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`UNITED STATES DEPARTMENT OF COMMERCE
`United States Patent and TrademarkOffice
`Address; COMMISSIONER FOR PATENTS
`P.O. Box 1450
`Alexandria, Virginia 22313-1450
`
`16/116,099
`
`08/29/2018
`
`Masaya NAKATANI
`
`083710-2219
`
`3503
`
`McDermott Will and Emery LLP
`The McDermott Building
`500 North Capitol Street, N.W.
`Washington, DC 20001
`
`ALLEN,JOSHUA 1.
`
`1795
`
`PAPER NUMBER
`
`NOTIFICATION DATE
`
`DELIVERY MODE
`
`04/30/2021
`
`ELECTRONIC
`
`Please find below and/or attached an Office communication concerning this application or proceeding.
`
`The time period for reply, if any, is set in the attached communication.
`
`Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
`following e-mail address(es):
`
`mweipdocket@mwe.com
`
`PTOL-90A (Rev. 04/07)
`
`

`

`
`
`Disposition of Claims*
`1-2,4-10 and 13-16 is/are pending in the application.
`)
`Claim(s)
`5a) Of the above claim(s) ___ is/are withdrawn from consideration.
`Cj] Claim(s)
`is/are allowed.
`Claim(s) 1-2,4-10 and 13-16 is/are rejected.
`S)
`) © Claim(s)____is/are objected to.
`Cj) Claim(s
`are subjectto restriction and/or election requirement
`)
`S)
`* If any claims have been determined allowable, you maybeeligible to benefit from the Patent Prosecution Highway program at a
`participating intellectual property office for the corresponding application. For more information, please see
`http://www.uspto.gov/patents/init_events/pph/index.jsp or send an inquiry to PPHfeedback@uspto.gov.
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`) )
`
`Application Papers
`10) The specification is objected to by the Examiner.
`11)0) The drawing(s) filedon__ is/are: a)(J accepted or b)() objected to by the Examiner.
`Applicant may not request that any objection to the drawing(s) be held in abeyance. See 37 CFR 1.85(a).
`Replacement drawing sheet(s) including the correction is required if the drawing(s) is objected to. See 37 CFR 1.121 (d).
`
`Priority under 35 U.S.C. § 119
`12)1) Acknowledgment is made of a claim for foreign priority under 35 U.S.C. § 119(a)-(d)or (f).
`Certified copies:
`c)Z None ofthe:
`b)() Some**
`a)C All
`1.2 Certified copies of the priority documents have been received.
`2.1.) Certified copies of the priority documents have been received in Application No.
`3.1.) Copies of the certified copies of the priority documents have been receivedin this National Stage
`application from the International Bureau (PCT Rule 17.2(a)).
`* See the attached detailed Office action for a list of the certified copies not received.
`
`Attachment(s)
`
`1)
`
`Notice of References Cited (PTO-892)
`
`2) (J Information Disclosure Statement(s) (PTO/SB/08a and/or PTO/SB/08b)
`Paper No(s)/Mail Date
`U.S. Patent and Trademark Office
`
`3) (J Interview Summary (PTO-413)
`Paper No(s)/Mail Date
`(Qj Other:
`
`4)
`
`PTOL-326 (Rev. 11-13)
`
`Office Action Summary
`
`Part of Paper No./Mail Date 20210426
`
`Application No.
`Applicant(s)
`16/116,099
`NAKATANI etal.
`
`Office Action Summary Art Unit|AIA (FITF) StatusExaminer
`JOSHUA L ALLEN
`1795
`No
`
`
`
`-- The MAILING DATEofthis communication appears on the cover sheet with the correspondence address --
`Period for Reply
`
`A SHORTENED STATUTORY PERIOD FOR REPLYIS SET TO EXPIRE 3 MONTHS FROM THE MAILING
`DATE OF THIS COMMUNICATION.
`Extensions of time may be available underthe provisions of 37 CFR 1.136(a). In no event, however, may a reply betimely filed after SIX (6) MONTHSfrom the mailing
`date of this communication.
`If NO period for reply is specified above, the maximum statutory period will apply and will expire SIX (6) MONTHSfrom the mailing date of this communication.
`-
`- Failure to reply within the set or extended period for reply will, by statute, cause the application to become ABANDONED (35 U.S.C. § 133}.
`Any reply received by the Office later than three months after the mailing date of this communication, evenif timely filed, may reduce any earned patent term
`adjustment. See 37 CFR 1.704(b).
`
`Status
`
`1) Responsive to communication(s) filed on 01/25/2021.
`C} A declaration(s)/affidavit(s) under 37 CFR 1.130(b) was/werefiled on
`
`2a)L) This action is FINAL. 2b)¥)This action is non-final.
`3)02 An election was madeby the applicant in responseto a restriction requirement set forth during the interview
`on
`; the restriction requirement and election have been incorporated into this action.
`4\0) Since this application is in condition for allowance except for formal matters, prosecution as to the merits is
`closed in accordance with the practice under Exparte Quayle, 1935 C.D. 11, 453 O.G. 213.
`
`

`

`Application/Control Number: 16/116,099
`Art Unit: 1795
`
`Page 2
`
`DETAILED ACTION
`
`Notice of Pre-AlA or AIA Status
`
`1.
`
`The present application is being examined under the pre-AlA first to invent
`
`provisions.
`
`Continued Examination Under 37 CFR 1.114
`
`2.
`
`A requestfor continued examination under 37 CFR 1.114, including the fee set
`
`forth in 37 CFR 1.17(e), wasfiled 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
`
`01/25/2021 has been entered.
`
`Status of the Rejection
`
`3.
`
`4.
`
`5.
`
`The claim objections have been overcome bythe applicant's amendments.
`
`New claim objections are necessitated by the amendments.
`
`New groundsof rejection under 35 U.S.C. § 112(b) are necessitated by the
`
`amendments.
`
`6.
`
`The rejections of claims 3 and 11-12 are obviated by Applicant’s cancellation of
`
`the claims.
`
`7.
`
`All 35 U.S.C. § 103 rejections from the previous office action are substantially
`
`maintained and modified only in response to the amendmentsto the claims.
`
`

`

`Application/Control Number: 16/116,099
`Art Unit: 1795
`
`Page 3
`
`8.
`
`New groundsof rejection under 35 U.S.C. § 103 are necessitated for new claims
`
`14-16.
`
`9.
`
`Claims 1 and 16 are objected to because ofthe following informalities:
`
`Claim Objections
`
`a.
`
`Claim 1, lines 21-22: please correct the typographical error to recite
`
`“ohysicochemical change’rather than “physiochemical change’.
`
`b.
`
`Claim 16, lines 8-9: please remove “the”to recite “among the plurality of
`
`[[the]] electrodes” (i.e., recite “the plurality of electrodes” rather than “the plurality
`
`of the electrodes”) to be consistent with the language throughout the claims.
`
`C.
`
`Claim 16,line 15: please add “is” between “the second electrode” and
`
`“providing” to recite “wherein the second electrode isprovided at a second
`
`position’.
`
`d.
`
`Appropriate correction is required.
`
`10.—The following is a quotation of 35 U.S.C. 112(b):
`
`Claim Rejections - 35 USC § 112
`
`(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-AlA), second paragraph:
`The specification shall conclude with one or moreclaims particularly pointing out and distinctly
`claiming the subject matter which the applicant regards as his invention.
`
`11.
`
`Claims 1-2, 4-10, and 13-16 are rejected under 35 U.S.C. 112(b) or 35 U.S.C.
`
`112 (pre-AlA), second paragraph, as being indefinite for failing to particularly point out
`
`

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`Application/Control Number: 16/116,099
`Art Unit: 1795
`
`Page 4
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`and distinctly claim the subject matter which the inventor or a joint inventor (or for
`
`applications subject to pre-AlA 35 U.S.C. 112, the applicant), regards as the invention.
`
`12.
`
`Claims 1 and 16 eachrecite “a first electrode”, “a second electrode’, “an
`
`innermostelectrode” and “an outermost electrode” wherein each of the electrodes are
`
`“among the plurality of electrodes”. It appears from the language of the claims that there
`
`are four distinct electrodes wherein the first and second electrodes are utilized in the
`
`measurements and wherein the “innermostelectrode” and “outermost electrode” are
`
`referenced relative to their location with respect to the placing area and inner wall,
`
`respectively. It is unclearif there are four distinct electrodes or if either one of or both of
`
`the first/second electrodes are the same as the inner/outer electrodes, respectively. For
`
`instance, the figures suggest a three electrode cell wherein at least one of the first or
`
`second electrode must be considered the inner or outer electrode. Although Fig. 3 does
`
`appearto display four electrodes, these electrodes are not disposed on the “first surface
`
`of the base’, which is the same surface as the placing area and the wall/inner wall, as
`
`required by the claims. Claims 2, 4-10 and 13-15 are further rejected by virtue of their
`
`dependence upon and becausetheyfail to cure the deficiencies of claim 1.
`
`Claim Rejections - 35 USC § 103
`
`13.
`
`The text of those sections of Title 35, U.S. Code not included in this action can
`
`be found in a prior Office action.
`
`14.
`
`Claim 1-2, 4-9, 13, and 16 are rejected under pre-AlA 35 U.S.C. 103(a) as being
`
`unpatentable over Dateet al. (Y. Date, S. Takano, H. Shiku, K. Ino, T. Ito-Sasaki, M.
`
`Yokoo, H. Abe, T. Matsue, Monitoring oxygen consumption of a single mouse embryos
`
`

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`Application/Control Number: 16/116,099
`Art Unit: 1795
`
`Page 5
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`using an integrated electrochemical microdevice, Biosensors and Bioelectronics 30
`
`(2011) 100-106) in view of Liu et al. (US 4,571,292 A2, cited in IDS), and further in view
`
`of Shacham-Diamondetal. (US 2015/0150493 A1, hereinafter referred to as
`
`Diamond for simplicity).
`
`15.
`
`Regarding claim 1, Date discloses a method of examining a substance of
`
`biological origin by an examination device (electrochemical microdevice and method for
`
`measuring oxygen consumption of an embryo[abstract]), comprising:
`
`e.
`
`measuring a first physicochemical change bya first electrode in response
`
`to the substance of biological origin (the first working electrode WE1 is used to
`
`measure the change in oxygen concentration and the total oxygen consumption
`
`of the embryo(i.e., a physicochemical change) between the bulk and the area
`
`near the sample as a result of the developmental growth of the embryo at three
`
`different developmental stages from the two-cell stage to a blastocyst stage [Pg.
`
`103, Equation 4; Pg. 104 through Pg. 105, Para. 1; Figs. 5a-5b]);
`
`f.
`
`measuring a second physiochemical change by a second electrodein
`
`responseto the substanceof biological origin (the second working electrode
`
`WE2 is used to measure the change in oxygen concentration and the total
`
`oxygen consumption of the embryo(i.e., a physicochemical change) between the
`
`bulk and the area near the sample as a result of the developmental growth of the
`
`embryo at three different developmental stages from the two-cell stage to a
`
`blastocyst stage [Pg. 103, Equation 4; Pg. 104 through Pg. 105, Para. 1; Figs.
`
`5a-5b; Note: WE1 and WE2 are measuredindividually so each one of the
`
`working electrodes would be measuring an independent change in the oxygen
`
`

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`Application/Control Number: 16/116,099
`Art Unit: 1795
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`Page 6
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`concentration and total oxygen consumption of the embryo and thus each
`
`individual electrode would be measuring an individual “physicochemical
`
`change’”]); and
`
`g.
`
`measuring a concentration gradient of a substance dissolving in a solution
`
`around the substanceof biological origin based on the measuredfirst
`
`physiochemical change and the measured second physiochemical change, the
`
`substance dissolving due to an activity of the substance of biological origin (the
`
`change in oxygen concentration and the total oxygen consumption of the embryo
`
`is recorded between the bulk and the area near the sample as a result of the
`
`developmental growth of the embryo at three different developmental stages
`
`from the two-cell stage to a blastocyst stage wherein the concentration profile
`
`around the embryo sample forms a hemispherical shape according to spherical
`
`diffusion theory wherein the oxygen concentration profile is in accordance with an
`
`ideal hemispherical diffusion [Pgs. 102-103, 2.6. Estimation of oxygen
`
`consumption based on spherical diffusion theory; Note: the limitation “obtaining a
`
`concentration gradient” does not imply that any measurement/detection of a
`
`concentration gradient has occurred, but rather that a concentration gradient
`
`itself is “obtained” (i.e., occurs). In the instant case, a dissolved oxygen
`
`concentration gradient inherently forms as suggested by the spherical diffusion
`
`theory model wherein the embryo consumes oxygen close to the embryo and a
`
`concentration gradient forms as other oxygen diffuses towards the embryo. Date
`
`therefore inherently discloses the step of “obtaining a concentration gradient of a
`
`substance dissolving in the solution around the substance of biological origin
`
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`Application/Control Number: 16/116,099
`Art Unit: 1795
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`based on the measuredfirst physiochemical change and the measured second
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`physiochemical change”as the dissolved oxygen would inherently form a
`
`concentration gradient/profile in accordance with an ideal hemispherical diffusion
`
`as taught by Date on Pg. 102 under equation (7) and both electrodes measure
`
`such dissolved oxygen]);
`
`h.
`
`wherein the examination device includes: (microdevice [Fig. 3]):
`
`
`
`L. a base havingafirst surface (a glass substrate hasafirst surface where
`
`the micropit is located [2.2. Device Fabrication, Fig. 3]);
`
`j.
`
`a wall provided on the first surface of the base, the wall having an inner
`
`wall, the first surface of the base and the inner wall of the wall constituting a
`
`measuring region (the device comprises a PDMS micro well that forms a wall
`
`wherein the inner surface of the wall and the substrate form a measuring region
`
`that comprises the embryo and measurement solution [2.2. Device Fabrication;
`
`2.4. Oxygen measurement using microelectrode array; Fig. 3]);
`
`K.
`
`a plurality of electrodes cercentteath_providedon the first surface of the
`
`base (electrodes W1-W3 are provided on the surface of the base [Fig. 3]);
`
`I.
`
`a placing area provided iAside-an innermost electrode among the plurality
`
`of electrodes on the first surface, on which the substance of biological origin is
`
`placed (the device comprises an area on the top surface of the substrate where
`
`the embryois placed that further includes a micropit etched into the top surface
`
`of the substrate wherein the microelectrodes (WE1/WE2) are disposed within the
`
`area that comprises the embryo on the top surface of the substrate [2.2. Device
`
`Fabrication; Fig. 3]);
`
`

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`Application/Control Number: 16/116,099
`Art Unit: 1795
`
`Page 8
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`m.
`
`wherein the plurality of electrodes include the first electrode and the
`
`second electrode (electrodes W1-W3 are provided on the surface of the base
`
`[Fig. 3]);
`
`n.
`
`wherein the first electrode is provided at a first position on the first surface
`
`andis-cennectedte-atirstinsttumentator-ampifier (working electrode 1
`
`(WE1) is
`
`disposedata first position on the top surface of the substrate [Pg. 101, 2.2.
`
`Device Fabrication, Para. 1; Fig. 3a-3c]);
`
`O.
`
`wherein the second electrode is provided at a second position, different
`
`from the first position, on the first surface andis-cennectedte-asecend
`
`
`
`instrumentation_ampliier diferenttremthe-firstinstumentamoptifier
`
`(working
`
`electrode 2 (WE2) is disposed on the top surface of the substrate [Pg. 101, 2.2.
`
`Device Fabrication, Para. 1; Fig. 3a-3c]); and
`
`p.
`
`wherein the measuring region is filled with a solution (the inner surface of
`
`the wall and the substrate form a measuring region that comprises the embryo
`
`and measurementsolution [2.2. Device Fabrication; 2.4. Oxygen measurement
`
`using microelectrode array; Fig. 3]); and
`
`q.
`
`wherein the substanceof biological origin is placed on the placing area to
`
`be examined (an embryois placed in the placing area on the micropit by adding
`
`the measurement medium ERAM-2 comprising the embryo to the micropit
`
`wherein the embryois immobilized on the micropit by gravity sedimentation [Pg.
`
`102, 2.5 Oxygen consumption measurement of single mouse embryo using
`
`amperometric detection; Figs. 2-3]).
`
`

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`Application/Control Number: 16/116,099
`Art Unit: 1795
`
`Page 9
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`16.
`
`Date discloses wherein the first and second working electrodes W1/W2 are
`
`circularly located around the micropit but fails to teach wherein the plurality of
`
`electrodes are “concentric”. Date is also silent on instrument amplifiers and thus fails to
`
`expressly teach wherein the first electrode is “connected to a first instrument amplifier”
`
`and wherein the second electrode is “connected to a second instrument amplifier
`
`different from the first instrument amplifier’.
`
`17.
`
`Liu discloses an electrochemicalcell for sensing electrochemically active species
`
`[abstract] wherein the electrodes 12/60, 14/63, and 13/64 are arranged concentrically to
`
`one another [Pg. 10:23-37; Fig. 6]. Liu further teaches that the current flow through the
`
`electrodes may be measured accurately by the meter wherein each electrode is
`
`connected to an amplifier 34/30/31 wherein the amplifier provides appropriate gain
`
`and/or impedance requirements for accurate current measurement wherein the
`
`information obtained by the working electrode amplifier 34, when employedin relation to
`
`the other amplifiers 30/31, allow for information to be obtained representing
`
`concentration of the electrochemically active species [Col. 8:59 through Col. 9:34; Col.
`
`11:40-45; Fig. 2].
`
`18.—It would have been obvious to one ofordinary skill in the art before the claimed
`
`invention to modify the circularly arranged pattern disclosed by Dateto instead include a
`
`circularly arranged concentric design of the electrodes because Liu discloses that
`
`concentric electrodes are a suitable alternative electrode arrangement for the analysis
`
`of electrochemically active species in an electrochemical sensor [Liu; abstract; Fig. 6;
`
`Note: the modification of Date in view of Liu would necessarily form the “placing area”
`
`inside of the innermost electrode]. The simple substitution of one known element for
`
`

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`Application/Control Number: 16/116,099
`Art Unit: 1795
`
`Page 10
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`another (i.e., substituting one circularly arranged electrode pattern for a concentrically
`
`arranged electrode pattern) is likely to be obvious when predictable results are achieved
`
`(i.e., monitoring/detecting the electrochemical properties of an electrochemically active
`
`species) [MPEP § 2143(B)]. Furthermore, differences in shape will not support the
`
`patentability of subject matter encompassedbythe prior art absent persuasive evidence
`
`that the particular configuration is significant. MPEP § 2144.04(IV)(B). Therefore, it
`
`would have been a matter of choice to use a concentric shape, especially considering
`
`the teachings of Liu in Fig. 6, which a person ofordinary skill in the art would have
`
`found obvious. It would have been obvious to one of ordinary skill in the art before the
`
`claimed invention to modify the electronic structure of Date to include instrument
`
`amplifiers connected to the electrodes because Liu further teaches that such amplifiers
`
`provides appropriate gain and/or impedance requirements for accurate current
`
`measurement and allow for information to be obtained representing the concentration of
`
`the electrochemically active species [Col. 8:59 through Col. 9:34; Col. 11:40-45; Fig. 2].
`
`Furthermore, the claimed amplifier limitations are obvious becauseall the claimed
`
`elements were knownin the prior art and one skilled in the art could have combined the
`
`elements as claimed by known methods with no change in their respective functions,
`
`and the combination yielded nothing more than predictable results (i.e., adding
`
`instrument amplifiers, which would be well known by one skilled in the art, by known
`
`methods with no change in their respective functions would provide the obvious and
`
`predictable benefit of amplifying the signal output of the electrodes, as taught by Liu)
`
`[MPEP 2143(A)].
`
`

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`Application/Control Number: 16/116,099
`Art Unit: 1795
`
`Page 11
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`19.
`
`Date and Liu are also silent with regards to the spacing between the electrodes
`
`and the wall and thus fail to expressly teach “wherein a distance between an outermost
`
`electrode among the plurality of electrodes and the inner wall is longer than a shortest
`
`distance between two ofthe plurality of electrodes’.
`
`20.
`
`Diamond teaches an electrochemical sensor for measuring the concentration of
`
`target substances including biological materials [Paras. 0003, 0067-0069, 0076]
`
`wherein the sensor can be formed inside of wells wherein a distance from the outer
`
`electrode to the inner surface of the well is longer than the inner electrode spacing
`
`[Paras. 0096; Figs. 7C-7D].
`
`21.
`
`‘It would have been obvious to one of ordinary skill in the art before the claimed
`
`invention to modify the structure of Date such that the electrodes are disposed at the
`
`center of the well, spaced apart from the inner surface of the well, because Diamond
`
`teaches that such structure is knownin the art for forming electrochemical sensors for
`
`measuring biological target species [Paras. 0096; Figs. 7C-7D] and one skilled in the art
`
`would appreciate that a larger well size would allow for a larger amount of sample to be
`
`added to the well while maintaining the same inter-electrode spacing (which would not
`
`modify the sensor sensitivity) and thus all the claimed elements were knownin the prior
`
`art and one skilled in the art could have combined the elements as claimed by known
`
`methods with no change in their respective functions, and the combination yielded
`
`nothing more than predictable results [MPEP 2143(A)]. Furthermore, it would have been
`
`an obvious matter of design choice to increase the size of the well while maintaining the
`
`same electrode spacing since applicant has not disclosed that the relative dimensions
`
`between the well wall and the inter-electrode spacing solves any stated problem or is for
`
`

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`Application/Control Number: 16/116,099
`Art Unit: 1795
`
`Page 12
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`any particular purpose and it appears that the invention would perform equally well with
`
`inner walls spaced closer than the inter-electrode spacing [MPEP 2144.04].
`
`22.
`
`Regarding claim 2, Date further discloses wherein said measuring the first
`
`physicochemical change comprises measuring a current flowing in the first electrode,
`
`and wherein said measuring the second physicochemical change comprises measuring
`
`a current flowing in the second electrode (the first working electrode WE1 and second
`
`working electrode WE2 both measure a current indicative of the change in oxygen
`
`concentration and the total oxygen consumption of the embryo(i.¢., a physicochemical
`
`change) between the bulk and the area near the sample as a result of the
`
`developmental growth of the embryoat three different developmental stages from the
`
`two-cell stage to a blastocyst stage [Pg. 103, Equation 4; Pg. 104 through Pg. 105,
`
`Para. 1; Figs. 46 and 5a; Note: WE1 and WE2 are measured individually so each one of
`
`the working electrodes measure an independent change in the oxygen concentration
`
`and total oxygen consumption of the embryo and thus eachindividual electrode would
`
`be measuring an individual current indicative of the “physicochemical change’]).
`
`23.
`
`Regarding claim 4, Date further discloses wherein the substance of biological
`
`origin in the examination device incudesa cell, a tissue, or an embryo (a single mouse
`
`embryo waspositioned in the micropit for analysis [abstract; Fig. 3c]).
`
`24.
`
`Regarding claim 5, Date further discloses wherein the base of the examination
`
`device is formed with glass, resin, silicon, or ceramics (the substrate is a synthetic
`
`quartz glass substrate wherein the micropit is formed in the glass [Pg. 101, 2.2. Device
`
`fabrication, Paras. 1-2]).
`
`

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`Application/Control Number: 16/116,099
`Art Unit: 1795
`
`Page 13
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`25.
`
`Regarding claim 6, Date further discloses wherein the first electrode and the
`
`second electrode in the examination device are on the same plane as the placing area
`
`where the substanceof biological origin is placed (the microelectrode array, including
`
`WE1-WE3, are disposedin the examination device on the same plane as the micropit
`
`“placing area” where the embryois disposed [Fig. 3a-3c; Note: the modification by Liu
`
`wherein the electrodes are concentric to one another would also put the WE1-WE3 in
`
`the same plane, only changing their shape to be concentric as outlined in Liu]).
`
`26.
`
`Regarding claim 7, Date further discloses wherein the first electrode and the
`
`second electrode in the examination device are made from platinum, gold or silver (the
`
`three microelectrodes WE1-WE3 are made of platinum [Pg. 103, 3. Results and
`
`Discussion, Para. 1; Figs. 3-4]).
`
`27.
`
`Regarding claim 8, Date further discloses wherein the first electrode and the
`
`second electrode in the examination device individually measure potential differences or
`
`currents between a reference electrode and the first electrode and the second
`
`electrode, respectively (the first working electrode WE1 and second working electrode
`
`WE2 both measure a current indicative of the change in oxygen concentration and the
`
`total oxygen consumption of the embryo between the bulk and the area near the sample
`
`as a result of the developmental growth of the embryo at three different developmental
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`stages from the two-cell stage to a blastocyst stage; the electrodes are each measured
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`as two electrode cells relative to the Ag/AgCl reference electrode [Pg. 102, 2.3.
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`Apparatus; Pg. 103, Equation 4; Pg. 104 through Pg. 105, Para. 1; Figs. 4b and 5a)).
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`28.
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`Regarding claim 9, Date further discloses wherein the wall of the examination
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`device is formed with glass, resin, silicon, or ceramics (the wall is formed with PDMS
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`and acrylic resin that is permanently bonded to the electrode patterned substrate [Pg.
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`101, 2.2. Device Fabrication, Para. 4).
`
`29.
`
`Regarding claim 13, Date, as modified by Liu above, further discloses wherein
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`the first electrode and the second electrode are circular when viewed in a direction
`
`facing the first surface (the electrodes are circular and are circumferentially arranged
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`around a central axis [Liu, Col. 10:23-37]).
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`30.
`
`Regarding claim 16, Date discloses an examination device (electrochemical
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`microdevice and method for measuring oxygen consumption of an embryo [abstract;
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`Note: The preamble "for examining a substance of biological origin" is a statement of
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`intended use that does notfurther limit the claimed invention [see MPEP 2111.02].
`
`While features of an apparatus mayberecited either structurally or functionally, claims
`
`directed to an apparatus must be distinguished from the prior art in terms of structure
`
`rather than function. In re Schreiber, 128 F.3d 1473, 1477-78, 44 USPQ2d 1429, 1431-
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`32 (Fed. Cir. 1997) [MPEP 2114]. Since the structure of the prior art teachesall of the
`
`structural limitations of the claim, the structure is considered capable of meeting the
`
`intended uselimitations]), comprising:
`
`
`
`a. a base havingafirst surface (a glass substrate hasafirst surface where
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`the micropit is located [2.2. Device Fabrication, Fig. 3]);
`
`b.
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`a wall provided on the first surface of the base, the wall having an inner
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`wall, the first surface of the base and the inner wall of the wall constituting a
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`measuring region (the device comprises a PDMS micro well that forms a wall
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`wherein the inner surface of the wall and the substrate form a measuring region
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`that comprises the embryo and measurement solution [2.2. Device Fabrication;
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`2.4. Oxygen measurement using microelectrode array; Fig. 3]);
`
`C.
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`a plurality of electrodes cercentteath_providedon the first surface of the
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`base (electrodes W1-W3 are provided on the surface of the base [Fig. 3]);
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`d.
`
`a placing area provided iAside-an innermost electrode among the plurality
`
`of electrodes on the first surface, on which the substance of biological origin is
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`placed (the device comprises an area on the top surface of the substrate where
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`the embryois placed that further includes a micropit etched into the top surface
`
`of the substrate wherein the microelectrodes (WE1/WE2) are disposed within the
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`area that comprises the embryo on the top surface of the substrate [2.2. Device
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`Fabrication; Fig. 3]);
`
`e.
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`wherein the plurality of electrodes include the first electrode and the
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`second electrode (electrodes W1-W3 are provided on the surface of the base
`
`[Fig. 3]);
`
`f.
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`wherein the first electrode is provided at a first position on the first surface
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`andis-cennectedte-atirstinsitumentater-ampifier (working electrode 1
`
`(WE1) is
`
`disposedata first position on the top surface of the substrate [Pg. 101, 2.2.
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`Device Fabrication, Para. 1; Fig. 3a-3c]);
`
`g.
`
`wherein the second electrode [is] provided at a second position, different
`
`from the first position, on the first surface andis-cennectedte-asecend
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`
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`instrumentation_ampliier diferenttremthe-firstinstumentamoptifier
`
`(working
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`electrode 2 (WE2) is disposed on the top surface of the substrate [Pg. 101, 2.2.
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`Device Fabrication, Para. 1; Fig. 3a-3c]); and
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`h.
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`wherein the measuring region is filled with a solution (the inner surface of
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`the wall and the substrate form a measuring region that comprises the embryo
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`and measurementsolution [2.2. Device Fabrication; 2.4. Oxygen measurement
`
`using microelectrode array; Fig. 3]).
`
`31.|Date discloses wherein the first and second working electrodes W1/W2 are
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`circularly located around the micropit but fails to teach wherein the plurality of
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`electrodes are “concentric”. Date is also silent on instrument amplifiers and thus fails to
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`expressly teach wherein the first electrode is “connected to a first instrument amplifier’
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`and wherein the second electrode is “connected to a second instrument amplifier
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`different from the first instrument amplifier’.
`
`32.
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`Liu discloses an electrochemical cell for sensing electrochemically active species
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`[abstract] wherein the electrodes 12/60, 14/63, and 13/64 are arranged concentrically to
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`one another [Pg. 10:23-37; Fig. 6]. Liu further teaches that the current flow through the
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`electrodes may be measured accurately by the meter wherein each electrodeis
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`connected to an amplifier 34/30/31 wherein the amplifier provides appropriate gain
`
`and/or impedance requirements for accurate current measurement wherein the
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`information obtained by the working electrode amplifier 34, when employedin relation to
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`the other amplifiers 30/31, allow for information to be obtained representing
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`concentration of the electrochemically active species [Col. 8:59 through Col. 9:34; Col.
`
`11:40-45; Fig. 2].
`
`33.
`
`It would have been obvious to one of ordinary skill in the art before the claimed
`
`invention to modify the circularly arranged pattern disclosed by Dateto instead include a
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`circularly arranged concentric design of the electrodes because Liu discloses that
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`concentric electrodes are a suitable alternative electrode arrangement for the analysis
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`of electrochemically active species in an electrochemical sensor [Liu; abstract; Fig. 6;
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`Note: the modification of Date in view of Liu would necessarily form the “placing area”
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`inside of the innermost electrode]. The simple substitution of one known element for
`
`another (i.e., substituting one circularly arranged electrode pattern for a concentrically
`
`arranged electrode pattern) is likely to be obvious when predictable results are achieved
`
`(i.e., monitoring/detecting the electrochemical properties of an electrochemically active
`
`species) [MPEP § 2143(B)]. Furthermore, differences in shape will not support the
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`patentability of subject matter encompassedbythe prior art absent persuasive evidence
`
`that the particular configuration is significant. MPEP § 2144.04(IV)(B). Therefore, it
`
`would have been a matter of choice to use a concentric shape, especially considering
`
`the teachings of Liu in Fig. 6, which a person of ordinary skill in the art would have
`
`found obvious. It would have been obvious to one of ordinary skill in the art before the
`
`claimed invention to modify the electronic structure of Date to include instrument
`
`amplifiers connected to the electrodes becauseLiu further teaches that such amplifiers
`
`provides appropriate gain and/or impedance requirements for accurate current
`
`measurement and allow for information to be obtained representing the concentration of
`
`the electrochemically active species [Col. 8:59 through Col. 9:34; Col. 11:40-45; Fig. 2].
`
`Furthermore, the claimed amplifier limi