DETAILED ACTION
Status of the Claims
1. Claims 1, 3-8 and 10-13 are pending.
Status of the Rejections
2. Rejection of claims 6 and 11 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph is being withdrawn in view of applicant’s amendment.
Claim Rejections - 35 USC § 103
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, 7, 10-11 and 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lindsay (US 2010/0084276) in view of Holt (US 2013/0260472).
Claim 1. Lindsay teach a method for detecting charged biopolymer molecules (detecting/performing sequence of ssDNA or dsDNA; [0018]), comprising:
providing a nanopore device defining a nanochannel (nanopore defining channel; see Fig 39A and [0061]), the device comprising
a first gating nanoelectrode addressing a first end of the nanochannel (first polarization electrode 11 addressing one end of the nanochannel; [0071] and Fig 1),
a second gating nanoelectrode addressing a second end of the nanochannel opposite the first end (second polarization electrode addressing second end of the nanochannel; [0071] and Fig 1),
a first sensing nanoelectrode addressing a first location in the nanochannel between the first and second ends (sensing electrode 392 in first location between the two ends of the channel; see Fig 39A), and
the first and second gating nanoelectrodes generating a first potential across the nanochannel to direct flow of the charged biopolymer molecules through the nanochannel from the first gating nanoelectrode to the second gating nanoelectrode (polarization electrodes generate potential to direct the ssDNA through the channel; [0071]).
Lindsay teach affinity elements or various linkers are connected to the electrode which defines the channel to impart functionality [0019][0233] but do not teach the affinity element is biopolymer probe and generating second potential across the nanochannel to direct flow of the charged biopolymer molecules through the nanochannel from the second gating nanoelectrode to the first gating nanoelectrode; and the first and second gating nanoelectrodes alternatively generating the first potential and the second potential across the nanochannel to direct alternating flow of the charged biopolymer molecules through the nanochannel between the first and second gating nanoelectrodes.
However, Holt et al. teach method for moving analyte such as DNA through nanowells 115 encompassing electrodes functionalized with small molecules or aptamers comprising the step of applying voltage to cause the analyte to ele, ctrophores in and out of the nanochannel by reversing the sign of applied voltage to remove either logged in or plugged in analyte [0102][0105][0115].
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the invention in view of Holt et al. teaching to use aptamer as the affinity element because it would impart same functionality of deducing sequence of DNA and it would have obvious to add the step of reversing/alternate the flow of the analyte through the nanochannel to remove any logged/plugged analyte from the nanochannel.
Combined teachings of Lindsay and Holt teach the first and second gating nanoelectrodes alternatively generating the first potential and the second potential across the nanochannel to direct alternating flow of the charged biopolymer molecules through the nanochannel between the first and second gating nanoelectrodes (the analytes are induced to move through nanochannel with bidirectional/reversible flow and the movement could be varied in their force, frequency and duration as desired for a given application (see Holt [0105]). Holt teaches one of the applications is functionalized nanomembrane with aptamers to render passing analytes immobile or retard analytes under appropriate conditions [0109]. Lindsay in view of Holt do not explicitly teach alternating flow increases an amount of hybridization of the charged biopolymer molecules and the first sensing biopolymer probe. However, it would be obvious in view of Holt teaching to adjust the duration/time the analyte spends in the nanochannel which would allow the analyte to spend more time in the nanomembrane to interact with probe/aptamer molecules and thereby would increase amount of hybridization between the analyte and the aptamer.
Claim 3. Lindsay teach a second sensing nanoelectrode addressing a second location in the nanochannel between the first and second ends (sensing electrode 394 in second location between the two ends of the channel; see Fig 39A).
Claim 4. Lindsay teach the nanopore device is integrated into microfluidic device, a nanofluidic device, a nanodevice, or a lab-on- chip system (integrated onto chip; [0151].
Claim 5. Lindsay teach the nanopore device is integrated into an all-in-one ASIC platform system for extraction and sensing of a targeted biopolymer (device is integrate onto chip for sensing/recognizing signals and extraction [0136][0151][0193], thus the chip reads on ASIC platform).
Claim 7. Lindsay in view of Holt et al. teach the nanopore device detecting hybridization of the first charged biopolymer molecule to the first biopolymer probe without amplification of the first charged biopolymer molecule or use of PCR (analyte bind to aptamers without amplification or use of PCR; see Holt [0125][0139] and Fig 5A and 5B).
Claim 10. Lindsay in view of Holt teach the first and second gating nanoelectrodes alternatively generating the first potential and the second potential across the nanochannel to direct alternating flow of the charged biopolymer molecules through the nanochannel between the first and second gating nanoelectrodes (the analytes are induced to move through nanochannel with bidirectional/reversible flow and the movement could also be varied in their force, frequency and duration as desired for a given application (see Holt [0105]). Lindsay in view of Holt do not explicitly teach increases an amount of time the first charge biopolymer molecule is exposed to the first biopolymer probe in the nanochannel, thereby increasing the amount of hybridization of the first charge biopolymer molecule and the first biopolymer probe. However, it would be obvious in view of Holt teaching to adjust the duration/time the analyte spends in the nanochannel which would allow analyte to interact with probe/aptamer molecules and thereby would increase amount of hybridization between the analyte and the aptamer.
Claim 11. Lindsay in view of Holt et al. teach the nanopore device further comprises a second biopolymer probe coupled to the interior surface of the device defining the nanochannel (Holt teach molecules used to functionalized an array could be identical or different from each other on a given array; [0025]), thus nanochannel functionalized with different aptamers would produce signal related to the first sensing nanoelectrode hybridize with first charged biopolymer molecule to the first biopolymer probe; and
the first sensing nanoelectrode detecting hybridization of a second charged biopolymer molecule to the second biopolymer probe.
Claim 13. Lindsay in view of Holt et al. teach the nanopore device detecting hybridization of the second charged biopolymer molecule to the second biopolymer probe without amplification of the second charged biopolymer molecule or use of PCR (analyte bind to aptamers without amplification or use of PCR; see Holt [0125][0139] and Fig 5A and 5B).
Claim(s) 6, 8 and 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lindsay and Holt et al. as applied to claims 1 and 11 above, and further in view of Huff et al. (US 2018/0188230).
Claims 6, 8 and 12 Lindsay in view of Holt teach detecting hybridization of the first/second charged biopolymer molecule to the first/second biopolymer probe (see rejection of claim 1 above) but do not explicitly teach minimum concentration of the first/second charged biopolymer molecule of about 10 femtomolar. Lindsay et al. further teach the device is integrated onto chip [0008] but do not teach nanopore device is integrated into a liquid biopsy panel platform to perform detection without biomolecule amplification or use of PCR.
However, Huff et al. teach method and device for analyte analysis using nanopore wherein the concentration of analyte in the fluid sample that was accurately determined is less than 10 femtomolar, wherein the device is integrated with needle aspiration biopsy [0186][0423].
Since, Huff et al. and Lindsay et al. are to same field of endeavor, therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the invention that nanopore device of Lindsay would be capable of detecting analyte/DNA on femtomolar scale and furthermore integrating needle aspiration biopsy platform with the nanopore device would make the device more versatile for detecting different DNA samples.
Response to Arguments
Applicant's arguments filed 11/20/2025 have been fully considered but they are not persuasive.
Applicant argues on page 10 of remarks that cited reference, Holt et al. mere mention of bidirectional/reversible analyte movements with respect to a given nanomembrane fails to disclose increasing an amount of hybridization of the charged biopolymer molecules and the first sensing biopolymer probe with alternating generating first potential and second potential across the nanochannel to direct alternating flow of the charged biopolymer molecules through the nanochannel between the first and second gating nanoelectrodes.
In response, examiner respectfully disagrees with applicant assertion. Holt et al. teach the analytes are induced to move through nanochannel with bidirectional/reversible flow and the movement could be varied in duration as desired for a given application (see Holt [0105]). Holt further teaches one of the applications is functionalized nanomembrane with aptamers to render passing analytes immobile or retard analytes under appropriate conditions [0109]. Applicant applies same strategy i.e. “ping-pong movement of charge biomolecules increases the amount of time the charge biomolecules are exposed to the neutral probes in the nanochannel, thereby increasing the amount of hybridization between the two molecules (see PGPUB [0061]), Thus, it would be obvious if not apparent, the bidirectional movement of analytes in a functionalized nanomembrane with aptamers would also increase amount of time analytes spends in functionalized nanomembrane and thereby would increase amount of hybridization between the analyte and the aptamer.
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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/GURPREET KAUR/
Primary Examiner
Art Unit 1759