DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . The amendment filed on 05/26/2023 has been entered. Claim 16 is cancelled. Claims 1-15 are pending in this application and are currently under examination.
Priority
This application is a 371 of PCT/JP2021/034207 filed on 09/17/2021 and claims foreign priority of JAPAN 2020-157294 filed on 09/18/2020.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e). Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 365(c) or 386(c) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. JAPAN 2020-157294, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Claims 1-15 recite “under a first elution condition to elute a first target biomolecule from the nanowire; and… under a second elution condition different from the first elution condition to elute a second target biomolecule from the nanowire”, “introducing a first eluent having a first eluting power to the nanowire, and… introducing a second eluent having a second eluting power different from the first eluting power to the nanowire”, “eluents are liberating agents of the same type but having different concentrations”, “eluents are phosphate-buffered saline (PBS)”, “eluting of the first target biomolecule… and… eluting of the second target biomolecule”, “a nucleic acid included in an EV”, “RNA is miRNA”, “heating is performed at 95°C”, and/or “EV disruption solution is a lysis buffer”, which are not disclosed or supported by the prior-filed Application No. JAPAN 2020-157294 (see machine English translation in the attached priority file). Thus, the priority of claims 1-15 is 09/17/2021.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 03/17/2023 has been considered.
Claim Objections
Claims 1, 7, and 11 are objected to because of the following informalities: In claim 1, change the incorrect recitation “a first target” (line 5) and “a second target” (line 8), which have been recited in the preceding clause, to “the first target” and “the second target”, respectively. In claim 7, change the incorrect recitation “ at least one of” (line 2) to “at least two of” because at least two target biomolecules are required in the preceding claim. In claim 11, insert the missing word “wherein” immediately after the recitation “Claim 10,”; and change the incorrect recitation “the first elution condition” (line 3), which has been completed in the preceding clause, to “the second elution condition”. Appropriate correction is required.
Claim Rejections - 35 USC § 102/103
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.
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.
(I) Claims 1-5 and 7-9 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Yasui et al. (Sci. Adv. 3: e1701133, 2017, including Supplemental Materials, hereinafter referred to as Yasui ‘2017, also listed in IDS filed on 03/17/2023).
With regard to structural limitations “a method comprising: introducing a solution including a first and a second target biomolecules (or at least two of an extracellular vesicle (EV), a nucleic acid included in an EV, and a cell-free nucleic acid, wherein the nucleic acid is miRNA) to a nanowire (or is composed of zinc oxide and/or aluminum oxide) to capture the first and the second target biomolecules; treating the nanowire under a first elution condition (or introducing a first eluent or phosphate-buffered saline (PBS) having a first eluting power) to elute a first target biomolecule from the nanowire; and treating the nanowire under a second elution condition different from the first elution condition (or introducing a second eluent or PBS having a second eluting power different from the first eluting power) to elute a second target biomolecule from the nanowire” (claims 1-5 and 7-9):
Yasui ‘2017 disclosed analyzing of microRNAs (miRNAs) within urine extracellular vesicles (EVs). In situ extraction of urine EV–encapsulated miRNAs using the nanowire-anchored microfluidic device. A 1-ml urine sample aliquot was introduced into the nanowire-anchored microfluidic device at a flow rate of 50 ml/min using a syringe pump. The miRNA extraction from the collected EVs on nanowires was performed using Cell Lysis Buffer M [20 mM tris-HCl (pH 7.4), 200 mM sodium chloride, 2.5 mM magnesium chloride, and 0.05 w/v% NP-40 substitute] introduced at a flow rate of 50 ml/min by the syringe pump. After introduction of EVs, PBS was introduced into a device with nanowires to remove uncollected EVs (page 15/31, left col., para. 4; page 16/31, left col., para. 3). ZnO/Al2O3 core-shell nanowires by covering the ZnO nanowires with about a 10-nm-thick Al2O3 layer have a nearly neutrally charged surface (that is, slightly positive or slightly negative) at pH 6 to 8 due to the isoelectric point value of Al2O3. Because urine EVs have a negatively charged surface at pH 6 to 8 (fig. S8), it makes sense that the ZnO nanowires with a relatively large surface area and a positively charged surface at pH 6 to 8 due to the isoelectric point value of ZnO could achieve highly efficient EV collection. The ZnO nanowires could collect EVs efficiently while ZnO/Al2O3 core-shell nanowires could collect EVs only slightly; these findings led us to conclude that the nanowire surface charge was the dominant factor. Furthermore, the capability of nanowires to collect EV-free miRNAs was conceivable because nucleic acids, including miRNAs, are known to have a negatively charged surface property at pH 6 to 8. Although the collection efficiency of miRNAs onto nanowires was not satisfactory, the recovery rate by introducing lysis buffer was almost 100% (fig. S9B:
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). The device offers high collection efficiency, low sample selectivity (exosomes, microvesicles, and EV-free miRNAs), and high collection ability (page 4/31, right col. para. 1; page 28/31, Fig. S7; page 6/31, left col., para. 1; right col. para. 1; page 29/31, fig. S9).
Thus, these teachings of Yasui ‘2017 anticipate Applicant’s claims 1-5 and 7-9 because (a) both negatively charged extracellular vesicles (EVs) and EV-free miRNA in urine are captured by the positively charged ZnO or ZnO/Al2O3 nanowire, and (b) the PBS wash and lower binding efficiency of EV-free miRNA than that of EV, described above, would allow elution or liberation of EV-free miRNA first during the PBS wash. Or, in an alternative, skilled artisan would follow the teachings of Yasui ‘2017 to collect EV and EV-free miRNA, separately, because the lower binding efficiency of EV-free miRNA than that of EV, described above.
(II) Claims 1-15 are rejected under 35 U.S.C. 103 as being unpatentable over Yasui et al. (Sci. Adv. 3: e1701133, 2017, including Supplemental Materials, hereinafter referred to as Yasui ‘2017, also listed in IDS filed on 03/17/2023) in view of Takahashi et al. (Nanomaterials 11, 1768, 2021, Published: July 7, 2021, hereinafter referred to as Takahashi ‘2021). Claims 1-5 and 7-9 are rejected here because they have been rejected by the primary reference under 102/103 above. Thus, above disclosure of the Yasui ‘2017 is incorporated in its entirety here, which further reads on the “under the second elution condition includes introducing an EV disruption solution (or a lysis buffer) to disrupt the EV”, and “a body fluid or a solution derived from a body fluid, wherein the body fluid is urine”, required by claims 10-15.
Yasui ‘2017 did not explicitly disclose the limitations “the eluting of the first target biomolecule from the nanowire (or the first elution condition) includes heating the nanowire”, and “the heating is performed at 95°C”, required by claims 6, 10, and 12.
Takahashi ‘2021 disclosed that the annealed ZnO/Al2O3 core-shell nanowire could capture RNAs with high efficiency compared to that of other circulating nucleic acids, including genomic DNA (gDNA) and cell-free DNA (cfDNA). The interaction mechanism between the annealed ZnO/Al2O3 core-shell nanowire and a single-stranded nucleic acid did not occur via the electrostatic interaction from phosphate groups, but by nucleobases through hydrogen bonding. For the qRT-PCR step, all reactions were performed with an initial denaturation step for 30 s at 95 °C, followed by 40 cycles of 95 °C for 3 s (page 1/9, Abstract; page 7/9, para. 1; page 4/9, para. 2).
Thus, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to combine the PBS wash step to liberate EV-free miRNA as taught by Yasui ‘2017 with heating or denaturing, for example, at 95 °C in view of Takahashi ‘2021 to liberate more single-stranded nucleic acids from the nanowire because the interaction mechanism between the annealed ZnO/Al2O3 core-shell nanowire and a single-stranded nucleic acid is by nucleobases through hydrogen bonding, described above. Thus, one of skill in the art would have a reasonable expectation that by combining the PBS wash step to liberate EV-free miRNA as taught by Yasui ‘2017 with heating, for example, at 95 °C in view of Takahashi ‘2021 to liberate more single-stranded nucleic acids from the nanowire, one would achieve Applicant’s claims 1-15. “[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” Id. at ___, 82 USPQ2d at 1395. See MPEP § 2141 [R-01.2024].
Conclusion
No claims are allowed.
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/YIH-HORNG SHIAO/Primary Examiner, Art Unit 1691