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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 1/20/2026 has been entered.
Status of the Claims
The amendment filed 8/18/2025 has been entered. Claims 16, 18, and 20-35 are pending in the application; claims 26-34 remain withdrawn; and claims 17 and 19 remain cancelled.
Regarding claim 25, Applicant’s amendments to the claim have overcome the 112(d) rejection, and accordingly, the rejection has been withdrawn.
Response to Arguments
Applicant’s arguments filed 1/20/2026 have been considered but they are moot in view of a new grounds of rejection necessitated by the amendments to the claims.
Applicant added limitations for the cell expansion device being configured to grow HCDCs that comprise at least 5 x 106 cells/mL to independent claim 16. This new limitation does not distinguish the claimed invention over the prior art. The Examiner acknowledges that neither Maggiore nor Veraitch et al. disclose a device configured to grow high density cells at a concentration of 5 x 106 cells/mL; however, it would have been obvious to modify the device of Maggiore in view of Singh et al. (US 2021/0214702 A1) which will be discussed in further detail in the 35 USC § 103 section below.
Claim Objections
Claim 35 is objected to because of the following informalities: the claim should conclude with a period. Appropriate correction is required.
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 16, 18, 20, 23-25, and 35 are rejected under 35 U.S.C. 103 as being unpatentable over Maggiore (US 2019/0048303 A1) (already of record) in view of Singh et al. (US 2021/0214702 A1).
Regarding claim 16, Maggiore teaches a system for an automated production of high cell density seed culture (HCDC) preparations, for cryo-preservation comprising: a cell expansion device (Fig. 1A 400 single-use chamber) for growing a HCDC in a medium inside a device volume of the cell expansion device, the cell expansion device being configured to grow HCDCs (para. 0085), at least one sensor (Fig. 1A 420 sensor and/or measurement device) for collecting data by at least temporally monitoring at least one parameter being indicative of a physiological state of the HCDC (para. 0049 “collect data internal to either the primary subchamber 402, the secondary subchamber 404, and/or the components within”); and
a control unit (para. 0215 “controlling device”) for processing the collected data (para. 0215 “data acquisition, data analysis”) to determine whether at least one predetermined criterion is fulfilled by the monitored parameter to control, based on whether the at least one predetermined criterion is fulfilled by the monitored parameter, at least a partial exchange of the medium by a cryo-protective agent (CPA) (para. 0215 “opening and closing of valves, activation and deactivation of pumps, venting, filtering and dispensing”);
wherein the cell expansion device comprises: at least one drain for draining at least a portion of the medium from the device volume towards an outside of the device volume (Fig. 1A 418 outlet piping); and
wherein the control unit is configured to initiate, based on whether or not the criterion is fulfilled, the steps of: draining at least a portion of the medium inside the device volume (para. 0215 “opening and closing of valves, activation and deactivation of pumps, venting, filtering and dispensing”); and,
adding the CPA to the HCDC in the device volume (para. 0215 “opening and closing of valves, activation and deactivation of pumps, venting, filtering and dispensing”), wherein the system comprises a transfer unit (para. 0048 “one section of piping 416 and at least one outlet piping 418 may contain at least one valve”), controlled by the control unit (para. 0215 “opening and closing of valves”), capable of transferring at least a portion of the HCDC with CPA from the device volume into one or more receiving devices (para. 0048 “one section of piping 416 between the primary subchamber 402 and the secondary subchamber 404”) to obtain HCDC-preparations for cryo-preservation; and
wherein the system further comprises: a centrifuge unit for centrifuging the HCDC with the medium (Fig. 2 142 centrifugation assembly);
at least one transfer unit (para. 0048 “one section of piping 416 and at least one outlet piping 418 may contain at least one valve”), controlled by the control unit (para. 0215 “opening and closing of valves”), capable of transferring at least a portion of the HCDC with the medium from the device volume into at least one centrifuge container of the centrifuge unit (para. 0048 “one section of piping 416 between the primary subchamber 402 and the secondary subchamber 404); and
wherein the control unit is configured to initiate, based on whether or not the criterion is fulfilled, a transfer of the least a portion of the HCDC with the medium from the device volume into the at least one centrifuge container of the centrifuge unit (para. 0215 “opening and closing of valves, activation and deactivation of pumps, venting, filtering and dispensing”), centrifuging with the centrifuge unit the transferred HCDC with the medium (para. 0215 “centrifugation”), separating at least partially the centrifuged medium from the HCDC (para. 0215 “perfusion… filtering and dispensing”), and adding the CPA to the HCDC (para. 0215 “mixing”).
Maggiore does not teach a cell retention device; however, Singh et al. teaches a cell retention device that retains cells during separation of liquid with a lower cell density and provides necessary surface area for efficient cell attachment (para. 0026). It would have been obvious to a person of ordinary skill in the art to use the Singh et al. configuration of a cell retention device in Maggiore’s device with a reasonable expectation that it would retain cells during separation of liquid with a lower cell density and provide necessary surface area for efficient cell attachment. This method for improving Maggiore’s device was within the ability of one of ordinary skill in the art based on the teachings of Singh 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 Maggiore and Singh et al. to obtain the invention as specified in claim 16.
Regarding the limitation “the cell expansion device being configured to grow HCDCs that comprise at least 5 x 106 cells/mL”, Maggiore discloses a device for culturing higher cell densities (para. 0085), but is silent to the cell density being at least 5 x 106 cells/mL. However, Singh et al. discloses high-cell density growth of greater than 140 x 106 cells/mL (para. 0038) which results in high yield production (abstract). It would have been obvious to a person of ordinary skill in the art to use the Singh et al. configuration of a cell density of greater than 140 x 106 cells/mL in Maggiore’s device with a reasonable expectation that it would result in high yield production. This method for improving Maggiore’s device was within the ability of one of ordinary skill in the art based on the teachings of Singh 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 Maggiore and Singh et al. to obtain the invention as specified in claim 16.
Regarding the limitation “cryo-protective agent (CPA)”, it has been held that the inclusion of the material or article worked upon by a structure being claimed does not impart patentability to the claims (MPEP § 2115). Therefore, the apparatus disclosed by Maggiore would be fully capable of achieving every claimed intended use because the prior art apparatus is disclosed to be for culturing higher cell densities (para. 0085) to undergo freezing for long-term storage (para. 0104) and is filled with nutrient rich media for generating biological material (para. 0041), and would be structurally capable of automating production of high cell density seed culture (HCDC) preparations for cryo-preservation and housing CPA, absent clear evidence otherwise.
Regarding claim 18, Maggiore teaches wherein the transfer unit is configured to automatically transfer at least a portion of the HCDC with CPA from the device volume into the one or more receiving devices to obtain HCDC-preparations for cryo-preservation (para. 0215 “the controlling device may control… opening and closing of valves, activation and deactivation of pumps, venting, filtering and dispensing” thus this would control the transfer unit (para. 0048 “one section of piping 416 and at least one outlet piping 418 may contain at least one valve”).
Regarding limitations “HCDC with CPA” and “obtain HCDC-preparations for cryo-preservation”, it has been held that the inclusion of the material or article worked upon by a structure being claimed does not impart patentability to the claims (MPEP § 2115). Therefore, the apparatus disclosed by Maggiore would be fully capable of achieving every claimed intended use because the prior art apparatus is disclosed to be for culturing higher cell densities (para. 0085) to undergo freezing for long-term storage (para. 0104), and is filled with nutrient rich media for generating biological material (para. 0041) and would be structurally capable of adding CPA and obtaining HCDC-preparations for cryo-preservation, absent clear evidence otherwise.
Regarding claim 20, Maggiore teaches wherein the sensor forms an integral unit with the cell expansion device (para. 0049 “sensor and/or measurement device 420 is connected to… flexible mixing assembly receptacle 406”).
Regarding claim 23, Maggiore teaches a cell expansion device (Fig. 1A 400 single-use chamber), but does not teach wherein a membrane element forms an integral unit with the cell expansion device. However, Veraitch et al. teaches wherein a membrane element forms an integral unit with the cell expansion device (Fig. 14c 140 filter membrane in container) which traps cells in one portion of the container while medium is ejected out (p. 29, lines 25-26). It would have been obvious to a person of ordinary skill in the art to use the Veraitch et al. configuration of a membrane forming an integral unit with the cell expansion device in Maggiore’s device with a reasonable expectation that it would trap cells in one portion of the container while medium is ejected out. This method for improving Maggiore’s device was within the ability of one of ordinary skill in the art based on the teachings of Veraitch 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 Maggiore and Veraitch et al. to obtain the invention as specified in claim 23.
Regarding claim 24, Maggiore teaches wherein the control unit is capable of, based on the monitored parameter, automatically controlling at least one second parameter, wherein the second parameter is configured to control and/or regulate the physiological status of the HCDC (para. 0215 “data acquisition, data analysis, power supplying, water supplying, centrifugation, mixing, perfusion, opening and closing of valves, activation and deactivation of pumps, venting, filtering and dispensing”).
Regarding claim 25, Maggiore teaches wherein at least one out of the cell expansion device, the at least one sensor, the centrifuge unit, the one or more receiving devices comprising a bag, a tube (Fig. 1A 416 piping) and/or a vial, and wherein at least a portion of the transfer unit is a single-use element and/or a single-use consumable (para. 0012 “single-use manufacturing system”; para. 0048 416 piping, 418 outlet piping, and valve in single-use container 400).
Regarding the limitation “single-use element and/or a single-use consumable”, 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 Maggiore would be fully capable of achieving every claimed intended use because the prior art apparatus is disclosed to be a single-use container disposed after one-time use (para. 0027) and would be structurally capable of being single-use absent clear evidence otherwise.
Regarding claim 35, Maggiore teaches a system for an automated production of high cell density seed culture (HCDC) preparations, for cryo-preservation comprising: a cell expansion device (Fig. 1A 400 single-use chamber) for growing a HCDC in a medium inside a device volume of the cell expansion device, the cell expansion device being configured to grow HCDCs (para. 0085), at least one sensor (Fig. 1A 420 sensor and/or measurement device) for collecting data by at least temporally monitoring at least one parameter being indicative of a physiological state of the HCDC (para. 0049 “collect data internal to either the primary subchamber 402, the secondary subchamber 404, and/or the components within”); and
a control unit (para. 0215 “controlling device”) for processing the collected data (para. 0215 “data acquisition, data analysis”) to determine whether at least one predetermined criterion is fulfilled by the monitored parameter to control, based on whether the at least one predetermined criterion is fulfilled by the monitored parameter, at least a partial exchange of the medium by a cryo-protective agent (CPA) (para. 0215 “opening and closing of valves, activation and deactivation of pumps, venting, filtering and dispensing”);
wherein the cell expansion device comprises: at least one drain for draining at least a portion of the medium from the device volume towards an outside of the device volume (Fig. 1A 418 outlet piping); and
wherein the control unit is configured to initiate, based on whether or not the criterion is fulfilled, the steps of: draining at least a portion of the medium inside the device volume (para. 0215 “opening and closing of valves, activation and deactivation of pumps, venting, filtering and dispensing”); and,
adding the CPA to the HCDC in the device volume (para. 0215 “opening and closing of valves, activation and deactivation of pumps, venting, filtering and dispensing”), wherein the system comprises a transfer unit (para. 0048 “one section of piping 416 and at least one outlet piping 418 may contain at least one valve”), controlled by the control unit (para. 0215 “opening and closing of valves”), capable of transferring at least a portion of the HCDC with CPA from the device volume into one or more receiving devices (para. 0048 “one section of piping 416 between the primary subchamber 402 and the secondary subchamber 404”) to obtain HCDC-preparations for cryo-preservation; and
Maggiore does not teach a cell retention device; however, Singh et al. teaches a cell retention device that retains cells during separation of liquid with a lower cell density and provides necessary surface area for efficient cell attachment (para. 0026). It would have been obvious to a person of ordinary skill in the art to use the Singh et al. configuration of a cell retention device in Maggiore’s device with a reasonable expectation that it would retain cells during separation of liquid with a lower cell density and provide necessary surface area for efficient cell attachment. This method for improving Maggiore’s device was within the ability of one of ordinary skill in the art based on the teachings of Singh 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 Maggiore and Singh et al. to obtain the invention as specified in claim 35.
Regarding the limitation “the cell expansion device being configured to grow HCDCs that comprise at least 5 x 106 cells/mL”, Maggiore discloses a device for culturing higher cell densities (para. 0085), but is silent to the cell density being at least 5 x 106 cells/mL. However, Singh et al. discloses high-cell density growth of greater than 140 x 106 cells/mL (para. 0038) which results in high yield production (abstract). It would have been obvious to a person of ordinary skill in the art to use the Singh et al. configuration of a cell density of greater than 140 x 106 cells/mL in Maggiore’s device with a reasonable expectation that it would result in high yield production. This method for improving Maggiore’s device was within the ability of one of ordinary skill in the art based on the teachings of Singh 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 Maggiore and Singh et al. to obtain the invention as specified in claim 35.
Regarding the limitation “cryo-protective agent (CPA)”, it has been held that the inclusion of the material or article worked upon by a structure being claimed does not impart patentability to the claims (MPEP § 2115). Therefore, the apparatus disclosed by Maggiore would be fully capable of achieving every claimed intended use because the prior art apparatus is disclosed to be for culturing higher cell densities (para. 0085) to undergo freezing for long-term storage (para. 0104) and is filled with nutrient rich media for generating biological material (para. 0041), and would be structurally capable of automating production of high cell density seed culture (HCDC) preparations for cryo-preservation and housing CPA, absent clear evidence otherwise.
Claims 21-22 are rejected under 35 U.S.C. 103 as being unpatentable over Maggiore (US 2019/0048303 A1) (already of record) in view of Singh et al. (US 2021/0214702 A1) as applied to claim 20 above, and further in view of Emmerson et al. (US 2017/0253848 A1) (already of record).
Regarding claim 21, Maggiore teaches wherein the sensor is connected to the cell expansion device (para. 0049 “sensor and/or measurement device 420 is connected to… flexible mixing assembly receptacle 406”), but is silent to the sensor being welded to a wall of the cell expansion device.
Regarding the limitation “the sensor is welded”, it has been held that the patentability of a product does not depend on its method of production; if the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior art product was made by a different process (MPEP § 2113 I). Therefore, the sensor connected to the cell expansion device disclosed by Maggiore would anticipate the sensor connected to the cell expansion device of the claimed invention even though both were made by a different process.
However, Emmerson et al. teaches a sensor welded to a wall of a cell expansion device (para. 0048 “sensor 41 permanently welded… into the side wall of the bag”). Emmerson et al. teaches that the welded sensor is left in place during which it is in contact with the contents, reducing contamination by eliminating extraction of the sample, and remains in place during sterilization of the reactor, and is not damaged or degraded thereby (para. 0041). It would have been obvious to a person of ordinary skill in the art to use the Emmerson et al. configuration of a sensor welded to a wall of the cell expansion device in modified Maggiore’s device with a reasonable expectation that it would be left in place during which it is in contact with the contents, reduce contamination by eliminating extraction of the sample, and remain in place during sterilization of the reactor, during which it is not damaged or degraded thereby. This method for improving modified Maggiore’s device was within the ability of one of ordinary skill in the art based on the teachings of Emmerson 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 Maggiore and Emmerson et al. to obtain the invention as specified in claim 21.
Regarding claim 22, Maggiore teaches a sensor in the device volume (Fig. 1A 420 sensor and/or measurement device), but does not explicitly teach wherein the sensor inserts into the device volume through a port of the cell expansion device. However, Emmerson et al. teaches a wherein the sensor inserts into the device volume through a port of the cell expansion device (para. 0049 “reaction vessel having a through-port into which the probe is inserted”). Emmerson et al. teaches that ports allow the sensor to reach directly into the contents of the bioreactor (para. 0049). It would have been obvious to a person of ordinary skill in the art to use the Emmerson et al. configuration of a port in modified Maggiore’s device with a reasonable expectation that it would allow the sensor to reach directly into the contents of the bioreactor. This method for improving modified Maggiore’s device was within the ability of one of ordinary skill in the art based on the teachings of Emmerson 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 Maggiore and Emmerson et al. to obtain the invention as specified in claim 22.
Conclusion
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/ASHLEY LOPEZLIRA/Examiner, Art Unit 1799
/MICHAEL A MARCHESCHI/Supervisory Patent Examiner, Art Unit 1799