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 .
Status of Application, Amendments, And/Or Claims
The Applicants amendments/remarks received 10/23/2026 are acknowledged. Claims 1-2, 5, 8, 25-26, 28-29 and 32 are amended; claims 4, 6-7, 9-24 are canceled; no claims are withdrawn; claims 35-40 are new; claims 1-3, 5, 8 and 25-40 are pending and have been examined on the merits.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994)
The disclosure of the prior-filed application, Provisional Application No. 62575669, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Specifically, 62575669 does not disclose that the electroporation electrodes are driven with an electric field generator and an amplifier; that the device comprises an arbitrary waveform generator configured to drive the electroporation electrodes; does not disclose measuring a current flow between the electroporation electrodes; does not disclose buffer switching by moving cells from a first fluid that is a cell incubation fluid to a second fluid that is an electroporation fluid; does not disclose any digital to analog converter and does not disclose imaging the cells in the microchannel system; thus, 62575669 fails to provide adequate support or enablement for claims 5, 26-27, 30, 35-36 and 38. The effective filing date for claims 1-3, 8, 25, 28-29, 31-34, 37 and 39-40 is the filing date of 62575669, 10/23/2017; the effective filing date of claims 5, 26-27, 30, 35-36 and 38 is the filing date of parent application 16168464, 10/23/2018.
Response to Arguments
Applicant's arguments filed 10/23/2026 have been fully considered but they are not persuasive. Regarding priority document support for claims 28-29 and 32 (Remarks, pp. 7-8), the amendment of claims 28-29 and 32 makes claims 28-29 and 32 consonant with the provisional application; hence, their effective filing date is 10/23/2017 as detailed above. The effective filing date of claims 5, 26-27, 30, 35-36 and 38 is the filing date of parent application 16168464, 10/23/2018, because the provisional application does not disclose that the electroporation electrodes are driven with an electric field generator and an amplifier; that the device comprises an arbitrary waveform generator configured to drive the electroporation electrodes; does not disclose measuring a current flow between the electroporation electrodes; does not disclose buffer switching by moving cells from a first fluid that is a cell incubation fluid to a second fluid that is an electroporation fluid; does not disclose any digital to analog converter and does not disclose imaging the cells in the microchannel system.
Claim Rejections - 35 USC § 112
The rejection of claim 28 under 35 U.S.C. § 112(a), as set forth at pp. 4-6 of the previous Office Action, is withdrawn in view of the amendment of the claim.
The rejection of claim 25 under 35 U.S.C. § 112(b), as set forth at p. 6 of the previous Office Action, is withdrawn in view of the amendment of the claims.
Claim Rejections - 35 USC § 103
The rejection of claims 1, 3, 25-28 and 31-34 under 35 U.S.C. § 103(a) over Kaduchak et al., US 2013/0292582 (cite B, PTO-892, 8/14/2024; herein “Kaduchak”) as set forth at pp. 8-13 of the previous Office Action, is withdrawn in view of the amendment of the claims.
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 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.
Claims 1, 3, 8, 25-28, 31-34 and 36-40 are rejected under 35 U.S.C. 103 as being unpatentable over Kaduchak et al., US 2013/0292582 (cite B, PTO-892, 8/14/2024; herein “Kaduchak”) in view of Rabbitt et al., US 2005/0118705 (cite A, attached PTO-892; herein “Rabbitt”).
NOTE: Claims 1-3, 5, 8 and 25-40 are drawn to an apparatus NOT a method. Intended use limitations in apparatus claims, for example, in independent claim 1, “configured to flow the cells between electroporation electrodes to deliver the payload into the cells” describing the intended use of the microchannel system, “configured to receive spent cargo/solution downstream of the electroporation electrodes” describing the intended use of two or more channels, “configured to focus the cells between the electroporation electrodes” describing the intended use of the acoustic transducer and “configured to detect the presence of cells in the microchannel system” describing the intended use of the sensing module, are met when the apparatus COULD be used for the intended method and do not require that the prior art teach the intended method.
Kaduchak teaches systems and methods for manipulating particles, which may be cells [0014], in the channels, i.e., microchannels, of the system (Abst.), wherein the method can comprise applying acoustic radiation pressure to move particles from a first laminar flow fluid to a second laminar flow fluid [0012-14], wherein the second fluid can be in the center of the channel [0013] and can be loaded with reagent for electroporation into cells ([0014], [0191-193]), i.e., an electroporation fluid, and the first fluid can be cell incubation fluid [0016].
Kaduchak teaches embodiments (Fig. 8; [0121]) for a device for laminar flow, sheath flow and buffer switching, such as is used in Kaduchak’s method of electroporation, wherein cells (801) are introduced into input channels of a tripartite input and reagent fluid (802), e.g., electroporation reagent, is introduced into a channel of the tripartite input; acoustic transducer (811), attached to a substrate in which the microchannel subsystem is formed, generates an acoustic radiation force, comprising a stable standing pressure wave across the width of the main channel ([0035], [0088-94], [0099], [0105], [0114], [0155]; Fig. 11), to precisely localize the cells to the center of the microchannel, thereby transferring the cells from the original fluid, e.g. cell incubation fluid, to the electroporation reagent fluid, wherein the cells exit through the center channel of a tripartite channel and waste solution exits through the outer outlets of the tripartite outlet.
Kaduchak shows a device for fusing hybridoma cells (Fig. 24) wherein an acoustic transducer (2411), attached to a substrate in which the microchannel subsystem is formed, generates an acoustic radiation force, comprising a stable standing pressure wave across the width of the main channel ([0035], [0088-94], [0099], [0105], [0114], [0155]; Fig. 11), to precisely localize the cells to the center of the microchannel, then the cells pass through electroporation electrodes (2413) to effect the fusion of the cells.
Kaduchak teaches that the system can also be for the detection, i.e., sensing, of cells passing through the channel by acoustically focusing the particles, i.e., cells, and flowing them between two electrodes through which current flows and detecting the impedance induced by the passage of the cell ([0023], [0054], [0265-268]; Fig. 14).
Kaduchak teaches that the device for practicing the method of sensing cells (Fig. 14) comprises an acoustic transducer (1413), attached to a substrate in which the microchannel subsystem is formed, generates an acoustic radiation force, comprising a stable standing pressure wave across the width of the main channel ([0035], [0088-94], [0099], [0105], [0114], [0155]; Fig. 11), to precisely localize the cells to the center of the microchannel, then the cells pass through sensing electrodes (1415) attached to electronics for detecting the signal (1417) from the sensing electrodes, i.e., a sensing module, to sense the cells.
Thus, Kaduchak teaches systems and methods for sensing cells in a microchannel using a sensing module comprising sensing electrodes and systems and methods for acoustically focusing and electroporating cells in a microchannel, but does not explicitly teach that the device is capable of energizing the electroporation electrodes in response to sensing the presence of cells; however, a person of ordinary skill in the art at the time of filing would have found it obvious for the sense electrodes to be located upstream of the electroporation electrodes and for the device to be capable of energizing the electroporation electrodes in response to sensing the presence of cells in view of the disclosure of Rabbitt.
Rabbitt teaches devices and methods for sensing particles in a microchannel and for electroporating cells in a microchannel (Abst.) wherein the sensing and electroporating can be in the same microchannel wherein the detection zone and electroporation zone are distinct from each other [0015], wherein a first pair of electrodes senses the presence of a cell in the microchannel and a second pair of electrodes downstream from the first pair of electrodes is used to effectuate electroporation ([0019], [0036]; Figs. 13-14) and wherein the sensing of the cells with the sensing electrodes triggers the electroporation with the electroporation electrodes ([0021], [0070-71], [0084]; Figs. 13-14). Rabbitt is clear that the sensing electrodes can be oriented transversally to the flow in the microchannel ([0029], Fig. 7; [0059], [0064-65], Fig. 5; [0081]) wherein the sense electrodes are upstream of the electroporation electrodes and detecting the presence of a cell by the sensing electrodes triggers the electroporation ([0015], [0019]). Rabbitt teaches that the device comprises the controllers, waveform generators and amplifiers necessary to effectuate Rabbitt’s methods ([0074], [0081]).
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to produce the device made obvious by Kaduchak in view of Rabbitt for acoustically focusing and electroporating cells comprising a microchannel system, electroporation electrodes, outlet channels downstream of the electroporation electrodes, an acoustic transducer before the electroporation electrodes and a sensing module, comprising sense electrodes separated orthogonal to the direction of cell flow, i.e., transversal to the flow in the microchannel, employed by the sensing module for detecting the presence of cells in the microchannel system wherein the sense electrodes are located upstream of electroporation electrodes separated orthogonal to the direction of cell flow, i.e., transversal to the flow in the microchannel, and a controller that energizes the electroporation electrodes in response to sensing the presence of cells, wherein the microchannel system could be used for flowing the cells between electroporation electrodes to facilitate delivery of a payload into the cells, the two or more channels could be after the electroporation electrodes for receiving spent cargo/solution downstream of the electroporation electrodes, wherein the acoustic transducer is used for focusing the cells between the electroporation electrodes; and the sensing module is used for detecting the presence of cells in the microchannel system to trigger the electroporation; therefore, claims 1, 3, 8, 25, 28, 31-34 and 36-40 are prima facie obvious.
Kaduchak teaches that the acoustically focused cells in microchannel systems can be imaged to determine the location of cells within the microchannel ([0020], [0117]; [0106-8], Figs. 6A-C; [0166-9], Figs. 21A-B; [0173], [0063], Fig. 23). Kaduchak demonstrates that the imaging allows the location of cells in the channel to be determined, e.g., whether the cell is in the center stream of the channel or not ([0106-8], Figs. 6A-C; [0173], [0063], Fig. 23). In the context of electroporation, Kaduchak teaches that the single line focusing (i.e. focusing the cells acoustically to the center line of the microchannel) allows precise control of the electroporation field parameters that the individual cell is exposed to [0193]; hence, imaging the location of the cells in the channel in an inter-electrode region between the electroporation electrodes would allow confirmation that the cells are appropriately positioned allowing for the fine control of the electroporation field parameters that the cell experiences.
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious for the device made obvious by Kaduchak in view of Rabbitt to further comprise an image capturing device for capturing images of the cells in the microchannel system and analyzing the images to determine the locations of the cells wherein the images are captured of an inter-electrode region between the electroporation electrodes; therefore, claims 26-27 are prima facie obvious.
Response to Arguments
Applicant's arguments filed 10/23/2026 have been fully considered but they are not persuasive. Arguments of the Applicant’s Response on pp. 6-8 regarding the rejections under 35 U.S.C. §§ 112(a), 112(b) and 103 over Kaduchak are moot as the rejections have been withdrawn.
Regarding the rejection of claims 1, 3, 6-8, 25-28 and 31-34 under 35 U.S.C. 103 over Kaduchak in view of Rabbitt, Applicant alleges (Remarks, pp. 8-11) that Rabbitt, citing Figs. 13-14, teaches that the sense electrodes are axially aligned, i.e., along the flow path of the microchannel, wherein the electroporation electrodes are between the sense electrodes rather than following the sense electrodes along the flow path of the microchannel. This is unpersuasive that the instant invention is not obvious over Kaduchak in view of Rabbitt because Figs. 13-14 are but embodiments of the teachings of Rabbitt and do not comprise the full scope of the disclosure of Rabbitt. As set forth in the rejection above, Rabbitt clearly teaches that the sense electrodes can be arranged where the direction between them is transverse to the flow of cells in the microchannel, i.e. wherein the sense electrodes are separated in the direction that is orthogonal to the direction of cell flow in the microchannel system, and wherein the sense electrodes can be upstream of the electroporation electrodes, i.e., a sensing module comprising sense electrodes upstream of each of the electroporation electrodes and configured to detect the presence of cells in the microchannel system. Hence, Applicant’s arguments are unpersuasive and the rejection is maintained with modification to address the amended claims, new claims and for clarity.
Claims 1-3, 5, 8, 25-29 and 31-40 are rejected under 35 U.S.C. 103 as being unpatentable over Kaduchak in view of Rabbitt and Longsine-Parker et al., 2013 (7th NPL cite, IDS, 12/19/2022)
The discussion of Kaduchak and Rabbitt regarding claims 1, 3, 8, 25-28, 31-34 and 36-40 set forth in the rejection above is incorporated herein.
Kaduchak discloses microchannel devices which could acoustically focus cells before electroporation and discloses the utility of tripartite outlets for separating cells from waste solutions but does not explicitly teach the microchannel system includes a substrate having a main channel ending in a trifurcating outlet in which the cells are directed to a cell output channel that couples with a center of the main channel downstream of the electroporation electrodes; however, a person of ordinary skill in the art at the time of filing would have found it obvious for the device made obvious by Kaduchak in view of Rabbitt to comprise a main channel ending in a trifurcating outlet in which the cells are directed to a cell output channel that couples with a center of the main channel downstream of the electroporation electrodes in view of the disclosure of Longsine-Parker.
Longsine-Parker also teaches methods of introducing a payload into cells comprising flowing the cells between electroporation electrodes to facilitate delivery of the payload into the cells (Abst.) wherein the device comprises three inlets, wherein the three inlets allow for sheath flow of the solution entered into the outer inlets around the solution entered into the center inlet (Fig. 2; p. 2146, “2.1. Design of the microfluidic 3D electrode electrosonoporation device”, ¶3; p. 2147, “2.6. Microchip electroporation protocol”, ¶4; p. 2148, “2.7. Microchip sonoporation protocol”, ¶2) and comprises three outlets (i.e., channels; Fig. 2; p. 2146, “2.1. Design of the microfluidic 3D electrode electrosonoporation device”, ¶3; p. 2148, “3.1. 3D electrode device testing”, ¶1) so that the electroporated cells exit from a center cell collection outlet and the buffer, cargo and untreated cells flow to two peripheral waste outlets. Hence, a person of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to fashion the device made obvious by Kaduchak in view of Rabbitt to further comprise three inlets, so that sheath flow around the center solution can be performed, and three outlets, with a central cell collection outlet to collect the electroporated cells and two peripheral waste outlets for the buffer, cargo and untreated cells to flow through to be disposed, because Longsine-Parker discloses the arrangement as an effective way to provide sheath flow around the cells entered into the system and to collect the cells to which payload has been delivered away from the spent cargo and reagents; therefore, claim 2 is prima facie obvious.
Longsine-Parker teaches that an arbitrary waveform generator, 33220A, which comprises a digital-to-analog converter, generates the waveform applied to the electroporation electrodes after being amplified by an amplifier (p. 2147, “2.6. Microchip electroporation protocol”, ¶3; p. 2148, “2.7. Microchip sonoporation protocol”, ¶1). Longsine-Parker teaches that the waveform generator, i.e., an electrical field generator, produces an AC square wave to drive the electroporation electrodes (p. 2147, “Microchip electroporation protocol”); hence, a person of ordinary skill in the art at the time of filing would have found it obvious for the device made obvious by Kaduchak in view of Rabbitt to further comprise an arbitrary waveform generator for driving the electroporation electrodes with an alternating electrical current having a sinusoid or pulse train electroporation waveform and an amplifier for amplifying the electroporation waveform for application to the electroporation electrodes; therefore, claims 5, 29 and 35 are prima facie obvious.
Response to Arguments
Regarding the rejection under 35 U.S.C. § 103 over Kaduchak in view of Rabbitt and Longsine-Parker, Applicant argues that “Longsine Parker and You fail to cure the deficiencies noted above with respect to Kaduchak and Rabbitt.” This is unpersuasive as the alleged deficiencies of Kaduchak in view of Rabbitt are discussed on pp. 10-11 above. The rejection is maintained with modification to address new claims and for clarity.
Claims 1-3, 5, 8 and 25-40 are rejected under 35 U.S.C. 103 as being unpatentable over Kaduchak in view of Rabbitt, Longsine-Parker and You et al., US 11071578 (cite A, PTO-892, 8/14/2024).
The discussion of Kaduchak, Rabbitt and Longsine-Parker regarding claims 1-3, 5, 8, 25-29 and 31-40 set forth in the rejection above is incorporated herein.
Rabbitt discloses feedback loops comprising measuring the electrical signal between the electroporation electrodes [0081] but does not state that analog to digital converters are used. However, a person of ordinary skill in the art at the time of filing would have found it obvious to use analog to digital converters to detect the voltage and current applied to the electroporation electrodes in view of the disclosure of You.
You discloses that the current between two electrodes can be used to provide feedback information via an analog to digital converter to a controller (col. 8, ll. 5-11); hence, a person of ordinary skill in the art at the time of filing would have found it obvious to produce the device made obvious by Kaduchak in view of Rabbitt and Longsine-Parker wherein the device comprises a first analog to digital converter for detecting a voltage applied to electroporation electrodes; and a second analog to digital converter for detecting a current flowing between the electroporation electrodes because Rabbitt discloses feedback loops comprising measuring the electrical signal between the electroporation electrodes and You discloses that converting the electrical parameter (voltage, current) into digital information via an analog to digital converter is useful as feedback to the controller; therefore, claim 30 is prima facie obvious.
Response to Arguments
Regarding the rejection under 35 U.S.C. § 103 over Kaduchak in view of Rabbitt, Longsine-Parker and You, Applicant argues that “Longsine Parker and You fail to cure the deficiencies noted above with respect to Kaduchak and Rabbitt.” This is unpersuasive as the alleged deficiencies of Kaduchak in view of Rabbitt are discussed on pp. 10-11 above. The rejection is maintained.
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 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Trent R Clarke whose telephone number is (571)272-2904. The examiner can normally be reached M-F 10-7 MST.
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/TRENT R CLARKE/ Examiner, Art Unit 1651
/DAVID W BERKE-SCHLESSEL/ Primary Examiner, Art Unit 1651