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 .
DETAILED ACTION
Amendments
In the reply filed 12/12/2025, Applicant has amended claims 26, 38 and 39, and added new claims 40-41.
Claim Status
Claims 18-32 and 35-41 are pending.
Claims 18-25 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. The election was made with traverse in the reply filed on 10/10/2023.
Claims 26-32 and 35-41 are considered on the merits.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 08/14/2025, 08/27/2025, 11/07/2025 and 02/02/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner. The corresponding signed and initialed PTO forms 1449 have been mailed with this action.
Withdrawn Claim Objections
The prior objection to the Claim 37 in the last page 6 because of a typographic error in numbering is withdrawn in light of Applicant’s amendment to change to claim 39.
Withdrawn Claim Rejections - 35 USC § 112(a)
The prior rejection of claims 26-32 and 35-38 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in light of Applicant’s argument that one of ordinary skill in the art would readily understand how any type of cells can be processed utilizing knowledge available in the art and/or routine experimentation (Remarks, p. 7-8). Applicant’s arguments have been fully considered that they are persuasive.
Withdrawn Claim Rejections - 35 USC § 102 and 103
The prior rejection of claims 26 and 39 under 35 U.S.C. 102 (a)(1), and the prior rejection of claims 26-32 and 35-39 under 35 U.S.C. 103, are withdrawn in light of Applicant’s amendments to claims 26 and 38 to recite new limitation of “sensing a weight of the bioreactor vessel using one or more load cells”, that is not addressed in the prior rejections.
New Claim Rejections - 35 USC § 103
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.
Claims 26-27, 35-37 and 39-41 are rejected under 35 U.S.C. 103 as being unpatentable over June et al (WO 2012/079000 A1. Prior art of record) in view of Singh (Cytotechnology. 1999; 30: 149-158. Prior art of record), GE Application note (“Perfusion culture of T lymphocytes in the WAVE Bioreactor™ System 2/10 software version 2.61”, GE Healthcare Life Sciences, Application note 28-9650-52 AC. Published Jan. 2010, p. 1-9. Prior art of record), Davis et al. (US 2016/0340633. Prior art of record), and GE Data file (“WAVE Bioreactor™ 2/10 and 20/50 systems”, GE Healthcare Life Sciences, Data file 28-9520-58 AB, first published Feb. 2009, p. 1-6).
It is noted that a new ground of rejection in view of new art GE Data file is applied to make obvious the new limitation of “sensing a weight of the bioreactor vessel using one or more load cells to determine a volume or a flow of the cells”.
With respect to claim 26, June teaches a method of preparing CAR-T cells for cancer therapy (see Example 1, p. 58, and see Fig 1B), thus teaches a bioprocessing method. June teaches the method comprises “addition of anti-CD3/CD28 coated paramagnetic beads for positive selection and activation of T cells” (p. 6, lines 9-10, and see Fig 1B “Day 0-1” when the beads and the cells are seeded in gas-permeable bags), thus teaches a step of activating cells of a population of cells to produce a population of activated cells. June teaches adding lentiviral vector to the cells (p. 6, line 10, and see Fig 1B “Day 0-1” for transduction w/ αCD19-41BBζ vector), thus teaches a step of genetically modifying the activated cells to produce a population of genetically modified cells. June teaches vectors are washed out on day 3 post culture initiation (p. 6, line 11, and see Fig 1B “Day 3”), thus teaches a step of washing the genetically modified cells. June teaches the cells are cultured “on a rocking platform device (WAVE Bioreactor System) for 8-12 days” (p. 6, lines 11-12, and see Fig 1B “Day 5”), thus teaches a step of expanding the population of genetically modified cells to produce an expanded population of transduced cells.
However, June does not specifically teach the steps being carried out in a single processing chamber of a bioprocessing system. Note that Applicant’s specification does not provide a special definition of the phrase “bioprocessing system”, and one of ordinary skill would reasonably interpret such a system as an incubator comprising a chamber.
Nevertheless, June teaches “the cells are maintained under conditions necessary to support growth, for example, an appropriate temperature (e.g., 37°C) and atmosphere (e.g., air plus 5% CO2)” (p. 48, lines 15-16). One of ordinary skill in the art would have understood that the most commonly used bioprocessing system with a processing chamber for maintaining cell growth is an incubator.
Furthermore, Singh teaches the WAVE Bioreactor system can be used inside an incubator and “temperature and pH control can be achieved by placing the entire unit inside a conventional cell culture CO2 incubator” (abstract, p. 150, right col, para 1 and p. 153, right col, para 1), and teaches “all additions and sampling were done in the incubator itself. No laminar flow cabinet was required” (p. 153, right col, para 4).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the bioprocessing method comprising the steps of activating, genetically modifying, washing and expanding that are carried out in a gas permeable bag and a Wave Bioreactor disclosed by June, by choosing to dispose the cell bag and the Wave Bioreactor in a single processing chamber of a bioprocessing system (e.g., an incubator) as taught by Singh with a reasonable expectation of success. Since it would have been understood that the most commonly used bioprocessing system with a processing chamber for maintaining cell growth is an incubator, and since Singh teaches the WAVE Bioreactor system can be used inside an incubator and “temperature and pH control can be achieved by placing the entire unit inside a conventional cell culture CO2 incubator” (abstract, p. 150, right col, para 1), one of ordinary skill in the art would have had a reason to choose an incubator to provide an optimized environment with temperature and pH control for cell processing. Since the WAVE Bioreactor system can be used inside an incubator as taught by Singh, there would have been a reasonable expectation of success to dispose the two vessels within a single chamber of an incubator as well.
However, June and Singh are silent on the steps being carried out without removing the cells from the single processing chamber.
Regarding the first vessel a gas permeable bag and the second vessel a WAVE Bioreactor used in June being suitable of being fluidly connected, GE Application note teaches a method of culturing T cells in a gas-permeable bag and the Wave Bioreactor system that are fluidly connected (see Fig 2 upper panel). GE Application note teaches T cells are activated in a gas-permeable VueLife™ culture bag (p. 3, para 1, equivalent to the gas-permeable bag used in June for activating, genetically modifying and washing), and teaches the cells in the VueLife bag are transferred to the Wave Bioreactor via an autoclaved assembly comprising a three-way connector, a silicon tubing and a connector to the feed line of the Bioreactor (p. 3, para 2, see Fig 2 middle panel) to prevent cross-contamination (p. 2, left col, last para). Thus, GE Application note teaches the first vessel a gas permeable bag and the second vessel a WAVE Bioreactor of June can be fluidly connected to prevent cross-contamination.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the bioprocessing method comprising the steps of activating, genetically modifying, washing and expanding that are carried out in a gas permeable bag and a Wave Bioreactor disposed within the single chamber of an incubator suggested by June and Singh, by choosing to fluidly connect the bag and the Wave Bioreactor in a functionally-closed manner as taught by GE Application note with a reasonable expectation of success. Since GE Application note teaches the Bioreactor system is completely contained (i.e., in a functionally-closed fluidly-connected manner) that makes them ideally suited for applications where the prevention of cross-contamination is critical (p. 2, left col, last para), one of ordinary skill in the art would have had a reason to choose to fluidly connect the gas permeable bag and the Wave Bioreactor of June in a functionally-closed manner as taught by GE Application note in order to prevent cross-contamination of the T cells for clinical applications in June (abstract).
Furthermore, since the above steps of June are carried out in the two vessels disposed in a single processing chamber of an incubator as suggested by June and Singh, and since Singh teaches “all additions and sampling were done in the incubator itself. No laminar flow cabinet was required” (p. 153, right col, para 4), one of ordinary skill in the art would have understood that the steps of June in view of Singh and GE Application note are carried out in the two vessels in a functionally-closed, fluidly-connected manner in the processing chamber of the incubator, without removing the cells from the single processing chamber.
However, June and Singh are silent on the steps being carried out in an automated manner under control of a controller.
Regarding the steps being carried out in an automated manner under control of a controller, as stated supra, June teaches the cells are activated, genetically modified and washed in a gas permeable bag and are expanded in a WAVE Bioreactor System (see Fig 1B). GE Application note teaches the Wave Bioreactor has automated exchange of media (p. 2, abstract) and the Wave Bioreactor System (software version 2.61) with Perfusion Controller (PERFCONT2E) can be set up according to the user manual (p. 4, 1st para), thus, GE Application note teaches the step of expanding is carried out in an automated manner under control of a controller.
Furthermore, Davis teaches a method of culturing cells comprising the use of closed systems on rocking platform bioreactors with cell bags (abstract). Davis teaches in Example 2 using a VueLife gas permeable bag in culturing cells (equivalent to the gas permeable bag used in June and GE Application note for activating, genetically modifying and washing) that is placed in an incubator (see [0168], beginning of p. 11), and teaches “a specific assembly of tubing connected to culture vessel that interacts with computer controlled peristaltic pumps to drive automated medium exchange” ([0077], also see [0157], [0182]), thus, Davis suggests cell culturing in a gas permeable bag can be carried out in an automated manner under control of a controller.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the bioprocessing method suggested by June in view of Singh and GE Application note, by combining a controller system so as to carry out the bioprocessing steps in an automated manner as taught by GE Application note and Davis with a reasonable expectation of success. Since GE Application note teaches the Wave Bioreactor can be set up in an automated manner under control of a controller (p. 4, 1st para) and Davis teaches the gas permeable bag can be connected to interact with computer controlled peristaltic pumps to drive automated medium exchange ([0077]), and since GE Application note teaches automated exchange of media reduces the hands-on-time and labor (abstract and conclusion), one of ordinary skill in the art would have had a reason to combine an automated controller system as taught by GE Application note and Davis in order to reduce the hands-on-time and labor in the bioprocessing method of June. Furthermore, since the above steps of June in view of Singh and GE Application note can be carried out in the two vessels in a single processing chamber of an incubator, one of ordinary skill in the art would have understood that the steps of June in view of Singh, GE Application note and Davis are carried out in the two vessels in an automated manner in the single processing chamber of the incubator, without removing the cells from the single processing chamber.
In regard to the new limitation sensing a weight of the bioreactor vessel using one more load cells to determine a volume or a flow of the cells, GE Application note teaches the weight of the empty Cellbag bioreactor was tared, and media was transferred to the Cellbag bioreactor (p. 3, para 1), indicating sensing a weight of the bioreactor vessel (i.e., to tare the empty bioreactor) before transferring media.
GE Data file teaches the WAVE Bioreactor™ system (the system used in June, Singh and GE Application note) has loadcells mounted under the holder tray to measure the Cellbag bioreactor weight during rocking and has a built-in pump controller used for feeding, harvesting, and perfusion operations (p. 4, left col, para 2).
Davis teaches for perfusion in a perfusion Cellbag, the weight based Xuri W25 (it is noted that this is the next generation WAVE bioreactor system, see [0070]) Unicorn software control was used to maintain the volume in a Cellbag at a specific level, regulating continuous spent medium removal and fresh medium addition using the medium controls. In this method, the weight of the bag was continually monitored to regulate the rates of fresh medium addition and spent medium removal (e.g., [0185]).
Accordingly, one of ordinary skill in the art would have immediately expected that the bioprocessing method comprising using the WAVE bioreactor suggested by June in view of Singh, GE Application note and Davis would have had load cells mounted under the holder tray to sense and monitor the Cellbag bioreactor weight so as to determine a volume or a flow of the genetically modified cells and media as suggested by GE Application note, GE Data file and Davis.
With respect to claim 27, as stated supra, June teaches and suggests the cells are activated, genetically modified and washed in a gas permeable bag (i.e., the first bioreactor vessel) and are expanded in a WAVE Bioreactor System (i.e., the second bioreactor vessel, see modified Fig 1B attached below) within the processing chamber.
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With respect to claim 35 directed to the first and the second bioreactor vessels being configured for selective fluid interconnection with one another, as discussed above, June, in view of Singh, GE Application note, Davis and GE Data file, suggests that the gas permeable bag and the Wave Bioreactor are connected in a functional-closed manner via an autoclaved assembly comprising a three-way connector, a silicon tubing and a connector to the feed line of the Bioreactor (GE Application note, p. 3, para 2, see Fig 2 middle panel), thus suggests the two bioreactor vessels are configured for selective fluid interconnection with one another.
With respect to claim 36 directed to the method further comprising oscillating the first and the second bioreactor vessels through a defined angle for a period of time, GE Application note teaches the Wave Bioreactor (i.e., the second bioreactor vessel) is set to rock at 10 rpm and an angle of 6 degree during expansion period for up to 11 days (p. 4, left col, para 2), and Davis teaches the gas permeable bag (i.e., the first bioreactor vessel) is rocked at 20 rpm, 9 degree rock angle for 4 days ([0168], see p. 11, 1st para). Accordingly, it would have been obvious for one of ordinary skill in the art to have combined the oscillating the first and the second vessels through a defined angle for a period of time as suggested by GE Application note and Davis in the method with a reasonable expectation of success. Since both GE Application note and Davis reduce to practice a method of culturing suspension cells by oscillating the bioreactor vessels, one of ordinary skill in the art would have had a reason to oscillate the first and the second bioreactor vessels in order to facilitate the cell culture as suggested by GE Application note and Davis.
With respect to claim 37 directed to the processing chamber being a slidable drawer, GE Data file teaches the WAVE Bioreactor System can be placed in a cabinet with slide-out shelves. GE Data file teaches the cabinet provides a space saving unit for multiple units of the WAVE Bioreactor system and slide-out shelves provide easy access to instrumentation (p. 3, para 1 “Cabinet”, and Fig 5).
Accordingly, it would have been obvious for one of ordinary skill in the art to have combined the cabinet with slide-out shelves as suggested by GE Data file in the bioprocessing method with a reasonable expectation of success. Since GE Data file teaches the cabinet provides a space saving unit for multiple units of the WAVE Bioreactor system and slide-out shelves provide easy access to instrumentation (p. 3, para 1 “Cabinet”, and Fig 5), one of ordinary skill in the art would have had a reason to combine the cabinet with slide-out shelves to place the WAVE Bioreactor system (i.e., the processing chamber being a slidable drawer) in order to save space and to provide easy access to instrumentation.
With respect to claim 39 directed to the cells being T cells, as stated supra, June teaches a method of preparing CAR-T cells for cancer therapy (see Example 1, p. 58, and see Fig 1B), thus teaches the cells are T cells.
With respect to claim 40 directed to one more sensors configured to measure the flow of fluid in the bioreactor vessel, and claim 41 directed to the sensors being an optical detector, GE Application note teaches in addition to cell counts and viability; pH, CO2, lactate, glucose, and glutamine levels were monitored for adjusting the perfusion rate (p. 5, para 1). GE Data file teaches the WAVE Bioreactor system has a dissolved oxygen optical monitor and an optical pH sensor (see e.g., p. 2, Table 1).
Accordingly, one of ordinary skill in the art would have immediately expected that the bioprocessing method using the WAVE Bioreactor system would have comprised one or more sensors, including an optical detector (e.g., a dissolved oxygen optical monitor and an optical pH sensor) that is configured to measure the flow of media in the bioreactor vessel for adjusting the perfusion rate as suggested by GE Application note and GE Data file.
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Response to Traversal:
Applicant’s arguments filed on 12/12/2025 are acknowledged.
Applicant argues that examiner has alleged the WAVE bioreactor system would be used inside an incubator without citing any reference or rationale to support this conclusion (Remarks, p. 11, last para).
Applicant’s arguments have been fully considered but they are not persuasive.
As stated in the prior Office action mailed on 06/12/2025, prior art Singh has been cited to support that one of ordinary skill in the art would have used the WAVE bioreactor system inside an incubator, as follows:
Singh teaches the WAVE Bioreactor system can be used inside an incubator and “temperature and pH control can be achieved by placing the entire unit inside a conventional cell culture CO2 incubator” (abstract, p. 150, right col, para 1 and p. 153, right col, para 1), and teaches “all additions and sampling were done in the incubator itself. No laminar flow cabinet was required” (p. 153, right col, para 4).
Thus, one of ordinary skill in the art would have had a reason to place the entire WAVE bioreactor system inside an incubator in order to achieve “temperature and pH control” as suggested by Singh.
Applicant further argues that a benefit of the present invention is that the method can take place in a single processing chamber (Remarks, p. 10, last para).
Applicant’s arguments have been fully considered but they are not persuasive.
Applicant is reminded that MPEP § 2145 states that a showing of beneficial results must be based on evidence, not argument or speculation. In re Mayne, 104 F.3d 1339, 1343-44, 41 USPQ2d 1451, 1455-56 (Fed. Cir. 1997) (conclusory statements that claimed compound possesses unusually low immune response or unexpected biological activity that is unsupported by comparative data held insufficient to overcome prima facie case of obviousness).
As stated supra, prior art June teaches a bioprocessing method comprising all the claimed steps to produce an expanded population of transduced cells. Applicant has not provided side-by-side comparative data supporting the argument of the claimed method having an “unexpected” benefit over the method of June in producing an expanded population of transduced cells by carrying out the claimed method in a single processing chamber.
Claims 28-32 are rejected under 35 U.S.C. 103 as being unpatentable over June et al (WO 2012/079000 A1. Prior art of record) in view of Singh (Cytotechnology. 1999; 30: 149-158. Prior art of record), GE Application note (“Perfusion culture of T lymphocytes in the WAVE Bioreactor™ System 2/10 software version 2.61”, GE Healthcare Life Sciences, Application note 28-9650-52 AC. Published Jan. 2010, p. 1-9. Prior art of record), Davis et al. (US 2016/0340633. Prior art of record), and GE Data file (“WAVE Bioreactor™ 2/10 and 20/50 systems”, GE Healthcare Life Sciences, Data file 28-9520-58 AB, first published Feb. 2009, p. 1-6), as applied to claims 26 and 27 above, and further in view of Wilson et al. (US 2015/0329815. Prior art of record).
With respect to claims 28, June teaches using a Wave Bioreactor system (i.e., a second bioreactor vessel) for expanding the genetically modified cells. GE Application note teaches the Wave Bioreactor comprises a feed port and a drain port, that are configured to permit additional cell culture medium into the cavity and removal of the genetically modified cells, cell culture medium and used cell culture medium from the cavity (see Fig 2 upper panel for a feed port and a drain port and lower panel for harvest cells). GE Application note teaches cell culture medium is added through the feed line and used cell culture medium is removed through the harvest line (see Fig 2, middle panel and lower panel), thus teaches removing the used cell culture medium through the drain port and introducing the additional cell culture medium through the feed port. GE Application note teaches the T cells are cultured in a perfusion manner (p. 4, left col, para 2), thus teaches removing and introducing cell culture medium such that a constant volume is maintained in the Wave Bioreactor. GE Application note teaches the cells are cultured and sampled daily for cell count (p. 4, right col, para 1), thus teaches the cells are expanded to a selected density. GE Application note teaches in order to sample the cells, it is suggested to “first increasing the rocking speed to 20 rpm for 1 min to ensure collection of a representative sample” (p. 4, right col, para 1, also related to claim 31) and teaches harvesting cells at the end of culture (abstract and conclusion), thus teaches resuspending the cells in the cell culture medium in the Wave Bioreactor and teaches resuspending is performed after the selected cell density is attained. GE Application note teaches harvesting cells at the end of culture (abstract and conclusion) and teaches a harvest line that can be used to remove cells and media through harvest pump (see Fig 2, lower panel). Accordingly, it would have been obvious for one of ordinary skill in the art to have understood that the method comprises a step of removing the resuspended cells and the cell culture medium through the harvest line (i.e., the drain port).
however, June, in view of Singh, GE Application note, Davis and GE Data file, is silent on the second bioreactor vessel comprising a gas permeable, liquid impermeable membrane positioned at a bottom of the second bioreactor vessel.
Wilson teaches a method of culturing and proliferating animal cells comprising adding medium and animal cells into a cell culture device through a feed port or a drain port into the cavity of the cell culture device ([0072, 0118, 0185, 0193], claim 1 of Wilson, see Fig 4). The device comprises a compartment with at least the bottom of the compartment being comprised of gas permeable, liquid impermeable material (#30 in Fig. 4; [0118, 0128]; Fig. 8; p.24, 2nd col., claim 28), and comprises two ports, i.e., a feed port and a drain port, labeled with “65” shown adjacently in Fig 4B. Wilson teaches in the Fig 4 description [0118] that access for medium can be made by ways of caps, septums and tubes (e.g. inlet and outlet tubes can be connected to medium source and waste bags) and septum configurations are shown in Fig 4B labeled as “65” [0118]. Thus, Wilson teaches the cell culture device comprises a gas permeable membrane (Fig 4) and 2 access ports (i.e., a feed port and a drain port) that are configured to permit additional cell culture medium into the cavity (from a medium source) and removal of the cells, cell culture medium and used cell culture medium from the cavity (e.g. to waste bags, see [0118]). Wilson teaches in Figures 4B and 4C that the suspension is in an amount sufficient to cover the gas permeable, liquid impermeable membrane positioned at the bottom of the cell culture vessel (also see [0119], [0132], [0135], Figs 5-6 and claims 1c-6). Thus, Wilson teaches introducing a suspension of cells in a cell culture medium through a feed port into a cavity of a cell culture device in an amount sufficient to cover a gas permeable, liquid impermeable membrane positioned at a bottom of the device in which the feed port and the drain port are configured to permit additional medium or removal of cells, cell culture medium and used medium to and from the cavity.
Wilson teaches the cells are intended to settle out of medium by gravity so as to allow uniform deposit of cells onto lower gas permeable material ([0119], see Fig 4B), thus teaches allowing the cells to settle on the gas permeable, liquid impermeable membrane by gravity.
Wilson teaches the gas permeable cell culture devices can be configured to function in the rolled mode in the vertical, horizontal or rolling position ([0128], [0132] for culturing suspension cells), and this configuration would allow resuspending cells in the vessel after cell expansion. Thus, Wilson teaches a cell culture device (a bioreactor vessel) that has a gas permeable, liquid impermeable membrane positioned at the bottom of the vessel that allows the cells to settle on the membrane by gravity and has a feed port and a drain port configured to permit addition and removal of cells and medium, and is configured to allow resuspending cells, thus teaches the limitations in claim 28.
Wilson teaches the used cell culture medium comprises “waste product” ([0123]), thus teaches removing the used cell culture medium comprising removing cell culture byproducts from within the cell culture vessel in claim 29.
Wilson teaches to maintain lower gas permeable material in a substantially horizontal state such that cells do not pile up in any low points and distribute evenly across lower gas permeable material ([0098], [0132], [0141], see Figs 5 and 10), thus teaches limitations in claim 30.
Wilson teaches that gas permeable cell culture devices can be configured to function in the rolled mode in the vertical, horizontal or rolling position ([0128], [0132] for culturing suspension cells), and this configuration would allow resuspending cells comprising oscillating the cell culture vessel at a defined angle for a period of time, thus teaches claim 31.
Wilson teaches the medium can be removed by “pouring” from the cell culture device (see [0118], [0147]) through an outlet tube or a septum, and this pouring method would allow removing the resuspended cells and the cell culture medium through the drain port by tilting the vessel to an angle to minimize a hold-up volume during removal, thus teaches claim 32.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the bioprocessing method comprising using a Wave Bioreactor (i.e. a second bioreactor vessel) for expanding cells suggested by June, in view of Singh, GE Application note, Davis and GE Data file, by substituting with the expanding method and vessel comprising a gas permeable, liquid impermeable membrane as taught by Wilson with a reasonable expectation of success. One of ordinary skill in the art would have had a reason to do so as taught by Wilson because Wilson’s bioprocessing method could scale up the genetically modified cells of June. Specifically, Wilson teaches that the Wave bioreactor system of June has certain limitations in regard to the scaling up of a cell culture [0071-0072], and substituting with the method of Wilson would allow sufficient numbers of expanded cells for the cell therapy methods of June (June, p. 49 and Example 1). Regarding a reasonable expectation of success, since Wilson teaches the vessel comprises a feed port and a drain port that can be configured with inlet and outlet tubes that can be connected to medium source and waste bags by way of a sterile tubing connection to create a closed container ([0118]), and since Davis teaches “a specific assembly of tubing connected to culture vessel that interacts with computer controlled peristaltic pumps to drive automated medium exchange” ([0077], also [0157], [0182]), one of ordinary skill in the art would have had a reasonable expectation of success in substituting with Wilson’s vessel in the expansion step of June, in view of Singh, GE Application note, Davis and GE Data file to carry out the bioprocessing steps in a functionally-closed, automated manner under control of a controller in a single processing chamber.
However, regarding the step of allowing the cells to settle on the gas permeable, liquid impermeable membrane by gravity and subsequently removing the used cell culture medium through the drain port and introducing the additional cell culture medium through the feed port, although Wilson recognizes to have cells in suspension gravitationally settle from suspension within medium ([0119], Example 4, [0169]; Example 5, [0175]), June, Singh, GE Application note, GE Data file and Wilson do not teach such settlement by gravity for the medium exchange in claim 28.
Davis teaches that the cells cultured in a cell bag are allowed to settle in the bag (e.g. a gravity setting chamber) by gravity to remove the used medium, and to resuspend and remove the cells afterward through the port ([0030], [0072], [0179], [0181]-[0183], and see Figs 11&23-24 and claim 4 of Davis), thus teaches medium exchange performed subsequent to gravitational settlement in claim 28.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the bioprocessing method suggested by June in view of Singh, GE Application note, Davis, GE Data file and Wilson, by combining the method of allowing the cells to settle on the bottom by gravity and subsequently removing the used cell culture medium and introducing the fresh medium using available ports for the medium exchange as taught by Davis with a reasonable expectation of success. Since it is known in the art that when cells are cultured in suspension culture condition, the medium exchange can be carried out after the cells are settled down on the bottom surface of the culture device, as exemplified and taught by Davis, one of ordinary skill in the art would have had a reason to combine Davis’ method of medium exchange with the bioprocessing method of June, in view of Singh, GE Application note, Davis, GE Data file and Wilson in order to efficiently change cell culture medium and to minimize disturbance to cells.
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Response to Traversal:
Applicant’s arguments filed on 12/12/2025 are acknowledged and have been discussed above.
Claim 38 is rejected under 35 U.S.C. 103 as being unpatentable over June et al (WO 2012/079000 A1. Prior art of record) in view of Singh (Cytotechnology. 1999; 30: 149-158. Prior art of record), GE Application note (“Perfusion culture of T lymphocytes in the WAVE Bioreactor™ System 2/10 software version 2.61”, GE Healthcare Life Sciences, Application note 28-9650-52 AC. Published Jan. 2010, p. 1-9. Prior art of record), and GE Data file (“WAVE Bioreactor™ 2/10 and 20/50 systems”, GE Healthcare Life Sciences, Data file 28-9520-58 AB, published Feb. 2009, p. 1-6).
With respect to claim 38, June teaches a method of preparing CAR-T cells for cancer therapy (see Example 1, p. 58, and see Fig 1B), thus teaches a bioprocessing method. June teaches the method comprises “addition of anti-CD3/CD28 coated paramagnetic beads for positive selection and activation of T cells” (p. 6, lines 9-10, and see Fig 1B “Day 0-1” when the beads and the cells are seeded in gas-permeable bags), thus teaches a step of activating cells of a population of cells to produce a population of activated cells. June teaches adding lentiviral vector to the cells (p. 6, line 10, and see Fig 1B “Day 0-1” for transduction), thus teaches a step of genetically modifying the activated cells to produce a population of genetically modified cells. June teaches vectors are washed out on day 3 post culture initiation (p. 6, line 11, and see Fig 1B “Day 3”), thus teaches a step of washing the genetically modified cells. June teaches the cells are cultured “on a rocking platform device (WAVE Bioreactor System) for 8-12 days” (p. 6, lines 11-12, and see Fig 1B “Day 5”), thus teaches a step of expanding the cells to produce an expanded population of transduced cells, and the steps are carried out in at least one rocking-type bioreactor vessel (i.e., WAVE Bioreactor).
However, June does not specifically teach a single processing chamber of a bioprocessing system. Note that Applicant’s specification does not provide a special definition of the phrase “bioprocessing system”, and one of ordinary skill would reasonably interpret such a system as an incubator comprising a chamber.
Nevertheless, June teaches “the cells are maintained under conditions necessary to support growth, for example, an appropriate temperature (e.g., 37°C) and atmosphere (e.g., air plus 5% CO2)” (p. 48, lines 15-16). One of ordinary skill in the art would have understood that the most commonly used bioprocessing system with a processing chamber for maintaining cell growth is an incubator.
Furthermore, Singh teaches the WAVE Bioreactor system can be used inside an incubator and “temperature and pH control can be achieved by placing the entire unit inside a conventional cell culture CO2 incubator” (abstract, p. 150, right col, para 1 and p. 153, right col, para 1), and teaches “all additions and sampling were done in the incubator itself. No laminar flow cabinet was required” (p. 153, right col, para 4).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the bioprocessing method comprising the steps of activating, genetically modifying, washing and expanding that are carried out in a gas permeable bag and a rocking-type bioreactor vessel (i.e., WAVE Bioreactor) disclosed by June, by choosing to dispose the cell bag and the Wave Bioreactor in a single processing chamber of a bioprocessing system (e.g., an incubator) as taught by Singh with a reasonable expectation of success. Since it would have been understood that the most commonly used bioprocessing system with a processing chamber for maintaining cell growth is an incubator, and since Singh teaches the WAVE Bioreactor system can be used inside an incubator and “temperature and pH control can be achieved by placing the entire unit inside a conventional cell culture CO2 incubator” (abstract, p. 150, right col, para 1), one of ordinary skill in the art would have had a reason to choose an incubator to provide an optimized environment with temperature and pH control for cell processing. Since the WAVE Bioreactor system can be used inside an incubator as taught by Singh, there would have been a reasonable expectation of success to dispose the two vessels within the single chamber of an incubator as well.
However, June and Singh are silent on the steps being carried out without removing the cells from the single processing chamber.
Regarding the first vessel a gas permeable bag and the second vessel a WAVE Bioreactor used in June being suitable of being fluidly connected, GE Application note teaches a method of culturing T cells in a gas-permeable bag and the Wave Bioreactor system that are fluidly connected (see Fig 2 upper panel). GE Application note teaches T cells are activated in a gas-permeable VueLife™ culture bag (p. 3, para 1, equivalent to the gas-permeable bag used in June for activating, genetically modifying and washing), and teaches the cells in the VueLife bag are transferred to the Wave Bioreactor via an autoclaved assembly comprising a three-way connector, a silicon tubing and a connector to the feed line of the Bioreactor (p. 3, para 2, see Fig 2 middle panel) to prevent cross-contamination (p. 2, left col, last para). Thus, GE Application note teaches the first vessel a gas permeable bag and the second vessel a WAVE Bioreactor of June can be fluidly connected to prevent cross-contamination.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the bioprocessing method comprising the steps of activating, genetically modifying, washing and expanding that are carried out in a gas permeable bag and a Wave Bioreactor disposed within the single chamber of an incubator suggested by June and Singh, by choosing to fluidly connect the bag and the Wave Bioreactor in a functionally-closed manner as taught by GE Application note with a reasonable expectation of success. Since GE Application note teaches the Bioreactor system is completely contained (i.e., in a functionally-closed fluidly-connected manner) that makes them ideally suited for applications where the prevention of cross-contamination is critical (p. 2, left col, last para), one of ordinary skill in the art would have had a reason to choose to fluidly connect the gas permeable bag and the Wave Bioreactor of June in a functionally-closed manner as taught by GE Application note in order to prevent cross-contamination of the T cells for clinical applications in June (abstract).
Furthermore, since the above steps of June are carried out in the two vessels disposed in a processing chamber of an incubator as suggested by June and Singh, and since Singh teaches “all additions and sampling were done in the incubator itself. No laminar flow cabinet was required” (p. 153, right col, para 4), one of ordinary skill in the art would have understood that the steps of June in view of Singh and GE Application note are carried out in the two vessels in a functionally-closed, fluidly-connected manner in the single processing chamber of the incubator, without removing the cells from the single processing chamber.
In regard to the new limitation sensing a weight of the at least one rocking-type bioreactor vessel using one more load cells to determine a volume or a flow of the cells, GE Application note teaches the weight of the empty Cellbag bioreactor was tared, and media was transferred to the Cellbag bioreactor (p. 3, para 1), indicating sensing a weight of the WAVE Cellbag bioreactor vessel (i.e., to tare the empty bioreactor) before transferring media.
GE Data file teaches the WAVE Bioreactor™ system (the system used in June, Singh and GE Application note) has loadcells mounted under the holder tray to measure the Cellbag bioreactor weight during rocking and has a built-in pump controller used for feeding, harvesting, and perfusion operations (p. 4, left col, para 2).
Accordingly, one of ordinary skill in the art would have immediately expected that the bioprocessing method comprising using the WAVE bioreactor suggested by June in view of Singh and GE Application note would have had load cells mounted under the holder tray to sense and monitor the rocking-type bioreactor vessel weight so as to determine a volume or a flow of the genetically modified cells and media as suggested by GE Application note and GE Data file.
Hence, the claimed invention as a whole was prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention in the absence of evidence to the contrary.
Response to Traversal:
Applicant’s arguments filed on 12/12/2025 are acknowledged and have been discussed above.
Withdrawn Double Patenting Rejection
The prior rejection of claims 26-32 and 35-39 on the ground of nonstatutory double patenting as being unpatentable over US Patent 11,920,119 in view of June, GE Application note, Davis, Wilson and Suzhou University, is withdrawn in light of Applicant’s amendment to claims 26 and 38 to recite new limitation of sensing a weight of the bioreactor vessel.
New Double Patenting Rejection
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP §§ 706.02(l)(1) - 706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 26-27, 35-37 and 39-41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 15-19 and 1-14 of US Patent 11,920,119 to Griffin(‘119) in view of June et al (WO 2012/079000 A1. Prior art of record), GE Application note (GE Healthcare Life Sciences, Application note 28-9650-52 AC. Published Jan. 2010, p. 1-9. Prior art of record), Davis et al. (US 2016/0340633. Prior art of record) and GE Data file (“WAVE Bioreactor™ 2/10 and 20/50 systems”, GE Healthcare Life Sciences, Data file 28-9520-58 AB, published Feb. 2009, p. 1-6). Although the claims at issue are not identical, they are not patentably distinct from each other.
Patented claims 15-19 recite a bioprocessing method comprising activating cells, genetically modifying cells, and expanding cells, wherein the activating and genetically modifying cells are performed in the first bioreactor vessel of the second module and expanding cells is performed in the second bioreactor vessel of the second module. Patented claims 1-14 recite a bioprocessing system comprising a second module (i.e., a single processing chamber) which is functionally closed comprising a sterile, closed fluid path with at least one input port and one output port. Note that the step of expanding cells naturally comprises medium change (as evidenced by [00028] & Fig. 79 of cited patent), thus a step of washing the genetically modified cells in the bioreactor (i.e. medium change) would be naturally present in the patented claims.
The claims differ with regard to the steps being carried out in an automated manner under control of a controller, sensing a weight of the bioreactor vessel, the processing chamber being a slidable drawer, the steps of oscillating the vessels through a defined angle for a period of time, the cells being T cells, and one or more sensors including optical detector configured to measure the flow.
Regarding the cells being T cells, June teaches a bioprocessing method of preparing CAR-T cells for cancer therapy (see Example 1, p. 58, and see Fig 1B). June teaches the method comprises activating and transducing cells in a gas permeable bag and expanding cells in a Wave Bioreactor (p. 6, lines 9-10, and see Fig 1B).
Regarding the automated manner, GE Application note teaches the Wave Bioreactor has automated exchange of media (p. 2, abstract) and the Wave Bioreactor System (software version 2.61) with Perfusion Controller (PERFCONT2E) can be set up according to the user manual (p. 4, 1st para), thus, GE Application note teaches the step of expanding is carried out in an automated manner under control of a controller. Furthermore, Davis teaches a method of culturing cells comprising the use of closed systems on rocking platform bioreactors with cell bags (abstract). Davis teaches “a specific assembly of tubing connected to culture vessel that interacts with computer controlled peristaltic pumps to drive automated medium exchange” ([0077], also see [0157], [0182]), thus, Davis suggests cell culturing in a gas permeable bag can be carried out in an automated manner under control of a controller.
Regarding the new limitation sensing a weight of the bioreactor vessel, GE Application note teaches the weight of the empty Cellbag bioreactor was tared, and media was transferred to the Cellbag bioreactor (p. 3, para 1), indicating sensing a weight of the WAVE Cellbag bioreactor vessel (i.e., to tare the empty bioreactor) before transferring media. GE Data file teaches the WAVE Bioreactor™ system (the system used in June and GE Application note) has loadcells mounted under the holder tray to measure the Cellbag bioreactor weight during rocking and has a built-in pump controller used for feeding, harvesting, and perfusion operations (p. 4, left col, para 2).
Regarding the processing chamber being a slidable drawer, GE Data file teaches the WAVE Bioreactor System can be placed in a cabinet with slide-out shelves. GE Data file teaches the cabinet provides a space saving unit for multiple units of the WAVE Bioreactor system and slide-out shelves provide easy access to instrumentation (p. 3, para 1 “Cabinet”, and Fig 5).
Regarding oscillating the first and the second bioreactor vessels through a defined angle for a period of time, GE Application note teaches the Wave Bioreactor (i.e., the second bioreactor vessel of June) is set to rock at 10 rpm and an angle of 6 degree during expansion period for up to 11 days (p. 4, left col, para 2), and Davis teaches the gas permeable bag (i.e., the first bioreactor vessel of June) is rocked at 20 rpm, 9 degree rock angle for 4 days ([0168], see p. 11, 1st para).
Regarding one or more sensors including optical detector configured to measure the flow, GE Application note teaches in addition to cell counts and viability; pH, CO2, lactate, glucose, and glutamine levels were monitored for adjusting the perfusion rate (p. 5, para 1). GE Data file teaches the WAVE Bioreactor system has a dissolved oxygen optical monitor and an optical pH sensor (see e.g., p. 2, Table 1).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the bioprocessing method recited in the patented claims 15-19 and 1-14 of ‘119, by choosing T cells and combining an automated manner for carrying out the steps, sensing a weight of the bioreactor vessel, choosing the processing chamber being a slidable drawer, combining the steps of oscillating the vessels, and combining sensors configured to measure the flow as taught by June, GE Application note, Davis and GE Data file with a reasonable expectation of success. One of ordinary skill in the art would have had a reason to choose T cells as suggested by June for cancer therapy (see June Example 1, p. 58), to use an automated manner as taught by GE Application note and Davis to reduce hands-on-time and labor (GE Application note, abstract and conclusion), to combine sensing a weight of the bioreactor vessel for media exchange (GE Application note and GE Data file), to choose the processing chamber being a slidable drawer to save space and easily access instrumentation (GE Data file), to use oscillating the vessels as taught by GE and Davis, and to combine sensors including optical detectors in order to facilitate culture and resuspension of cells.
Since the instant application claims are obvious over cited patented claims of ‘119, in view of June, GE Application note, Davis and GE Data file, said claims are not patentably distinct.
Claims 28-32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 15-19 and 1-14 of US Patent 11,920,119 to Griffin(‘119) in view of June et al (WO 2012/079000 A1. Prior art of record), GE Application note (GE Healthcare Life Sciences, Application note 28-9650-52 AC. Published Jan. 2010, p. 1-9. Prior art of record), Davis et al. (US 2016/0340633. Prior art of record) and GE Data file (“WAVE Bioreactor™ 2/10 and 20/50 systems”, GE Healthcare Life Sciences, Data file 28-9520-58 AB, published Feb. 2009, p. 1-6), and further in view of Wilson et al. (US 2015/0329815. Prior art of record). Although the claims at issue are not identical, they are not patentably distinct from each other.
The patented claims are silent on the second bioreactor vessel comprising two ports and a gas permeable, liquid impermeable membrane, and are silent on media exchange by gravity settlement.
Regarding the second bioreactor vessel comprising two ports and a gas permeable, liquid impermeable membrane, Wilson teaches a method of culturing and proliferating animal cells comprising adding medium and animal cells into a cell culture device through a feed port or a drain port into the cavity of the cell culture device ([0072, 0118, 0185, 0193], claim 1 of Wilson, see Fig 4). The device comprises a compartment with at least the bottom of the compartment being comprised of gas permeable, liquid impermeable material (#30 in Fig. 4; [0118, 0128]; Fig. 8; p.24, 2nd col., claim 28), and comprises two ports, i.e., a feed port and a drain port, labeled with “65” shown adjacently in Fig 4B. Wilson teaches in the Fig 4 description [0118] that access for medium can be made by ways of caps, septums and tubes (e.g. inlet and outlet tubes can be connected to medium source and waste bags) and septum configurations are shown in Fig 4B labeled as “65” [0118]. Thus, Wilson teaches the cell culture device comprises a gas permeable membrane (Fig 4) and 2 access ports (i.e., a feed port and a drain port) that are configured to permit additional cell culture medium into the cavity (from a medium source) and removal of the cells, cell culture medium and used cell culture medium from the cavity (e.g. to waste bags, see [0118]). Wilson teaches in Figures 4B and 4C that the suspension is in an amount sufficient to cover the gas permeable, liquid impermeable membrane positioned at the bottom of the cell culture vessel (also see [0119], [0132], [0135], Figs 5-6 and claims 1c-6). Thus, Wilson teaches introducing a suspension of cells in a cell culture medium through a feed port into a cavity of a cell culture device in an amount sufficient to cover a gas permeable, liquid impermeable membrane positioned at a bottom of the device in which the feed port and the drain port are configured to permit additional medium or removal of cells, cell culture medium and used medium to and from the cavity.
Wilson teaches the cells are intended to settle out of medium by gravity so as to allow uniform deposit of cells onto lower gas permeable material ([0119], see Fig 4B), thus teaches allowing the cells to settle on the gas permeable, liquid impermeable membrane by gravity.
Wilson teaches the gas permeable cell culture devices can be configured to function in the rolled mode in the vertical, horizontal or rolling position ([0128], [0132] for culturing suspension cells), and this configuration would allow resuspending cells in the vessel after cell expansion. Thus, Wilson teaches a cell culture device (a bioreactor vessel) that has a gas permeable, liquid impermeable membrane positioned at the bottom of the vessel that allows the cells to settle on the membrane by gravity and has a feed port and a drain port configured to permit addition and removal of cells and medium, and is configured to allow resuspending cells, thus teaches the limitations in claim 28.
Regarding the media exchange by gravity settlement, Davis teaches that the cells cultured in a cell bag are allowed to settle in the bag (e.g. a gravity setting chamber) by gravity to remove the used medium, and to resuspend and remove the cells afterward through the port ([0030], [0072], [0179], [0181]-[0183], and see Figs 11&23-24 and claim 4 of Davis), thus teaches medium exchange performed subsequent to gravitational settlement in claim 28.
With respect to claims 29-32, Wilson teaches the used cell culture medium comprises “waste product” ([0123]), thus teaches removing the used cell culture medium comprising removing cell culture byproducts from within the cell culture vessel in claim 29. Wilson teaches to maintain lower gas permeable material in a substantially horizontal state such that cells do not pile up in any low points and distribute evenly across lower gas permeable material ([0098], [0132], [0141], see Figs 5 and 10), thus teaches limitations in claim 30. Wilson teaches that gas permeable cell culture devices can be configured to function in the rolled mode in the vertical, horizontal or rolling position ([0128], [0132] for culturing suspension cells), and this configuration would allow resuspending cells comprising oscillating the cell culture vessel at a defined angle for a period of time, thus teaches claim 31. Wilson teaches the medium can be removed by “pouring” from the cell culture device (see [0118], [0147]) through an outlet tube or a septum, and this pouring method would allow removing the resuspended cells and the cell culture medium through the drain port by tilting the vessel to an angle to minimize a hold-up volume during removal, thus teaches claim 32.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the bioprocessing method recited in the patented claims 15-19 and 1-14 of ‘119 in view of June, GE Application note, Davis and GE Data file, by substituting with the expanding method and vessel comprising two ports and a gas permeable, liquid impermeable membrane as taught by Wilson with a reasonable expectation of success. One of ordinary skill in the art would have had a reason to do so as taught by Wilson because Wilson’s bioprocessing method could scale up the genetically modified cells. Specifically, Wilson teaches that the Wave bioreactor system of June has certain limitations in regard to the scaling up of a cell culture [0071-0072], and substituting with the method of Wilson would allow sufficient numbers of expanded cells for the cell therapy methods as claimed in ‘119. Regarding reasonable expectation of success, since Wilson teaches the vessel comprises a feed port and a drain port that can be configured with inlet and outlet tubes that can be connected to medium source and waste bags by way of a sterile tubing connection to create a closed container ([0118]), and since Davis teaches “a specific assembly of tubing connected to culture vessel that interacts with computer controlled peristaltic pumps to drive automated medium exchange” ([0077], also [0157], [0182]), one of ordinary skill in the art would have had a reasonable expectation of success in substituting with Wilson’s vessel in the expansion step of ‘119 in view of June, GE Application note, Davis and GE Data file to carry out the bioprocessing steps in a functionally-closed, automated manner under control of a controller in a single processing chamber. Furthermore, since it is known in the art that when cells are cultured in suspension culture condition, the medium exchange can be carried out after the cells being settled down on the bottom surface of the culture device, as exemplified and taught by Davis, one of ordinary skill in the art would have been motivated to combine Davis’ method of medium exchange with the bioprocessing method in order to efficiently change cell culture medium and to minimize disturbance to cells.
Since the instant application claims are obvious over cited patent claims of ‘119, in view of June, GE Application note, Davis, GE Data file and Wilson, said claims are not patentably distinct.
Claim 38 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 15-19 and 1-14 of US Patent 11,920,119 to Griffin(‘119) in view of June et al (WO 2012/079000 A1. Prior art of record) and GE Data file (“WAVE Bioreactor™ 2/10 and 20/50 systems”, GE Healthcare Life Sciences, Data file 28-9520-58 AB, published Feb. 2009, p. 1-6). Although the claims at issue are not identical, they are not patentably distinct from each other.
Patented claims 15-19 recite a bioprocessing method comprising activating cells, genetically modifying cells, and expanding cells, wherein the activating and genetically modifying cells are performed in the first bioreactor vessel of the second module and expanding cells is performed in the second bioreactor vessel of the second module. Patented claims 1-14 recite a bioprocessing system comprising a second module (i.e., a processing chamber) which is functionally closed comprising a sterile, closed fluid path with at least one input port and one output port. Note that the step of expanding cells naturally comprises medium change (as evidenced by [00028] & Fig. 79 of cited patent), thus a step of washing (medium exchange) the genetically modified cells in the bioreactor would be naturally present in the patented claims. Patented claim 2 recites the steps are carried out without removal of the population of cells from the bioreactor vessel.
However, the cited patented claims are silent on at least one rocking-type bioreactor vessel or sensing a weight of the bioreactor vessel.
Regarding a rocking-type bioreactor vessel used in a bioprocessing method, June teaches a method of preparing CAR-T cells for cancer therapy (see Example 1, p. 58, and see Fig 1B), thus teaches a bioprocessing method. June teaches the cells are expanded “on a rocking platform device (WAVE Bioreactor System) for 8-12 days” (p. 6, lines 11-12, and see Fig 1B “Day 5”), thus teaches a step of expanding the population of genetically modified cells that is carried out in a rocking-type bioreactor vessel (i.e., WAVE Bioreactor).
Regarding the new limitation sensing a weight of the bioreactor vessel, GE Data file teaches the WAVE Bioreactor™ system (the system used in June) has loadcells mounted under the holder tray to measure the Cellbag bioreactor weight during rocking and has a built-in pump controller used for feeding, harvesting, and perfusion operations (p. 4, left col, para 2).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the bioprocessing method recited in the patented claims 15-19 and 1-14 of ‘119, by choosing a rocking-type bioreactor vessel (e.g., a rocking platform device) as taught by June and choosing sensing a weight of the bioreactor vessel as suggested by GE Data file with a reasonable expectation of success. One of ordinary skill in the art would have had a reason to choose a rocking-type bioreactor vessel and sensing a weight of the vessel as taught by June and GE Data file in order to facilitate culturing cells in suspension.
Since the instant application claims are obvious over cited patented claims of ‘119, in view of June and GE Data file, said claims are not patentably distinct.
Response to Traversal:
Applicant’s arguments filed on 12/12/2025 are acknowledged and have been discussed above.
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 extension fee 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 date of this final action.
No claims are allowed.
Examiner Contact Information
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/JIANJIAN ZHU/Examiner, Art Unit 1631
/JAMES D SCHULTZ/Supervisory Patent Examiner, Art Unit 1631