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 allowance or after an Office action under Ex Parte Quayle, 25 USPQ 74, 453 O.G. 213 (Comm'r Pat. 1935). 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, prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant's submission filed on 10/02/2025 has been entered.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1, 12, 19 and 20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Turner (WO 2017024049 A1).
Regarding claim 1, Turner disclosed a sensor comprising a first electrode, a second electrode, a conduction channel operably connecting the first electrode to the second electrode
"[0060] A nanowire can be used as the gate in the nanoFET, with electrodes attached to either side of the nanowire acting as the source and the drain."
and a primed template nucleic acid that is immobilized at the sensor
See Fig. 12, which shows a primed template immobilized at the sensor via an immobilized polymerase bound to the primed template.
contacting the primed template nucleic acid with a polymerase and the next correct nucleotide, thereby forming a stabilized ternary complex comprising the primed template nucleic acid, the polymerase and the next correct nucleotide, wherein the stabilized ternary complex is prevented from covalently incorporating the next correct nucleotide into the primed template nucleic acid
See Fig. 12 and paragraph [00140]: “In alternative sequencing modes of the invention, unincorporatable (e.g. nonhydrolizable) nucleotides are bound to the surface of the nanowire with different length linkers for each base. A schematic representation of such an embodiment is provided in Fig. 12. A low concentration of free native nucleotide is provided in solution that allows the system to slowly move forward. While the polymerase is waiting for each next incorporatable base, it will repeatedly and unproductively sample against the tethered nucleotides producing a signal comprising one or more cognate sampling events. Since the voltage or current will be affected by the length of the tether used for each base, the signal will be different for each nonhydrolizable nucleotide during the sampling events. Typically, multiple sampling events are averaged to calculate a signal that indicates which nonhydrolizable nucleotide is being sampled.”
monitoring the sensor to detect a signal produced by the stabilized ternary complex, whereby the next correct nucleotide is identified from the signal
See Fig. 12 and paragraph [00140]: “In alternative sequencing modes of the invention, unincorporatable (e.g. nonhydrolizable) nucleotides are bound to the surface of the nanowire with different length linkers for each base. A schematic representation of such an embodiment is provided in Fig. 12. A low concentration of free native nucleotide is provided in solution that allows the system to slowly move forward. While the polymerase is waiting for each next incorporatable base, it will repeatedly and unproductively sample against the tethered nucleotides producing a signal comprising one or more cognate sampling events. Since the voltage or current will be affected by the length of the tether used for each base, the signal will be different for each nonhydrolizable nucleotide during the sampling events. Typically, multiple sampling events are averaged to calculate a signal that indicates which nonhydrolizable nucleotide is being sampled.”
Regarding claim 12, Turner’s sensor is a FET (field effect transistor); paragraph [0060]: “A nanowire can be used as the gate in the nanoFET, with electrodes attached to either side of the nanowire acting as the source and the drain.” As such, the primed template would necessarily have to be within an electric field of the sensor in order to work.
Regarding claims 19 and 20, as all four types of nucleotides are available to the primed template, one will be the “next correct nucleotide” and the other three would be a second nucleotide of a different type than the “next correct nucleotide”. Also, the linkers attaching each different nucleotide to the nanowire serve as exogenous labels that produce distinguishable signals.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 2, 5 and 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Turner (WO 2017024049 A1).
The teachings of Turner have been discussed. In the embodiment of Fig. 12, the polymerase is attached to the sensor by a linker. However, Turner also disclosed ([0061]): “In some cases, the template nucleic acid can be attached to the nanowire, either directly, or, for example, through hybridization with a primer attached to the nanowire.” Either whatever attaches the template “directly” to the nanowire, or the primer in the case of the primer being attached to the nanowire, would serve as a “linker” that “directly” attaches the “primed template” to the conduction channel (which is the nanowire).
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the application to modify the embodiment of Turner’s Fig. 12 by attaching either the template or the primer to the nanowire, as Turner taught both of these as alternatives for attaching the ternary complex to the sensor.
Claim(s) 3, 13, 14, 16 and 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Turner (WO 2017024049 A1) as applied to claims 2, 5 and 6 above, and further in view of Boyanov (US 10,545,115).
The teachings of Turner have been discussed. Turner did not teach that the linkage between the template (in the case of attachment of the template to the nanowire) or primer (in the case of attachment of the primer to the nanowire) was conductive as recited in claim 3, or that the immobilized nucleotides comprised charge labels connected by linkers as recited in claims 13 and 14, or that the polymerase comprised charge labels connected by linkers as recited in claims 16 and 17.
Boyanov, in a similar setup (see Fig. 12). Boyanov disclosed (column 5, lines 4-7): “…the optional use of a conducting tether assists in transmitting the charge disturbance to the gate and minimizes the undesirable effects of screening from the biological solution…”.
Boyanov also taught that the nucleotides could be labeled with charge labels via a linker (column 30, lines 22-46): “The binding of a nucleotide to a nucleic acid binding enzyme, such as a polymerase, can be detected based on the recruitment of a charge label to the enzyme which in turn causes a detectable perturbation in the field around the charge sensor to which the enzyme is attached.”
Boyanov also taught that the polymerase could be labeled with charge labels (column 35, lines 15-20): “A particularly useful label moiety that can be attached to a polymerase or other nucleic acid enzyme used in a method or apparatus set forth herein is a negative charge label, examples of which include, but are not limited to, a phosphate group, carboxyl group, amino acid, DMT and/or FMOC.”
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the application to modify the method of Turner by using conductive linkages to tether the template, primer, or polymerase to the nanowire FET in order to obtain the advantage of doing do taught by Boyanov.
It would also have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the application to modify the method of Turner by modifying the nucleotide analogs in Turner’s Fig. 12 or the polymerase by appending charge labels via linkers. As with the case of using conductive tethers, the use of charge labels would have contributed to perturbance of the charge field of the sensor, facilitating detection.
Conclusion
Claims 4, 7-11, 15 and 18 are 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMUEL C WOOLWINE whose telephone number is (571)272-1144. The examiner can normally be reached 9am-5:30pm.
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/SAMUEL C WOOLWINE/Primary Examiner, Art Unit 1681