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 .
Response to Amendment
This is an office action in response to Applicant’s arguments and remarks filed on 27 May 2026. Claims 1-20 are pending in the application. Claims 14, 15, and 17-20 are previously withdrawn. Claims 1-13 and 16 are being examined herein.
Status of Objections and Rejections
The objection to claim 1 is maintained.
The objections to claims 4-13 are withdrawn in view of amendments.
The interpretation of “process control for controlling” under 32 U.S.C. § 112(f) is maintained.
The rejections of claims 2, 4, 6-7, and 12-13 under 32 U.S.C. § 112(b) are maintained.
The rejections of claims 1, 3, 5, 8-11, and 16 under 32 U.S.C. § 112(b) are withdrawn.
The rejections of claims 1-9, 11, and 16 under 32 U.S.C. § 103 in view of Mehta, et. al. (US 20160137976 A1) in view of Ma, et. al. (CN 109401962 A) and Teixeira, et. al. ("Advances in on-line monitoring and control of mammalian cell cultures: Supporting the PAT initiative") are withdrawn in view of amendments.
The rejection of claim 10 under 32 U.S.C. § 103 in view of Mehta, et. al. (US 20160137976 A1) in view of Ma, et. al. (CN 109401962 A) and Teixeira, et. al. ("Advances in on-line monitoring and control of mammalian cell cultures: Supporting the PAT initiative") in further view of Dadgar, et. al. (WO 2019126212 A1) is withdrawn in view of amendments.
The rejection of claim 12 under 32 U.S.C. § 103 in view of Mehta, et. al. (US 20160137976 A1) in view of Ma, et. al. (CN 109401962 A) and Teixeira, et. al. ("Advances in on-line monitoring and control of mammalian cell cultures: Supporting the PAT initiative") in further view of Griffin, et. al. (WO 2019106207) is withdrawn in view of amendments.
The rejection of claim 13 under 32 U.S.C. § 103 in view of Mehta, et. al. (US 20160137976 A1) in view of Ma, et. al. (CN 109401962 A) and Teixeira, et. al. ("Advances in on-line monitoring and control of mammalian cell cultures: Supporting the PAT initiative") in further view of Griffin, et. al. (WO 2019106207) and Wu, et. al. ("Design of a Conductance and Capacitance Combination Sensor for water holdup measurement in oil-water two-phase flow”) is withdrawn in view of amendments.
Response to Arguments
Applicant's arguments filed 27 May 2026 have been fully considered but they are not persuasive.
Applicant first argues the combination of Mehta in view Ma is incompatible because Mehta teaches a continuous system and Ma teaches a non-continuous system (Remarks, pg. 9; par. 02).
Examiner respectfully disagrees. Mehta teaches sensors and signals from said sensors influencing controller actions (Mehta, par. 0125). Mehta is modified in view of Ma to further include sensors at certain points in the fluidic network to influence controller actions (Ma, Fig. 2; par. 0023). Ma specifically teaches these sensors help optimize interconnectivity of the overall device (Ma, par. 0009) which creates an efficient and automated cell preparation system (Ma, par. 0023). The sensors of both devices influence the controller actions. Because the Mehta teaches sensors that provide feedback modifying the sensors to be located at different locations, specifically within the liquid lines as taught by Ma, creates a system that has improved interconnectivity and automated efficiency (Ma, par. 0009, 00023) with reasonable expectation of success. The location of the sensors bares no weight on the continuous or non-continuous nature of the device.
Applicant’s arguments, see Remarks pages 8-12, filed 27 May 2026, with respect to the rejections of claims 1-9, 11, and 16 under 32 U.S.C. § 103 in view of Mehta in view of Ma and Teixeira have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Mehta in view of Ma and Teixeira and in further view of Tijsterman (US 20150299644 A1).
Applicant additionally argues that the liquid sensors of Ma do not teach the ability to determine biomass levels (Remarks, pg. 9, par. 03-04).
Examiner agrees that Ma does not specifically teach biomass sensors but liquid sensors. However, the rejection of specifically the biomass sensors of claim 1 in made in view of Teixeira. The device, specifically the sensors, of Ma are used to modify the location of the sensors to be within the fluidic network, not the type of sensors.
Applicant further argues Mehta in view of Ma and Teixeira do not teach the newly amended features of claim 1 (Remarks, pg. 9, par. 03-05).
Examiner agrees, Mehta in view of Ma and Teixeira do not teach or fairly disclose the newly amended features of claim 1. Examiner maintains the use of Mehta in view of Ma and Teixeira in the rejection in further view of Tijsterman to remedy the remaining features.
Applicant provides no additional arguments for claims 2-13 and 16 aside from their dependence to newly amended claim 1 (Remarks, pg. 10, par. 01 - pg. 11, par. 02).
Claim Objections
Examiner notes claim 1 recites, “wherein the centrifuge setup is designed to execute a loading cycle, during which cell broth is pumped to the chamber inlet, during which a buffer is pumped to the chamber inlet, the biomass is held back in the chamber and the supernatant is flowing to the chamber outlet, and a discharging cycle, during which a buffer is pumped to the chamber outlet” in lines 9-12. Examiner believes between “during which cell broth is pumped to the chamber inlet” and “during which a buffer is pumped to the chamber inlet” reference should be made to the washing cycle. This is based on the description of the washing cycle from the specification of the instant application (pg. 05, line 29 – pg. 06, line 2) and claim 3. Appropriate correction is required.
Examiner notes claim 2 recites “a liquid line of the plurality of liquid lines” in lines 2-3 of the claim. “A liquid line…” is previously recited in claim 1; however, Examiner believes these to be two separate lines based on the provided Figures. Examiner wanted to note amending claim 2 to recite “a second liquid line of the plurality of liquid lines” provides further clarity for the scope of the claim.
Claim Interpretation
Examiner notes the claims use functional language to attribute features to the device within the apparatus claims, specifically to the functions of the process control. Examiner recommends amending all relevant parts in all claims to use “configured to” language; for example, “wherein the process control is configured to control the valve arrangement and/or…” in claim 1.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier. Such claim limitation(s) is/are: : “wherein the centrifuge setup comprises a process control for controlling at least the centrifuge, the liquid pumping arrangement and the valve arrangement” in claim 1.
“A process control” is the process control is a control unit that controls all/most of components and realized as a centralized or decentralized microprocessor that runs software (specification pg. 14, line 29 - pg. 15, line 2) or other equivalents thereof.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 1 recites the limitation, “wherein the centrifuge setup is designed to execute a loading cycle, during which cell broth is pumped to the chamber inlet, during which a buffer is pumped to the chamber inlet, the biomass is held back in the chamber and the supernatant is flowing to the chamber outlet, and a discharging cycle, during which a buffer is pumped to the chamber outlet” in lines 9-12. Examiner believes between the limitation “during which a buffer is pumped to the chamber inlet” reference should be made to the washing cycle. This is based on the description of the washing cycle from the specification of the instant application (pg. 05, line 29 – pg. 06, line 2) and Figures 4 and 5 of the instant application. It is unclear what actions, particularly those of the buffer, are a part of the loading cycle and which are part of the washing cycle. The following proposed amendments are based on Figures 4 and 5 of the instant application. Examiner recommends amending the claim to recite, “wherein the centrifuge setup is designed to execute a loading cycle, during which cell broth is pumped to the chamber inlet and the biomass is held back in the chamber and the supernatant is flowing to the chamber outlet, a washing cycle during which a buffer is pumped to the chamber inlet, and a discharging cycle, during which a buffer is pumped to the chamber outlet” or an equivalent thereof. Examiner draws attention to claim 3 which going into further detail about each cycle and notes if claim 1 is amended to recited “a washing cycle” that further amendments need to be made to remaining dependent claims, specifically claim 3.
Claims 2-13 and 16 are rejected based on their dependence to claim 1.
Claim 2 recites the limitation “an occurrence level” in line 3 of the claim. “An occurrence level” is previously recited in claim 1. It is unclear if these are the same occurrence levels. Examiner believes these are not the same occurrence levels. Examiner recommends amending the claim to recite “an occurrence level of supernatant” or an equivalent thereof.
Claims 6-7 and 12-13 are rejected based on their dependence to claim 2.
Claim 4 recites the limitation "a biomass filling level" in line 3 of the claim. "A biomass filling level” is previously recited in claim 1. Examiner believes these are the same biomass filling levels. Examiner recommends amending claim to recite "the biomass filling level."
Claim 5 is rejected based on its dependence to claim 4.
Claim 6 recites the limitation “an occurrence level of supernatant” in line 3 of the claim. “An occurrence level” is previously recited in claims 1 and 2. It is unclear if these are the same occurrence levels. Examiner believes these are not the same occurrence levels for claim 1, but the same occurrence levels in claim 2. Examiner recommends amending the claim to recite “the occurrence level of supernatant” or an equivalent thereof to match the amended claim 2.
Claim 7 is rejected based on its dependence to claim 6.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-9, 11, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Mehta, et. al. (US 20160137976 A1) in view of Ma, et. al. (CN 109401962 A; citations made with respect to provided English machine translation and original copy provided with IDS dated 05 January 2023), Teixeira, et. al. ("Advances in on-line monitoring and control of mammalian cell cultures: Supporting the PAT initiative;" citations made with respect to previously provided copy), and Tijsterman (US 20150299644 A1).
Regarding claim 1, Mehta teaches a system to physically manipulate (separate) biomaterials by rotating chamber (Abstract, par. 0081) (an automated centrifuge setup of a bioprocessing installation for the separation of a cell broth by centrifugation). Mehta teaches the device is to be used for cells (biomass) within a cell culture (supernatant) (wherein the cell broth comprises a biomass and a supernatant) (par. 0103). Mehta teaches an embodiment of the system that comprises:
An apparatus 4 that holds rotating chamber 5 with an inlet and an outlet (the top and bottom lines respectively attached to rotating chamber 5 in figure) (Fig. 21-23; par. 0122) (wherein, for the centrifugation, the centrifuge setup comprises a centrifuge) (wherein the centrifuge comprises at least one centrifuge chamber with a chamber inlet and a chamber outlet).
The inlet and outlet of the rotating chamber 5 is connected to a series of liquid pathways (see the series of solid and dashed lines leading from box to box in the figures) with the flow being driven by bi-directional pump 3 (Fig. 21-23; 0122-0124) (wherein the centrifuge setup comprises a liquid pumping arrangement and a liquid network with a number of liquid lines communicating with the liquid pumping arrangement).
The pathways are paired with a series of valves 15, 17, 21, 24, 27 that are opened and closed to influence the flow of liquid through a predetermined pathway (par. 0122-0125) (wherein the centrifuge setup comprises a valve arrangement, that allows to activate and deactivate at least one of the liquid lines).
The device is driven by a controller (not pictured) that controls the pump(s), flow rate, rotation, and valves (par. 0027-0028; 0144) (wherein the centrifuge setup comprises a process control for controlling at least the centrifuge, the liquid pumping arrangement and the valve arrangement).
Mehta teaches the system operates according to the following methods (wherein the centrifuge setup is designed to execute) (Fig. 21-23; par. 0121-0124):
a cell capture mode wherein cell containing media flows from the bioreactor 1 to rotating chamber 5 through the inlet (Fig. 21; par. 0122) (a loading cycle, during which cell broth is pumped to the chamber inlet) and during rotation cells form a fluidized bed in rotating chamber 5 and media flow out of apparatus 4 through pathway 6 (par. 0122) (the biomass is held back in the chamber and the supernatant is flowing to the chamber outlet)
a media/buffer exchange mode wherein buffer or new media is pumped from the container 22 to rotating chamber 5 through the inlet (Fig. 22; par. 0123) (during which a buffer is pumped to the chamber inlet)
a cell capture mode wherein buffer or new media is pumped from container 26 to rotating chamber 5 through the outlet (Fig. 22; par. 0124) (a discharging cycle, during which a buffer is pumped to the chamber outlet)
Examiner draws attention to the small triangles/arrows along the pathways in Figures 21-23 that indicate the flow path taken and direction in each operating mode.
Finally, Mehta teaches that detectors and sensors, like bubble detectors, can be used in the system to trigger next stages of the process (par. 0125) (wherein the centrifuge setup comprises a sensor arrangement). Because Mehta teaches the controller is influenced by the signal from the sensor/detector, that occurrence signal must be calculated by the controller (that the process control calculates an occurrence level… in the respective liquid line based on the sensor signals of the… sensor arrangement) (wherein the process control controls the valve arrangement and/or the liquid pumping arrangement during the loading cycle).
Examiner notes the loading and discharging cycles are drawn to the intended use of the flow of liquid through the series of pathways and valves. The prior art made of record, Mehta, teaches a system that has the appropriate vessels connected to the appropriate pathways/liquid lines and valves so that it is capable of performing each of the different cycles without modifying the system's structure.
Mehta is silent to in which (biomass) sensor arrangement is assigned to a liquid line of the plurality of liquid lines.
Ma teaches a cell preparation and separation system that uses sensors throughout the system (Abstract). Ma teaches a system comprising multiple containers for holding cells, waste, and other liquids associated with cell preparation all connected, a centrifuge tank, and a fluidic network with valves (Fig. 2; par. 0024-0029, 0050, 0056). Ma teaches a first liquid sensor 44 embedded in the fluidic network (Fig. 2) (wherein the centrifuge setup comprises a sensor arrangement with at least one… sensor arrangement, which… sensor arrangement is assigned to a liquid line of the plurality of liquid lines). Ma teaches including inline liquid sensors regulate the key steps and components of the device ultimately to create an efficient and automated cell preparation system (par. 0022-0023).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the detectors of Mehta to be sensors embedded within the fluidic network lines as taught by Ma because this in-line arrangement allows for the automation of the system and creates a more efficient cell preparation system (Ma, par. 0022-0023 with reasonable expectation of success. MPEP 2143(I)(G).
Modified Mehta is silent to the sensor arrangement with at least one biomass sensor arrangement, that the process control calculates an occurrence level, of biomass in the respective liquid line based on the sensor signals of the biomass sensor arrangement.
Teixeira summarizes the advances made in on-line monitoring of cells in bioprocessing systems (Abstract). Teixeira teaches dielectric capacitance is a well-known technique for monitoring biomass in bioprocessing systems (Table 1, Section 2.4 "Dielectric spectroscopy") (at least one biomass sensor) (an occurrence level, of biomass in the respective liquid line based on the sensor signals of the biomass sensor arrangement). Teixeira teaches dielectric capacitance sensor are especially preferred for monitoring of bioprocessing systems because they offer essentially real-time feedback and control for the systems and they are easily incorporated into systems (pg. 727, col. 2, lines 11-16).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the detectors of modified Mehta to specifically be biomass sensors as taught by Teixeira because it allows for the systems to receive real-time feedback and control for the system (Teixeira, pg. 727, col. 2, lines 11-16) with reasonable expectation of success. Because all systems use sensors for analyzing biomass, it would be obvious to try the specific detector of Teixeira because only a finite number of detectors will monitor biomass and therefore would be obvious to try with a reasonable expectation of success. MPEP 2143(I)(E).
Examiner wishes to clarify that the locations of the sensors along the fluidic line is taught by Ma and the type of sensors is taught by Teixeira.
Modified Mehta is silent to wherein, during the loading cycle, the process control calculates a biomass filling level of the centrifuge chamber based on sensor signals of the biomass sensor arrangement, and wherein the process control controls based on the calculated biomass filling level, preventing overloading the centrifuge chamber with biomass, while supernatant is flowing from the chamber inlet to the chamber outlet.
Tijsterman teaches a cell culturing system with bioreactors and separation means (Abstract). Tijsterman teaches the system comprises bioreactors 10, 15 connected through a series of fluidic lines leading to a separator 30 that further comprises a centrifuge 35 (Fig. 1; par. 0029-0032). Tijsterman teaches the system further comprises a detector for detecting cell count or density within the bioreactors (par. 0031) (at least one biomass sensor arrangement, which biomass sensor arrangement). Tijsterman teaches the detector has a predetermined threshold value to determine when the cell culture will move from the bioreactor 10, 15 to the centrifuge 35 (par. 0031, 0034) (during the loading cycle, the process control calculates a biomass filling level of the centrifuge chamber based on sensor signals of the biomass sensor arrangement). Because this detection level can be determined by calculation a level can be selected that will prevent too much of the solution from moving to the bioreactor to the centrifuge (par. 0031) (wherein the process control controls based on the calculated biomass filling level, preventing overloading the centrifuge chamber with biomass, while supernatant is flowing from the chamber inlet to the chamber outlet). Tijsterman teaches this embodiment, with multiple reactors that have a detector that determine when the solution will move to the centrifuge, results in a higher yield of the biological substance (par. 0009).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the detectors of modified Mehta to determine the filling level of the centrifuge as taught by Tijsterman because it results in a higher yield from the system (Tijsterman, par. 0009) with reasonable expectation of success. MPEP 2143(I)(G).
Regarding claim 2, modified Mehta in view of Ma teaches a second liquid sensor 45 embedded in a second line of the fluidic network (Ma, Fig. 2). Because supernatant is a liquid it is understood by those of ordinary skill in the art that a liquid sensor can detect the presence of the supernatant (wherein the sensor arrangement comprises at least one supernatant sensor arrangement, which is assigned to a liquid line of the liquid network). Modified Mehta teaches that detectors, like bubble detectors, can be used in the system to trigger next stages of the process (Mehta, par. 0125). In claim 1 above, it is established the detector of Mehta can be modified to be a sensor as provided by Mah; therefore, because Mehta teaches the controller is influenced by the signal from the sensor/detector, that occurrence signal must be calculated by the controller (and that the process control calculates an occurrence level).
Regarding claim 3, modified Mehta teaches a fluidic line connecting bioreactor 1 to the inlet of chamber 5 (see line 2 in Figure 21) (wherein the liquid network comprises an inlet feed line between the chamber inlet and a cell broth source) and a line connecting the chamber 5 outlet to a waste container 23 (see line 6 and 25 in Figure 21) (an outlet waste line between the chamber outlet and a waste reception).
When performing the cell capture mode, as seen in Figure 21 when following the small triangles, cells flow out of bioreactor 1 through pathway 2 and valve 15 by pump 3, until it reached the inlet of chamber 5 (that during a loading cycle the cell broth may be pumped by the liquid pumping arrangement from the cell broth source to the chamber inlet via the inlet feed line) and moves from the outlet of chamber 5 through pathway 6 and 25 and valve 24 to waste container 23 (from the chamber outlet to a waste reception via the outlet waste line) (par. 0122).
Modified Mehta further teaches a new buffer/media container 22 connected to the pump 3 and chamber 5 through pathway 20 and the outlet of chamber 5 through pathway 6 and 25 and valve 24 to waste container 23 (Fig. 22; par. 0123) (that the liquid network comprises an inlet buffer line between the chamber inlet and a buffer source and an outlet waste line between the chamber outlet and a waste reception).
When in the media/buffer exchange mode (seen in Figure 22, following the small triangles) new buffer is pumped from the new media/buffer container 22, to the inlet of chamber 5 and finally to waster container 23 (par. 0123) (that during a washing cycle the buffer may be pumped by the liquid pumping arrangement from the buffer source to the chamber inlet via the inlet buffer line and from the chamber outlet to the waste reception via the outlet waste line).
When in the dispense mode (seen in Figure 23, following the small triangles) new buffer is pumped from new media/buffer container 26 through pathways 28 and 6 through the chamber 5 outlet (that during a discharging cycle the buffer may be pumped from the buffer source to the chamber outlet via the outlet buffer line), through chamber 5 taking the cells in the chamber 5, and finally to dispensed cell harvest container 45 through pathway 2 and 19 (par. 0124) (while the buffer including solid particles, is flowing from the chamber inlet to the cell harvest reception via the inlet cell harvest line).
Regarding claim 4, modified Mehta in view of Ma teaches first sensor 44 is in line between sample container 35 and centrifuge 29 (found within temperature module 48) (Ma, Fig. 2) (wherein a biomass sensor arrangement is located in the inlet feed line). Ma teaches operation step 1 wherein the sample is drawn from the sample container to the centrifuge tank (and that, during the loading cycle) and during that process first sensor 44 monitors the movement of the sample through the fluidic line before a drawing process is stopped (Ma, par. 0063-0064). In other words, the first sensor 44 triggers when to stop the sample drawing process in operation step 1 that fills the centrifuge tank. As established in claim 1 above, the first sensor 44 of Ma can be modified to be a biomass sensor in view of Teixeira. Further, modified Mehta teaches that detectors can be used in the system to trigger next stages of the process (Mehta, par. 0125). Because Mehta teaches the controller is influenced by the signal from the sensor/detector, that occurrence signal must be calculated by the controller. Putting these together, the system of Mehta that includes a processor that converts detector signals to an operational output, the detectors of Mehta are modified in view of Ma to be sensors and specifically biomass sensors in view of Teixeira, in the process of filling the centrifuge tank with the sample, the sensor will monitor the filling process monitoring the biomass level of the sample moved into the centrifuge tank (the process control calculates a biomass filling level of the centrifuge chamber based on the sensor signals of the biomass sensor arrangement).
Regarding claim 5, modified Mehta teaches a cell capture mode wherein cell containing media flows from the bioreactor 1 to rotating chamber 5 through the inlet (Mehta, Fig. 21; par. 0122) (a loading cycle). Modified Mehta in view of Ma teaches the system pumps the liquid from the container holding the sample to the first liquid sensor (Ma; par. 0064) . Ma teaches once the first liquid sensor is triggered by the sample, the drawing of the same is stopped (Ma; par. 0064). Modified Mehta teaches that detectors, like bubble detectors, can be used in the system to trigger next stages of the process (Mehta, par. 0125). Because Mehta teaches the controller is influenced by the signal from the sensor/detector, that occurrence signal must be calculated by the controller as liquid passes through a sensor (wherein a maximum biomass filling level is defined in the process control and that, during the loading cycle, the process control terminates the loading cycle, when the maximum biomass filling level is reached by the calculated biomass filling level).
Regarding claim 6, modified Mehta in view of Ma teaches second liquid sensor 45 is located in the outlet fluid line from the centrifuge tank (surrounded by temperature control unit 48) (Ma, Fig. 2) (wherein the supernatant sensor arrangement is located in the outlet supernatant line). Ma teaches the second liquid sensor 45 analyzes the liquid passing through to be sorted further by a valve (Ma, par. 0064). Modified Mehta teaches that detectors, like bubble detectors, can be used in the system to trigger next stages of the process (Mehta, par. 0125). Because Mehta teaches the controller is influenced by the signal from the sensor/detector, that occurrence signal must be calculated by the controller as liquid passes through a sensor (during the loading cycle, the process control calculates an occurrence level of supernatant in the outlet supernatant line based on the sensor signals of the supernatant sensor arrangement).
Regarding claim 7, modified Mehta in view of Ma teaches the second liquid sensor 45 analyzes the liquid passing through to be sorted further by a valve to be sorting into different collection containers each with their own fluid line(Ma, Fig. 2; par. 0064). As previously stated, because Mehta teaches the controller is influenced by the signal from the sensor/detector, including triggering cycles (Mehta, par. 0125), the controller of Mehta would be able to change valves to control what fluid lines the liquid moves to and terminate and begin cycles (wherein a supernatant switching level is defined in the process control and that, during the loading cycle and/or the washing cycle, the process control switches between the outlet supernatant line and the outlet waste line or another liquid line).
Regarding claim 8, Modified Mehta teaches a fluid line 19 that leads to a cell harvest container 45 and a waste line 23 leading to a waste container 23 (Mehta, Fig.22-23) (the inlet cell harvest line or the inlet waste line). Modified Mehta in view of Ma teaches a first liquid sensor 44 embedded in the fluidic network (Ma, Fig. 2) and Teixeira teaches dielectric capacitance is a well-known technique for monitoring biomass online in bioprocessing systems (Teixeira, Table 1, Section 2.4 "Dielectric spectroscopy") (wherein the centrifuge setup comprises a biomass sensor arrangement of the sensor arrangement). Modified Mehta in view of Ma teaches the second liquid sensor 45 analyzes the liquid passing through to be sorted further by a valve to be sorting into different collection containers each with their own fluid line(Ma, Fig. 2; par. 0064). As previously stated, because Mehta teaches the controller is influenced by the signal from the sensor/detector, including triggering cycles (Mehta, par. 0125), the controller of Mehta would be able to change valves to control what fluid lines the liquid moves to and terminate and begin cycles (during the discharging cycle, the process control calculates an occurrence level of biomass in the inlet cell harvest line or the inlet waste line based on the sensor signals of the biomass sensor arrangement).
Modified Mehta is silent to the sensor arrangement specifically being in the inlet cell harvest line or the inlet waste line.
Modified Mehta in view of Ma teaches a second liquid sensor 45 embedded in a second line of the fluidic network (Ma, Fig. 2). Ma teaches the second liquid sensor 45 analyzes the liquid passing through to be sorted further by a valve to be sorting into different collection containers each with their own fluid line(Ma, Fig. 2; par. 0064). Further, rearranging the parts so that a sensor is located in a different fluidic line that handles biomass matter, does not change the operation and steps of the system to monitor biomass within the system. MPEP § 2144 (VI)(C). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filling data of the invention to rearrange the location of the biomass sensor to be located in the inlet cell harvest line or the inlet waste line.
Regarding claim 9, modified Mehta in view of Ma teaches the second liquid sensor 45 analyzes the liquid passing through to be sorted further by a valve to be sorting into different collection containers each with their own fluid line(Ma, Fig. 2; par. 0064). As previously stated, because Mehta teaches the controller is influenced by the signal from the sensor/detector, including triggering cycles (Mehta, par. 0125), the controller of Mehta would be able to change valves to control what fluid lines the liquid moves to and terminate and begin cycles (wherein the centrifuge setup comprises a biomass sensor arrangement of the sensor arrangement in the inlet cell harvest line or the inlet waste line and that, during the discharging cycle, the process control calculates an occurrence level of biomass in the inlet cell harvest line or the inlet waste line based on the sensor signals of the biomass sensor arrangement).
Regarding claim 11, modified Mehta in view of Ma teaches a first liquid sensor 44 embedded in the fluidic network (Ma, Fig. 2) and Teixeira teaches dielectric capacitance is a well-known technique for monitoring biomass online in bioprocessing systems (Teixeira, Table 1, Section 2.4 "Dielectric spectroscopy") (wherein the biomass sensor arrangement comprises a biomass sensor, which is realized as a capacitance biomass sensor).
Regarding claim 16, modified Mehta teaches the centrifuge chamber 5 is part of a larger cell culture system, and the cell sample is stored in a bioreactor 1 for processing the cell samples (Mehta, Fig. 21; par. 0103-0104) (a bioprocess installation with a centrifuge setup according to claim 1 and with a cell broth source in the form of a production vessel, or a storage vessel).
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Mehta, et. al. (US 20160137976 A1) in view of Ma, et. al. (CN 109401962 A), Teixeira, et. al. ("Advances in on-line monitoring and control of mammalian cell cultures: Supporting the PAT initiative"), and Tijsterman (US 20150299644 A1) as applied to claim 1 above, and further in view of Dadgar, et. al. (WO 2019126212 A1; citations made with respect to attached copy).
Regarding claim 10, modified Mehta in view of Ma teaches a first liquid sensor 44 embedded in the fluidic network (Ma, Fig. 2) and Teixeira teaches dielectric capacitance is a well-known technique for monitoring biomass online in bioprocessing systems (Teixeira, Table 1, Section 2.4 "Dielectric spectroscopy") (wherein the biomass sensor arrangement comprises a biomass sensor).
Modified Mehta is silent to adding a flow sensor in combination.
Dadgar teaches a bioprocessing system controlled by a processor (Abstract). Dadgar teaches the system comprises a series of sensors that send electronic signals back to the electronic components of the system (par. 0112). Dadgar teaches the sensor arrangements exist as assemblies to monitor several components simultaneously, like a presence and flow sensor (par. 0112) (a flow sensor in combination). Dadgar specifically teaches a flow sensor can be a capacitive sensor (par. 0121). Dadgar teaches the addition of the flow sensor allows for the system to be monitored for bubbles or inconsistent flow which can lead to errors in the system (par. 0122).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the capacitive biomass sensor of modified Mehta to further include a flow sensor as taught by Dadgar because it allows the system to monitor for bubbles or inconsistent flow (Dadgar, par. 0122) with reasonable expectation of success. MPEP 2143(I)(G).
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Mehta, et. al. (US 20160137976 A1) in view of Ma, et. al. (CN 109401962 A), Teixeira, et. al. ("Advances in on-line monitoring and control of mammalian cell cultures: Supporting the PAT initiative"). and Tijsterman (US 20150299644 A1) as applied to claim 1 above, and further in view of Griffin, et. al. (WO 2019106207 A1; citations made with respect to attached copy).
Regarding claim 12, Modified Mehta in view of Ma teaches a second liquid sensor 45 embedded in a second line of the fluidic network (Ma, Fig. 2). Because supernatant is a liquid it is understood by those of ordinary skill in the art that a liquid sensor can detect the presence of the supernatant (wherein the supernatant sensor arrangement comprises a supernatant sensor).
Modified Mehta is silent to the supernatant sensor being realized as a conductivity sensor.
Griffin teaches a bioprocessing system for sorting and collecting cells (Abstract). Griffin teaches the system comprises sensors to monitor each process the system performs (par. 00246). Griffin teaches conductivity sensors are installed around the circulation loop the fluid takes around the system (par. 00246) (which is realized as a conductivity sensor). Griffin teaches conductivity detectors provide data about the sample fluid in real time (when circulated) instead of during post-collection analysis (par. 000246).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the liquid (supernatant) sensor of modified Mehta to be a conductivity sensor as taught by Griffin because it provides real-time feedback data on the circulating fluid (Griffin, par. 000246) with reasonable expectation of success. MPEP 2143(I)(G).
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Mehta, et. al. (US 20160137976 A1) in view of Ma, et. al. (CN 109401962 A) and Teixeira, et. al. ("Advances in on-line monitoring and control of mammalian cell cultures: Supporting the PAT initiative"), and Tijsterman (US 20150299644 A1) as applied to claim 1 above, and further in view of Griffin, et. al. (WO 2019106207 A1; citations made with respect to attached copy) and Wu, et. al. (“Design of a Conductance and Capacitance Combination Sensor for water holdup measurement in oil–water two-phase flow;” citations made with respect to attached copy)
Regarding claim 13, Modified Mehta in view of Ma teaches a first liquid sensor 44 embedded in the fluidic network and a second liquid sensor 45 embedded in a second line of the fluidic network (Ma, Fig. 2). Modified Mehta in view of Teixeira teaches wherein one sensor uses dielectric capacitance as a well-known technique for monitoring biomass in bioprocessing systems (Teixeira, (Table 1, Section 2.4 "Dielectric spectroscopy") (wherein the biomass sensor and the supernatant sensor) (derives an occurrence level of biomass based on a capacitance measurement).
Modified Mehta is silent to the sensor derives an occurrence level of supernatant based on a conductivity measurement.
Griffin teaches a bioprocessing system for sorting and collecting cells (Abstract). Griffin teaches the system comprises sensors to monitor each process the system performs (par. 00246). Griffin teaches conductivity sensors are installed around the circulation loop the fluid takes around the system (par. 00246) (sensor derives an occurrence level of supernatant based on a conductivity measurement). Griffin teaches conductivity detectors provide data about the sample fluid in real time (when circulated) instead of during post-collection analysis (par. 000246).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the liquid (supernatant) sensor of modified Mehta to be a conductivity sensor as taught by Griffin because it provides real-time feedback data on the circulating fluid (Griffin, par. 000246) with reasonable expectation of success. MPEP 2143(I)(G).
Modified Mehta is silent to the sensors (being) provided by a combined sensor with at least two sensor electrodes, the capacitance measurement using the electrodes, and the conductivity measurement using the electrodes.
Wu teaches a sensor that measures capacitance and conductivity in solutions comprising at least two different phases (Abstract). Wu teaches a combined probe that that comprises four conductance probes (electrodes) and two capacitance electrodes (Fig. 1) (a combined sensor with at least two sensor electrodes, the capacitance measurement using the electrodes, and the conductivity measurement using the electrodes). Wu teaches the combined electrode allows for testing of complex samples, specifically samples with different, immiscible phases (pg. 227, section 6 “Conclusions”).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the invention to modify the sensors of modified Mehta to be a combined capacitance and conductance electrode sensor as taught by Wu because it allows for quick monitoring of different properties of complex solutions (Wu, pg. 227, section 6 “Conclusions”) with reasonable expectation of success. MPEP 2143(I)(G).
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/M.T.H./Examiner, Art Unit 1758
/MARIS R KESSEL/Supervisory Patent Examiner, Art Unit 1758
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