts of collecting and comparing known information in Classen Immunotherapies, Inc. v. Biogen IDEC, 659 F.3d 1057, 1067, 100 USPQ2d 1492, 1500 (Fed. Cir. 2011) and collecting information, analyzing it, and reporting certain results of the collection and analysis in Electric Power Group v. Alstom, S.A., 830 F.3d 1350, 1353-54, 119 USPQ2d 1739, 1741-42 (Fed. Cir. 2016) that the courts have identified as concepts that can be practically performed in the human mind. Therefore, each of the above recited limitations fall under the “Mental Processes” grouping of abstract ideas. Furthermore, the steps as claimed for calculating scores for each of the sets of candidate cells using a multivariate selection function with an objective function, predicting values for the incomplete data, and applying mechanistic modelling to the received data to obtain additional values equate to organizing information and manipulating information through mathematical correlations and reciting a mathematical equation, similar to the concepts of taking existing information, manipulating the data using mathematical functions, and organizing this information into a new form in Digitech Image Techs., LLC v. Electronics for Imaging, Inc., 758 F.3d 1344, 1350, 111 USPQ2d 1717, 1721 (Fed. Cir. 2014). Therefore, these limitations also fall under the “Mathematical Concepts” grouping of abstract ideas. Claims 11-12 further quantify the judicial exceptions. As such, claims 1-2 and 4-16 recite an abstract idea (Step 2A, Prong 1: YES).
Claims found to recite a judicial exception under Step 2A, Prong 1 are then further analyzed to determine if the claims as a whole integrate the recited judicial exception into a practical application or not (Step 2A, Prong 2). This judicial exception is not integrated into a practical application because the claims do not recite an additional element that reflects an improvement to technology or applies or uses the recited judicial exception to affect a particular treatment for a condition. Rather, the instant claims recite additional elements that amount to mere data gathering and outputting, and mere instructions to implement the abstract idea in a generic computing environment. Specifically, the claims recite the following additional elements:
Claim 1 and 14 recite a computer, receiving data collected from a plurality of processes, wherein each of the processes produces a distinct set of candidate cells, wherein the candidate cells are biological cells, wherein each of the processes is carried out by a process control device comprising a plurality of online in-situ sensors coupled to a controller and configured to collect the received data, the received data including values of process parameters and process outputs of the processes, each of the process outputs being a product quality attribute or a key performance indicator for selecting the target cells; wherein the values of the process parameters include time series values, and wherein the process parameters including time series values were measured by the plurality of online in-situ sensors during each of the processes; receiving multivariate evaluation criteria for the selected process parameters and/or the selected process outputs, the multivariate evaluation criteria including prioritization ranges and/or targets, wherein each target is an extremum and/or a target value, and wherein one of the multivariate evaluation criteria is inversely correlated with another one of the multivariate evaluation criteria; and using the target cells in or to host a chemical, pharmaceutical, biopharmaceutical and/or biological product.
Claim 2 recites wherein the target cells are at least one of the following: a cell line, a cell strain, a clone.
Claim 4 recites wherein the received data includes values for each process parameter and values for each process output.
Claim 9 recites wherein the evaluation criteria further comprise: a time based profile of one or more of the process parameters, a profile describing one or more of the process outputs, a trajectory describing time based development of one or more of the process parameters.
Claim 10 recites displaying the correlated data for the selected process parameters and/or the selected process outputs, comprising, displaying correlation patterns for the glycan profiles of the sets of candidate cells.
Claim 13 recites wherein there are at least 5 sets of candidate cells, at least 10 sets of candidate cells, at least 20 sets of candidate cells, at least 30 sets of candidate cells, or at least 50 sets of candidate cells.
Claim 14 also recites a process control device.
Claim 15 recites a process control device comprising a plurality of vessels, each of the vessels being configured to contain fluid including one of the sets of candidate cells; a robot capable of addressing each of the vessels, dispensing fluid to each of the vessels, and extracting samples of fluid from each of the vessels; a plurality of online in-situ sensors, wherein each in-situ sensor is coupled to a corresponding one of the plurality of vessels; and a controller operable to: control, at least partly in parallel, conditions in each of the vessels; receive data collected from a plurality of processes, wherein each of the processes produces a distinct set of candidate cells, the received data including values of process parameters and process outputs of the processes, each of the process outputs being a product quality attribute or a key performance indicator for selecting the target cells; receive a selection of the process parameters and a selection of the process outputs; and wherein the process parameters including time series values were measured by the plurality of online in-situ sensors coupled to the controller during each of the processes; receive a selection of the process parameters and a selection of the process outputs; receive multivariate evaluation criteria for the selected process parameters and/or the selected process outputs, the multivariate evaluation criteria including prioritization ranges and/or targets, wherein each target is an extremum and/or a target value, and wherein one of the multivariate evaluation criteria is inversely correlated with another one of the multivariate evaluation criteria.
Claim 16 recites wherein the each of the vessels has at least one of the following characteristics: it is a bioreactor or a microbioreactor; it includes stirring means
Claim 17 recites wherein the corresponding one of the plurality of online in-situ sensors is disposed at a bottom of the vessel.
Claim 18 recites wherein the plurality of online in-situ sensors are configured to conduct measurements at a frequency of at least once per hour.
Claim 19 recites wherein the process control device further comprises a plurality of vessels, wherein each vessel is configured to contain fluid including one of the sets of candidate cells, wherein each vessel is coupled to a corresponding one of the plurality of online in-situ sensors configured to measure process parameters including time series values, and wherein the corresponding one of the plurality of online in-situ sensors is disposed at a bottom of each vessel.
Claim 20 recites wherein the plurality of online in-situ sensors are configured to conduct measurements at a frequency of at least once per hour.
Claim 21 recites wherein the plurality of online in-situ sensors are configured to measure at least one of the following: pH, dissolved oxygen, and temperature.
Claims 1, 14 and 15 recite limitation for receiving data, and claims 2, 4, 9-10 and 13 provide further information about the received data. Claims 1, 14-15 and 16-21 also recite limitation of a device used to gather data. These limitations equate to mere data gathering and selecting a particular data source or type of data to be manipulated and data outputting, which the courts have found to be insignificant extra-solution activity (see MPEP 2106.05(g)). Claims 1 and 15 recites an insignificant activity, as it generically recites using and synthesizing compounds based on the output of abstract ideas (see MPEP 2106.05(g)). Claims 1 and 14 also merely recite using generic computing systems and computer program products to carry out instructions to implement an abstract idea on a computer. The computer system and computer program product as claimed fails to recite details of how a solution to a problem is accomplished and only recites the idea of a solution or outcome. There are no limitations that indicate that the claimed steps require anything other than generic computing systems. As such, these limitations equate to mere instructions to implement the abstract idea on a generic computer that the courts have stated does not render an abstract idea eligible in Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. See also 573 U.S. at 224, 110 USPQ2d at 1984. Use of a computer or other machinery in its ordinary capacity for economic or other tasks (e.g., to receive, store, or transmit data) or simply adding a general purpose computer or computer components after the fact to an abstract idea (e.g., a fundamental economic practice or mathematical equation) does not integrate a judicial exception into a practical application. See Affinity Labs v. DirecTV, 838 F.3d 1253, 1262, 120 USPQ2d 1201, 1207 (Fed. Cir. 2016) (cellular telephone); TLI Communications LLC v. AV Auto, LLC, 823 F.3d 607, 613, 118 USPQ2d 1744, 1748 (Fed. Cir. 2016) (computer server and telephone unit). As discussed above, the use of sensors amounts to an insignificant extra-solution activity, and therefore the addition of in-situ sensors coupled with the computer does not implement a judicial exception with, or using a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim, because it amounts to necessary data gathering and all uses of the recited judicial exceptions require such data gathering, as discussed in MPEP 2106.05(g). There is no indication that any of these additional elements provide a practical application of the recited judicial exception outside of the judicial exception itself. As such, claims 1-2 and 4-21 are directed to an abstract idea (Step 2A, Prong 2: NO).
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). Further analyzing the additional elements under step 2B, the additional elements as described above do not rise to the level of significantly more than the judicial exception. As set forth in the MPEP, determinations of whether or not additional elements (or a combination of additional elements) may provide significantly more and/or an inventive concept rests in whether or not the additional elements (or combination of elements) represents well-understood, routine, conventional activity. Said assessment is made by a factual determination stemming from a conclusion that an element (or combination of elements) is widely prevalent or in common use in the relevant industry, which is determined by either a citation to an express statement in the specification or to a statement made by an applicant during prosecution that demonstrates a well-understood, routine or conventional nature of the additional element(s); a citation to one or more of the court decisions as discussed in MPEP 2106(d)(II) as noting the well-understood, routine, conventional nature of the additional element(s); a citation to a publication that demonstrates the well-understood, routine, conventional nature of the additional element(s); and/or a statement that the examiner is taking official notice with respect to the well-understood, routine, conventional nature of the additional element(s).
With respect to the instant claims under the 2B analysis, the use of a computer or other machinery in its ordinary capacity for economic or other tasks (e.g., to receive, store, or transmit data) or simply adding a general purpose computer or computer components after the fact to an abstract idea (e.g., a fundamental economic practice or mathematical equation) does not provide significantly more. See Affinity Labs v. DirecTV, 838 F.3d 1253, 1262, 120 USPQ2d 1201, 1207 (Fed. Cir. 2016) (cellular telephone); TLI Communications LLC v. AV Auto, LLC, 823 F.3d 607, 613, 118 USPQ2d 1744, 1748 (Fed. Cir. 2016) (computer server and telephone unit).
With respect to the process control device of claims 1, 14, 15 and 16-21, the prior art to Betts and Baganz (Microb Cell Fact 2006, 5, 21; previously cited; hereafter referred to as Betts), reviews current practices and future opportunities related to miniature bioreactors, and discloses bioreactor systems with microbioreactors (i.e. vessels) that contain fluid and cells and can perform many cell cultivation in parallel, stirrers, impellers, and pH sensors, used in conjunction with automated robotic systems to perform liquid-handling tasks such as inoculation, feeding and sampling and other miniature process units to deliver a fully-integrated, high-throughput (HT) solution for cell cultivation process development and using the products for subsequent steps is routine, well-understood and conventional in the art (title; abstract; table 1; p 7, col 1, para 1; p 11, col 2, para 3-p12, col 1, para 3). The prior art to Beutel and Henkel (Appl Microbiol Biotechnol (2011) 91:1493–1505; newly cited) also reviews in-situ sensor techniques in modern bioprocess monitoring and discloses that the use of online in-situ sensors disposed at the bottom of the vessel, that can measure pH, dissolved oxygen, etc. at desired frequencies is well known in the art (abstract; p 1493, col 2, para 3-p1494, col 2, para 2; fig 1).
Therefore, the 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, and the claims do not amount to significantly more than the judicial exception itself (Step 2B: NO). As such, claims 1-2 and 4-21 are not patent eligible.
Response to applicant’s arguments
Applicant states claim 1 is not a merely analyze information claims, but is directed to a concrete technological improvement in the operation of the bioprocess control devices and the selection of the biological cell sets, similar to CellsDirect, and that the claims recite a specific, structured, multi-step process for selecting biological cell population, including downstream use of the cells, and recite specific steps that constrain how the analysis is performed, similar to those found to be patent-eligible in McRo, and therefore, even if certain steps are mathematical, the claims as a whole are directed to an integrated biotechnical process, not an abstract idea (Applicant’s Arguments, p 9, para 3 – p 10, para 5).
It is respectfully submitted that this is not persuasive. As discussed above, the additional elements amount to insignificant extra-solution activity and mere instructions to implement the abstract idea in a generic computing environment. The improvement appears to be solely provided by the recited judicial exceptions themselves, and to the judicial exceptions itself, through an improved analysis for selecting sets of candidate cells, and as discussed in MPEP 2106.05(a), the judicial exception alone cannot provide the improvement and the improvement cannot be to the judicial exception itself. The downstream use of the selected cells in generically recited and does not impose meaningful limits on the claim, and amounts to an insignificant application, similar to cutting hair after first determining the hair style, In re Brown, 645 Fed. App'x 1014, 1016-1017 (Fed. Cir. 2016) (non-precedential) or printing or downloading generated menus, Ameranth, 842 F.3d at 1241-42, 120 USPQ2d at 1854-55. See MPEP 2106.05(g). There is no indication that any of these additional elements provide a practical application of the recited judicial exception outside of the judicial exception itself. As such, claims 1-2 and 4-21 are directed to an abstract idea.
Applicant further states the claims as a whole recite an inventive concept that includes the use of in-situ process sensors generating domain-specific time-series process parameters, analysis/ranking steps and downstream physical use of selected target cells in manufacturing processes, and request withdrawal of the rejection (Applicant’s Arguments, p 11, para 1-5).
It is respectfully submitted that this is not persuasive. As discussed in MPEP 2106.05, an "inventive concept" is furnished by an element or combination of elements that is recited in the claim in addition to (beyond) the judicial exception, and an inventive concept "cannot be furnished by the unpatentable law of nature (or natural phenomenon or abstract idea) itself. Therefore, only the additional elements of the claims are evaluated both individual and in combination to determine whether they amount to an inventive concept under step 2B, and the analysis/ranking steps of the instant claims, which were found to recite judicial exceptions, are not evaluated under Step 2B. With respect to the recited additional elements, under Step 2B, as discussed above, the process control device of claims 1, 14-15 and 16-21 is disclosed by the prior art to Betts, which reviews current practices and future opportunities related to miniature bioreactors, and discloses bioreactor systems with microbioreactors (i.e. vessels) that contain fluid and cells and can perform many cell cultivation in parallel, stirrers, impellers, and pH sensors, used in conjunction with automated robotic systems to perform liquid-handling tasks such as inoculation, feeding and sampling and other miniature process units to deliver a fully-integrated, high-throughput (HT) solution for cell cultivation process development and using the products for subsequent steps is routine, well-understood and conventional in the art (title; abstract; table 1; p 7, col 1, para 1; p 11, col 2, para 3-p12, col 1, para 3). The prior art to Beutel and Henkel (Appl Microbiol Biotechnol (2011) 91:1493–1505; newly cited) also reviews in-situ sensor techniques in modern bioprocess monitoring and discloses that the use of online in-situ sensors disposed at the bottom of the vessel, that can measure pH, dissolved oxygen, etc. at desired frequencies is well known in the art (abstract; p 1493, col 2, para 3-p1494, col 2, para 2; fig 1).Therefore, the 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, and the claims do not amount to significantly more than the judicial exception itself under Step 2B. The rejection is maintained.
Claim Rejections - 35 USC § 103
The rejections of claims 1-2 and 4-21 under 35 U.S.C. 103 as being unpatentable over Brühlmann et al. (Biotechnology and bioengineering 2017, 114.7: 1448-1458; previously cited; hereafter referred to as Brühlmann), as evidenced by Sokolov et al. (Biotechnology progress 2017, 33.1: 181-191; previously cited; hereafter referred to as Sokolov), further in view of Legmann et al. (Biotechnol Progress 2011, 27: 757-765; previously cited; hereafter referred to as Legmann), Sokolov et al. (Biotechnology journal 2018, 13(4), p 1-10; newly cited), and Beutel and Henkel (Appl Microbiol Biotechnol (2011) 91:1493–1505; newly cited; hereafter referred to as Beutel) are withdrawn in view of the claim amendments filed 02/02/2026, as the cited art does not appear to disclose one of the multivariate evaluation criteria is inversely correlated with another one of the criteria and in view of Applicant arguments which state that retrofitting DWPs of Brühlmann with in-situ pH and dissolved-oxygen sensors would be impractical, which was found to be persuasive.
Conclusion
No claims allowed.
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.
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/N.D./ Examiner, Art Unit 1686
/Karlheinz R. Skowronek/ Supervisory Patent Examiner, Art Unit 1687