Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 03 April 2025 has been entered.
DETAILED OFFICE ACTION
This Office Action is in response to the papers filed on 10 December 2024.
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WITHDRAWN REJECTIONS
The previous rejections have been withdrawn due to claim amendment.
NEW GROUNDS OF REJECTION
New grounds of rejection have been necessitated by claim amendment.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-3, 7-9, 12-15, 17-19 and 22-23 are rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter.
.
Based on the claims as a whole, claims 1-3, 7-9, 12-15, 17-19 and 22-23 are determined to be directed to a law of nature/natural principle. The rationale for the determination is explained below.
Claim 1 is directed to an automated method for producing transduced T cells in a closed system.
Question 1: Is the claim to a process, machine manufacture or composition of matter? Yes, the invention recited in claim 1 is a process.
Question 2A Prong 1: Is the claim directed to a law of nature, a natural phenomenon, or an abstract idea (judicially recognized exceptions)? Yes, claim 1 is directed to a law of nature.
(a) The limitations in the claim that set forth the law of nature is:
The 2019 PEG explains that the abstract idea exception includes the following groupings of subject matter:
Mathematical concepts – mathematical relationships, mathematical formulas or equations, mathematical calculations;
Certain methods of organizing human activity – fundamental economic principles or practices (including hedging, insurance, mitigating risk); commercial or legal interactions (including agreements in the form of contracts; legal obligations; advertising, marketing or sales activities or behaviors; business relations); managing personal behavior or relationships or interactions between people (including social activities, teaching, and following rules or instructions); and
Mental processes – concepts performed in the human mind (including an observation, evaluation, judgment, opinion).
Claim 1 has been amended to require continuously flowing the cell culture medium by
assessing one or more parameters of the used cell culture medium and recycling if the parameters meet a predetermined threshold.
The PG Pub of the specification discloses the parameter can be a concentration of a compound, pH or cell number ([0032] [0131]). The specification teaches information is displayed visually to a user ([0141]). The specification discloses a system with a video display unit ([0150]). Therefore the assessment can be made by viewing automated data on a screen and making a mental determination. Mental observations and evaluations fall within the “mental processes” grouping of abstract idea set forth in the 2019 PEG. 2019 PEG Section I, 84 Fed. Reg. at 52. Medium is recycled if the parameters meet a predetermined threshold. This is a mathematical equation, and a judicial exception
Question 2A Prong 2: Does the claim recite additional elements that integrate the judicial exception into a practical application? No. While claim 1 recites flowing a suspension of T cells into the first culture chamber, perfusing the cells, transducing the cells, flowing media into the first chamber and transferring cells to the second chamber, these are necessary steps required to perform the judicial exceptions.
Question 2B: Do the claims recite any additional elements? Yes.
With respect to Step 2B, limitations that were found to be enough to qualify as “significantly more” when recited in a claim with a judicial exception include:
Improvements to another technology or technical field.
Improvements to the functioning of the computer itself.
Applying the judicial exception with, or by use of, a particular machine.
Effecting a transformation or reduction of a particular article to a different state or thing
Adding a specific limitation other than what is well-understood, routine and conventional in the field, or adding unconventional steps that confine the claim to a particular useful application.
Other meaningful limitations beyond generally linking the use of the judicial exception to a particular technological environment.
With respect to Step 2B, limitations that were found not to be enough to qualify as “significantly more” when recited in a claim with a judicial exception include:
Adding the words ‘‘apply it’’ (or an equivalent) with the judicial exception, or mere instructions to implement an abstract idea on a computer
Simply appending well-understood, routine and conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, e.g., a claim to an abstract idea requiring no more than a generic computer to perform generic computer functions that are well understood, routine and conventional activities previously known to the industry
Adding insignificant extrasolution activity to the judicial exception, e.g., mere data gathering in conjunction with a law of nature or abstract idea
Generally linking the use of the judicial exception to a particular technological environment or field of use.
Does the additional element result in the claim amounting to significantly more?
No.
Regarding claim 1: As set forth above, the additional steps recited in claim 1 (flowing a suspension of T cells into the first culture chamber, perfusing the cells, transducing the cells, flowing media into the first chamber and transferring cells to the second chamber) are necessary steps that are required to perform the judicial exceptions now recited in claim 1.
Regarding claim 2: the limitations directed to chamber size do not result in significantly more than the recited judicial exceptions.
Regarding claim 3: the limitations directed to chamber material do not result in significantly more than the recited judicial exceptions.
Regarding claims 7 and 14-15: the recitation of a sterile vessel and tube does not result in significantly more than the recited judicial exceptions.
Regarding claim 8: the amount of medium flowed into the first culture chamber does not result in significantly more than the recited judicial exceptions.
Regarding claim 9: The claim recites how T cells are activated. The additional method steps are not performed in response to the judicial exceptions, but are required necessary data gathering step in order to make the assessments now required in claim 1.
Regarding claims 12-13: Washing and cryopreserving (claim 12) and harvesting cells (claim 13) cells is well known, routine and conventional in the art (as evidenced by Shi). The steps do not result in more than the recited judicial exceptions.
Regarding claims 17-19 and 22-23: The claims are directed to perfusion, transduction and culture of the cells in the first chamber. The additional method steps are required in order to make the assessments now required in claim 1.
Therefore claims 1-3, 7-9, 12-15, 17-19 and 22-23 are not eligible subject matter under 35 USC 101.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-3, 7-9, 12-15, 17-19 and 22-23 are rejected 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.
The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 recites “flowing a suspension comprising activated T cells into the first gas-impermeable culture chamber”. Therefore T cells are activated before being flowed into the first chamber. The claim also recites the activated T cells are perfused with a soluble activation agent. The speciation states T cells are activated using an activation reagent (page 7, lines 11-12). As written, claim 1 encompasses subjecting activated T cells to a second activation in the first chamber.
The specification discloses T cells are activated in the first culture chamber (page 5, line 23). In another embodiment, the specification discloses activated T cells from another connected chamber are flowed into the first chamber to contact the DCs and further culture the T cells (see page 28, lines 19-22). The specification does not provide support for flowing activated T cells into the first chamber, and treating them with an activation reagent.
A consideration of the four corners of the specification does not reflect that applicants have actually invented the claimed invention. All dependent claims are included in this rejection.
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 cell culture chamber”. There is a lack of antecedent basis for “the cell culture chamber”. It is unclear what chamber the claim is referring to. The metes and bounds of the claim are unclear. Appropriate correction is required. All dependent claims are included in this rejection.
Claim 1 recites flowing a suspension comprising activated T cells into the first gas-impermeable culture chamber. This is interpreted to mean the T cells flowing into the first chamber are already activated. The claim recites “perfusing the activated T cells in the first chamber with a soluble activation agent”. The specification states T cells are activated using an activation reagent (page 7, lines 11-12). It is unclear if the claim means T cells that have already been activated are flowed into the first reactor and perfused with a soluble activation reagent for a second activation. The metes and bounds of the claim are unclear. 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 Shi et al. (previously cited; End-To-End Cell Therapy Automation. US Patent 11447745, Published 06 June 2019) in view of 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) and Murthy et al. (previously cited; Cell Culture Chambers And Methods Of Use Thereof. WO2018/005521 04 January 2018) and
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 or retroviral 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 a system comprises a plurality of chambers (column 15, lines 18-52). The chambers comprise an inlet port and a port for cell removal (hence, an outlet) (column 29, lines 15-19). 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). It is noted Shi teaches activating an immune cell (T cell) in a first chamber and transferring the activated cell from the first chamber to a second chamber (see column 2, line 60 bridging line 3 of column 3).
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). One or more pumps moves fluid through the system (column 28, lines 10-12). Pumps are used to transfer cells (column 54, line 41).
Shi teaches a satellite volume fluidically connected to a cell culture chamber for providing additional media (column 3, lines 25-30; column 29, lines 24-34). The satellite volume is a bag (column 29, lines 24-34). The satellite volume is interpreted to be a fluid reservoir. The art teaches multiple bags to contain various reagents and waste (column 47, lines 32-33). A bag for waste is interpreted to be a waste reservoir.
Shi teaches a system that continuously recirculates media throughout the chambers without disturbing the cells. The continuous circulation can improve the uniform distribution of positive factors and uniform removal of negative factors, which reduces localized effects that are caused by uneven distribution, without disturbing the cells (column 30, line 61, bridging line 3 of column 31).
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 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).
Shi teaches an automated method of producing T cells comprising:
activating T cells;
transducing activated T cells with a soluble activation agent comprising a virus expressing CAR; and
expanding T cells.
Shi teaches perfusion and continuous recirculation.
Shi teaches a closed, automated system comprising multiple chambers, pumps, fluid reservoirs and waste reservoirs.
The deficiencies of Shi are:
Shi does not explicitly teach recycling as recited in claim 1.
While Shi teaches the use of the use of a virus expressing CAR, the art is silent as to whether it is “inactive”.
Shi does not teach interchangeable chambers that are received and retained on a substrate.
Shi does not teach chambers of different shapes and/or sizes.
Shi does not teach the chamber material recited in claim 1.
Shi does not teach the first and second chamber are connected to a separate pump.
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).
Murthy et al. disclose an invention that provides “cell culture chambers and methods of use thereof” (Abstract). The cell culture 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). Murthy teaches a closed environment (hence, a closed system) (page 10, lines 4-5).
The system can include 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). Murthy teaches reactors (chambers) of different shapes (see Figures 4A-D). 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.
Murthy teaches the following regarding chamber material:
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.
As set forth by the specification, 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 polystyrene surface for T-cell stimulation is tremendously valuable from a bioprocess standpoint as it eliminates a large number of transfer steps , allowing for a closed system (see line 26 page 10 through line 2 of page 11).
The following is also taught by Murthy:
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). Each chamber comprises an inlet and outlet which fluidically couple the chamber via a fluidic connector with one additional vessel(s) (page 15, lines 1-3; Figure 3). Murthy teaches “the cell culture chamber further includes 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 chamber” (page 4, lines 20-22). The cell culture chambers are connected via a sterile connection (page 15, lines 10-11).
Murthy teaches waste fluid reservoirs (page 10, lines 15-16). Pumps move fluids between the chambers and the reservoirs (page 10, lines 14-19). Murthy teaches each bioreactor includes its own fluid and waste collection reservoirs, pumps, and associated tubing (page 15, lines 22-23).
Murthy teaches expansion and stimulation of T-cells using autologous antigen presented cells (Abstract). The art teaches the use of dendritic cells as antigen presenting cells (page 5, fourth paragraph). As evidenced by Shi et al., dendritic cells activate T cells (see claim 1 of Shi; see Figure 1). Therefore stimulation with a dendritic cells, as taught by Murthy, is interpreted to read on activation.
Figure 2 teaches antigen-presenting cells and peripheral mononuclear blood cells are provided to a cell culture chamber (step 1). The Figure teaches “perfusion fluid is perfused to the chamber”. The reference teaches the use of pumps to supply medium to the chamber (page 4, lines 20-22). Therefore the art teaches perfusion with one or more pumps. Because Step 2 discloses coculturing produces expanded T cells, “peripheral mononuclear blood cells” are interpreted to be a suspension comprising T cells. Examiner notes Figure 2 discloses a cell culture in Step 1 and a “subsequent cell culture chamber” in Step 3. Therefore the art teaches a first and a second cell culture chamber. It is of note the art teaches T cells are partially expanded in the first culture chamber (page 7, lines 20-21).
Murthy teaches the devices of the invention can include reagents (see page 22, line 30).
Murthy teaches the following (page 116, lines 5-8):
In certain embodiments, 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.
It would have been obvious to remove culture medium, assess a parameter in the medium and recycle at least a portion of the medium if the parameter(s) meet a predetermined threshold. The skilled artisan would have monitored the parameters taught by Shi (e.g., oxygen, carbon dioxide, optical density) to improve uniform distribution of positive factors and uniform removal of negative factors during 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.
It would have been obvious to use an inactive virus. One would have been motivated to do so since Shi uses a virus for transduction and Chang teaches self-inactivated viruses are 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 perform the method taught by Shi in a system comprising components taught in Murthy. Shi produces therapeutic T cells and Murthy produces therapeutic cells by culturing in a system comprising multiple interchangeable gas-impermeable chambers, each connected to its own pump and reservoirs. One would have been motivated to do so to eliminate a large number of transfer steps, as taught by Murthy. One would have expected similar results since both references are directed to methods of making therapeutic T cells. 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. As such, the antigen-presenting cells will remain within the culture chamber because of their mass. In other words, 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 Shi in view of Chang and Murthy et al. 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. 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 cab 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 Shi in view of Chang and Murthy as 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. The art teaches sterile tubing in a closed, sterile system. 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 process cells obtained from blood (hence, blood components). Therefore claim 15 is rendered obvious.
Therefore Applicant’s invention is rendered obvious as claimed.
APPLICANT’S ARGUMENTS
The arguments made in the response filed on 03 April 2025. The Applicant argues the cited references do not teach the amended claim limitations. New grounds of rejection have been set forth above.
Conclusion
No claims are allowed.
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) 270-8439.
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/NATALIE M MOSS/ Examiner, Art Unit 1653