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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 04/14/2026 was filed before the mailing date of the final action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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 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, 6-13, and 16-18 are rejected under 35 U.S.C. 103 as being unpatentable over Nishiyama et al (US20060040374A1 published 02/23/2006; hereinafter Nishiyama), as evidence by Verkouteren et al (Inkjet Metrology II: Resolved Effects of Ejection Frequency, Fluidic Pressure, and Droplet Number on Reproducible Drop-on-Demand Dispensing; published 08/02/2011), in view of Xu et al (US20150299730A1 published 10/22/2015; hereinafter Xu).
Regarding claim 1, Nishiyama a compound introduction apparatus for introducing a compound into a cell, comprising:
a cell suspension storage part (a feed controlling apparatus 130A – Fig. 2A-B) containing a cell suspension containing the compound (a capillary 143 of an injector 140 with gene and medication solutions – paragraph 57 and Figs. 2A-B) and the cell before introduction of the compound (the cells C before the capillary 143 of the injector 140 – Figs. 2A-B and paragraph 57);
a supply flow channel (a channel 131a – Fig. 2A) for supplying the cell suspension (the channel 131a holding the cells, genes, and medication solution – Fig. 2A and paragraph 59);
an introduction unit (the injector 140 comprising a drive unit 135 and the capillary 143 – paragraph 57 and Fig. 1) that includes an energy generation element (a drive unit 135 such as a piezoelectric element – paragraph 56 and Figs. 1, 4C) in a height direction of the supply flow channel (the drive unit 135 is capable of generating energy in a height direction of the channel 131a via friction – paragraph 56 and Figs. 1, 4C) and is configured to introduce the compound into the cell by applying at least mechanical energy generated by the energy generation element (the capillary 143 to inject genes and medication solutions into the cells – Fig. 2A and paragraph 59); and
an ejection port (a space between gates 133a/133b by cell C – Fig. 4B) for ejecting the cell suspension containing the cell in which the compound has been introduced (the gate 133a/133b controls the feeding of the cell C along the channel 131a – Fig. 4B and paragraph 55); and
a processing chamber (a groove 137 for each gate 133a/133b – Figs. 4A-C and paragraph 53) in which the energy generation element is arranged (the gate 133a/133b is arranged in the grooves 137 – Figs. 4A-C and paragraph 53),
wherein the ejection port is arranged directly below the energy generation element and the processing chamber (the space by cell C is directly below the gate 133a/133b and grooves 137 – Fig. 4B), wherein a height of the supply flow channel relative to a flow direction of the cell suspension flowing through the supply flow channel is more than 1.0 times a diameter of the cell to less than 2.0 times the diameter of the cell (the channel 131 has a width and height of 30 to 50 µm and the cell C has a diameter of 15 to 25 µm – Fig. 2A and paragraph 45), and a width of the supply flow channel relative to the flow direction is more than 1.0 times the diameter of the cell to less than 2.0 times the diameter of the cell (the channel 131 has a width and height of 30 to 50 µm and the cell C has a diameter of 15 to 25 µm – Fig. 2A and paragraph 45),
wherein a diameter of the ejection port is more than 1.0 times the diameter of the cell to less than 2.0 times the diameter of the cell (the space between the gate 133a/133b is the same dimension as the channel 131a when the gate 133a/133b is opened; therefore, the space has a width and height of 30 to 50 µm while the cell C has a diameter of 15 to 25 µm – Fig. 4B and paragraph 56),
wherein the supply flow channel is configured to supply the cell suspension from the cell suspension storage part to the ejection port (the channel 131a supplies cells from the recovery part to space between the gates 133a/133b – Fig. 2B and paragraph 14).
However, Nishiyama does not teach wherein the energy generation element is (i) a heat generation element configured to introduce the compound into the cell by bubbles generated in the cell suspension by heat from the heat generation element, or (ii) a piezoelectric element configured to introduce the compound into the cell by exerting a mechanical action on the cell suspension through displacement of the piezoelectric element.
Xu teaches a method using thermal inkjets (paragraph 54) for transfecting cells comprising an energy generation element that is a heat generation element (heating element – paragraph 54 and Fig. 1) configured to introduce the compound into the cell by bubbles generated in the cell suspension (the heating element creates ink bubble that apply shear stress to facilitate the transfer of compounds of interest into the cells – Fig. 1 and paragraph 36, 45) by heat from the heat generation element (a heating element vaporizes ink to create a bubble – Fig. 1 and paragraph 50). Xu teaches to use the inkjet and z-axis module for higher cell viability after transfection (paragraph 17).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the transfection system, as taught by Nishiyama, with the inkjet, taught by Xu, to gain higher cell viability after transfection. One of ordinary skill would have expected that this modification could have been performed with a reasonable expectation of success because Nishiyama and Xu teach cell transfection systems.
Regarding claim 3, Nishiyama, modified by Xu, teaches the compound introduction apparatus according to claim 1, wherein the introduction unit is the heat generation element (the heating element creates ink bubble that apply shear stress to facilitate the transfer of compounds of interest into the cells – Fig. 1 and paragraph 36, 45 – Xu paragraph 36, 45).
Regarding claim 6, Nishiyama, modified by Xu, teaches the compound introduction apparatus according to claim 4, wherein in a case where the heat generation element generates heat (a heating element vaporizes ink to create a bubble – Xu Fig. 1 and paragraph 50), a stress resulting from bubble generation caused by the heat generation is applied to the cell suspension inside the processing chamber (the heating element creates ink bubble that apply shear stress to facilitate the transfer of compounds of interest into the cells – Fig. 1 and paragraph 36, 45 – Xu paragraph 36, 45).
Regarding claim 7, Nishiyama, modified by Xu, teaches the compound introduction apparatus according to claim 6, wherein the stress is exerted for 1µs to 10µs (shear stress applied for a limited period of time of 0.5 to 10 microseconds – Xu paragraph 36) and consequently a droplet of the cell suspension is discharged from the ejection port at a speed of 0.5 m/s to 30 m/s (Nishiyama, modified by Xu, teaches a thermal inkjet and is capable of discharging a droplet of cells at a speed of 0.5 m/s to 30 m/s – Xu paragraph 54) (As evidenced by Verkouteren inkjet produce ejections velocities between 0.5-8 m/s – Verkouteren Fig. 3).
Regarding claim 8, Nishiyama, modified by Xu, teaches the compound introduction apparatus according to claim 3, wherein a time for which the heat generation element generates heat is 0.1 µs to 5 µs (the cells are exposed to heat for a limited period of time e.g., from 10−5 to 10−7 seconds – Xu paragraph 40).
Regarding claim 9, Nishiyama, modified by Xu, teaches the compound introduction apparatus according to claim 1.
However, Nishiyama (Fig. 4B), modified by Xu, does not teach wherein the diameter of the ejection port is larger than the height of the supply flow channel.
Nishiyama (Fig. 11) teaches another embodiment wherein the diameter of the ejection port is larger than the height of the supply flow channel (the nozzle 182 to simultaneously supply a predetermined number of cells – paragraph 71) (the nozzle 182 is wider that the pipeline 177b because the pipeline 177b is not wide enough to simultaneously supply multiple cells – Fig. 11). Nishiyama (Fig. 11) teaches to use a nozzle to move and store the cells in a treatable unit to confirm the cloning of the cell and effect expressions of introduced gene and medication (paragraph 71).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the device, as taught by Nishiyama (Fig. 4B) as modified by Xu, with a nozzle to move and store the cells, taught by Nishiyama (Fig. 11), to confirm the cloning of the cell and effect expressions of introduced gene and medication. One of ordinary skill would have expected that this modification could have been performed with a reasonable expectation of success because Nishiyama teaches multiple embodiments of the same invention.
Regarding claim 10, Nishiyama, modified by Xu, teaches the compound introduction apparatus according to claim 1, wherein the diameter of the cell is 1 µm to 100 µm (the channel 131 has a width and height of 30 to 50 µm and the cell C has a diameter of 15 to 25 µm – Fig. 2A and paragraph 45).
Regarding claim 11, Nishiyama, modified by Xu, teaches the compound introduction apparatus according to claim 1, wherein the height and the width of the supply flow channel are each more than 1 µm and less than 200 µm (the channel 131 has a width and height of 30 to 50 µm and the cell C has a diameter of 15 to 25 µm – Fig. 2A and paragraph 45).
Regarding claim 12, Nishiyama, modified by Xu, teaches the compound introduction apparatus according to claim 1, wherein the cell is a eukaryotic cell (biogenetic cells, such as leukocytes' antibody generation – Nishiyama paragraph 2) (the examiner points out that leukocytes are eukaryotic cells).
Regarding claim 13, Nishiyama, modified by Xu, teaches the compound introduction apparatus according to claim 1, wherein the height of the supply flow channel is a length (the channel 131 has a width and height of 30 to 50 µm and the cell C has a diameter of 15 to 25 µm – Fig. 2A and paragraph 45) thereof in a direction of gravity (the height of the channel 131 is in the direction of gravity – Fig. 2A).
Regarding claim 16, Nishiyama, modified by Xu, teaches the compound introduction apparatus according to claim 1, wherein the height of the supply flow channel relative to the flow direction is more than 1 µm to less than 200 µm (the channel 131 has a width and height of 30 to 50 µm and the cell C has a diameter of 15 to 25 µm – Fig. 2A and paragraph 45), and the width of the supply flow channel relative to the flow direction is 1 µm to less than 200 µm (the channel 131 has a width and height of 30 to 50 µm and the cell C has a diameter of 15 to 25 µm – Fig. 2A and paragraph 45).
Regarding claim 17, Nishiyama, modified by Xu, teaches the compound introduction apparatus according to claim 1, wherein the diameter of the ejection port is 15 µm to 23 µm (the space between the gate 133a/133b is 5 to 10 µm when the 133a/133b are closed – paragraph 56) (the space between the gate 133a/133b is the same dimension as the channel 131a, 30 to 50 µm, when the gate 133a/133b is fully opened; therefore, there is a period of time while the gates are opening such that the space between the gates is between 15 µm to 23 µm – Fig. 4B and paragraph 56).
Regarding claim 18, Nishiyama, modified by Xu, teaches the compound introduction apparatus according to claim 1, wherein the cell suspension storage part is detachably configured with respect to a main body of the compound introduction apparatus (the feed controlling apparatus 130A is capable of being detached from the injector 140 by disconnecting a pipeline 102 – Fig. 1 and paragraph 41).
Response to Arguments
Point 1: The applicant’s argument that “Nishiyama fails to disclose or suggest a compound introduction apparatus with the claimed energy generation element, which is (i) a heat generation element configured to introduce the compound into the cell by bubbles generated in the cell suspension by the heat from the heat generation element” is not persuasive.
Applicant’s addition arguments with respect to the 102 rejections of the claims have been considered, and the prior art rejection has been modified in order to address the amended claim language. Nishiyama, modified by Xu, teaches a heat generation element configured to introduce the compound into the cell by bubbles generated in the cell suspension by the heat from the heat generation element (a heating element vaporizes ink to create a bubble – Xu Fig. 1 and paragraph 50).
Point 2: The applicant’s argument that “Nishiyama does not disclose or suggest arranging the ejection port directly below the energy generation element and the processing chamber” is not persuasive.
Applicant’s addition arguments with respect to the 102 rejections of the claims have been considered, and the prior art rejection has been modified in order to address the amended claim language. Nishiyama, modified by Xu, teaches the space by cell C is directly below the gate 133a/133b and grooves 137 (Nishiyama Fig. 4B).
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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
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/T.C.S./Examiner, Art Unit 1796
/CHARLES CAPOZZI/Supervisory Patent Examiner, Art Unit 1798
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