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 the Claims
The amendment filed 9/17/2025 has been entered. Claims 1-25 remain pending in the application and claims 11-25 remain withdrawn. Applicant’s amendments to the claims have overcome the objection and 112(b) rejection previously set forth in the Non-Final Office Action mailed 6/17/2025.
Response to Arguments
Applicant's arguments filed 9/17/2025 have been fully considered but they are not persuasive.
Applicant argues on p. 9 that Konry et al. merely describes an array of identical chambers which transfer cell spheroids from one chamber to the next by chain configuration, and not by fluid flow across a microfluidic channel between two non-identical chambers. This is not persuasive. The working unit, capture chamber, and culture chamber of the claimed invention are only claimed as working units comprising a capture chamber “fluidically connected to one side of the first channel and a first pressure port” and a culture chamber “fluidically connected to an opposite side of the first channel and a second pressure port, wherein the culture chamber is fluidically connected at opposite sides of the chamber to two microfluidic channels that in turn are each fluidically connected to the second pressure port”. These features are not claimed as “non-identical chambers”, and thus the microchambers disclosed by Konry et al. read on the claimed working units and capture chambers.
The Examiner acknowledges that Konry et al. does not explicitly teach both capture chambers and culture chambers. However, Konry et al. discloses capture chambers (Fig. 1A 42 microchambers) and Unger et al. remedies the deficiency of Konry et al. not disclosing culture chambers (Fig. 1A 106 reaction sites), which will be discussed in further detail in the 35 USC § 103 section below.
Applicant argues on pp. 9-10 that Unger et al. is designed for thermocycling reactions for nucleic acid amplification, and is therefore non-analogous art. This is not persuasive, as a reference is analogous art to the claimed invention if: (1) the reference is from the same field of endeavor as the claimed invention (even if it addresses a different problem); or (2) the reference is reasonably pertinent to the problem faced by the inventor (even if it is not in the same field of endeavor as the claimed invention) (MPEP § 2141.01(a)). Thus, the device of Unger et al. being directed to a device that conducts nucleic acid amplification still qualifies as analogous art even if the invention addresses a different problem as the device is disclosed to amplify nucleic acids (Col. 2, lines 20-23) whereas the claimed invention is for amplifying cells; and the device of Unger et al. is reasonably pertinent to the problem faced by the inventor (culture chambers and pressure ports connected to microfluidic channels), which will be discussed in the 35 USC § 103 section below.
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.
Claims 1-2, 5-8, and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Konry et al. (US 2017/0199173 A1) (already of record) in view of Unger et al. (US 8,828,663 B2) (already of record).
Regarding claim 1, Konry et al. teaches a microfluidic device capable of capture and pairing of two or more single cells (abstract), the device comprising: a cell suspension inlet (Fig. 1A 10 first inlet) and a cell suspension outlet (Fig. 1A 45 outlet); a first microfluidic channel fluidically connected at a first end to the inlet and at a second end to the outlet (Fig. 1A channel throughout microfluidic device from inlet 10 to outlet 45); a working zone (Fig. 1A 41 collecting space) comprising a plurality of working units (Fig. 1A 42 microchambers), each working unit comprising: a portion of said first microfluidic channel (Fig. 1A channel throughout microfluidic device); a capture chamber fluidically connected to one side of the first channel (Fig. 1A 42 other microchamber); wherein the first channel provides a continuous fluid pathway from the cell suspension inlet through each working unit in sequence and then to the cell suspension outlet (Fig. 1A channel throughout microfluidic device from inlet 10 to outlet 45).
Konry et al. does not teach a first pressure port or a culture chamber fluidically connected to an opposite side of the first channel and a second pressure port, wherein the culture chamber is fluidically connected at opposite sides of the chamber to two microfluidic channels that in turn are each fluidically connected to the second pressure port. However, Unger et al. teaches a first pressure port (Fig. 1A 108 row valves) and a culture chamber (Fig. 1A 106 reaction sites) fluidically connected to a second pressure port (Fig. 1A 110 column valves) and each culture chamber (Fig. 1A 106 reaction site) is fluidically connected at opposite sides of the chamber to two microfluidic channels (Fig. 1A 102 vertical flow channels, 104 horizontal flow channels) that in turn are each fluidically connected to a pressure port (Fig. 1A 108 row valves, 110 column valves). Unger et al. teaches that the column valves and row valves regulate solution flow (Col. 18, lines 1-3), and samples and reagents in each flow channel mix at the reaction sites, allowing samples to react with different reagents (Col. 18, lines 16-31).
It would have been obvious to a person of ordinary skill in the art to use the Unger et al. configuration of each culture chamber fluidically connected at opposite sides of the chamber to two microfluidic channels that in turn are each fluidically connected to a pressure port in Konry et al.’s device with a reasonable expectation that it would regulate solution flow, and samples and reagents in each flow channel mix at the reaction sites, allowing samples to react with different reagents. This method for improving Konry et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of Unger et al. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Konry et al. and Unger et al. to obtain the invention as specified in claim 1.
Regarding claim 2, Konry et al. teaches a microfluidic device comprising culture chambers and pressure ports, but does not teach wherein the two microfluidic channels fluidically connected at opposite sides of the chamber are separated by a separation structure.
However, Unger et al. teaches two microfluidic channels fluidically connected at opposite sides (Fig. 2 204 flow channel, 210 control channel) which are separated by a separation structure (Fig. 2 212 membrane). Unger et al. teaches that the membrane can be deflected into or retracted from the flow channel to slow or entirely block solution flow through the channel (Col. 13, line 62-Col. 14, line 1).
It would have been obvious to a person of ordinary skill in the art to use the Unger et al. configuration of a membrane/separation structure in Konry et al.’s device with a reasonable expectation that it would slow or entirely block solution flow through the channel. This method for improving Konry et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of Unger et al. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Konry et al. and Unger et al. to obtain the invention as specified in claim 2.
Regarding claim 5, Konry et al. teaches a microfluidic device wherein the width, depth, and height of the capture chambers and the culture chambers (claim 9 “about 70 microns to about 900 microns”) are each 2-fold to 20-fold times larger than the average diameter of single cells (para. 0090 “cell spheroids can be on the order of about 50 to about 900 microns in diameter”) intended for analysis in the device. A capture chamber (microchamber) having a diameter of 900 microns can be read as a diameter 18-fold times larger than a single cell having a diameter of 50 microns, or 2-fold times larger than a cell spheroid having a diameter of 450 microns.
Regarding claim 6, Konry et al. teaches a microfluidic device wherein the width, depth, and height of the capture chambers and the culture chambers are each in the range from 20 to 200 microns (claim 9 “about 70 microns to about 900 microns”).
Regarding claim 7, Konry et al. teaches a microfluidic device that permits light microscopic observation, imaging, spectrophotometric, and/or fluorescence analysis of cells in the capture and/or culture chambers of the device (claim 4).
Regarding claim 8, Konry et al. teaches a microfluidic device comprising at least 96 working units (para. 0085 “microchambers or docking stations can be arranged in an array of 1000 or more”).
Regarding claim 10, Konry et al. teaches a microfluidic device further comprising one or more paired single cells in a culture chamber of the device (claim 18 “a cell spheroid comprising two or more cell types adhered to an essentially spherical polymer scaffold”).
Claims 3-4 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Konry et al. (US 2017/0199173 A1) (already of record) in view of Unger et al. (US 8,828,663 B2) (already of record), as applied to claim 1 above, and further in view of Kido (US 2007/0125942 A1) (already of record).
Regarding claim 3, Konry et al. teaches a microfluidic device comprising microchannels having a diameter (claim 11 “about 50 microns to about 400 microns”) smaller than a diameter of cells intended for capture (para. 0090 “cell spheroids can be on the order of about 50 to about 900 microns in diameter”). A channel having a diameter of about 400 microns is smaller than a cell spheroid having a diameter of about 900 microns. Modified Konry et al. is silent to a constricted portion at the connection to the culture chamber.
However, Kido teaches a constricted portion at the connection to a chamber (Fig. 5 40 constricted channel). Kido teaches that the constricted channel holds back cell/virus debris from entering the clarification chamber (para. 0079).
It would have been obvious to a person of ordinary skill in the art to use the Kido configuration of a channel having a constricted portion at the connection to a chamber in modified Konry et al.’s device with a reasonable expectation that the constricted channel would hold back cell/virus debris from entering the chamber. This method for improving modified Konry et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of Kido. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of modified Konry et al. and Kido to obtain the invention as specified in claim 3.
Regarding claim 4, modified Konry et al. teaches a microfluidic device wherein each capture chamber is fluidically connected, at a side opposite to the first channel, to a constricted channel (claim 11 “microchannels connected to the microchambers”), wherein a diameter of the constricted channel (claim 11 “about 50 microns to about 400 microns”) is smaller than a diameter of cells intended for capture in the capture chamber (para. 0090 “cell spheroids can be on the order of about 50 to about 900 microns in diameter”). A channel having a diameter of about 400 microns is smaller than a cell spheroid having a diameter of about 900 microns. Modified Konry et al. is silent to a constricted portion at the connection to the capture chamber.
However, Kido teaches a constricted portion at the connection to a chamber (Fig. 5 40 constricted channel). Kido teaches that the constricted channel holds back cell/virus debris from entering the clarification chamber (para. 0079).
It would have been obvious to a person of ordinary skill in the art to use the Kido configuration of a channel having a constricted portion at the connection to a chamber in modified Konry et al.’s device with a reasonable expectation that the constricted channel would hold back cell/virus debris from entering the chamber. This method for improving modified Konry et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of Kido. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of modified Konry et al. and Kido to obtain the invention as specified in claim 4.
Regarding claim 9, modified Konry et al. teaches a microfluidic device comprising first and second pressure ports connected to each culture chamber, but does not teach wherein the second pressure port connected to each individual culture chamber has a separate fluidic connection to an individual port or collection chamber in the device or external to the device for the collection of cells or cell lysates from the culture chamber.
However, Kido teaches a port (Fig. 5 38 clarification chamber) having a separate fluidic connection to an individual port or collection chamber in the device or external to the device for the collection of cells or cell lysates from the culture chamber (Fig. 5 44 collection chamber). Kido teaches that a lysed sample circulates to the collection chamber, which stores a clarified liquid containing capture reagents or amplification reagents to isolate or amplify a target analyte (para. 0076).
It would have been obvious to a person of ordinary skill in the art to use the Kido configuration of a port having a separate fluid connection to an individual port or collection chamber in the device in modified Konry et al.’s device with a reasonable expectation that a lysed sample circulates to the collection chamber, which stores a clarified liquid containing capture reagents or amplification reagents to isolate or amplify a target analyte. This method for improving modified Konry et al.’s device was within the ability of one of ordinary skill in the art based on the teachings of Kido. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of modified Konry et al. and Kido to obtain the invention as specified in claim 9.
Conclusion
THIS ACTION IS MADE FINAL. 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 ASHLEY LOPEZLIRA whose telephone number is (703)756-5517. The examiner can normally be reached Mon - Fri: 8:30-5:00.
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/ASHLEY LOPEZLIRA/Examiner, Art Unit 1799
/MICHAEL A MARCHESCHI/Supervisory Patent Examiner, Art Unit 1799