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 OFFICE ACTION
This Office Action is in response to the papers filed on 17 April 2026.
CLAIMS UNDER EXAMINATION
Claims 1-3, 7-9, 12-15, 17-19 and 22-23 are pending and have been examined on their merits.
PRIORITY
The Provisional Applications filed on 21 October 2019 are acknowledged.
WITHDRAWN REJECTIONS
The rejection of claims 1-3, 7-9, 12-15, 17-19 and 22-23 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, has been withdrawn due to claim amendment.
The rejection of claims 1-3, 7-9, 12-15, 17-19 and 22-23 under 35 U.S.C. 101 has been withdrawn due to claim amendment.
REJECTIONS
The previous rejections have been modified to address the amended claims.
.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-3, 7-9, 12-15, 17-19 and 22-23 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 has been amended to recite “removing used cell culture medium from the culture chamber”. Claim 1 recites “a plurality of culture chambers”, “a first gas-impermeable culture chamber” and “at least a separate second gas-impermeable culture chamber”. It is unclear if the amended claim limitation is referring to the second gas-impermeable chamber. Appropriate correction is required. All dependent claims are included in this rejection.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-3, 8-9, 13-14, 17-19 and 22-23 are rejected under 35 U.S.C. 103 as being unpatentable over Murthy et al. (previously cited; Cell Culture Chambers And Methods Of Use Thereof. WO2018/005521 04 January 2018) in view of Shi et al. (previously cited; End-To-End Cell Therapy Automation. US Patent 11447745, Published 06 June 2019) and Chang et al. (previously cited; Disease therapy with chimeric antigen receptor (car) constructs and t cells (car-t) or nk cells (car-nk) expressing car constructs. US20160361360A1)
Murthy et al. disclose an invention that provides “cell culture chambers and methods of use thereof” (Abstract). The chambers produce therapeutic T cells (see line 32 of page 2 bridging line 2 of page 3). The process is automated (page 2, line 15). The environment is closed (hence, a closed system) (page 10, lines 4-5).
The system comprises the following:
2-100, or more, chambers fluidically connected with one another in a series (page 15, lines 5-8);
the chambers have inlets and outlets (page 2, lines 25-26) which fluidically couple the chamber via a fluidic connector with one additional vessel(s) (page 15, lines 1-3; Figure 3);
the reactors (chambers) can have different shapes (see Figures 4A-D).
the cell culture chambers are connected via a sterile connection (page 15, lines 10-11);
Figure 3 illustrates the cell culture chamber (120) is placed on a surface. Said surface is broadly interpreted to be a substrate configured for simultaneously receiving and retaining a chamber. Because the art meets the structural limitations of the claimed substrate, the chambers are interpreted to be interchangeable on the substrate;
the chambers comprise one or more pumps to flow fluid through each chamber and between chambers (page 4, lines 17-18);
each chamber can comprise its own pump (page 4, lines 17-18);
the pumps perfuse perfusion medium into the chambers (page 13,11-12);
the cell culture chambers include one or more fluid reservoirs that are operably coupled to the one or more pumps;
the fluid reservoirs are configured to supply medium, which includes nutrients and cytokines, to the chambers (page 4, lines 20-22);
the system includes waste fluid reservoirs (page 10, lines 15-16);
pumps move fluids between the chambers and the reservoirs (page 10, lines 14-19); and
each bioreactor includes its own fluid and waste collection reservoirs, pumps, and associated tubing (page 15, lines 22-23).
Regarding the chamber material, Murthy teaches the following:
In one embodiment, all surfaces of the cell culture chamber, such as the bottom, side, and top walls, comprise the first material ( e.g., polystyrene) and are joined together using ultrasonic welding, with at least a portion of the first material in the side and/or top walls cut out to allow for the insertion of a second material ( e.g., a silicone material), as shown in FIG. 5.
The Instant Specification discloses the following ([0027]):
In another aspect, the disclosure provides a gas-impermeable cell culture chamber, wherein a top, a bottom, and both side walls are comprised of a gas-impermeable material. The gas-impermeable material may also be a material to which cells adhere. The gas-impermeable material may be polystyrene.
The specification discloses a gas-impermeable cell culture chamber is one wherein a top, a bottom and both side walls comprise a gas-impermeable material. Murthy teaches a cell culture chamber where the top, bottom and side walls are comprised of a gas impermeable material. Therefore the chambers taught by Murthy are gas-impermeable.
Murthy teaches the following steps to produce therapeutic T cells:
The first step in the culture process comprises generating dendritic cells by differentiating monocytes using a culture media containing, for example, IL4 and GM-CSF ( page 10, lines 30-21). It is well known that these are cytokines. Therefore the art teaches a cytokine-containing medium. Murthy teaches using polystyrene for the bottom surface, where culturing occurs, to enrich monocytes from a heterogenous suspension of PBMCs (page 10, lines 26-30). The art teaches cells adhere to polystyrene (page 11, lines 24-25). Therefore it is configured to receive monocytes and promote differentiation adherent dendritic cells. The art teaches dendritic cells are antigen-presenting cells (page 20, line 21).
In order to initiate stimulation (hence, activation) and expansion of T-cells from the interaction of APCs with T-cell containing cells, the APCs need to be stimulated. Murthy teaches using one or more stimulatory molecules. The stimulatory molecule is either non-tumor specific or tumor-specific. The stimulatory molecule can be antigen peptides specific to an individual’s tumor (See page 16, lines 30 bridging line 1 of page 17). The art teaches dendritic cells/APCs are “pulsed” with antigen (page 17, line 17).
In order to stimulate (hence, activate) and expand antigen-specific T-cells, the art teaches co-culturing T-cell containing cells (PBMCs) with APCs in a cell culture chamber. In a particular embodiment, the T-cell containing cells include peripheral blood mononuclear cells (PBMCs) and the APCs include dendritic cells (DCs) (page 16, lines 20-24). Therefore the art teaches the cells are in the same chamber. Because the art teaches co-culturing in the same chamber, antigen-specific T cells are generated as recited in instant claim 1. Cytokines are perfused into the chamber such that more consistent levels can be maintained (page 2, lines 21-22; page 19, lines 18-19). T cells are expanded in the first chamber (page 7, lines 20-21). Because a cytokine is a protein which produces a cellular response (Merriam Webster), it is broadly interpreted to be an activation agent. Therefore the art teaches a soluble activation agent and expanding antigen-presenting T cells in the first chamber.
The medium is continuously perfused during culturing (page 19, lines 14-15).
During culturing of the two cell types, a supernatant is formed containing lighter non-adherent T-cells, whereas the heavier, mature APCs (e.g., dendritic cells) adhere to the bottom surface. See page 17, lines 6-10. The fluid flow rate is maintained below the sedimentation rate of the antigen-presenting cells. The antigen-presenting cells will remain within the culture chamber because of their mass. The antigen-presenting cells will sink toward the bottom of the cell culture chamber and therefore remain in the cell culture chamber. See page 18, lines 14-16. During the T-cell stimulation and expansion process that occurs in the cell culture chamber, mature APCs will develop and preferably adhere to the bottom surface whereas the T-cells remain in the supernatant above the bottom surface, making it easier to separately obtain the expanded T-cells (see page 10, lines 22-25).
Multiple cycle T-cell stimulation involves the culturing of cells in a first cell culture chamber in a manner that generates a supernatant comprising a first cell product, the provision of a second cell culture chamber, and the subsequent transfer of supernatant from the first cell culture chamber to the second cell culture chamber by introducing a gas flow into the first cell culture chamber (see Figure 2; see page 20, lines 16-20). An injection of sterile air will then transfer the supernatant from the first reactor to the second reactor (see page 20, lines 26-27).
Antigen-specific T-cells can be automatically transferred between chambers to allow for further culturing and expansion of the T-cells into a second culture chamber(see page 2, lines 28-32).
Murthy also teaches the following:
Chimeric antigen receptor T cell (CAR-T) therapy and T cell receptor therapy are promising for certain types of cancer (page 1, lines 16-20).
The art teaches a control system for controlling the movement of fluid through the system and monitoring various parameters (page 24, lines 4-6). The cell culture chamber can also include one or more sensors to measure one or more parameters, including glucose concentration (nutrient supply), within the cell culture chamber (page 4, lines 23-25). Examiner notes glucose would be present in the culture media. Because it is measured, it must be sampled (removed). A central processing unit is coupled to the one or more sensors and configured to adjust an operating state of the one or more pumps as a function of the one or more parameters measured (page 4, lines 25-30).
Murthy teaches the devices of the invention can include reagents (see page 22, line 30).
The one or more biological reactors can be produced in a system containing modules for effectuating various other processes prior to, concurrent with, or subsequent to the process occurring with the cell culture chambers of the biological reactors. (page 116, lines 5-8).
The art does not teach transducing T cells in the first chamber by flowing a transducing reagent comprising an inactive virus expressing CAR or TCR.
The art does not explicitly teach recycling used media.
Shi teaches an automated method of producing immune cells in a fully enclosed system (column 1; lines 14-17). Shi teaches T cells (column 13, line 20). Shi teaches perfusion (column 44, lines 48-52). Cells are activated with an activation agent (column 2, line 60). Shi teaches a soluble antibody can be used for activation (hence, a soluble activation agent; see column 14 lines 50-51). Activated cells are transduced with a lentiviral vector with a chimerical antigen receptor (CAR), expanded, concentrated and harvested (column 3, lines 26-33; see Figure 1; column 14, lines 59-60).
Shi teaches each of the activating, transducing, expanding, concentrating, and harvesting steps is performed in a different chamber of the plurality of chambers of the cell engineering system (column 30, lines 31-36). Alternatively, the steps can be performed in the same chamber (column 30, lines 38-42).
The process is self-adjusting (column 13, lines 48-49). The system determines the modifications and conditions required to optimize the process. Conditions are monitored using a temperature sensor, a pH sensor, a glucose sensor, an oxygen sensor, a carbon dioxide sensor, and an optical density sensor. The sensors are used at various times and locations to provide optimization (column 13, lines 50-60). The system provides the option to pull cell and media samples at various points in the process to confirm that specific unit operations meet product specification checkpoints (line 65 of column 10, bridging column 11, line 1).
Shi teaches “recirculation” of nutrients (column 15, lines 18-19; column 17, lines 51-52). Recirculation aids in the production of a large number of viable cells (same section). Recirculation is interpreted to read on recycling. While spent media (depleted of nutrients) is removed (column 24, line 51). Media is continuously recirculated (hence, recycled) through additional chambers (column 30, lines 10-12; lines 61-62). Shi teaches waste can be recirculated (column 17, lines 50-51).
Shi teaches modifying and controlling the flow rate of the media provided to the cells to optimize growth conditions (column 15, lines 27-30). As the cells begin to grow, the circulation rate of the media provided is increased, which improves gas exchange and allows oxygen and carbon dioxide to either enter or leave the cell culture (column 15, lines 30-35). Higher oxygen levels support increased cell growth and proliferation (column 30, lines 59-61).
While Shi teaches the use of the use of a virus expressing CAR, the art is silent as to whether it is “inactive”.
Chang et al. is directed to CAR, CAR-T and CAR-NK constructs (Abstract). The art teaches the use of a third generation self-inactivating lentiviral vector ([0207] [0217]). The art teaches a method of Transduction of T Cells (Example 5; [0225]):
For certain purposes, T cells from normal individuals may be used with the subject CAR constructs for construct testing and design. Primary human CD4+ and CD8+ T cells are isolated from the PBMCs of healthy volunteer donors following leukapheresis by negative selection with RosetteSep kits (Stem Cell Technologies). T cells are cultured in complete media (RPMI 1640 supplemented with 10% heat-inactivated FCS, 2 mM glutamine, 100 U/mL penicillin, 100 μg/mL streptomycin sulfate, and 10 mM HEPES), stimulated with monoclonal anti-CD3 and anti-CD28 coated beads for 12 to 24 h, and transduced with a lentiviral vector of interest at MOI (multiplicity of infection) of 5 to 10. Human recombinant IL-2 is added every other day to a 50 U/mL final concentration and a cell density of 0.5 to 1.0×106/mL is maintained.
Chang teaches following stimulation, cells are transduced with retroviral vectors (supra).
It would have been obvious to combine the teachings of the prior art by transducing the
T cells taught by Murthy. Murthy makes therapeutic T cells and teaches CAR-T therapy is a promising treatment for some cancer. One would transduce the cells to produce CAR therapeutic T cells as taught by Shi. One would have had a reasonable expectation of success since Shi teaches T-cells produced in a multi-chamber system can be reduced. It would have been obvious to include a transduction reagent since Shi teaches using a transduction agent (i.e. a lentiviral vector comprising CAR) to transduce cells. Murthy teaches medium is continuously perfused during culturing. Therefore one would perfuse medium comprising the transduction reagent to produce transduced T cells. One would have had a reasonable expectation of success since Shi teaches T cells can be transduced and Murthy teaches different processes can be conducted using the disclosed system. One would have expected similar results since both references produce therapeutic T cells.
It would have been obvious to use an inactive virus. One would have been motivated to
do so since Shi teaches the use of viruses for transduction and Chang teaches self-
inactivated viruses can be used for T cell transduction. One would have had a
reasonable expectation of success since Chang teaches self-inactivated viruses can
successfully transduce T cells with CAR. One would have expected similar results since
Shi and Chang are both directed to viral transduced T cells.
It would have been obvious to combine the teachings of the prior art by recycling media through the system. Murthy teaches continuous perfusion in a multi-chamber system. Shi teaches continuously recirculating (nutrients) in a multi-chamber system and removing nutrient-depleted media from the system. One would have been motivated to do so since Shi teaches recirculation aids in the production of a large number of viable cells. Murthy teaches measuring the parameter and adjusting the operating state based on the result. One would remove medium from the waste reservoir since Shi teaches waste can be recycled. The skilled artisan would add it to a second chamber since Shi teaches continuous recirculation. It would have been obvious to base the rate of recycling on the required gas exchange for cell culture. Shi teaches gas exchange can be improved by increasing the circulation rate. Higher oxygen increases cell growth and proliferation. One would base the recirculation rate on the gas exchange to produce the optimum oxygen levels in the culture. One would have had a reasonable expectation of success since Shi teaches the system can be used to determine the conditions required to optimize the process. Therefore claim 1 is rendered obvious.
Murthy teaches the second culture chamber can be larger in size than the first culture chamber (page 20, lines 19-20). Therefore claim 2 is included in this rejection.
Murthy teaches the chambers can comprise polystyrene (page 4, line 9; page 10, line 26). Therefore claim 3 is included in this rejection.
Claim 8 recites flowing cell culture medium into the first culture chamber comprises eliminating headspace in said chamber. The claim does not recite how much headspace is eliminated. Examiner notes the instant specification discloses “In some embodiments, the cell culture chambers are filled completely with little or no headspace” (page 24, line 14). This is interpreted to mean filling the chamber eliminates headspace. Murthy teaches culture medium is added to the culture chamber. Because culture medium is added to Murthy’s chamber, headspace is eliminated. Therefore claim 8 is included in this rejection.
Murthy teaches T cells are stimulated (hence, activated) in the first culture chamber (supra). Further, Chang teaches cells are stimulated with anti-CD3 antibody (supra). Because the cells are stimulated, they are interpreted to be activated. Therefore claim 9 is rendered obvious.
Shi teaches a harvesting chamber (column 29, line 10-11).s Shi teaches the chambers are connected in a closed system. Therefore a harvesting vessel as recited in claim 13 is rendered obvious.
Shi teaches sterile tubes (supra). Claim 14 is included in this rejection.
Murthy teaches in certain aspects, the fluid flow rate is maintained below the sedimentation rate of the antigen-presenting cells. Antigen-presenting cells will remain within the culture chamber because of their mass. The antigen-presenting cells will sink toward the bottom of the cell culture chamber and therefore remain in the cell culture chamber (page 18, second paragraph). Therefore claim 17 is included in this rejection.
Murthy teaches the medium can be continuously perfused during culturing. Continuous perfusion helps to maintain a near constant culture volume throughout the process (page 19, second full paragraph). Therefore claim 18 is included in this rejection.
Murthy teaches in order to ensure that the antigen-specific T-cells and other cells involved in the culturing process remain in the chamber during perfusion, one or more inlets and outlets of the cell culture chamber are arranged to move fluid within the cell culture chamber at least in part along a vertical flow path upon exiting the chamber (page 2, lines 23-28). Therefore claim 19 is included in this rejection.
Shi teaches in embodiments, the steps of the method are performed in the same chamber (see column30, lines 39-40). The skilled artisan would perfuse an activation and transduction reagent since the art teaches steps (e.g. activation and transduction) can occur in the same chamber. Therefore claim 22 is included in this rejection.
Following transduction, Chang teaches cells are cultured human recombinant IL-2 is added every other day to a 50 U/mL final concentration and a cell density of 0.5 to 1.0×106/mL is maintained (supra). The art teaches transduced cells are expanded ([0226] [0228) to achieve the desired T cell dose ([0228]). It is noted the art teaches transduced cells can be expanded for 48 to 72 hours ([0239]). It would have been obvious to culture transduced cells for about three days. One would do so since Chang teaches cells are cultured to obtain the desired number of cells, and teaches cells can be expanded for 72 hours following transduction. Therefore claim 23 is included in this rejection.
Therefore Applicant’s Invention is rendered obvious as claimed.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Murthy in view of Shi and Chang as applied to claim 1 above, and further in view of Crisman et al. (previously cited; Methods for Transduction And Cell Processing. US 2016/0122782 2016).
Claim 1 is rendered obvious on the grounds set forth above. The teachings of the prior art are reiterated. Murthy is silent regarding transduction. Shi teaches T cell transduction. Shi teaches cells are expanded, washed and cryopreserved (See Tables 1 and 2; see column 2, line 9). It is noted Shi teaches reagents can be removed by draining a culture chamber (see column 15, lines 55-60).
Shi does not teach washing the T cells with a buffer and flowing a cryopreservation medium into the chamber.
Crisman teaches cryopreservation medium can be added to transduced cells ([0258]). Further steps of washing and suspending, such as for dilution, concentration or buffer exchange can be performed prior to or subsequent to the above step ([0258]). Crisman teaches the cells are isolated, separated or selected, stimulated, transduced, washed, and formulated, all within a closed system ([0260]). Crisman teaches transduced and expanded cells can be washed to replace the medium with cryopreservation solution ([0320]). The art teaches the use of a buffer for washing ([0319]).
It would have been obvious to combine the teachings of the prior art by performing the claimed steps. One would have been motivated to do so since Crisman teaches removing culture medium, washing transduced and expanded cells and replacing medium with cryopreservation solution. The skilled artisan would do so to preserve Shi’s cells for later use. One would have had are a reasonable expectation of success since Crisman teaches cells that have been expanded and transduced can be formulated in a cryopreservation solution. One would have had a reasonable expectation of success since Murthy teaches additional methods can be performed subsequently using the disclosed system. One would have expected similar results since both Murphy and Crisman are both directed to methods of preparing T cells for medicinal use. Therefore claim 12 is rendered obvious.
Therefore Applicant’s Invention is rendered obvious as claimed.
Claims 7 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Murthy in view of Shi and Chang applied to claims 1 and 14 above, and further in view of TERUMO BCT (previously cited; Sterile Tubing Welder with or without accessory information system. 2017, Pages 1-6).
Claims 1 and 14 are rejected on the grounds set forth above. Murthy teaches chambers are connected through a “sterile connection” (page 15, lines 10-11). Shi teaches cells are transferred from one chamber to another (See column 30, lines 30-43). Shi teaches sterile closed connection tubing to transfer cells (see column 18, lines 65-66; column 19, line 3). Shi teaches gas permeable tubing (column 44, lines 15-48). Shi does not teach the use of sterile tube welding.
Terumo BCT discloses a sterile connecting device that is used to connect two closed internally sterile components such as a blood collection container, apheresis set, transfer set or needle set by making a sterile weld in the tubing connected to these components. These welds may consist of dry-to-dry, wet-to-dry or wet-to-wet connections. The resulting sterile component may be used in blood collection, blood component processing or transfusion applications (see page 2, “TSCD-II Sterile Tubing Welder”).
It would have been obvious to connect Shi’s reservoir using sterile tube welding. One would have been motivated to do so since Terumo teaches sterile tube welding is used to connect sterile components. One would have had a reasonable expectation of success since Terumo teaches the said welding can be used for processing a blood component, and Murthy processes cells obtained from blood (hence, blood components). Therefore claim 7 is rendered obvious.
It would have been obvious to connect sterile tubes by sterile tube welding as recited in instant claim 15. One would have been motivated to do so since Terumo teaches sterile tube welding is used to connect sterile components. One would have had a reasonable expectation of success since Terumo teaches the said welding can be used for processing a blood component, and Murthy processes cells obtained from blood (hence, blood components). Therefore claim 15 is rendered obvious.
Therefore Applicant’s invention is rendered obvious as claimed.
RESPONSE TO APPLICANT’S ARGUMENTS
The arguments made in the response filed on 17 April 2016 are acknowledged.
Argument 1: The Applicant argues Shi does not support dendritic cell-based antigen-specific T cell generation as required in claim 1. The Applicant agues Shi uses artificial reagents, including anti-CD3/anti-CD28 beads to generate active T cells.
Response: New grounds of rejection have been set forth above. Examiner notes claim 9 recites the activated T cells in the first culture chamber have been contacted with “activating antibodies”. This reads on the use of antibodies taught in Shi. Claim 1 recites activated T cells are flowed into the chamber (hence, already activated), and co-cultured with antigen-presenting dendritic cells to generate antigen-specific T cells.
Murthy teaches co-culturing dendritic cells with T cells to stimulate and produce antigen-specific T cells. The argument is not persuasive.
Argument 2: The Applicant argues Shi does not teach an adherent surface for receiving and differentiating monocyte to produce dendritic cells.
Response: New grounds of rejection have been set forth above. Murthy teaches culturing monocytes an adherent surface in a chamber made of gas-impermeable material. The argument is not persuasive.
Argument 3: The Applicant argues Shi does not teach “iterative antigen-specific restimulation cycles or perfusion drive culturing with continuous medium recycling”.
Response: New grounds of rejection have been set forth above. Examiner notes claim 1 does not recite iterative (repeated) antigen-specific restimulation cycles. Claim 1 recites “one or more of” T cell stimulation and restimulation. Murthy teaches multiple cycles of T-cell stimulation (supra). The claim does not recite continuous medium recycling. The claim does not require recycling. Murthy teaches continuous perfusion.
Argument 4: The Applicant argues the Examiner dismissed Shi, which does not disclose dendritic cell-mediated generation of transduced T cells.
Response: The limitations directed to monocyte culture and differentiation to produce dendritic cells was not previously presented. These are new limitations.
Argument 5: The Applicant argues Murthy and Shi are silent on perfusing T cells with a transduction reagent.
Response: Shi teaches perfusion (column 44, lines 48-52). Shi teaches a soluble antibody can be used for activation (hence, a soluble activation agent; see column 14 lines 50-51). Activated cells are transduced with a lentiviral vector with a chimerical antigen receptor (CAR), expanded, concentrated and harvested (column 3, lines 26-33; see Figure 1; column 14, lines 59-60).
Argument 6: The Applicant argues Shi does not teach a perfusion system.
Response: Shi teaches “as the T cells require stable contact with other cells or the activating agent, media exchanges, washing and recirculation for gas exchange can be performed via perfusion” (column 44, lines 48-52).
Argument 7: The Applicant argues Murthy and Shi do not teach continuous perfusion with a “fresh” cell culture medium,
Response: While claim 1 recites perfusing the transduced T cells continuously, it does not recite “fresh” culture medium. This is not a claim limitation. The argument is not persuasive.
Argument 8: The Applicant argues Shi does not teach recycling.
Response: Examiner notes claim 1 does not require recycling. Recycling only occurs if an assessed parameter meets a predetermined threshold. Shi teaches continuous recirculation through multiple chambers. Therefore the art is interpreted to teach continuous recycling across multiple chambers. Nutrient-depleted can be removed. One of ordinary skill would recycle media since Shi teaches recirculation aids in the production of a large number of viable cells.
Argument 9: The Applicant argues Chang teaches spinoculation for transduction.
Response: Chang is not relied upon to teach transduction. Shi teaches transduction using a virus. Shi is silent as to whether the virus is inactive. Chang is relied upon because it teaches inactivate virus is used to transduce T cells.
Argument 10: The Applicant argues Crisman and Terumo do not cure the deficiencies of Murthy and Shi.
Response: Crisman and Terumo are not relied upon to teach the limitations recited in claim 1. Crisman is relied upon because it teaches washing the T cells with a buffer and flowing a cryopreservation medium into a chamber.
Murthy teaches a “sterile connection” moving fluid between chambers. Shi teaches a sterile tube to move fluid. Terumo is relied upon because it teaches a sterile tube welding.
CONCLUSION
No Claims Are Allowed
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE MOSS whose telephone number is (571) 270-7439. The examiner can normally be reached on Monday-Friday, 8am-5pm EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached on (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is (571) 273-8300.
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/NATALIE M MOSS/ Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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