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 .
Response to Amendment
Applicant amendments filed 04/13/2026 have been entered. Applicant amendments do not overcome each and every 112(b) rejection set forth in the Office Action mailed 11/12/2025, please see 112(b) section below.
Election/Restrictions
Newly submitted claims 38-44 are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons:
In the requirement for restriction/election filed 05/02/2024, group I was directed to claims 1-6 and 13-14, group II was to claims 15-19, group III was to claims 21, 23-27, and 30-31. Groups I through III were found to lack unity of invention because the technical feature is not a special technical feature as it did not make a contribution over the prior art in view of Sbrana et al. (Sensors and Actuators B: Chemical, 2016, 223:440; cited on the IDS submitted 10/21/2021), and Kim (US-2014/065660).
Newly submitted claims 38-42, group IV, are directed to a microfluidic device for determining the transepithelial electrical resistance (TEER) of a cell layer or a cell assembly and/or for determining the impedance of cells, a cell layer, or a cell assembly.
Newly submitted claim 43, group V, is directed to a method for determining the transepithelial electrical resistance (TEER) of a cell layer (9) or a cell assembly (10, 11).
Newly submitted claim 44, group VI, is directed to a method for determining the impedance of cells, a cell layer (9) or cell assembly (10).
Had claims 38-44 been presented at the time of the original restriction/election filed 05/02/2024, they would still lack unity as the technical feature would not make a contribution over the prior art (Sbrana in view of Kim).
Also, even with respect to the newly amended claims, the amended claims to not make a contribution over the prior art (i.e., Groups I and II still lack the same or corresponding special technical feature) because the groups do not make a contribution over the prior art, namely Wikswo (US-2018/0326417-A1) in view of Achyuta (US-2015/0140581-A1), as set forth in the 103 section below.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 38-44 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Status of Claims
Claims 1, 3-6, 13-19, 36-44 remain pending in the application, with claims 1, 3-6, 13-14, 36-37 being examined, and claims 15-19, 38-44 being withdrawn.
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.
Claims 5, 14 are 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 5 recites “wherein the at least two porous membranes (4) and the bottom wall (7) and/or the upper wall (6) comprise at least one additional electrode”
From lines 17-19 of claim 1 the upper wall or bottom wall comprises at least one additional electrode, where therefore it is unclear if when the bottom wall and/or upper wall comprise at least one additional electrode for claim 5 if this electrode is the same or different from the one described in claim 1.
For examination, it will be interpreted that if the at least one additional electrode is on the bottom and/or upper wall that it is the same as the at least one additional electrode described in claim 1.
Further, there appears to still be some clarity issues when it is the at least two porous membranes comprising at least one additional electrode. This is due to claim 1 describing “wherein at least one of the at least two porous membranes (4) comprises on its surface at least one electrode (5)”. For example, if claim 1 has a total of two membranes, and one of them has an electrode, does that mean in claim 5 there will be one membrane with one electrode and another membrane with two electrodes?
Claim 14 recites “and the upper wall (6) and/or one of the side walls (8) of the upper compartment (2) and/or the bottom wall (7) and/or one of the side walls (8) of the lower compartment (3) comprises at least one additional electrode (5) on its surface,” on lines 4-6.
Because claim 1 on lines 17-19 now recites that the upper wall (6) or bottom wall (7) comprises at least one additional electrode, it is unclear if the additional electrode in claim 14 is the same or different from that described in claim 1.
Bullet b is unclear due to the usage of “and/or”. Specifically bullet b describes “at least one of said at least two porous membranes (4) comprises the at least one electrode (5) facing the lower compartment (3) and/or the at least one inner compartment (12) and the upper wall (6) and/or one of the side walls (8) of the upper compartment (2) and/or the bottom wall (7) and/or one of the side walls (8) of the lower compartment (3) comprises at least one additional electrode (5) on its surface,” where it is unclear where the limitation for the at least one electrode ends at the limitation for the at least one additional electrode begins.
For examination, based on the amendment to bullet a where a semicolon was placed between “and/or the at least one inner compartment (12); and the upper wall (6)”, bullet b will be interpreted as being split the same way.
Further, as described above, claim 1 on lines 17-19 now recites that the upper wall or bottom wall comprises at least one additional electrode, where it is unclear if for bullet b if the additional electrode is the same or different from the one described in claim 1.
And for examination for both bullets a and b, it will be interpreted that the at least one additional electrode of claim 14 is the same as the one described in claim 1.
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.
Claim(s) 1, 3, 5-6, 14, 36-37 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wikswo (US-2018/0326417-A1) in view of Achyuta (US-2015/0140581-A1).
Regarding claim 1, Wikswo teaches a microfluidic device for determining the transepithelial electrical resistance (TEER) of a cell layer or a cell assembly and/or for determining the impedance of cells, the cell layer or the cell assembly, said device comprising:
at least one microchannel comprising at least a lower compartment (chamber 264) and an upper compartment (chamber 261) separated by at least two porous membranes (filter membranes 266 and 267) ([0134, Figure 2B); and
at least one inner compartment (chamber 262) positioned between the lower compartment (264) and the upper compartment (261) ([0134], Figure 2B),
wherein the lower compartment (264) comprises a bottom wall (glass plate 209) and side walls ([0133], [0134], Figures 2A-B, further see Figure 2B in particular where there are understood to be side walls for each chamber 261, 262, 263, and 264 where together that make the side walls),
wherein the upper compartment (261) comprises an upper wall (upper window 239) and the side walls, and the bottom wall (209) ([0133], [0134], Figures 2A-B, see Figure 2B where there are side walls for each chamber 261, 262, 263, and 264 that together that make the side walls),
wherein the upper wall (239), and the side walls, and the at least two porous membranes (266 and 267) define compartment volumes ([0133], [0134], Figures 2A-B),
wherein the at least two porous membranes (266 and 267) and the side walls define the volume of the at least one inner compartment (262) (see Figure 2B where chamber 262 is between membranes 266 and 267).
Wikswo does teach where pumps, valves, and tubing can be configured with current-injection electrodes, voltage-sensing electrodes, and a fixed-or swept-frequency analyzer to create an integrated instrument that is capable of measuring transendothelial electrical resistance (Wikswo; [0032]), Wikswo does not teach wherein at least one of the at least two porous membranes comprise on its surface at least one electrode.
In the analogous art of measuring transendothelial electrical resistance, Achyuta teaches a device with a first and second layer of electrodes (Achyuta; [0008], [0081]).
Specifically, Achyuta teaches where a device 400 has a first layer of electrodes 432 that are countersunk into base layer 402 and a top layer of electrodes 430 on roof 430 (from Figure 4A and description of the roof being element 430, it is understood that the electrodes should be reference number 431) (Achyuta; [0081]). It is seen in Figure 4A that the electrodes 432 are on the surface of barrier 410, where from [0052] the barrier is a porous barrier that includes a membrane. Additionally, [0013] describes that the method includes measuring trans-endothelial electrical resistance across the cells, visualizing the cells in the device by microscopy, and/or removing the cells from the device and performing biochemical analysis or microscopy on the removed cells.
Examiner further finds that the prior art contained a device/method/product (i.e., a five-layer microfluidic bioreactor) which differed from the claimed device by the substitution of component(s) (i.e., electrodes in the pumps, valves, and tubing) with other component(s) (i.e., electrodes on the filter membrane and upper window), and the substituted components and their functions were known in the art as above set forth. An ordinarily skilled artisan could have substituted one known element with another (i.e., the electrodes in the pumps, valves, and tubing and instead have the electrodes on the membranes and upper window), and the results of the substitution (i.e., measuring TEER) would have been predictable.
Therefore, pursuant to MPEP §2143 (I), Examiner concludes that it would have been obvious to an ordinarily skilled artisan to substitute the electrode position of reference Wikswo with the electrode position of reference Achyuta, since the result would have been predictable.
The upper window 239 will therefore comprise at least one additional electrode, and the at least one additional electrode on the upper window 239 and the at least one electrode on filter membrane 266 will be positioned at opposing sides of chamber 261 (upper compartment).
Regarding claim 3, modified Wikswo teaches the device according to claim 1. In the device of Wikswo, there will now be electrodes on membranes 266, 267, and 268 and the upper window 239 as taught by Achyuta. It is understood that the electrodes on membrane 267 will face chamber 264, 263, 261 depending on what side of the electrodes is being used as a reference point.
Regarding claim 5, modified Wikswo teaches the device according to claim 1. Wikswo has been modified with Achyuta such that the membranes 266, 267, and 268 have electrodes and upper window 239 has electrodes.
Regarding claim 6, modified Wikswo teaches the device according to claim 1. Wikswo has been modified with Achyuta such that filter membranes 266, 267, and 268 have electrodes on their surface, where taking filter membranes 266 and 267 the electrodes on these two membranes will be positioned substantially opposite to each other.
Regarding claim 14, modified Wikswo teaches the device according to claim 1. The device of Wikswo has been modified with Achyuta where there are electrodes on membranes 266, 267, and 268. The electrodes on membranes 266 or 267 will face chamber 262.
Please note because of “or” on lines 6 and 11, bullets a and b are not required.
Regarding claim 36, modified Wikswo teaches the device according to claim 1. Wikswo has been modified with Achyuta such that the upper window 239 (upper wall) comprises electrodes, however it would have been obvious to one skilled in the art to rearrange the position of the electrodes on the upper window 239 to instead be on the glass/plastic plate 209 of Wikswo seen in Figure 2A because moving the position of the electrodes from upper window 239 to glass/plastic plate 209 (the bottom wall) would not modify the operation of the electrodes (i.e., they would still be measuring TEER), please see MPEP 2144.04 VI.C.
Wikswo describes the upper window 239 to seal the topmost chamber, and the glass/plastic plate 209 forms the bottom of the first assembly, and thus both the upper window 239 and glass/plastic plate 209 may be considered cover slips (Wikswo; [0133]). And [0081] of Achyuta describes that the roof 430 is a cover slip, and it is seen in Figure 4A that the roof 430 has the electrodes.
Regarding claim 37, modified Wikswo teaches the device according to claim 1. Wikswo has been modified with Achyuta such that the upper window 239 (upper wall) comprises electrodes.
Claim(s) 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wikswo (US-2018/0326417-A1) and Achyuta (US-2015/0140581-A1), and in further view of Guimera (WO-2015/181322-A1).
Regarding claim 13, modified Wikswo teaches the device according to claim 1. Wikswo has been modified by Achyuta such that there are now electrodes on filter membranes 266, 267, and 268, however the electrodes are not arranged as interdigitated electrodes having a plurality of digits forming an electrode pattern. It is further described by [0135] of Wikswo that the vertical distance between the lowest chamber and top of the upper chamber is minimized as to allow cells in the various chambers to be within the working length of a high-power, high numerical aperture microscope objective, and [0013] of Achyuta that the method includes measuring trans-endothelial electrical resistance across the cells, visualizing the cells in the device by microscopy, and/or removing the cells from the device and performing biochemical analysis or microscopy on the removed cells.
In the analogous art of measuring trans-layer electrical impedance in an in vitro model of a cell barrier, Guimera teaches electrodes that are arranged in an interdigitated manner (Guimera; page 1 lines 7-10, page 4 lines 14-17).
Specifically, Guimera teaches where interdigitated electrodes means a plurality of electrodes arranged in an interlocking comb-shape, where each electrode comprises an array of parallel fingers, where in Figure 1 there is a first set of electrodes 6 that comprises a first electrode 6a and a second electrode 6b that are arranged in an interdigitated manner on the upper inner surface of upper chamber 1 (Guimera; page 10 lines 13-15, page 13 lines 9-12).
It would have been obvious to one skilled in the art to modify the electrodes of Wikswo that are now on the filter membranes as taught by Achyuta such that they are interdigitated electrodes as taught by Guimera because it is taught by Guimera that interdigitated electrodes are an optimal electrode configuration that allows a similar sensitivity along a defined cell culture area without impairing the optical visualization of the cell culture (Guimera; page 13 lines 19-24).
Allowable Subject Matter
Claim 4 objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter:
Regarding claim 4, the closest prior art of record is Wikswo (US-2018/0326417-A1) in view of Achyuta (US-2015/0140581-A1). While Wikswo has been modified by Achyuta so that now there are electrodes on the upper window 239 and on membranes 266, 267, and 268, it would not have been obvious to one skilled in the art to modify Wikswo for the side walls of the one or more compartments to comprise at least one additional electrode on its surface. The at least one additional electrode in claim 4 is understood to be different from the at least one additional electrode described on the upper wall or bottom wall in claim 1.
Response to Arguments
Applicant’s amendments to the claims and arguments, see page 12 of 16, filed 04/13/2026, with respect to the rejection(s) of claim(s) 1, 3-6, and 14 under 35 USC 103 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Wikswo (US-2018/0326417-A1) and Achyuta (US-2015/0140581-A1).
Please note that Wikswo in view of Achyuta were previously used in the Office Action mailed 04/13/2026.
Applicant argues on page 13 of 16 that Achyuta does not teach or suggest at least one additional electrode positioned on an upper wall or lower wall of the device such that the two electrodes are arranged at opposing sides of the same compartment.
Examiner respectfully disagrees. While claim 1 does say that the at least one electrode and the at least one additional electrodes are positioned at opposing sides of either the upper compartment or lower compartment, claim 1 does not provide additional detail as to what “opposing sides” entails.
Therefore, based on Figure 4A of Achyuta the electrodes 431 on the roof 430 and the electrodes 432 are positioned on opposing sides of cell culture chamber 412. The limitation of claim 1 does not require that the electrodes are within the same volume of either the upper compartment or lower compartment. Claim 1 only requires that opposing sides of either compartment has the electrodes. Therefore, the electrodes on the upper window 239 and electrodes on the filter membrane 266 will meet this limitation.
With respect to applicant arguments on page 14 of 16 in reference to [0081] of Achyuta and it discloses electrodes located on different structural layers that are associated with different compartments of the device rather than being arranged on opposing sides of a single or same compartment as required by claim 1, it is agreed that the electrodes are located on different structural layers. However, electrodes 432 in Figure 4A of Achyuta are still on a side that opposes the roof 430. It is again respectfully noted that claim 1 does not require the electrodes being within the same volume as each other.
Applicant argues on page 14 of 16 that the electrodes 432 of Achyuta are integrated into the base layer 402 and are not independently disposed on porous membrane 410. It is agreed that Achyuta describes in [0081] that electrodes 432 are countersunk in base layer 402, however the electrodes 432 still directly contact the porous barrier 410 and thus the porous barrier 410 will comprise on its surface at least one electrode.
Applicant arguments on page 14 of 16 regarding there being no electrodes on the top surface of the membrane nor that there is any textural support for placing electrodes on both sides of the membranes appears to be arguing that the electrodes of Achyuta would not be opposed to each other within the same compartment. Examiner respectfully maintains that claim 1 does not require that the electrodes are within the same volume of either compartment. Roof 430 and porous barrier 410 are opposing sides that have electrodes on them, and thus the electrodes in Wikswo will be opposed to one another as well.
In response to applicant's argument on page 14 of 16 that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., when the porous membrane 410 is separated from base layer 402, the electrodes 432 of Achyuta will remain in the base layer and not on the membrane itself) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Claim 1 only recites that at least one of the at least two porous membranes comprises on its surface at least one electrode, claim 1 does not require the electrodes to remain on the porous membrane if the device is disassembled.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
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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/S.Y.L./Examiner, Art Unit 1796
/MELVIN C. MAYES/Supervisory Patent Examiner, Art Unit 1759
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