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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 09/15/2026 has been entered.
Claim Rejections - 35 USC § 112
The previous 35 U.S.C. § 112(b) rejection is withdrawn in light of the amendments.
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.
Claims 1, 6, and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Tandon (US 20190119624) (previously cited in the IDS) in view of Tsinberg (US 20070161051) (previously cited) and Sadri (US 20150093743) (previously cited).
Regarding claim 1, Tandon discloses: a cell transfection apparatus (paragraph [0011]) comprising:
a microfluidic chip (paragraph [0045]; Fig. 2B, element 8 “substrate”) comprising:
a fluid input port (paragraph [0047]);
a cell sorter … configured to sort the target cells from the non-target cells in fluid received through the fluid input port (paragraph [0069]) and to direct the target cells into a first microfluidic channel (paragraphs [0047]-[0048]; Fig. 1, element 30 “main channel”) including a cell transfection region (paragraph [0077]; Fig. 1, elements 62 and 64 “the pair of electroporation electrodes”);
the cell transfection region comprising an electroporation region (paragraph [0077]; Fig. 1, elements 62 and 64 “the pair of electroporation electrodes”) configured to receive the target cells sorted from the non-target cells (paragraph [0069]); and
a fluid ejector (paragraph [0048]; Fig. 1, element 34 “cell output channel”) located in the first microfluidic channel (paragraphs [0047]-[0048]; Fig. 1, element 30 “main channel”) and configured to dispense a transfected target cell received from the cell transfection region (paragraph [0048]; Fig. 2A, element 34 “a cell output channel”).
Tandon does not disclose:
a cell sorter comprising a plurality of spaced pillars extending within a microfluidic passage of the microfluidic chip, the pillars spaced apart by a distance to allow target cells to pass therebetween and to inhibit passage of non-target cells, the plurality of spaced pillars configured to sort the target cells from the non-target cells
and the non-target cells into a second microfluidic channel not including the cell transfection region
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Tandon, Fig. 1
However, regarding feature 1, Tandon discloses that acoustophoresis channels can be used to sort cells prior to electroporation (paragraph [0068]). Also, feature 1 is partially a form of intended use of the invention because it describes sorting “target cells” from “non-target cells”, and what is considered a target cell is deemed by the user. Therefore, Tandon’s disclosure of acoustophoresis channels that can be used to sort living cells from dying cells reads on this feature. Nevertheless, the exact configuration of a first and second microfluidic channel with location of the cell transfection region in only the first microfluidic channel and not the second microfluidic channel is not present in Tandon.
Regarding feature 1, Tsinberg discloses a cell sorter (abstract) comprising a plurality of spaced pillars (paragraph [0009] “posts”) extending within a microfluidic passage (paragraph [0011] “microchannel”) of the microfluidic chip (paragraph [0025] “chip”), the pillars spaced apart by a distance to allow target cells to pass therebetween and to inhibit passage of non-target cells (paragraphs [0004] and [0046]), the plurality of spaced pillars configured to sort the target cells from the non-target cells (paragraphs [0004] and [0046]).
In the analogous art of a device for cell separation, it would have been obvious to one skilled in the art before the effective filing date to modify Tandon with the posts of Tsinberg in order to achieve cell separation via an affinity-based sorting that uses affinity ligands attached to posts within a microchannel. The non-target cells are washed out of the microfluidic device, while target cells remain until elution and collection (Tsinberg, paragraphs [0046]-[0047]).
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Tsinberg, Figs. 1-3
Regarding the phrase “allow target cells to pass and to inhibit passage of non-target cells”, this is an intended use limitation. The manner of operating or intended use of a claimed apparatus does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of modified Tandon would be fully capable of operating in this manner given modified Tandon’s posts.
Regarding “a second microfluidic channel”, Sadri discloses a cell sorter (paragraphs [0090]-[0092]) configured to sort target cells from non-target cells (paragraphs [0090]-[0092] “according to their sensed characteristics”) in fluid received through the fluid input port and to direct the target cells into a first microfluidic channel (paragraphs [0091]-[0092] “particle of interest” … “dispensing channels”) and the non-target cells into a second microfluidic channel (paragraph [0090] “waste collection area … input of a channel”).
In the analogous art of particle dispensing systems, it would have been obvious to one skilled in the art before the effective filing date to modify the device of modified Tandon with the particle diverting system of Sadri in order to divert and dispense cells according to their sensed characteristics (Sadri, paragraph [0092]) for molecular and cellular analyses (Sadri, paragraph [0002]).
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Sadri, Fig. 1
Regarding feature 2, regarding the phrases “including a cell transfection region” and “not including a cell transfection region”, the cell transfection region is already disclosed above by Tandon. Placing the cell sorter in such a configuration to have a cell transfection region in one of the outlets of modified Tandon in view of Sadri would have been obvious to one skilled in the art before the effective filing date in order to transfect cells so that the cell transfection region is more effective at transfection over time (as it would be used on already sorted viable target cells).
If it is deemed that Tandon does not disclose “a fluid ejector located in the first microfluidic channel”, Sadri discloses a fluid ejector located in the first microfluidic channel (Fig. 1; paragraph [0092] “dispensing channels” are used for “cells [to be] diverted and dispensed according to their sensed characteristics”).
In the analogous art of particle dispensing systems, it would have been obvious to one skilled in the art before the effective filing date to modify the device of modified Tandon with the fluid ejector located in the first microfluidic channel of Sadri in order to dispense cells according to their sensed characteristics (Sadri, paragraph [0092]) such as cellular viability (Sadri, paragraph [0030]).
Regarding the phrases “configured to sort the target cells from the non-target cells in fluid received through the fluid input port and to direct the target cells into a first microfluidic channel including a cell transfection region and the non-target cells into a second microfluidic channel not including the cell transfection region” and “configured to dispense a transfected target cell received from the cell transfection region”, this is a form of intended use of the instant invention. Regarding the limitation, the manner of operating or intended use of a claimed apparatus does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of modified Tandon would be fully capable of operating in this manner given the cell sorter and microfluidic channels of modified Tandon.
Regarding claim 6, Tandon discloses: wherein the target cells are first target cells (paragraph [0070] “using antibody labeling to distinguish cells … then separated into multiple smaller channels or bins … each channel may contain … each subset of cells”), and
a second cell transfection region comprising a second single cell electroporation region to receive second target cells (paragraph [0070]), different than the first target cells, from the cell sorter (paragraph [0069]); and
a second fluid ejector (paragraphs [0017] and [0048] “trifurcating outlet”) to dispense a transfected second target cell received from the second cell transfection region (paragraph [0070], each separate channel inherently has at least one outlet to each separate channel).
If it is deemed that the limitation above is not met by Tandon, the limitation “a second fluid ejector to dispense a transfected second target cell received from the second cell transfection region”, mere duplication of parts has no patentable significance unless a new and unexpected result is produced. MPEP § 2144.04(VI)(B). It would have been obvious to one skilled in the art before the effective filing date to modify the apparatus of modified Tandon with a second fluid ejector to dispense transfected second target cells in order to collect a second transfected cell product different from the first cell product collected for a different therapy.
Regarding claim 9, Tandon discloses wherein the cell sorter is affinity based (paragraph [0069]-[0070] “antibody labeling”).
Tandon does not disclose [sorting] the target cells from the non-target cells using negative enrichment of the non-target cells.
Regarding the limitation “so as to sort the target cells from the non-target cells using negative enrichment of the non-target cells”, the manner of operating or intended use of a claimed apparatus does not patentably distinguish it from the prior art. MPEP § 2114(II). The device of Tandon would be fully capable of operating in this manner given the antibody labeling distinguishing cells apart from each other (Tandon, paragraph [0070]).
If it is deemed that the cell sorter of Tandon does not describe the limitation above, Tsinberg discloses: wherein the cell sorter (abstract “separating or isolating cells”) is affinity based (paragraphs [0039]-[0042]) so as to sort the target cells from the non-target cells using negative enrichment of the non-target cells (paragraph [0057]).
In the analogous art of cell separation, it would have been obvious to one skilled in the art before the effective filing date to modify the device of modified Tandon with the affinity based cell sorter of Tsinberg in order to isolate and collect rare cells from a heterogeneous cell population for use in disease diagnosis and treatment, e.g. gene therapy (Tsinberg, paragraph [0002]).
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Tandon (US 20190119624) (previously cited in the IDS) in view of Tsinberg (US 20070161051) (previously cited) and Sadri (US 20150093743) (previously cited) as applied to claim 1, in view of McGuinness (US 20160334323) (previously cited).
Regarding claim 2, Tandon discloses the fluid ejector (paragraph [0048]; Fig. 2A, element 34 “a cell output channel”).
Modified Tandon does not disclose wherein the fluid ejector comprises a fluid actuator selected from a group of fluid actuators consisting of a thermoresistive fluid actuator and a piezo-membrane based fluid actuator.
McGuinness discloses wherein the fluid ejector comprises a fluid actuator selected from a group of fluid actuators consisting of a thermoresistive fluid actuator (paragraphs [0034] and [0038] “thermal inkjet (TIJ) pump”) and a piezo-membrane based fluid actuator (paragraph [0034] “piezo element (PZT) pumps”).
In the analogous art of microfluidic sensing devices, it would have been obvious to one skilled in the art before the effective filing date to modify the apparatus of modified Tandon to have the fluid actuator of McGuinness in order to either drive or draw fluid containing particles across the microfluidic device (McGuinness, paragraph [0033]).
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Tandon (US 20190119624) (previously cited in the IDS) in view of Tsinberg (US 20070161051) (previously cited) and Sadri (US 20150093743) (previously cited) as applied to claim 1, further in view of Kornilovich (US 20160318015) (previously cited).
Regarding claim 3, Tandon discloses moving the target cells through the cell transfection region (paragraph [0053]).
Modified Tandon does not disclose wherein the microfluidic chip further comprises an inertial pump to move the target cells through the cell transfection region.
Kornilovich discloses wherein a microfluidic chip further comprises an inertial pump (paragraph [0037]).
In the analogous art of microfluidic systems and networks, it would have been obvious to one skilled in the art before the effective filing date to modify the apparatus of modified Tandon with the inertial pump of Kornilovich in order to pump fluids containing biological samples from one channel or reservoir into other channels or reservoirs (Kornilovich, paragraph [0037]).
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Tandon (US 20190119624) (previously cited in the IDS) in view of Tsinberg (US 20070161051) (previously cited) and Sadri (US 20150093743) (newly cited) as applied to claim 1, further in view of McAfee (US 20200181562) (previously cited).
Regarding claim 4, Tandon discloses wherein the microfluidic chip (paragraph [0045]; Fig. 2B, element 8 “substrate”) comprises the electroporation region (paragraph [0077]; Fig. 1, elements 62 and 64 “the pair of electroporation electrodes”) and the fluid ejector (paragraph [0048]; Fig. 2A, element 34 “a cell output channel”).
Modified Tandon does not disclose a cell propagation chamber between the electroporation region and the fluid ejector.
McAfee discloses a cell propagation chamber (paragraph [0052]).
In the analogous art of cell culture apparatuses, it would have been obvious to one skilled in the art before the effective filing date to modify the device of modified Tandon with the cell propagation chamber of McAfee in order to allow for cell growth and expansion after being genetically modified (McAfee, paragraphs [0032]-[0033]).
Regarding the limitation “a cell propagation chamber between the electroporation region and the fluid ejector”, rearrangement of parts would have been obvious to one of ordinary skill in the art as an obvious matter of design choice and would not have modified the operation of the device. MPEP § 2144.04(VI)(C). It would have been obvious to one skilled in the art before the effective filing date to modify the device of modified Tandon with the cell propagation chamber of McAfee in order to allow for cell growth and expansion after being genetically modified for producing cell populations for the sake of cell therapy for patients (McAfee, paragraphs [0003] and [0032]-[0033]).
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Tandon (US 20190119624) (previously cited in the IDS) in view of Tsinberg (US 20070161051) (previously cited), Sadri (US 20150093743) (newly cited) and McAfee (US 20200181562) (previously cited) as applied to claim 4, further in view of Kornilovich (US 20160318015) (previously cited).
Regarding claim 5, modified Tandon does not disclose:
a reagent supply passage for connection to a first reagent source;
a first inertial pump within the reagent supply passage for pumping cell growth media from the first reagent source through the reagent supply passage to the cell propagation chamber;
a lift off supply passage for connection to a second reagent source; and
a second inertial pump within the lift off supply passage for pumping reagent to the cell propagation chamber.
Kornilovich discloses:
a first inertial pump (paragraphs [0033]-[0034]); and
a second inertial pump (paragraphs [0033]-[0034]).
In the analogous art of microfluidic systems and networks, it would have been obvious to one skilled in the art before the effective filing date to modify the device of modified Tandon with the first and second inertial pumps of Kornilovich in order to have integrated inertial pumps as fluid actuators to have microfluidic pressures and flows in microfluidic devices without bulky or difficult to program external pumps (Kornilovich, paragraphs [0019] and [0021]-[0022]).
McAfee discloses:
a reagent supply passage (paragraph [0074]; Fig. 5, element 540 “fluidic pathways”) and a reagent source with a cell growth media (paragraphs [0033] and [0050]; Fig. 2A, element 224 “Pre-warming: Satellite bag warms fluid before delivery of [sic] to the cells”); and the cell propagation chamber (paragraph [0052]).
In the analogous art of cell isolation for use in automated bioreactors, it would have been obvious to one skilled in the art before the effective filing date to modify the device of modified Tandon with the fluidic passage and reagent source of McAfee in order to hold cell media and to increase the overall volume for the apparatus (McAfee, paragraphs [0050] and [0074]).
Additionally, regarding the limitations “a second inertial pump”, “[a lift off supply] passage”, “a second reagent source”, and “reagent”, mere duplication of parts has no patentable significance unless a new and unexpected result is produced. MPEP § 2144.04(VI)(B). It would have been obvious to one skilled in the art before the effective filing date to modify modified Tandon to duplicate these components in order to increase the capacity of the device to have multiple reservoirs of reagents for differently sorted cells in a cell propagation chamber.
Regarding the microfluidic connectivity of the claim elements, it would have been obvious to one skilled in the art before the effective filing date to modify the networks and connectivity of the microfluidic channels of modified Tandon to be able to transport reagents in order to carry out various automated methods to produce genetically modified immune cell cultures (McAfee, paragraph [0033]).
Claims 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Tandon (US 20190119624) (previously cited in the IDS) in view of Tsinberg (US 20070161051) (previously cited) and Sadri (US 20150093743) (previously cited) as applied to claim 1, further in view of Conway (US 20160177244) (previously cited).
Regarding claim 11, Tandon teaches:
the transfected target cell (paragraph [0011]), the fluid ejector (paragraph [0048]; Fig. 2A, element 34 “a cell output channel”);
the microfluidic chip (paragraph [0045]; Fig. 2B, element 8 “substrate”).
Regarding the limitation “the fluid ejector”, if it is deemed that Tandon does not disclose this feature, Sadri discloses a fluid ejector (Fig. 1; paragraph [0092] “dispensing channels” are used for “cells [to be] diverted and dispensed according to their sensed characteristics”).
In the analogous art of particle dispensing systems, it would have been obvious to one skilled in the art before the effective filing date to modify the device of modified Tandon with the fluid ejector located in the first microfluidic channel of Sadri in order to dispense cells according to their sensed characteristics (Sadri, paragraph [0092]) such as cellular viability (Sadri, paragraph [0030]).
Regarding the phrase “microfluidic chip”, if Tandon is deemed not to disclose a microfluidic chip, Sadri discloses a microfluidic chip (paragraph [0036]).
In the analogous art of lab-on-a-chip devices or microfluidic chips, it would have been obvious to one skilled in the art before the effective filing date to modify the device of modified Tandon with the microfluidic chip of Sadri in order to contain structures that allow for the integrated manipulation of small volumes of fluid, including moving and/or storing fluid, and particles associated therewith (Sadri, paragraph [0040]).
Modified Tandon does not disclose:
a multi-well plate to receive the transfected target cell from the fluid ejector;
a liquid handler to supply a cell growth media to the multi-well plate; and
an incubator containing the microfluidic chip, the multi-well plate and the liquid handler while maintaining temperature and carbon dioxide concentration levels within the incubator.
Conway discloses a multi-well plate (abstract) to receive the transfected target cell (abstract);
a liquid handler (paragraphs [0048]-[0050]) to supply a cell growth media (paragraph [0042]) to the multi-well plate (paragraph [0042]); and
an incubator (paragraph [0030] “incubator”), the multi-well plate (paragraph [0042]) and the liquid handler (paragraphs [0048]-[0050]) [and] maintaining temperature and carbon dioxide concentration levels within the incubator (paragraphs [0099] and [0104] “Incubate 96 well in 37 C incubator, 5% CO2”).
In the analogous art of automated cell culture systems, it would have been obvious to one skilled in the art before the effective filing date to modify the device of modified Tandon with the liquid handler and incubator of Conway in order to automate cell cultivation without the need for human handling and to reduce potential for contamination (Conway, paragraph [0007]).
Regarding the limitation “an incubator containing the microfluidic chip, the multi-well plate and the liquid handler while maintaining temperature and carbon dioxide concentration levels within the incubator”, the claim limitation is obvious under MPEP § 2144.04(IV)(A), which states that “where the only difference between the prior art and the claims was a recitation of relative dimensions … [and the claimed device] would not perform differently than the prior art device, the claimed device was not patentably distinct from the prior art device”. It would have been obvious to one skilled in the art before the effective filing date to modify the size and dimensions of modified Tandon to have an incubator to hold a liquid handler and other components in order to keep the cell culture at a temperature and carbon dioxide concentration suitable for viability and continued expansion of the cell line.
Regarding claim 12, Tandon discloses an imager to image cells (paragraphs [0024]-[0025] and [0079]).
Modified Tandon does not disclose the multi-well plate.
Conway discloses the multi-well plate (paragraph [0042] and [0046] and claim 9).
In the analogous art of automated cell culture systems, it would have been obvious to one skilled in the art before the effective filing date to modify the device of modified Tandon with the multi-well plate of Conway in order to automate cell cultivation with a plurality of wells to test cell culture for scale-up of cell production for screening to identify optimal conditions for growth while minimizing time and material cost (Conway, paragraph [0028]).
Additional Prior Art References
The prior art made of record and not relied upon is considered pertinent to Applicant’s disclosure.
Indermuhle (US 20010036674) (newly cited) – A chip with affinity-based pillars.
Craighead (US 20220016629) (newly cited) – A chip with affinity-based pillars or exclusion based on size-elasticity.
Response to Arguments
Applicant’s arguments filed 09/15/2026 have been fully considered but they are not persuasive.
Regarding Applicant arguments, pg. 5 of 9, written description for the amendments has been found in paragraphs [0050] and [0060] of the instant specification.
Regarding Applicant arguments, pg. 5 of 9, the 35 U.S.C. § 112(b) rejection has been withdrawn in light of the amendments.
Regarding Applicant arguments, pgs. 6-7 of 9, the amended feature is discussed. However, the cell sorter comprising spaced pillars is disclosed in Tsinberg. Motivation is given for the combination of modified Tandon.
Regarding Applicant arguments, pg. 7 of 9, regarding a first and a second microfluidic channel, wherein the first microfluidic channel includes a cell transfection region and the second microfluidic channel does not include the cell transfection region … modified Tandon teaches these features in light of Tandon’s electroporation electrodes (paragraph [0077]; Fig. 1, elements 62 and 64 “the pair of electroporation electrodes”) in a first microchannel; and modifications in view of Sadri teach sending the non-target cells into a second microfluidic channel (paragraph [0090] “waste collection area … input of a channel”). Motivation is given for the combination of modified Tandon.
Regarding Applicant arguments, pg. 8 of 9, regarding the dependent claims, these claims are rejected as the independent claim is still rejected and no further arguments were made regarding the dependent claims.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATHAN G ESPERON whose telephone number is 571-272-9807. The examiner can normally be reached 9 am - 6 pm Monday through Thursday, and 9 am - 6 pm every other Friday.
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/N.G.E./Examiner, Art Unit 1799
/MICHAEL A MARCHESCHI/Supervisory Patent Examiner, Art Unit 1799
