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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on March 27, 2026 has been entered.
Notes
All the objections and rejections in the previous Office Action not reiterated herein have been withdrawn.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tolstrup et al. (previously cited, US 2011/0117605; hereinafter “Tolstrup”) in view of Wasson et al. (previously cited, US 2016/0124009) (hereinafter “Wasson”), Galliher et al. (US 2009/0035856; hereinafter “Galliher”), Berteau et al. (previously cited, US 2016/0145563; hereinafter “Berteau”) and Taniguchi et al. (JP 2009-189362-A, with English machine translation; hereinafter “Taniguchi”).
Regarding claims 1, 10 and 12-13, Tolstrup discloses a system comprising: a seed train preparation station comprising a seed preparation container holding a plurality of different seed types for transfer for automated fermentation (see annotated FIG. 2 below: seed train preparation region including a cell bank (i.e., container) holding a plurality of vials; [0042], [0052] and [0069]-[0076]);
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a fermentation station disposed adjacent to the automated seed train preparation station, the fermentation station utilizing a cell culture conveying means for transferring the plurality of different seed types from the seed train station to the fermentation station (FIG. 2: multiple culture vessels in the separate production phase at a first region (reads on the instant fermentation station) are disposed adjacent to and fluidly connected to the seed train preparation station to receive different seed types via cell culture conveying means prior to start of the fermentation process; [0026], [0042], [0052] and [0077]-[0082]), a plurality of modular bioreactors disposed in the fermentation station (FIG. 2: multiple culture vessels in the separate production phase at a first region (reads on the instant fermentation station); [0026], [0042], [0052] and [0077]-[0082]) and configured to receive one or more seeds from the seed train preparation station with the aid of the cell culture conveying means (culture vessels are configured to receive seed from the seed train station; FIG. 2; [0053] and [0177]), wherein each of the plurality of modular bioreactors is configured to be individually attachable and removable from the fermentation station (culture vessels in the separate production phase include disposable vessels, thus the culture vessels can be attached and removed from the first region; [0026], [0052] and [0177]; further, each of the culture vessels can comprise stirrer element therein and thus would have been intrinsic in the system of Tolstrup to have secured the modular bioreactors to the first region so as to secure the culture vessels and thereby prevent the disposable culture vessels from moving around during stirring process; further, the culture vessels are structurally the same as the instant modular bioreactors and thus fully capable of being individually attachable and removable from the first region); and wherein each of the plurality of modular bioreactors comprises a sensor (culture parameters are monitored and controlled in each of the culture vessels of Tolstrup during the production phase; [0177]; and thus intrinsically includes monitoring means such as a sensor, and controlling means such a controller), and a control board (processor) that is configured to (i) control corresponding modular bioreactor, and (ii) process sensor data captured by the sensor of the corresponding modular bioreactor to monitor real-time conditions (each culture vessel includes a sensor for monitoring culture parameters, and each of the culture vessels is coupled to a controller for controlling the culture parameters; [0078] and [0177]). Assuming arguendo that the seed train preparation station of Tolstrup is not automated. However, it would have been a prima facie obvious to one of ordinary skill in the art at the time of the effective filing date to have automated the seed train preparation station in order to prevent user errors during seed preparation. Tolstrup does not explicitly disclose wherein the cell culture conveying means is a robotic arm. However, Wasson is related to a system for culturing cells, wherein the system comprises a sample handling system including a robotic component (e.g., robotic arm) for transferring samples between vessel and/or transferring vessels between stations of the system (Wasson, ¶¶ [0380], [0471] and [0582]-[0585]). The robotic arm includes sample/fluid transfer means (e.g., robots with pipetting capability) for transferring samples between components of the system (Wasson, [0544] and [0582]). The sample handling system is coupled to a remote server or a cloud computing infrastructure for automating the robotic arm (Wasson, ¶ [0394]). In view of Wasson, it would have been prima facie obvious to one of ordinary skill in the art at the time of the effective filing date to have employed the robotic component coupled to a cloud computing infrastructure as disclosed by Wasson in place of cell culture conveying means of Tolstrup for the purpose of automating the transfer of cell culture between the seed train station and fermentation station. Further, one of ordinary skill in the art would have made said modification, because said modification would have been the simple substitution of one known sample/fluid transferring means for another for the predictable result of transferring a sample/fluid between components of a system. Assuming arguendo that the modular bioreactors of Tolstrup are not configured to be individually attachable and removable from the fermentation station. Galliher discloses a system comprising a culturing station including a platform (base plate at a first culturing station; [0080]) and a bioreactor attached to the platform ([0080]). The bioreactor is configured to be attachable and removable from the culturing station (bioreactor can be attached to the base plate reversibly or irreversibly; [0080]). The system of Galliher intrinsically includes a locking arrangement for reversibly or irreversibly securing the base plate to the bioreactor. In view of Galliher, it would have been obvious to one of ordinary skill in the art at the time of the effective filing date to have employed the locking arrangement of Galliher with the system of Tolstrup for the purpose of securing the modular bioreactor to the first region as disclosed by Galliher ([0080]). One of ordinary skill in the art would have made said modification so as to stabilize the plurality of modular bioreactors on the first region and to prevent the bioreactors from moving during stirring process. Tolstrup discloses wherein each of the modular bioreactors can be used to culture different types of cells and/or culturing cells under different conditions (Tolstrup, [0078]). Tolstrup further discloses wherein the modular bioreactors can be employed for culturing cells under different culturing modes ([0080]). Although not specifically disclosed by Tolstrup, it would have been intrinsic in the system of Tolstrup to comprise a control board (processor) coupled to each of the bioreactors in order to ascertain that each cell culture of the bioreactors are maintained at desired optimum culturing conditions. Assuming arguendo that Tolstrup fails to disclose a first local control board (processor) that is configured to (i) control corresponding modular bioreactor, and (ii) execute a fist set of local stored computer-executable instructions, and (iii) process sensor data captured by the sensor of the corresponding modular bioreactor to monitor real-time conditions according to the first set of locally stored computer- executable instructions, and wherein the control boards is in communication with a cloud server of a network and configured to receive instructions for affecting an operation of the corresponding module bioreactor. Berteau discloses a system comprising a plurality of bioreactors (FIG. 3: modular bioreactors (304,306,308,310,312)), a sensor coupled to each of the bioreactors (FIG. 7: step 714; [0086], and a local control board coupled to each of the bioreactors ([0081], [0086], [0093] and [0141]; FIGS. 7 and 13). Each of the sensors is coupled to a control device and configured to (i) control corresponding modular bioreactor, and (ii) execute local stored computer-executable instructions, and (iii) process sensor data captured by the sensor of the corresponding modular bioreactor to monitor real-time conditions according to the locally stored computer-executable instructions (computing device 338,1300 (corresponds to the instant control board), and configured to automatically control operation of each of the bioreactors independently in real-time based on sensed data; [0081], [0086], [0093] and [0141]; FIGS. 7 and 13). The control board is in communication with a cloud server over a network and configured to receive instructions for affecting an operation of the corresponding modular bioreactor (system includes a control device configured to automatically and remotely control operation of each bioreactor, [0054]; and the control device is in communication and capable of running on one or more cloud machine instances which includes cloud server; [0141]). The local control board of Berteau is structurally the same as the instant first local control boards and thus considered to be fully capable of executing a set of instructions. In view of Berteau, it would have been obvious to one of ordinary skill in the art at the time of the effective filing date to have employed the sensors and control boards of Berteau with each of the bioreactors of Tolstrup. One of ordinary skill in the art would have made said modification, because said modification would have resulted in a system having the added advantage of independently and simultaneously monitoring and controlling the culture parameters within each of the bioreactors. Further, one of ordinary skill in the art would have made said modification such that each bioreactors can be controlled individually, since Tolstrup discloses that the bioreactors can be employed for culturing cells under different culturing modes and/or culturing different cell types (Tolstrup, [0080]). Modified Tolstrup does not explicitly disclose wherein the plurality of modular bioreactors are configured to receive the media container. Taniguchi discloses wherein containers containing contents (e.g., thawed cells) to be transferred to a bioreactor can be transported to the bioreactor (FIG. 29; [0202]-[0024]). In view of Taniguchi, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have configured the modular bioreactors of modified Tolstrup to receive the media container as disclosed by Taniguchi (FIG. 29; [0202]-[0024]). One of ordinary skill in the art would have made said modification because said modification would have facilitated ease of transfer of materials between the modular bioreactors and media container.
Regarding claim 2, modified Tolstrup discloses a sensor coupled to the modular bioreactors, but does not explicitly disclose wherein the sensor is a camera. Taniguchi further discloses wherein a cell observation unit is coupled to the culture vessel including a camera having an image sensor ([0077]). In view of Taniguchi, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have replaced the sensor of modified Tolstrup with the image sensor of Taniguchi to arrive at the claimed invention. One of ordinary skill in the art would have made said modification because said modification would have been the simple substitution of one known sensor for the another for the predictable result of monitoring conditions within the bioreactor modules. Furthermore, the limitation “to monitor activity within the corresponding modular bioreactor” is drawn to intended use of the claimed invention. It is noted that a recitation directed to the manner in which a claimed apparatus is intended to be used does not distinguish the claimed apparatus from the prior art, if the prior art has the capability to so perform. Apparatus claims must distinguish from the prior art in terms of structure rather than function (see MPEP 2114).
Regarding claim 3, the camera of modified Tolstrup is fully capable of measuring an optical density of a culture in the corresponding modular bioreactor.
Regarding claim 4, the control board of modified Tolstrup is structurally the same as the instant control board and thus fully capable of monitoring real-time conditions including an error condition.
Regarding claim 5, the camera and the control board of modified Tolstrup are structurally the same as the instant camera and the control board and thus considered to configurable by the cloud server for monitoring the real-time conditions.
Regarding claim 6, the limitation of the claim does not add any additional structural limitations to the claimed system. The instructions can be provided by a user via a remote terminal.
Regarding claim 7, the robotic arm of modified Tolstrup is structurally the same as the instant robotic arm and thus fully capable of transferring material between the fermentation station and a sample handling station.
Regarding claims 8-9, modified Tolstrup further discloses wherein the automated seed train preparation station comprises mammalian cells (Tolstrup, [0078]-[0080]).
Regarding claim 11, the control board of modified Tolstrup is structurally the same and thus fully capable of processing instructions received from the cloud server. Furthermore, the term “can be” renders the claim limitations optional.
Regarding claims 14-15, Tolstrup discloses a system comprising: a seed train preparation station configured to prepare a plurality of different types of respective seeds for transfer for automated fermentation (see annotated FIG. 2 below: seed train preparation region including a cell bank (i.e., container) holding a plurality of vials; [0042], [0052] and [0069]-[0076]);
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a fermentation station disposed adjacent to the automated seed train preparation station, the fermentation station utilizing a cell culture conveying means for transferring the plurality of different seed types from the seed train station to the fermentation station (FIG. 2: multiple culture vessels in the separate production phase at a first region (reads on the instant fermentation station) are disposed adjacent to and fluidly connected to the seed train preparation station to receive different seed types via cell culture conveying means prior to start of the fermentation process; [0026], [0042], [0052] and [0077]-[0082]), a plurality of modular bioreactors disposed in the fermentation station (FIG. 2: multiple culture vessels in the separate production phase at a first region (reads on the instant fermentation station); [0026], [0042], [0052] and [0077]-[0082]) and configured to receive one or more seeds from the seed train preparation station with the aid of the cell culture conveying means (culture vessels are configured to receive seed from the seed train station; FIG. 2; [0053] and [0177]), wherein each of the plurality of modular bioreactors is configured to be individually attachable and removable from the fermentation station (culture vessels in the separate production phase include disposable vessels, thus the culture vessels can be attached and removed from the first region; [0026], [0052] and [0177]; further, each of the culture vessels can comprise stirrer element therein and thus would have been intrinsic in the system of Tolstrup to have secured the modular bioreactors to the first region so as to secure the culture vessels and thereby prevent the disposable culture vessels from moving around during stirring process; further, the culture vessels are structurally the same as the instant modular bioreactors and thus fully capable of being individually attachable and removable from the first region); and wherein each of the plurality of modular bioreactors comprises a sensor (culture parameters are monitored and controlled in each of the culture vessels of Tolstrup during the production phase; [0177]; and thus intrinsically includes monitoring means such as a sensor, and controlling means such a controller), and a control board (processor) that is configured to (i) control corresponding modular bioreactor, and (ii) process sensor data captured by the sensor of the corresponding modular bioreactor to monitor real-time conditions (each culture vessel includes a sensor for monitoring culture parameters, and each of the culture vessels is coupled to a controller for controlling the culture parameters; [0078] and [0177]). Assuming arguendo that the seed train preparation station of Tolstrup is not automated. However, it would have been a prima facie obvious to one of ordinary skill in the art at the time of the effective filing date to have automated the seed train preparation station in order to prevent user errors during seed preparation. Tolstrup does not explicitly disclose wherein the cell culture conveying means is a robotic arm. However, Wasson is related to a system for culturing cells, wherein the system comprises a sample handling system including a robotic component (e.g., robotic arm) for transferring samples between vessel and/or transferring vessels between stations of the system (Wasson, ¶¶ [0380], [0471] and [0582]-[0585]). The robotic arm includes sample/fluid transfer means (e.g., robots with pipetting capability) for transferring samples between components of the system (Wasson, [0544] and [0582]). The sample handling system is coupled to a remote server or a cloud computing infrastructure for automating the robotic arm (Wasson, ¶ [0394]). In view of Wasson, it would have been prima facie obvious to one of ordinary skill in the art at the time of the effective filing date to have employed the robotic component coupled to a cloud computing infrastructure as disclosed by Wasson in place of cell culture conveying means of Tolstrup for the purpose of automating the transfer of cell culture between the seed train station and fermentation station. Further, one of ordinary skill in the art would have made said modification, because said modification would have been the simple substitution of one known sample/fluid transferring means for another for the predictable result of transferring a sample/fluid between components of a system. Assuming arguendo that the modular bioreactors of Tolstrup are not configured to be individually attachable and removable from the fermentation station. Galliher discloses a system comprising a culturing station including a platform (base plate at a first culturing station; [0080]) and a bioreactor attached to the platform ([0080]). The bioreactor is configured to be attachable and removable from the culturing station (bioreactor can be attached to the base plate reversibly or irreversibly; [0080]). The system of Galliher intrinsically includes a locking arrangement for reversibly or irreversibly securing the base plate to the bioreactor. In view of Galliher, it would have been obvious to one of ordinary skill in the art at the time of the effective filing date to have employed the locking arrangement of Galliher with the system of Tolstrup for the purpose of securing the modular bioreactor to the first region as disclosed by Galliher ([0080]). One of ordinary skill in the art would have made said modification so as to stabilize the plurality of modular bioreactors on the first region and to prevent the bioreactors from moving during stirring process. Tolstrup discloses wherein each of the modular bioreactors can be used to culture different types of cells and/or culturing cells under different conditions (Tolstrup, [0078]). Tolstrup further discloses wherein the modular bioreactors can be employed for culturing cells under different culturing modes ([0080]). Although not specifically disclosed by Tolstrup, it would have been intrinsic in the system of Tolstrup to comprise a control board (processor) coupled to each of the bioreactors in order to ascertain that each cell culture of the bioreactors are maintained at desired optimum culturing conditions. Assuming arguendo that Tolstrup fails to disclose a local control board (processor) that is configured to (i) control corresponding modular bioreactor, and (ii) execute local stored computer-executable instructions, and (iii) process sensor data captured by the sensor of the corresponding modular bioreactor to monitor real-time conditions according to the locally stored computer-executable instructions, and wherein the control boards is in communication with a cloud server of a network and configured to receive instructions for affecting an operation of the corresponding module bioreactor. Berteau discloses a system comprising a plurality of bioreactors (FIG. 3: modular bioreactors (304,306,308,310,312)), a sensor coupled to each of the bioreactors (FIG. 7: step 714; [0086], and a control board coupled to each of the bioreactors ([0081], [0086], [0093] and [0141]; FIGS. 7 and 13). Each of the sensors is coupled to a local control device and configured to (i) control corresponding modular bioreactor, and (ii) execute local stored computer-executable instructions, and (iii) process sensor data captured by the sensor of the corresponding modular bioreactor to monitor real-time conditions according to the locally stored computer-executable instructions (computing device 338,1300 (corresponds to the instant control board) and configured to automatically control operation of each of the bioreactors independently in real-time based on sensed data; ¶ [0081], [0086], [0093] and [0141]; FIGS. 7 and 13). The control board is in communication with a cloud server over a network and configured to receive instructions for affecting an operation of the corresponding modular bioreactor (system includes a control device configured to automatically and remotely control operation of each bioreactor, [0054]; and the control device is in communication and capable of running on one or more cloud machine instances which includes cloud server; [0141]). In view of Berteau, it would have been obvious to one of ordinary skill in the art at the time of the effective filing date to have employed the sensors and control boards of Berteau with each of the bioreactors of Tolstrup. One of ordinary skill in the art would have made said modification, because said modification would have resulted in a system having the added advantage of independently and simultaneously monitoring and controlling the culture parameters within each of the bioreactors. Further, one of ordinary skill in the art would have made said modification such that each bioreactors can be controlled individually, since Tolstrup discloses that the bioreactors can be employed for culturing cells under different culturing modes and/or culturing different cell types (Tolstrup, [0080]). Modified Tolstrup does not explicitly disclose wherein at least two of the plurality of modular bioreactors have different sensors. Tolstrup, however, does disclose wherein each of the modular bioreactor can be used for culturing different cell types and/or cells under different conditions (Tolstrup, [0078]). Tolstrup further discloses wherein the modular bioreactors can be employed for culturing cells under different culturing modes (different cultivation modes using batch process or perfusion process; and culturing different cell types such as mammalian cells and bacteria cells; Tolstrup, [0078]-[0080]). It would therefore have been obvious to one of ordinary skill in the art to have employed different sensors with at least two bioreactors of modified Tolstrup (e.g., flow sensors with perfusion process, different gases for different cell cultures, and environmental sensors for different culturing modes), since Tolstrup discloses that the bioreactors can be employed to culture different cell types and/or cells under different conditions/modes (Tolstrup, [0078]-[0080]). One of ordinary skill in the art would have made said modification in order to maintain the bioreactors at optimum culturing conditions. Modified Tolstrup does not explicitly disclose wherein the plurality of modular bioreactors are configured to receive the media container. Taniguchi discloses wherein containers containing contents (e.g., thawed cells) to be transferred to a bioreactor can be transported to the bioreactor (FIG. 29; [0202]-[0024]). In view of Taniguchi, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have configured the modular bioreactors of modified Tolstrup to receive the media container as disclosed by Taniguchi (FIG. 29; [0202]-[0024]). One of ordinary skill in the art would have made said modification because said modification would have facilitated ease of transfer of materials between the modular bioreactors and media container.
Regarding claim 16, modified Tolstrup does not explicitly disclose wherein at least two of the plurality of modular bioreactors have different reactor vessel shapes. However, it would have been obvious to one of ordinary skill in the art at the time the invention was made to have modified the shape of at least two bioreactors of the plurality of bioreactors of modified Tolstrup, since it has been held that a mere change in shape of an element is generally recognized as being within the level of ordinary skill in art when the change in shape is not significant to the function of the combination (see also MPEP 2144.04 IV.B.).
Regarding claim 17, modified Tolstrup discloses the claimed local control boards. The local control boards of modified Tolstrup are structurally the same as the instant of control boards and thus fully capable of receiving the claimed instructions from one or more control boards of one or more other modular bioreactors.
Regarding claim 18, modified Tolstrup discloses at least four modular bioreactors (see FIG. 2), each separately coupled to a local control board (which reads on at least one modular bioreactor having a second local control boards that is different than another modular bioreactor among the plurality of modular bioreactors).
Regarding claim 19, the automated seed train preparation station of modified Tolstrup is structurally the same as the instant of automated seed train preparation station and thus fully capable “to prepare respective seeds from a plurality of different seed types from the group comprised of biomass, viable cellular material, phage, extracellular metabolites, intracellular components, enzymes, proteins, a substrate, and bacteria.”
Claim(s) 1-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tolstrup et al. (previously cited, US 2011/0117605; hereinafter “Tolstrup”) in view of Duetz et al. (US 2004/0077063; hereinafter “Duetz”), Wasson et al. (previously cited, US 2016/0124009) (hereinafter “Wasson”), Galliher et al. (US 2009/0035856; hereinafter “Galliher”), Berteau et al. (previously cited, US 2016/0145563; hereinafter “Berteau”) and Taniguchi et al. (JP 2009-189362-A, with English machine translation; hereinafter “Taniguchi”). This is alternative rejection to the rejection of claims 1-19.
Regarding claims 1, 10 and 12-13, Tolstrup discloses a system comprising: a seed train preparation station comprising a seed preparation container holding a plurality of different seed types for transfer for automated fermentation (see annotated FIG. 2 below: seed train preparation region including a cell bank (i.e., container) holding a plurality of vials; [0042], [0052] and [0069]-[0076]);
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a fermentation station disposed adjacent to the automated seed train preparation station, the fermentation station utilizing a cell culture conveying means for transferring the plurality of different seed types from the seed train station to the fermentation station (FIG. 2: multiple culture vessels in the separate production phase at a first region (reads on the instant fermentation station) are disposed adjacent to and fluidly connected to the seed train preparation station to receive different seed types via cell culture conveying means prior to start of the fermentation process; [0026], [0042], [0052] and [0077]-[0082]), a plurality of modular bioreactors disposed in the fermentation station (FIG. 2: multiple culture vessels in the separate production phase at a first region (reads on the instant fermentation station); [0026], [0042], [0052] and [0077]-[0082]) and configured to receive one or more seeds from the seed train preparation station with the aid of the cell culture conveying means (culture vessels are configured to receive seed from the seed train station; FIG. 2; [0053] and [0177]), wherein each of the plurality of modular bioreactors is configured to be individually attachable and removable from the fermentation station (culture vessels in the separate production phase include disposable vessels, thus the culture vessels can be attached and removed from the first region; [0026], [0052] and [0177]; further, each of the culture vessels can comprise stirrer element therein and thus would have been intrinsic in the system of Tolstrup to have secured the modular bioreactors to the first region so as to secure the culture vessels and thereby prevent the disposable culture vessels from moving around during stirring process; further, the culture vessels are structurally the same as the instant modular bioreactors and thus fully capable of being individually attachable and removable from the first region); and wherein each of the plurality of modular bioreactors comprises a sensor (culture parameters are monitored and controlled in each of the culture vessels of Tolstrup during the production phase; [0177]; and thus intrinsically includes monitoring means such as a sensor, and controlling means such a controller), and a control board (processor) that is configured to (i) control corresponding modular bioreactor, and (ii) process sensor data captured by the sensor of the corresponding modular bioreactor to monitor real-time conditions (each culture vessel includes a sensor for monitoring culture parameters, and each of the culture vessels is coupled to a controller for controlling the culture parameters; [0078] and [0177]). Assuming arguendo that the seed train preparation station of Tolstrup is not automated. However, it would have been a prima facie obvious to one of ordinary skill in the art at the time of the effective filing date to have automated the seed train preparation station in order to prevent user errors during seed preparation. Tolstrup does not explicitly disclose wherein the cell culture conveying means is a robotic arm. However, Wasson is related to a system for culturing cells, wherein the system comprises a sample handling system including a robotic component (e.g., robotic arm) for transferring samples between vessel and/or transferring vessels between stations of the system (Wasson, ¶¶ [0380], [0471] and [0582]-[0585]). The robotic arm includes sample/fluid transfer means (e.g., robots with pipetting capability) for transferring samples between components of the system (Wasson, [0544] and [0582]). The sample handling system is coupled to a remote server or a cloud computing infrastructure for automating the robotic arm (Wasson, ¶ [0394]). In view of Wasson, it would have been prima facie obvious to one of ordinary skill in the art at the time of the effective filing date to have employed the robotic component coupled to a cloud computing infrastructure as disclosed by Wasson in place of cell culture conveying means of Tolstrup for the purpose of automating the transfer of cell culture between the seed train station and fermentation station. Further, one of ordinary skill in the art would have made said modification, because said modification would have been the simple substitution of one known sample/fluid transferring means for another for the predictable result of transferring a sample/fluid between components of a system. Assuming arguendo that the plurality of different seed types of Tolstrup are not contained within a single container. Duetz discloses that multiple strains can be contained within a single container ([0055]). In view of Duetz, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the seed train preparation station of Tolstrup such that the plurality of different seed types are contained within a single container as disclosed by Duetz to arrive at the claimed invention with a reasonable expectation of success. Assuming arguendo that the modular bioreactors of Tolstrup are not configured to be individually attachable and removable from the fermentation station. Galliher discloses a system comprising a culturing station including a platform (base plate at a first culturing station; [0080]) and a bioreactor attached to the platform ([0080]). The bioreactor is configured to be attachable and removable from the culturing station (bioreactor can be attached to the base plate reversibly or irreversibly; [0080]). The system of Galliher intrinsically includes a locking arrangement for reversibly or irreversibly securing the base plate to the bioreactor. In view of Galliher, it would have been obvious to one of ordinary skill in the art at the time of the effective filing date to have employed the locking arrangement of Galliher with the system of Tolstrup for the purpose of securing the modular bioreactor to the first region as disclosed by Galliher ([0080]). One of ordinary skill in the art would have made said modification so as to stabilize the plurality of modular bioreactors on the first region and to prevent the bioreactors from moving during stirring process. Tolstrup discloses wherein each of the modular bioreactors can be used to culture different types of cells and/or culturing cells under different conditions (Tolstrup, [0078]). Tolstrup further discloses wherein the modular bioreactors can be employed for culturing cells under different culturing modes ([0080]). Although not specifically disclosed by Tolstrup, it would have been intrinsic in the system of Tolstrup to comprise a control board (processor) coupled to each of the bioreactors in order to ascertain that each cell culture of the bioreactors are maintained at desired optimum culturing conditions. Assuming arguendo that Tolstrup fails to disclose a first local control board (processor) that is configured to (i) control corresponding modular bioreactor, and (ii) execute a fist set of local stored computer-executable instructions, and (iii) process sensor data captured by the sensor of the corresponding modular bioreactor to monitor real-time conditions according to the first set of locally stored computer- executable instructions, and wherein the control boards is in communication with a cloud server of a network and configured to receive instructions for affecting an operation of the corresponding module bioreactor. Berteau discloses a system comprising a plurality of bioreactors (FIG. 3: modular bioreactors (304,306,308,310,312)), a sensor coupled to each of the bioreactors (FIG. 7: step 714; [0086], and a local control board coupled to each of the bioreactors ([0081], [0086], [0093] and [0141]; FIGS. 7 and 13). Each of the sensors is coupled to a control device and configured to (i) control corresponding modular bioreactor, and (ii) execute local stored computer-executable instructions, and (iii) process sensor data captured by the sensor of the corresponding modular bioreactor to monitor real-time conditions according to the locally stored computer-executable instructions (computing device 338,1300 (corresponds to the instant control board), and configured to automatically control operation of each of the bioreactors independently in real-time based on sensed data; [0081], [0086], [0093] and [0141]; FIGS. 7 and 13). The control board is in communication with a cloud server over a network and configured to receive instructions for affecting an operation of the corresponding modular bioreactor (system includes a control device configured to automatically and remotely control operation of each bioreactor, [0054]; and the control device is in communication and capable of running on one or more cloud machine instances which includes cloud server; [0141]). The local control board of Berteau is structurally the same as the instant first local control boards and thus considered to be fully capable of executing a set of instructions. In view of Berteau, it would have been obvious to one of ordinary skill in the art at the time of the effective filing date to have employed the sensors and control boards of Berteau with each of the bioreactors of Tolstrup. One of ordinary skill in the art would have made said modification, because said modification would have resulted in a system having the added advantage of independently and simultaneously monitoring and controlling the culture parameters within each of the bioreactors. Further, one of ordinary skill in the art would have made said modification such that each bioreactors can be controlled individually, since Tolstrup discloses that the bioreactors can be employed for culturing cells under different culturing modes and/or culturing different cell types (Tolstrup, [0080]). Modified Tolstrup does not explicitly disclose wherein the plurality of modular bioreactors are configured to receive the media container. Taniguchi discloses wherein containers containing contents (e.g., thawed cells) to be transferred to a bioreactor can be transported to the bioreactor (FIG. 29; [0202]-[0024]). In view of Taniguchi, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have configured the modular bioreactors of modified Tolstrup to receive the media container as disclosed by Taniguchi (FIG. 29; [0202]-[0024]). One of ordinary skill in the art would have made said modification because said modification would have facilitated ease of transfer of materials between the modular bioreactors and media container.
Regarding claim 2, modified Tolstrup discloses a sensor coupled to the modular bioreactors, but does not explicitly disclose wherein the sensor is a camera. Taniguchi further discloses wherein a cell observation unit is coupled to the culture vessel including a camera having an image sensor ([0077]). In view of Taniguchi, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have replaced the sensor of modified Tolstrup with the image sensor of Taniguchi to arrive at the claimed invention. One of ordinary skill in the art would have made said modification because said modification would have been the simple substitution of one known sensor for the another for the predictable result of monitoring conditions within the bioreactor modules. Furthermore, the limitation “to monitor activity within the corresponding modular bioreactor” is drawn to intended use of the claimed invention. It is noted that a recitation directed to the manner in which a claimed apparatus is intended to be used does not distinguish the claimed apparatus from the prior art, if the prior art has the capability to so perform. Apparatus claims must distinguish from the prior art in terms of structure rather than function (see MPEP 2114).
Regarding claim 3, the camera of modified Tolstrup is fully capable of measuring an optical density of a culture in the corresponding modular bioreactor.
Regarding claim 4, the control board of modified Tolstrup is structurally the same as the instant control board and thus fully capable of monitoring real-time conditions including an error condition.
Regarding claim 5, the camera and the control board of modified Tolstrup are structurally the same as the instant camera and the control board and thus considered to configurable by the cloud server for monitoring the real-time conditions.
Regarding claim 6, the limitation of the claim does not add any additional structural limitations to the claimed system. The instructions can be provided by a user via a remote terminal.
Regarding claim 7, the robotic arm of modified Tolstrup is structurally the same as the instant robotic arm and thus fully capable of transferring material between the fermentation station and a sample handling station.
Regarding claims 8-9, modified Tolstrup further discloses wherein the automated seed train preparation station comprises mammalian cells (Tolstrup, [0078]-[0080]).
Regarding claim 11, the control board of modified Tolstrup is structurally the same and thus fully capable of processing instructions received from the cloud server. Furthermore, the term “can be” renders the claim limitations optional.
Regarding claims 14-15, Tolstrup discloses a system comprising: a seed train preparation station configured to prepare a plurality of different types of respective seeds for transfer for automated fermentation (see annotated FIG. 2 below: seed train preparation region including a cell bank (i.e., container) holding a plurality of vials; [0042], [0052] and [0069]-[0076]);
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a fermentation station disposed adjacent to the automated seed train preparation station, the fermentation station utilizing a cell culture conveying means for transferring the plurality of different seed types from the seed train station to the fermentation station (FIG. 2: multiple culture vessels in the separate production phase at a first region (reads on the instant fermentation station) are disposed adjacent to and fluidly connected to the seed train preparation station to receive different seed types via cell culture conveying means prior to start of the fermentation process; [0026], [0042], [0052] and [0077]-[0082]), a plurality of modular bioreactors disposed in the fermentation station (FIG. 2: multiple culture vessels in the separate production phase at a first region (reads on the instant fermentation station); [0026], [0042], [0052] and [0077]-[0082]) and configured to receive one or more seeds from the seed train preparation station with the aid of the cell culture conveying means (culture vessels are configured to receive seed from the seed train station; FIG. 2; [0053] and [0177]), wherein each of the plurality of modular bioreactors is configured to be individually attachable and removable from the fermentation station (culture vessels in the separate production phase include disposable vessels, thus the culture vessels can be attached and removed from the first region; [0026], [0052] and [0177]; further, each of the culture vessels can comprise stirrer element therein and thus would have been intrinsic in the system of Tolstrup to have secured the modular bioreactors to the first region so as to secure the culture vessels and thereby prevent the disposable culture vessels from moving around during stirring process; further, the culture vessels are structurally the same as the instant modular bioreactors and thus fully capable of being individually attachable and removable from the first region); and wherein each of the plurality of modular bioreactors comprises a sensor (culture parameters are monitored and controlled in each of the culture vessels of Tolstrup during the production phase; [0177]; and thus intrinsically includes monitoring means such as a sensor, and controlling means such a controller), and a control board (processor) that is configured to (i) control corresponding modular bioreactor, and (ii) process sensor data captured by the sensor of the corresponding modular bioreactor to monitor real-time conditions (each culture vessel includes a sensor for monitoring culture parameters, and each of the culture vessels is coupled to a controller for controlling the culture parameters; [0078] and [0177]). Assuming arguendo that the plurality of different seed types of Tolstrup are not contained within a single container. Duetz discloses that multiple strains can be contained within a single container ([0055]). In view of Duetz, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the seed train preparation station of Tolstrup such that the plurality of different seed types are contained within a single container as disclosed by Duetz to arrive at the claimed invention with a reasonable expectation of success. Assuming arguendo that the seed train preparation station of Tolstrup is not automated. However, it would have been a prima facie obvious to one of ordinary skill in the art at the time of the effective filing date to have automated the seed train preparation station in order to prevent user errors during seed preparation. Tolstrup does not explicitly disclose wherein the cell culture conveying means is a robotic arm. However, Wasson is related to a system for culturing cells, wherein the system comprises a sample handling system including a robotic component (e.g., robotic arm) for transferring samples between vessel and/or transferring vessels between stations of the system (Wasson, ¶¶ [0380], [0471] and [0582]-[0585]). The robotic arm includes sample/fluid transfer means (e.g., robots with pipetting capability) for transferring samples between components of the system (Wasson, [0544] and [0582]). The sample handling system is coupled to a remote server or a cloud computing infrastructure for automating the robotic arm (Wasson, ¶ [0394]). In view of Wasson, it would have been prima facie obvious to one of ordinary skill in the art at the time of the effective filing date to have employed the robotic component coupled to a cloud computing infrastructure as disclosed by Wasson in place of cell culture conveying means of Tolstrup for the purpose of automating the transfer of cell culture between the seed train station and fermentation station. Further, one of ordinary skill in the art would have made said modification, because said modification would have been the simple substitution of one known sample/fluid transferring means for another for the predictable result of transferring a sample/fluid between components of a system. Assuming arguendo that the modular bioreactors of Tolstrup are not configured to be individually attachable and removable from the fermentation station. Galliher discloses a system comprising a culturing station including a platform (base plate at a first culturing station; [0080]) and a bioreactor attached to the platform ([0080]). The bioreactor is configured to be attachable and removable from the culturing station (bioreactor can be attached to the base plate reversibly or irreversibly; [0080]). The system of Galliher intrinsically includes a locking arrangement for reversibly or irreversibly securing the base plate to the bioreactor. In view of Galliher, it would have been obvious to one of ordinary skill in the art at the time of the effective filing date to have employed the locking arrangement of Galliher with the system of Tolstrup for the purpose of securing the modular bioreactor to the first region as disclosed by Galliher ([0080]). One of ordinary skill in the art would have made said modification so as to stabilize the plurality of modular bioreactors on the first region and to prevent the bioreactors from moving during stirring process. Tolstrup discloses wherein each of the modular bioreactors can be used to culture different types of cells and/or culturing cells under different conditions (Tolstrup, [0078]). Tolstrup further discloses wherein the modular bioreactors can be employed for culturing cells under different culturing modes ([0080]). Although not specifically disclosed by Tolstrup, it would have been intrinsic in the system of Tolstrup to comprise a control board (processor) coupled to each of the bioreactors in order to ascertain that each cell culture of the bioreactors are maintained at desired optimum culturing conditions. Assuming arguendo that Tolstrup fails to disclose a local control board (processor) that is configured to (i) control corresponding modular bioreactor, and (ii) execute local stored computer-executable instructions, and (iii) process sensor data captured by the sensor of the corresponding modular bioreactor to monitor real-time conditions according to the locally stored computer-executable instructions, and wherein the control boards is in communication with a cloud server of a network and configured to receive instructions for affecting an operation of the corresponding module bioreactor. Berteau discloses a system comprising a plurality of bioreactors (FIG. 3: modular bioreactors (304,306,308,310,312)), a sensor coupled to each of the bioreactors (FIG. 7: step 714; [0086], and a control board coupled to each of the bioreactors ([0081], [0086], [0093] and [0141]; FIGS. 7 and 13). Each of the sensors is coupled to a local control device and configured to (i) control corresponding modular bioreactor, and (ii) execute local stored computer-executable instructions, and (iii) process sensor data captured by the sensor of the corresponding modular bioreactor to monitor real-time conditions according to the locally stored computer-executable instructions (computing device 338,1300 (corresponds to the instant control board) and configured to automatically control operation of each of the bioreactors independently in real-time based on sensed data; ¶ [0081], [0086], [0093] and [0141]; FIGS. 7 and 13). The control board is in communication with a cloud server over a network and configured to receive instructions for affecting an operation of the corresponding modular bioreactor (system includes a control device configured to automatically and remotely control operation of each bioreactor, [0054]; and the control device is in communication and capable of running on one or more cloud machine instances which includes cloud server; [0141]). In view of Berteau, it would have been obvious to one of ordinary skill in the art at the time of the effective filing date to have employed the sensors and control boards of Berteau with each of the bioreactors of Tolstrup. One of ordinary skill in the art would have made said modification, because said modification would have resulted in a system having the added advantage of independently and simultaneously monitoring and controlling the culture parameters within each of the bioreactors. Further, one of ordinary skill in the art would have made said modification such that each bioreactors can be controlled individually, since Tolstrup discloses that the bioreactors can be employed for culturing cells under different culturing modes and/or culturing different cell types (Tolstrup, [0080]). Modified Tolstrup does not explicitly disclose wherein at least two of the plurality of modular bioreactors have different sensors. Tolstrup, however, does disclose wherein each of the modular bioreactor can be used for culturing different cell types and/or cells under different conditions (Tolstrup, [0078]). Tolstrup further discloses wherein the modular bioreactors can be employed for culturing cells under different culturing modes (different cultivation modes using batch process or perfusion process; and culturing different cell types such as mammalian cells and bacteria cells; Tolstrup, [0078]-[0080]). It would therefore have been obvious to one of ordinary skill in the art to have employed different sensors with at least two bioreactors of modified Tolstrup (e.g., flow sensors with perfusion process, different gases for different cell cultures, and environmental sensors for different culturing modes), since Tolstrup discloses that the bioreactors can be employed to culture different cell types and/or cells under different conditions/modes (Tolstrup, [0078]-[0080]). One of ordinary skill in the art would have made said modification in order to maintain the bioreactors at optimum culturing conditions. Modified Tolstrup does not explicitly disclose wherein the plurality of modular bioreactors are configured to receive the media container. Taniguchi discloses wherein containers containing contents (e.g., thawed cells) to be transferred to a bioreactor can be transported to the bioreactor (FIG. 29; [0202]-[0024]). In view of Taniguchi, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to have configured the modular bioreactors of modified Tolstrup to receive the media container as disclosed by Taniguchi (FIG. 29; [0202]-[0024]). One of ordinary skill in the art would have made said modification because said modification would have facilitated ease of transfer of materials between the modular bioreactors and media container.
Regarding claim 16, modified Tolstrup does not explicitly disclose wherein at least two of the plurality of modular bioreactors have different reactor vessel shapes. However, it would have been obvious to one of ordinary skill in the art at the time the invention was made to have modified the shape of at least two bioreactors of the plurality of bioreactors of modified Tolstrup, since it has been held that a mere change in shape of an element is generally recognized as being within the level of ordinary skill in art when the change in shape is not significant to the function of the combination (see also MPEP 2144.04 IV.B.).
Regarding claim 17, modified Tolstrup discloses the claimed local control boards. The local control boards of modified Tolstrup are structurally the same as the instant of control boards and thus fully capable of receiving the claimed instructions from one or more control boards of one or more other modular bioreactors.
Regarding claim 18, modified Tolstrup discloses at least four modular bioreactors (see FIG. 2), each separately coupled to a local control board (which reads on at least one modular bioreactor having a second local control boards that is different than another modular bioreactor among the plurality of modular bioreactors).
Regarding claim 19, the automated seed train preparation station of modified Tolstrup is structurally the same as the instant of automated seed train preparation station and thus fully capable “to prepare respective seeds from a plurality of different seed types from the group comprised of biomass, viable cellular material, phage, extracellular metabolites, intracellular components, enzymes, proteins, a substrate, and bacteria.”
Claim(s) 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tolstrup in view of Wasson, Galliher, Berteau and Taniguchi as applied to claim 1 above, and further in view of Alfredsson et al. (US 2009/0305392; hereinafter “Alfredsson”).
Regarding claim 17, modified Tolstrup discloses the system according to claim 1 as set forth above. Assuming arguendo that modified Tolstrup fails to disclose the limitation of claim 17, Alfredsson discloses a system comprising a plurality of modules, each module comprising a dedicated local control board (microcontroller) adapted to receive instructions from other local control boards of other modules and a main control board ([0012], [0053], [0066], [0068]-[0069] and [0113]). in view of Alfredsson, it would have been prima facie obvious to one of ordinary skill in the art to have modified the system of modified Tolstrup such that the local control boards communicate with each other as disclosed by Alfredsson ([0012] and [0113]). One of ordinary skill in the art would have made said modification for the purpose of reducing operation errors, as suggested by Alfredsson ([0009]).
Response to Arguments
Applicant’s arguments with respect to claim(s) 1-19 have been considered but are moot in view of the new ground of rejection.
In response to the Applicant’s argument regarding Tolstrup, as discussed in the rejection above, Tolstrup discloses at least four vials of different strains contained within a single container (individual GMP banking). Conclusion
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/LIBAN M HASSAN/Primary Examiner, Art Unit 1799
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