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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 September6 has been entered.
Status of Objections and Rejections
All rejections from the previous office action are withdrawn in view of Applicant’s amendment.
New grounds of rejection are necessitated by the amendments.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 16 and 19-21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Temiz (US 2020/0108385) in view of Kim (US 2018/0143209), and further in view of O’Reilly (US 2016/0025670).
Regarding claim 16, Temiz teaches a biomarker sensor (Fig. 1: microfluidic device; ¶7: analytes are biomarkers), wherein the sensor has a multielectrode array structure (Fig. 1-2) which comprises a carrier substrate (Fig. 1; ¶56: substrate 12) on which at least two separate electrode sets are arranged (Fig. 1-2; ¶57: a set of electrodes 31, 32, 40-42; here each pair of the electrodes 41, 42 at each sensing portion is deemed to be one electrode set), each electrode set comprising one or more electrodes (e.g. Fig. 2A: eight pairs of electrodes 41, 42), and each electrode set being divided into, in the following order
(i) an incubation zone (Fig. 1-2: the exposed parts of electrodes 41, 42 inside the flow path on the surface 20; ¶60: the electrode sensing portions are naked electrode, i.e., not passivated) in which at least one specific receptor is bound to the one or more electrodes (¶117: surface-immobilized receptors; here, the test area is the pattern of spots 61, 62 formed within the same flow path (¶117), and material spots 61, 62 are formed only on a subset of the sensing portions 40-42 of the electrode (¶58); thus the receptor is immobilized on the surface of the electrode),
(ii) a passivation zone in which a passivation layer covers the one or more electrodes (Fig. 1-2: the portion of the electrodes 41, 42 outside of the flow path on the surface 20; ¶60: other electrode portions (those portions that are not meant to be exposed to the liquid, because they are located outside of the flow path) could be passivated),
(iii) a contact zone in which the one or more electrodes are configured to be electrically contacted (Fig. 1-2; ¶57: electrical contacts 51,52), and
contact zones of the individual electrode sets together forming a common contact zone (Fig. 1-2; ¶57: a set of or more electrical contacts 50-52; e.g., the right part of Fig. 1, electrical contacts 51, 52, is a common contact zone).
Temiz does not explicitly disclose the receptor is aptamer.
However, Kim teaches an aptasensor using an aptamer which is bound to the female-specific trace of blood (¶1), for example, using aptamer immobilized gold electrode chip (¶48). The application of the aptamer in the diagnosis and analysis is very natural because the aptamer has a target affinity comparable to that of antibodies, a size much smaller than that of antibodies, and an ability to bind to various target molecules with high binding force (¶9).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Temiz by substituting the antibody receptor with aptamer to be immobilized on the electrode surface as taught by Kim because the aptamer does not only have a target affinity comparable to that of antibodies, but a size much smaller than that of antibodies, and an ability to bind to various target molecules with high binding force (Kim, ¶9).
Temiz does not disclose incubation zones of individual electrode sets or incubation zones and a part of up to 95% of a length of passivation zones of the individual electrode sets being configured to be movable, in each case independently of those of the other electrode sets, by attaching various further parts to the carrier substrate and connecting them via joints or by manufacturing the carrier substrate from a flexible material.
However, O’Reilly teaches a block of individually packaged test strips attached together as shown in Fig. 23 (¶244). The test devices 200 have cuts 90 in between neighboring devices (Fig. 23; ¶239), and frangible interconnecting junctions 72 may be formed in various layers (¶239, also see Fig. 6; ¶212: junctions 72). Thus, O’Reilly teaches each electrode set, i.e., singulated test strip, is independent of other electrode sets, and neighboring test strips are connecting with each other via joints, i.e., junctions 72. Further, the cuts 130 defines a removable cap forming part and another removable part including the incubation zones and less than 95% of the length of passivation zones (Fig. 22; also see Fig. 6: window 64, insulating layer 62).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Temiz and Kim by making incubation zones and up to 95% of a length of passivation zones of individual electrode set movable with the singulated test strip because making the parts separable, like a attachable module, without changing the functions of all components are prima facie obvious. MPEP 2144.04(V)(C). Further, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Temiz and Kim by incorporating the junctions connecting neighboring test strips provide a means to keep materials and test devices in web format as an array and thus reduce the cost of manufacture as taught by O’Reilly (¶224).
Regarding claims 19-21, Temiz teaches wherein teach electrode set comprises two separate electrode sets (claim 19) or at least two electrodes (claim 20) or at least four electrodes (claim 21) (Fig. 2A: the electrode 31 having eight electrodes 41 and the electrode 32 having eight electrode 42, which results in eight electrode pairs 41, 42).
Claim(s) 17-18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Temiz in view of Kim and O’Reilly, and further in view of Esfandyarpour (US 2015/0376692).
Regarding claims 17-18, Temiz, Kim, and O’Reilly disclose all limitations of claim 1, but fail to teach wherein the carrier substrate is manufactured from polydimethylsiloxane (PDMS) (claim 17) or wherein the carrier substrate is manufactured from a flexible material (claim 18).
However, Esfandyarpour teaches an integrated microfluidic devices may be formed from a substrate wherein a plurality of microfluidic channels may be embedded into the substrate (¶332). The substrate material may be PDMS (¶228: polydimethylsiloxane), and depending on the particular application, the substrate material may be rigid or it may be flexible (¶332).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Temiz, Kim, and O’Reilly by substituting the substrate with PDMS or a flexible substrate as taught by Esfandyarpour because PDMS is a suitable material of the substrate of microfluidic devices and a flexible substrate would be suitable for particular applications (¶332). The suggestion for doing so would have been that the selection of a known material, which is based upon its suitability for the intended use, is within the ambit of one of ordinary skill in the art. MPEP § 2144.07.
Claim(s) 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Temiz in view of Kim and O’Reilly, and further in view of Mohapatra (US 2008/0023325).
Regarding claim 22, Temiz, Kim, and O’Reilly disclose all limitations of claim 16, and Temiz further discloses metallic electrodes are patterned in channels of the device (¶3). Temiz and Kim fail to teach the one or more electrodes are made of noble metal or carbon.
However, Mohapatra teaches a microfluidic sensor for detection of biomarkers ([Abstract]). The materials of electrode is preferably comprising noble metals, and most preferably comprises gold, platinum, and carbon (¶21).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Temiz, Kim, and O’Reilly by substituting the metallic electrode with one made of noble metal or carbon as taught by Mohapatra (¶21). The suggestion for doing so would have been that the selection of a known material, which is based upon its suitability for the intended use, is within the ambit of one of ordinary skill in the art. MPEP § 2144.07.
Claim(s) 23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Temiz in view of Kim and O’Reilly, and further in view of Cheung (Y-W Cheung, Aptamer-mediated Plasmodium-specific diagnosis of malaria, Biochimie 2018(145), pp. 131-136).
Regarding claim 23, Temiz, Kim, and O’Reilly disclose all limitations of claim 16, but fails to teach wherein the at least one specific aptamer is 2008s aptamer.
However, Cheung teaches a DNA aptamer, 2008s, that targets P. falciparum lactate dehydrogenase (PfLDH) and a sensitive aptamer-tethered enzyme capture (APTEC) assay ([Abstract]). The 2008s aptamer can be used as bio-recognition molecules for aptamer-based biosensing with advantages including ease of manipulation, ease of synthesis, high stability, high sensitivity and tailored specificity (p. 131, col. 2, para. 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Temiz, Kim, and O’Reilly by substituting the aptamer with 2008s as taught by Cheung because aptamer 2008s has specific target affinity (Kim, ¶9) for biosensing with tailored specificity, ease of manipulation, ease of synthesis, high stability, and high sensitivity (Cheung, p. 131, col. 2, para. 2). Here, the claimed limitations are obvious because all the claimed elements were known in 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(I)(A). The substitution of one specific aptamer for its specific target for another would yield nothing more than predictable results. MPEP 2141(III)(B).
Claim(s) 24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Temiz in view of Kim and O’Reilly, and further in view of Torabi (R. Torabi, Aptamers, the bivalent agents as probes and therapies for coronavirus infections: A systematic review, Molecular and Cellular Probes 2020(53), 101636, pp. 1-8).
Regarding claim 24, Temiz, Kim, and O’Reilly disclose all limitations of claim 16, but fails to teach wherein the at least one specific aptamer is NG1 aptamer.
However, Torabi teaches aptamers are multipotent biological probes for design of sensitive and specific biosensors and therapeutics to treat coronavirus, e.g., for the SARS-CoV-2 ([Abstract]). For example, NG1 aptamer (p. 6, Table 2) is a therapeutic for the target SARS-CoV Helicase because the drug can bind to the helicase and inhibit its activity through blocking the binding to nucleic acids (p. 5, col. 2, para. 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Temiz, Kim, and O’Reilly by substituting the aptamer with NG1 aptamer as taught by Torabi because aptamer has specific target affinity (Kim, ¶9) and NG1 is one aptamer against coronavirus by binding the target, SARS-CoV Helicase (Torabi, Table 2). Here, the claimed limitations are obvious because all the claimed elements were known in 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(I)(A). The substitution of one specific aptamer for its specific target for another would yield nothing more than predictable results. MPEP 2141(III)(B).
Claim(s) 25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Temiz in view of Kim and O’Reilly, and further in view of Xiao (US 2007/0154909).
Regarding claim 25, Temiz, Kim, and O’Reilly disclose all limitations of claim 16, but fails to teach wherein different aptamers or aptamer mixtures are bound in each electrode set.
However, Xiao teaches aptamer-based detector (¶15) including an array of microelectrode in the format of N “pixels” with each pixel containing a unique oligonucleotide structure and with all microelectrodes electrochemically addressable, thereby enabling detection of N different targets (¶55).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Temiz, Kim, and O’Reilly by using different aptamers bound to each electrode set as taught by Xiao because it would enable detection of multiple different target detection (¶55). Here, the claimed limitations are obvious because all the claimed elements were known in 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(I)(A).
Claim(s) 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Temiz in view of Kim, O’Reilly, and Xiao, and further in view of Torabi
Regarding claim 26, Temiz, Kim, O’Reilly, and Xiao disclose all limitations of claim 25, but fails to teach wherein the different aptamers or aptamer mixtures bound in each electrode set are (1) in a first electrode set 2008s aptamer and in a second electrode set 2106s aptamer and in a third electrode set pL1 aptamer and in a fourth electrode set LDHp11 aptamer or (2) in a first electrode set C7 aptamer and in a second electrode set C11 aptamer or (3) in at least two electrode sets aptamers selected from one or more of C5 aptamer, C7 aptamer, C9 aptamer, C11 aptamer, C15 aptamer or Il aptamer, IH1 aptamer, SG1 aptamer, HCS1 aptamer, and NG1 aptamer.
However, Torabi teaches aptamers are multipotent biological probes for design of sensitive and specific biosensors and therapeutics to treat coronavirus, e.g., for the SARS-CoV-2 ([Abstract]). For example, NG1 aptamer (p. 6, Table 2) is a therapeutic for the target SARS-CoV Helicase because the drug can bind to the helicase and inhibit its activity through blocking the binding to nucleic acids (p. 5, col. 2, para. 2). Further, Kim teaches each aptamer exhibits specifically high affinity for its target substances with high affinity and specificity (¶¶7-8). Xiao teaches an array of microelectrode of the aptamer-based detector in the format of N “pixels” with each pixel containing a unique oligonucleotide structure and with all microelectrodes electrochemically addressable, thereby enabling detection of N different targets (¶55).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Temiz, Kim, O’Reilly, and Xiao by using different aptamers or aptamer mixtures bound in each electrode set, e.g., using NG1 aptamer in at least two electrode sets, as recited because all microelectrodes electrochemically addressable (Xiao, ¶55) and each electrode set would be individually used to detect the specific target. Here, the claimed limitations are obvious because all the claimed elements were known in 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(I)(A).
Claim(s) 27 is/are rejected under 35 U.S.C. 103 as being unpatentable over Temiz in view of Kim and O’Reilly, and further in view of Khattak (US 2015/0136599).
Regarding claim 27, Temiz, Kim, and O’Reilly disclose all limitations of claim 16, but fails to teach wherein the sensor further comprises collectively a reference electrode and a counter electrode.
However, Khattak teaches a microfluidic device for molecule detection (¶2), wherein a plurality of sensors 758 are disposed within the analysis channel 732 (Fig. 18A; ¶130). In this embodiment, each sensor 758 is formed of a working electrode 758a, a reference electrode 758b, and a counter electrode 758c (Fig. 18A; ¶130). In the other embodiment, two or more working electrodes configured to share a same reference electrode (claim 16) and share a same counter electrode (claim 17; also see claim 18).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified Temiz, Kim, and O’Reilly by using a collective reference electrode and a counter electrode shared by all sensing electrodes as taught by Khattak because it would reduce the number of electrodes and provide a compact electrode configuration. Here, the claimed limitations are obvious because all the claimed elements were known in 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(I)(A).
Response to Arguments
Applicant’s arguments have been considered but are unpersuasive.
Applicant amended to add a limitation “by attaching various further parts to the carrier substrate and connecting them via joints or by manufacturing the carrier substrate from a flexible material” and argues the limitation “the individual electrode sets being configured to be movable, in each case independently of those of the other electrode sets” is not merely a functional limitation (Response, p. 12, para. 2). This argument is moot because the prior art, Belgrader, is now relied on to teach these limitations.
Applicant argues Temiz discloses a set of electrodes 31, 32, 40-42 and points out that electrodes 31 and 32 form an electrode set, while the reference numerals 40-42 designate sensing portions (p. 13, para. 1-4), and the second set of electrode pairs would be the timing electrodes as shown in Fig. 11 (p. 13, para. 4); otherwise, they are not “separate” sets of electrodes. This argument is unpersuasive because Temiz teaches multiple sensing portions having electrode pairs 41 and 42, and thus each of the electrode pair is deemed to be an electrode set. Since they are within the different location along the flow path, they are deemed to be “separate.”
Applicant argues Temiz does not suggest that the sensing portions (40-42) may be provided with immobilized receptors (p. 14, para. 3). This argument is unpersuasive because Temiz disclose the pattern of spots 61, 62 may be formed within the flow path so that a line or an area (e.g., rectangle) along the test line comprising surface-immobilized receptors (Temiz, ¶117), and material spots 61, 62 are formed only on a subset of the sensing portions 40-42 of the electrode (¶58). Thus, the receptor must be immobilized on the electrode surface. Further, Kim also discloses the aptamer is immobilized on gold electrode (Kim, ¶48).
Applicant notes the limitation “the contact zones of the individual electrode sets together form a common contact zone” (Response, p. 14, para. 4). Examiner responds that the contact zones of the individual electrode sets together forming a common contact zone (Temiz, Fig. 1-2; ¶57: a set of or more electrical contacts 50-52; e.g., the right part of Fig. 1, electrical contacts 51, 52, is a common contact zone).
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning (Response, p. 15, para. 3), 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). Here, Temiz teaches using surface-immobilized receptor to detect a specific analyte upon binding (Temiz, ¶117), and Kim teaches an aptasensor using an aptamer for analysis because the aptamer has an ability to bind to various target molecules with high binding force (Kim, ¶9). Thus, one of ordinary skill in the art would find it obvious to substitute the receptor with aptamer for detecting analyte because aptamer has versality to bind various target molecules with high binding force. Here, the claimed limitations are obvious because all the claimed elements were known in 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(I)(A).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAITLYN M SUN whose telephone number is (571)272-6788. The examiner can normally be reached on M-F: 8:30am - 5:30pm.
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/C. SUN/Primary Examiner, Art Unit 1795
