DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-9) in the reply filed on Sept. 15, 2025 is acknowledged. Claims 10-13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 10-13 are withdrawn.
Claims 1-9 are examined below.
Priority
The instant application claims foreign priority 35 U.S.C. 119(a)-(d) to Japanese Patent App. No. JP2021-200173 and JP2022-193110, filed on Dec. 9, 2021 and Dec. 1, 2022, respectively.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Thus, the earliest possible priority for the instant application is Dec. 9, 2021.
Information Disclosure Statement
The information disclosure statement filed Dec. 7, 2022 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS has been considered by the examiner.
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.
Claim 6 is 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 6 recites “wherein the cell to be processed is a cell selected from the cell group through a mesh filter,” which does not make sense.
For the purpose of examination, the claim is interpreted as reciting “selected from the cell group that has been processed through a mesh filter”.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
Claim(s) 1-9 are rejected under 35 U.S.C. 103 as being unpatentable over Xu et al. (U.S. Patent App. No. 2010/0160183 A1, cited in the IDS filed on Dec. 7, 2022) in view of Migita et al. (Anal Methods, 2010), as evidenced by Jones (Phil. Trans R Soc B, 2019) for claim 7.
The claims are directed to methods of introducing a target substance into a cell by preparing a cell suspension with the cell and the target substance and using shear force. The cells used are proliferating cells where the cells have been size selected to have a diameter that is larger than the mode of the group of proliferating cells.
With respect to independent claim 1, Xu et al. teach transfection of cells using shear stress applied through inkjet printing to introduce nucleic acids, proteins, nanoparticles, molecules or drugs to the cell. (Abstract). More specifically, Xu et al. teach that during the nozzle firing in the print head, compounds of interest are transferred into the living cells and that the compounds of interest and cells (“cell suspension”) are either loaded into the ink cartridge together or they are premixed prior to loading. (para. [0053]).
Xu et al. do not teach that the cells are from a group of cells in a proliferation process and that the selected cell has a diameter larger than a mode in a cell diameter distribution of the group of cells.
Migita et al. teach that mammalian cells can be size sorted using a microfluidic device to enable noninvasive cell cycle synchronization. (Abstract). Migita et al. further teach that “[t]he damage-free separation of living cells in different phases of the cell cycle represents a potentially promising technology for the investigation of gene transfection and gene expression.” (Abstract, see also pg. 660 “Conclusion”). While cell cycle synchronization based on size separation depends on the specific cell type, it can be used to synchronize the phase of the cell cycle based on the relationship between cell size and cell cycle phase. (pg. 660, 1st col. 1st and 2nd full para.).
It would have been obvious for one of ordinary skill in the art at the time of the effective filing date to have tried modifying the cell transfection method taught by Xu et al. to incorporate a size separation step to synchronize the phase of the cell cycle (as taught by Migita et al.) because it would have been obvious to combine prior art elements according to known methods to yield predictable results. Incorporating this modification would have led to predictable results with a reasonable expectation of success because both Xu et al. and Migita et al. address transfection of cells. Therefore, trying the transfection technique taught by Xu et al. after using the size/cell cycle separation technique taught by Migita et al. would enable researchers to understand which phase of cell cycles are best suited to transfection of specific genetic material, proteins or drugs. It further would have been obvious to choose a cell/cells with a diameter that is larger than the mode of cell diameter in a proliferating cell group size (see e.g. Migita et al., Fig. 2, Outlet 2) in order to determine if cells that were larger than average provide better transfection for specific nucleic acids or proteins, as the person of ordinary skill would be choosing from a finite number of identified, predictable solutions with a reasonable expectation of success.
With respect to claim 2, it would have been obvious to have selected a cell with a diameter that is 1.3 or more times the mode of the cell group, as Migita et al. teach that the size separation they used produces this level of separation, which correlates with cell cycle. (see e.g. Fig. 2, Outlet 2).
With respect to claim 3, Yu et al. teach that the shear stress is provided by the orifice when the cell suspension is forced through it. (para. [0011]).
With respect to claim 4, Yu et al. teach that the orifice is part of a liquid ejection head and introduction of the target substance into the cell is performed by ejecting the suspension from the head. (Fig. 1, [0016], [0053]).
With respect to claim 5, Yu et al. teach that a plurality of nozzles can be provided and that the nozzles can have different diameters or sizes (paras. [0055]-[0059]), rendering obvious the claimed modification in light of Migita et al. teaching that size separation to sync cell cycle is a desirable outcome prior to transfection.
With respect to claim 6, Migita et al. teach that the cell suspension can be strained through a mesh filter. (pg. 658, “Cell preparation”).
With respect to claim 7, Migita et al. teach that the cells are taken from a group of adherent cells. (pg. 660, 1st col., 1st partial para. “Thus, two different types of adherent mammalian cel (HepG2 and NIH/3T3 cell lines) were successfully separated depending on their size using the microfluidic device.”). As evidenced by Jones et al., cells that are in different cell cycle stages have different adherent properties (pg. 2-3 “Links between the cell-cycle machinery and adhesion (a) Cell adhesion changes in a cell-cycle-dependent manner”). Therefore, selecting the cell by its size (which is related to its cell cycle) would inherently have selected a cell that had a change in adherence.
With respect to claims 8 and 9, Yu et al. teach the target substance is a protein or a nucleic acid. (Abstract).
Conclusion
No claims are allowed.
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/TERESA E KNIGHT/Primary Examiner, Art Unit 1634