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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 10/20/2025 has been entered.
Response to Arguments
Applicant’s arguments filed 10/20/2025 have been considered but they are moot in view of a new grounds of rejection necessitated by the amendments to the claims.
Applicant argues on pp. 10-12 of Remarks that neither Bovard et al. (WO 2019/043130 A1) nor Kato et al. (WO 2006/043642 A1) teach or suggest “a mixed flow generation path” or “the flow path wider part and the flow path deeper part are constituted by a curved surface”, and the Examiner agrees. However, Di Carlo et al. (US 2013/0171628 A1) discloses a microfluidic device which includes these features, and it would have been obvious to modify the device of Bovard et al. based on the teachings of Di Carlo et al., as will be discussed in further detail in the 35 U.S.C. § 103 section below.
Applicant’s amendments to the “flow path width change unit” and “flow path depth change unit” in claim 1 have overcome each of the 112(f) claim interpretation, the 112(a) rejection for failing to comply with the written description requirement, and the 112(b) rejection for failing to disclose the corresponding structure, material, or acts for performing the entire claimed function and to clearly link the structure, material, or acts to the function. Accordingly, the 112(f) claim interpretation, 112(a) rejection, and 112(b) rejection have been withdrawn.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 (i.e., changing from AIA to pre-AIA ) 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.
Claims 1-4, 8, 11, and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Bovard et al. (WO 2019/043130 A1) (already of record) in view of Di Carlo et al. (US 2013/0171628 A1).
Regarding claim 1, Bovard et al. teaches a cell production device, comprising: a cell production plate (abstract “cell culture plate”) that includes a fluid circuit (Fig. 3c 23a fluid transmission channel, 23b well communication channel, 39 externally located loop) in which a plurality of functional sites are integrated; and a closed connector that connects the fluid circuit to an external space in a closed manner (Fig. 3c 28 connectors), wherein the fluid circuit comprises, as the plurality of functional sites, an injection and discharge unit configured to inject or discharge a fluid into or out of the fluid circuit via the closed connector (Fig. 3c 25, 26 openings), a cell induction and culture unit configured to perform induction and culture of cells based on the injected fluid (Fig. 3a 17 well), and a fluid mixing unit configured to mix a plurality of mutually immiscible fluids (p. 19 “positive displacement pump that is operable to circulate fluid”; p. 26 “culture media is circulated… mixing of the different cell culture media will occur”).
Bovard et al. does not teach wherein the fluid mixing unit includes a fluid merging path configured to merge the plurality of mutually immiscible fluids into a single flow path, wherein the fluid mixing unit includes a mixed flow generation path configured to generate a mixed flow in the fluids merged in the fluid merging path, wherein the mixed flow generation path alternately includes a flow path wider part, which expands a flow path width in a direction different from a direction of fluid flow, and a flow path deeper part, which increases a flow path depth in the direction different from the direction of fluid flow, with respect to the direction of fluid flow, and wherein the flow path wider part and the flow path deeper part are each constituted by a curved surface.
However, Di Carlo et al. teaches a fluid merging path (Fig. 1A inlet 18 combining the fluids from inlet 18’ and inlet 18’’; para. 0043) and a mixed flow generation path (Fig. 1A microfluidic channel 16 contains mixed fluid from inlet 18’ and inlet 18’’; para. 0043), wherein the mixed generation path includes a flow path wider parts (Fig. 1A expansion regions 30 on top of microfluidic channel 16) and a flow path deeper parts (Fig. 1A expansion regions 30 on the bottom of microfluidic channel 16); wherein the flow path wider parts and flow path deeper parts are each constituted by a curved surface (Fig. 1E semi-circular geometry of the expansion regions 30). Di Carlo et al. teaches that the expansion regions create a vortex which traps then releases cells which reduces the flow rate of solution through the microfluidic channel (para. 0008).
It would have been obvious to a person of ordinary skill in the art to use the Di Carlo et al. configuration of a fluid merging path, a mixed flow generation path, and expansion regions in Bovard et al.’s device with a reasonable expectation that they would create a vortex which traps then releases cells which reduces the flow rate of solution through the microfluidic channel. This method for improving Bovard et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of Di Carlo et al. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Bovard et al. and Di Carlo et al. to obtain the invention as specified in claim 1.
Regarding claim 2, Bovard et al. teaches a cell production device further comprising a variable volume unit capable of storing a fluid that is extruded or withdrawn by the injected or discharged fluid (Fig. 8 67 pipettor), wherein the variable volume unit comprises a physical or chemical variable volume material (p. 32 “sensors… motors to control the operation”). Bovard et al. discloses these features in the embodiment shown in Figure 8, which is a sampling device incorporating the cell culture plate, but does not teach these features as part of the embodiment shown in Figure 3. Nonetheless, it would have been obvious to one of ordinary skill in the art to combine embodiments and rearrange the orientation of the variable volume unit and the physical or chemical variable volume material of the claimed invention. It has been held that rearrangement of parts is unpatentable because the shifting of parts would not modify the operation of the device (MPEP § 2144.04 VI).
Modifying the device of Bovard et al. such that the variable volume unit and the physical or chemical variable volume material are part of the cell culture plate instead of the sampling device would amount to merely rearrangement of parts, as such a modification would predictably result in a cell culture device that can introduce fluid directly to the wells of the cell culture plate. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to include a variable volume unit and physical or chemical variable volume material to obtain the invention as specified in claim 2.
Regarding claim 3, Bovard et al. teaches a cell production device wherein the physical variable volume material is a pipettor (Fig. 8 67 pipettor), but does not teach a flexible bag or a syringe. However, Di Carlo et al. teaches that a syringe is a known element in the art which sustains an overall flow rate ranging between 10 µl/min and 4.5 ml/min (para. 0044).
Though Bovard et al. does not teach a syringe, it would have been obvious to a person of ordinary skill in the art to use a syringe because the substitution of one known element for another would have yielded predictable results with reasonable expectation that this would result in a pump which sustains an overall flow rate ranging between 10 µl/min and 4.5 ml/min. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to substitute the teachings of modified Bovard et al. with the teachings of Di Carlo et al. to obtain the invention as specified in claim 3.
Regarding claim 4, Bovard et al. teaches a cell production device wherein the fluid circuit further comprises a transfer unit configured to transfer the injected fluid within the fluid circuit (Fig. 5 29 pump).
Regarding claim 8, Bovard et al. teaches a cell production device wherein the injection and discharge unit comprises an injection and discharge channel configured to discharge or inject fluid containing the cells subjected to at least one of the induction or the culture as a sample outside the fluid circuit or into the fluid circuit (Fig. 3c 23a fluid transmission channel, 23b well communication channel, 39 externally located loop).
Regarding claim 11, Bovard et al. teaches a cell production device wherein the fluid circuit further comprises a cell separation unit configured to separate cells or cell masses (Fig. 3c 17 wells).
Regarding claim 13, Bovard et al. teaches a cell production device wherein the fluid circuit comprises a first flow path extending in a first direction (Fig. 3c 23a fluid transmission channel) and a second flow path extending in a second direction different from the first direction (Fig. 3c 23b well communication channel), and the first flow path comprises a detour path (Fig. 3c 39 externally located loop) that extends toward a back side of the cell production plate and detours the second flow path (Fig. 3c). Bovard et al. does not teach that the flow path is on a front side of the cell production plate, but does teach the flow path on the bottom of the cell production plate (Fig. 4). Nonetheless, it has been held that rearrangement of parts is unpatentable because the shifting of parts would not modify the operation of the device (MPEP § 2144.04 VI).
Modifying the device of Bovard et al. such that the flow path is on a front side of the cell production plate instead of on the bottom of the cell production plate would amount to merely rearrangement of parts, as such a modification would predictably result in a flow path that circulates fluid between wells over the top of the wells. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device of Bovard et al. to obtain the invention as specified in claim 13.
Claims 5-6 are rejected under 35 U.S.C. 103 as being unpatentable over Bovard et al. (WO 2019/043130 A1) (already of record) in view of Di Carlo et al. (US 2013/0171628 A1) as applied to claim 4 above, and further in view of Corso (US 2017/0283761 A1) (already of record).
Regarding claim 5, Bovard et al. teaches a cell production device, but does not teach a flow measurement unit upstream or downstream of the transfer unit. However, Corso teaches a flow measurement unit (para. 0062 “flow sensor”). Corso teaches that a flow sensor monitors flow rate and provides closed loop feedback to the pump control system which ensures accuracy (para. 0062).
It would have been obvious to a person of ordinary skill in the art to use the Corso configuration of a flow sensor in modified Bovard et al.’s device with a reasonable expectation that it would monitor flow rate and provide closed loop feedback to the pump control system, ensuring accuracy. This method for improving modified Bovard et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of Corso. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of modified Bovard et al. and Corso to obtain the invention as specified in claim 5.
Regarding claim 6, Bovard et al. teaches a cell production device, but does not teach a flow rate sensor provided adjacent to at least one of a flow path or a reservoir tank communicating with the transfer unit. However, Corso teaches a flow measurement unit (para. 0062 “flow sensor”). Corso teaches that a flow sensor monitors flow rate and provides closed loop feedback to the pump control system which ensures accuracy (para. 0062).
It would have been obvious to a person of ordinary skill in the art to use the Corso configuration of a flow sensor in modified Bovard et al.’s device with a reasonable expectation that it would monitor flow rate and provide closed loop feedback to the pump control system, ensuring accuracy. This method for improving modified Bovard et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of Corso. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of modified Bovard et al. and Corso to obtain the invention as specified in claim 6.
Claim 7 are rejected under 35 U.S.C. 103 as being unpatentable over Bovard et al. (WO 2019/043130 A1) (already of record) in view of Di Carlo et al. (US 2013/0171628 A1) and Corso (US 2017/0283761 A1) (already of record) as applied to claim 5 above, and further in view of Mason et al. (US 2017/0307502 A1) (already of record).
Regarding claim 7, Bovard et al. teaches a cell production device, but does not teach a flow measurement unit comprising an image recognition sensor configured to capture images of fluid succession changes in at least one of a flow path or a reservoir tank communicating with the transfer unit. However, Mason et al. teaches an image recognition sensor (para. 0272 “imaging sensor”) capable of capturing images of fluid succession changes. Mason et al. teaches that parameters can be adjusted based on images captured by the imaging sensors (para. 0251).
Regarding the limitation “capture images of fluid succession changes in at least one of a flow path or a reservoir tank communicating with the transfer unit”, it has been held that a claim containing a recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus if the prior art apparatus teaches all the structural limitations of the claim (MPEP § 2114 II). Therefore, the apparatus disclosed by Mason et al. would be fully capable of achieving every claimed intended use because the prior art apparatus is disclosed to be for capturing images and adjusting parameters in response to the data from the captured images (para. 0251) and would be structurally capable of capturing images of fluid succession changes in at least one of a flow path or a reservoir tank communicating with the transfer unit absent clear evidence otherwise.
It would have been obvious to a person of ordinary skill in the art to use the Mason et al. configuration of imaging sensors in modified Bovard et al.’s device with a reasonable expectation that it would allow parameters to be adjusted based on images captured by the imaging sensors. This method for improving modified Bovard et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of Mason et al. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of modified Bovard et al. and Mason et al. to obtain the invention as specified in claim 7.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Bovard et al. (WO 2019/043130 A1) (already of record) in view of Di Carlo et al. (US 2013/0171628 A1) as applied to claim 1 above, and further in view of Kohoutek et al. (US 2019/0185805 A1) (already of record).
Regarding claim 12, Bovard et al. teaches a cell production device comprising a cell production plate (see claim 1 above), but does not explicitly teach wherein at least a portion of the cell production plate is transparent. However, Di Carlo et al. teaches that a microfluidic device made of glass (transparent material) is known in the art (para. 0042). Kohoutek et al. teaches that transparent plates allow a camera to capture image data of wells (para. 0013).
Though Bovard et al. does not explicitly teach a transparent cell production plate, it would have been obvious to a person of ordinary skill in the art to use a transparent material because one of ordinary skill in the art would reasonably expect that a transparent plate would allow a camera to capture image data of the plate. This method of improving Bovard et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of both Di Carlo et al. and Kohoutek et al. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Bovard et al., Di Carlo et al., and Kohoutek et al. to obtain the invention as specified in claim 12.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Bovard et al. (WO 2019/043130 A1) (already of record) in view of Di Carlo et al. (US 2013/0171628 A1) as applied to claim 13 above, and further in view of Kujala et al. (US 2020/0269234 A1) (already of record).
Regarding claim 14, Bovard et al. teaches a cell production device wherein the cell production plate comprises a flat plate (p. 11 “flat plate”) and a lid covering the flat plate (p. 2 “fitted with a lid”). Modified Bovard et al. does not teach that the path comprises a plurality of through holes penetrating from the front side to the back side of the flat plate, and a communication path communicating between the through holes at the back side of the flat plate. However, Kujala et al. teaches a path comprising a plurality of through holes penetrating from the front side to the back side of the flat plate (Fig. 1B 210 inlet fluid port, 211 inlet aperture, 212 outlet fluid port, 215 outlet aperture), and a communication path communicating between the through holes at the back side of the flat plate (Fig. 1B 225 inlet channel). Kujala et al. teaches that the ports and channels allow a fluid passing through the device to exit to a fluid collector or another appropriate component (para. 0140).
It would have been obvious to a person of ordinary skill in the art to use the Kujala et al. configuration of through holes and a communication path in modified Bovard et al.’s device with a reasonable expectation that it would allow a fluid passing through the device to exit to a fluid collector or another appropriate component. This method for improving modified Bovard et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of Kujala et al. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of modified Bovard et al. and Kujala et al. to obtain the invention as specified in claim 14.
Claims 15-16 are rejected under 35 U.S.C. 103 as being unpatentable over Bovard et al. (WO 2019/043130 A1) (already of record) in view of Di Carlo et al. (US 2013/0171628 A1) as applied to claim 1 above, and further in view of Szita et al. (US 20150231634A1).
Regarding claim 15, Bovard et al. teaches a cell production device further comprising a base plate connected to the cell production plate (Fig. 4 34 waterproof housing) and a plate sealing member attached to the cell production plate and the base plate (Fig. 4 38 lid). Bovard et al. does not explicitly teach that the base plate is detachably connected to the cell production plate. However, Szita et al. teaches a tissue culture substrate detachable from a microfluidic device (para. 0069) which allows the substrate to be removed so that any material on the substrate can be analyzed more easily (para. 0069).
It would have been obvious to a person of ordinary skill in the art to use the Szita et al. configuration of a detachable tissue culture substrate in modified Bovard et al.’s device with a reasonable expectation that it would allow the substrate to be removed so that any material on the substrate can be analyzed more easily. This method for improving modified Bovard et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of Szita et al. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of modified Bovard et al. and Szita et al. to obtain the invention as specified in claim 15.
Regarding claim 16, Bovard et al. teaches a cell production device comprising a base plate that is connected to the cell production plate (Fig. 4 34 waterproof housing), wherein the fluid circuit comprises a peristaltic pump configured to transfer the injected fluid in the fluid circuit (p. 2 “peristaltic pump”), and a drive unit configured to drive the peristaltic pump (p. 2 “motor… is housed in a waterproof box”). Bovard et al. does not explicitly teach that the base plate is detachably connected to the cell production plate. However, Szita et al. teaches a tissue culture substrate detachable from a microfluidic device (para. 0069) which allows the substrate to be removed so that any material on the substrate can be analyzed more easily (para. 0069).
It would have been obvious to a person of ordinary skill in the art to use the Szita et al. configuration of a detachable tissue culture substrate in modified Bovard et al.’s device with a reasonable expectation that it would allow the substrate to be removed so that any material on the substrate can be analyzed more easily. This method for improving modified Bovard et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of Szita et al. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of modified Bovard et al. and Szita et al. to obtain the invention as specified in claim 16.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Bovard et al. (WO 2019/043130 A1) (already of record) in view of Di Carlo et al. (US 2013/0171628 A1) and Szita et al. (US 20150231634A1) as applied to claim 16 above, and further in view of Mason et al. (US 2017/0307502 A1) (already of record).
Regarding claim 17, Bovard et al. teaches a cell production device comprising a peristaltic pump (p. 2), but does not teach a cell production device comprising an image recognition sensor configured to capture a state of rotational movement of the peristaltic pump in an image. However, Mason et al. teaches an image recognition sensor (para. 0272 “imaging sensor”) capable of capturing a state of rotational movement of a peristaltic pump in an image. Mason et al. teaches that parameters can be adjusted based on images captured by the imaging sensors (para. 0251).
Regarding the limitation “captures a state of rotational movement of the peristaltic pump in an image”, it has been held that a claim containing a recitation with respect to the manner in which a claimed apparatus is intended to be employed does not differentiate the claimed apparatus from a prior art apparatus if the prior art apparatus teaches all the structural limitations of the claim (MPEP § 2114 II). Therefore, the apparatus disclosed by Mason et al. would be fully capable of achieving every claimed intended use because the prior art apparatus is disclosed to be for capturing images and adjusting parameters in response to the data from the captured images (para. 0251) and would be structurally capable of capturing a state of rotational movement of a peristaltic pump in an image absent clear evidence otherwise.
It would have been obvious to a person of ordinary skill in the art to use the Mason et al. configuration of imaging sensors in modified Bovard et al.’s device with a reasonable expectation that it would allow parameters to be adjusted based on images captured by the imaging sensors. This method for improving modified Bovard et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of Mason et al. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of modified Bovard et al. and Mason et al. to obtain the invention as specified in claim 17.
Citation of Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Toner et al. (US 2009/0014360 A1) discloses a curved microchannel with wider and deeper sections.
Conclusion
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/ASHLEY LOPEZLIRA/Examiner, Art Unit 1799
/MICHAEL A MARCHESCHI/Supervisory Patent Examiner, Art Unit 1799