CTNF 18/246,944 CTNF 87582 DETAILED ACTION This Office action details a first action on the merits for the above referenced application No. Claims 1-8 are pending in this application. Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Priority This application is a 35 USC 371 National Stage filing of international application No. PCT/KR2021/012021 filed on 6 Sep. 2021 and claims benefit under 35 USC 119(a)-(d) for foreign application No. Korea 10-2020-0126084 filed on 28 Sep. 2020. Information Disclosure Statement The information disclosure statement (IDS) submitted on 28 Mar. 2023 has been considered by the examiner. Claim Rejections - 35 USC § 103 07-06 AIA 15-10-15 In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status. 07-20-aia AIA 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. 07-23-aia AIA 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. 07-20-02-aia AIA 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. 07-21-aia AIA Claim (s) 1-7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Suh et al. (US 9,482,618 B2; issued 1 Nov. 2016; see attached 892), in view of Zhou et al. (Anal. Bioanal. Chem.; published 5 Jul. 2019; see attached 892) . Suh et al. teach a single nanoparticle having a nanogap between a core material and a shell material and preparation method thereof (see title). The invention provides for a nanoparticle comprising a core, a shell surrounding the core, and a nanogap formed between the core and shell (col. 4). The thickness of the nanogap is between 0.01 nm and 100 nm (col. 5) or 1.2 nm (col. 15). In a preferred aspect the nanoparticle consists of a gold core and gold shell and has a nanogap formed between the gold core and gold shell (see col. 5). The nanogap enables amplification of Raman signal and can be used for detection of amplified optical signal. The reproducibility of the nanogap is very high and when the SERS signal is acquired, the probe can be dramatically improved (col. 5). It is possible to position an optical signal substance such as a Roman molecule on the surface of the core, in the nanogap or inside the shell, and control precisely the position and number thereof by combining the optical signals substance such as Raman active molecule with the oligonucleotide (col 6). Any polymer material used in the layer by layer assembly without limitation can be used for example positively charged polymer poly-allyl amine (col. 7). The optical active molecule for measuring Raman signal may be used without limitation including metal ion chelate. Raman active molecules include malachite green isothiocyanate, etc (col. 7). The shell may be formed by reacting the precursor e.g. HAuCl 4 , reducing agent, and PVP. The nanoparticle of core-nanogap-shell can be prepared in high yield (col. 8). Suh et al. teach the preparation of core-gap-shell nanoparticle (example 1), preparation of nanoparticle with modified location of Raman dye (example 3), and preparation of nanoparticle with adjusted amount of dye (example 4). Signal with high uniformity and reproducibility is considered to be originated from the dye molecule which are distributed homogeneously on the surface of the core gold and quantitatively controlled (col. 19). Suh et al. teach ROXgap-AuNP probe (col. 18). Suh et al. do not teach a nanoparticle comprising a macrocyclic host molecule exhibiting hydrophobicity inside and hydrophilicity outside and a Raman active material inserted into the macrocyclic host molecule a provided on the surface of the core structure and the macrocyclic molecule and Raman active material fill the nanogap. Suh et al. do not further teach a method of synthesizing the nanoparticle comprising attaching a macrocyclic host molecule onto a surface of a core structure optionally by mixing and incubating to form a modified core structure and inserting a Raman active material by mixing the modified core structure with Raman active material Zhou et al. teach HS-β-cyclodextrin functionalized Ag@Fe 3 O 4 @Ag nanoparticles as surface enhanced Raman spectroscopy substrate for sensitive detection of butyl benzyl phthalate (see title). Zhou et al. teach that β-CD has also proved useful in Raman detection because CD is a weak Raman scatterer. Ouyang et al. investigated the host-guest interactions between various analytes. Zhang et al. created a Ag@β-CD substrate that exhibited the SERS amplifying coffee-ring effect in order to detect phenformin HCL (see pg. 5692). Zhang et al teach the nanoparticle PNG media_image1.png 108 261 media_image1.png Greyscale (scheme 1). Malachite green (MG) was employed as a SERS probe to test sensitivity and repeatability of the substrate (see pg. 5692). Ag@Fe 3 O 4 @Ag/β-CD is almost ideal SERS substrate and can be used in practical applications (pg. 5696). Zhang et al. teach mono-6-thio-β-cyclodextrin (SH-β-CD) (pg. 5692). Zhang et al. teach that when MG was used as a probe molecule, the SERS-active substrate was found to have high sensitivity and stability (pg. 5700). It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify the nanoparticle composition of Suh et al. (nanoparticle having a core structure and a shell structure separated from the core structure by a nanogap wherein Raman active material fills the nanogap and wherein the core structure and shell structure comprise Au or Ag and wherein the nanogap is about 1.2 nm) so that the mono-6-thio-β-cyclodextrin exhibiting hydrophobicity inside and hydrophilicity outside fills the nanogap and the Raman active molecule such as MG inserts into the host molecule provided on the surface of the core structure and binds by Raman active optionally MG by non-covalent interaction as taught by Zhang et al. because the mono-6-thio-β-cyclodextrin attached to the core structure would have been expected to enable formation of a nanogap and advantageously enable the encapsulation of a wide range of chemically unmodified Raman active molecules and advantageous SERS signal enhancement. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Suh et al. so that the obvious nanoparticle gets prepared by mixing and incubating the core structure with the mono-6-thio-β-cyclodextrin to attach the mono-6-thio-β-cyclodextrin to a surface of the core structure to form a modified core structure and then insert the Raman active molecule into the β-CD by mixing the modified core structure with the Raman active molecule prior to synthesizing the shell structure on the surface of the modified core structure inserted with the Raman active material as taught by Suh et al. and Zhang et al. because that method of synthesizing would have been expected to enable formation of a nanogap between core structure and shell structure and advantageously enable a simple loading of the Raman active material onto the core structure by mixing . 07-21-aia AIA Claim (s) 1-8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Suh et al. (US 9,482,618 B2; issued 1 Nov. 2016; see attached 892), in view of Zhou et al. (Anal. Bioanal. Chem.; published 5 Jul. 2019; see attached 892), in further view of Kuo et al. (J. Phys. Chem.; published 2018; see attached 892) . Suh et al. teach as discussed above. Suh et al. do not further teach providing a core structure capped with cetyltrimethylammonium bromide and providing a core structure capped with CTAC by reacting the CTAB-capped core structure with L-ascorbic acid and HAuCl4 wherein the macrocyclic host molecule is attached to the CTAC-capped core structure to form a modified core structure. Zhou et al. teach as discussed above. Kuo et al. teach systematic shape evolution of gold nanocrystals achieved through adjustment in the amount of HAuCl 4 solution used (see title). Kuo et al. teach reported conditions to grow gold nanocubes using a fixed volume of ascorbic acid and HAuCl 4 . CTAC acts as a coordinating species to the metal source and provides halides to influence the cell potential (see abstract). Kuo et al. teach that CTAC and CTAB surfactants are not innocent acting only as capping agents because of the halides they carry. Tuning ΔG means tuning the driving force for the reaction, and tunable reduction rates in the formation of various particle morphologies (pg. 25118). All species added to the mixture take part in the redox reaction, including halide ions and CTAC surfactants (pg. 25119). Kuo et al. teach the preparation of a gold seed solution using CTAC and HAuCl 4 to form gold particles. Kuo et al. teach the synthesis of Gold nanocrystals by adding the seed solution to a growth solution. Kuo et al. teach L-sodium ascorbate (see pg. 25119). It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Suh et al. so that the obvious method of synthesizing the nanoparticle further comprises a step of providing a core structure capped with CTAB, and providing a core structure capped with CTAC by reacting the CTAB-capped core structure with L-ascorbic acid and HAuCl 4 and wherein the macrocyclic host gets attached onto the CTAC-capped core structure to form the modified core structure as further taught by Kuo et al. because the core capped by CTAB would have been expected to advantageously provide and seed solution and because the reacting the CTAB capped core structure with L-ascorbic acid and HAuCl4 core to provide the CTAC capped core structure would have been expected provide a CTAC capped core structure having a tunable size . Double Patenting 08-33 AIA The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg , 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman , 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi , 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum , 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel , 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington , 418 F.2d 528, 163 USPQ 644 (CCPA 1969). A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b). The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13. The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA/25, or PTO/AIA/26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer. 08-36 AIA Claim s 1-8 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim s 1-20 of U.S. Patent No. 9,482,618 B2 in view of Suh et al. (US 9,482,618 B2; issued 1 Nov. 2016; see attached 892), Zhou et al. (Anal. Bioanal. Chem.; published 5 Jul. 2019; see attached 892), and Kuo et al. (J. Phys. Chem.; published 2018; see attached 892) . Claims 1-20 of U.S. Patent No. 9,482,618 B2 claim a nanoparticle comprising: a core, a shell surrounding the core, and a linear polymer connected to the core wherein alkyl thiol group is attached to the linear polymer, a Raman active dye such as malachite green isothiocyanate is covalently attached to the alkyl group and a spacer oligonucleotide attached to the Raman active dye, and a nanogap positioned between the core and shell in which the Raman active dye is positioned within the nanogap wherein core and shell are composed of a metal showing surface plasma resonance. Claims 1-20 of U.S. Patent No. 9,482,618 B2 do claim the instant nanoparticle wherein a macrocyclic host molecule such as cyclodextrin and Raman active material inserted into the macrocyclic host molecule are provided on a surface of the core structure and the macrocyclic host molecule and Raman active material fill the nanogap and wherein the core and shell are made from Au and Ag and wherein the nanogap has the size of 0.1 nm to 10 nm or the instant method for synthesizing that nanoparticle optionally wherein the method comprises providing a CTAC capped core structure by reacting a CTAB capped core with L-ascorbic acid and HAuCl4. Suh et al. teach as discussed above. Zhou et al. teach as discussed above. Kuo et al. teach as discussed above. It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify claims 1-20 of U.S. Patent No. 9,482,618 B2 by substituting the core attached alkyl thiol covalently attached to the Raman active dye attached to the oligonucleotide spacer with a core attached alkyl thiol attached cyclodextrin spacer (mono-6-thio-β-cyclodextrin) with a Raman active molecules such as malachite green non-covalently inserted into the cyclodextrin on the surface of the core structure and wherein the cyclodextrin and Raman active material fill the nanogap and wherein the core and shell comprise Au or Ag and the nanogap has a size of a between 0.1 nm to 10 nm (1.2 nm) as taught by Suh et al. and Zhou et al. because that nanoparticle would have been expected to enable an equivalent nanoparticle capable of Raman spectroscopy and capable of hosting a wide range of chemically unmodified Raman active molecules and an enhanced SERS signal. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify claims 1-20 of U.S. Patent No. 9,482,618 B2 so that the obvious nanoparticle gets prepared by mixing and incubating the core structure with the mono-6-thio-β-cyclodextrin to attach the mono-6-thio-β-cyclodextrin to a surface of the core structure to form a modified core structure and then insert the Raman active molecule into the β-CD by mixing the modified core structure with the Raman active molecule prior to synthesizing the shell structure on the surface of the modified core structure inserted with the Raman active material as taught by Suh et al. and Zhang et al. because that method of synthesizing would have been expected to enable the formation of a nanogap between core structure and shell structure and enable an advantageous simple loading of the Raman active material onto the core structure by mixing. It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify claims 1-20 of U.S. Patent No. 9,482,618 B2 so that the obvious method of synthesizing the nanoparticle further comprises a step of providing a core structure capped with CTAB, and providing a core structure capped with CTAC by reacting the CTAB-capped core structure with L-ascorbic acid and HAuCl 4 and wherein the macrocyclic host gets attached onto the CTAC-capped core structure form the modified core structure as further taught by Kuo et al. because the core capped by CTAB would have been expected to advantageously provide and seed solution and because the reacting the CTAB capped core structure with L-ascorbic acid and HAuCl 4 core to provide the CTAC capped core structure would have been expected provide a CTAC capped core structure having a tunable size. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN R DONOHUE whose telephone number is (571)270-7441. The examiner can normally be reached on Monday - Friday, 8:00 - 5:00 EST. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Hartley can be reached on (571)272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. / SEAN R. DONOHUE/ Examiner, Art Unit 1618 /Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618 Application/Control Number: 18/246,944 Page 2 Art Unit: 1618 Application/Control Number: 18/246,944 Page 3 Art Unit: 1618 Application/Control Number: 18/246,944 Page 4 Art Unit: 1618 Application/Control Number: 18/246,944 Page 5 Art Unit: 1618 Application/Control Number: 18/246,944 Page 6 Art Unit: 1618 Application/Control Number: 18/246,944 Page 7 Art Unit: 1618 Application/Control Number: 18/246,944 Page 8 Art Unit: 1618 Application/Control Number: 18/246,944 Page 9 Art Unit: 1618 Application/Control Number: 18/246,944 Page 10 Art Unit: 1618 Application/Control Number: 18/246,944 Page 11 Art Unit: 1618 Application/Control Number: 18/246,944 Page 12 Art Unit: 1618