CTNF 18/343,768 CTNF 70681 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia 1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Election/Restrictions 08-25-01 AIA 2. Applicant’s election without traverse of Group I, claims 1-9 and 14 , in the reply filed on 20 March 2026 is acknowledged. Claim Status 3. Claims 1-20 are pending. Claims 10-13 and 15-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Claims 1-9 and 14 read on the elected invention and have been examined herein. Claim Rejections - 35 USC § 112(b) - Indefiniteness 07-30-02 AIA 4. The following is a quotation of 35 U.S.C. 112(b): (b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention. The following is a quotation of 35 U.S.C. 112 (pre-AIA), second paragraph: The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention. 07-34-01 Claims 3, 4 and 9 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Claims 3 and 4 are indefinite over the final wherein clause of “and wherein structured nucleic acid (DNAO) template” (see claim 3) because this phrase is incomplete. Regarding claim 9, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). Additionally, claim 9 is indefinite over the recitation of “by bi-functional molecules that covalently react with DNA strands constituting the DNAO” because it is not clear as to what is meant by this phrase. For instance, it is unclear as to whether the DNAO further comprises bifunctional molecules that are crosslinked to the DNA or if the DNAO comprises the DNA strands crosslinked to one another and the DNA strands are being characterized as bifunctional. Claim Rejections - 35 USC § 103 07-06 AIA 15-10-15 5. 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. 07-20-02-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) 1-4, 6, 7, and 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Agarwal et al (Block Copolymer Micellization as a Protection Strategy for DNA Origami. Angew. Chem. Int. Ed. 2017. 56: 5460-5464 and Supporting Information, 30 pages total) in view of Jing et al (Solidifying framework nucleic acids with silica. Nature Protocols. August 2019. 14: 2416-2436 and Supporting Information, 59 pages total) . Agarwal teaches a construct comprising: (a) a structured nucleic acid polymer micelle (DOPM), comprising:(i) a structured nucleic acid (DNAO) template; (ii) one or more functional moiety attached to the DNAO template; and (iii) polymers that interact with nucleic acid present in the DNAO template to form the DOPM (see, e.g., abstract; p. 2460, col. 2) and Figure 1). Agarwal coated the DNA origami structures with a cationic poly(ethyleneglycol)–polylysine block (PEG-Lys) copolymer (p. 2460, col. 2). Agarwal (p. 5460, col. 2) states: “We hypothesized that the positive lysine residues would be electrostatically attached to the negative phosphate residues of DNA to form DNA origami polyplex micelles(DOPMs). The shape of the structures would thus be maintained, and the polymer shell would protect the DNA origami structures as they do in gene therapy (Figure 1).” Agarwal (p. 5462, col. 2) also teaches: “functional molecules or materials are attached to DNA origami structures by coupling them to oligonucleotides and hybridizing these to complementary strands displayed on the DNA origami. To test whether the DOPM strategy is compatible with functionalization, we attached sterically demanding AuNPs (17 nm diameter plus oligonucleotide shell) as described previously and streptavidin-coated QDs to 6-HB structures(Figure 4), which allowed for the clear detection of the presence of the ligands by tSEM and AG.” Agarwal does not teach that the construct further comprises an inorganic shell comprising silica surrounding the DOPM However, Jing teaches a DNA origami construct that is coated with a silica (inorganic) shell (e.g., abstract; p. 2416; Figures 1, 5 and Supplemental Fig. 1A). Jiang (p. 2416) states: “The molecular recognition between nucleic acids and their inorganic counterparts can be facilitated by the electrostatic interaction between the DNA phosphate backbone and the cationic molecule/ions. Therefore, customized designer DNA nanostructures are ideal candidates to serve as structural frameworks/templates to direct the growth of inorganics in a controllable and programmable manner. Here, we describe a DOS approach to create complex DNA–silica hybrid composites with various programmable morphologies by using chemical reactions to deposit silica onto the surface of DNA frameworks. “ Jing teaches that the silica layer creates a porous nanostructure; that the thickness of the silica layer can be precisely tuned; and “the hybrid structures can be up to ten times tougher than the DNA frameworks while maintaining considerable flexibility” (Fig. 1b; see p. 2417; and p. 2434). It is stated that the DNA origami silicification (DOS) method disclosed therein “can better preserve the structural information of DNA scaffolds in their native environment because it never changes the solution environment of DNA origami (p. 2418). It is also stated that “The DOS method can be used in DNA-origami-templated nanofabrication for transferring designer DNA nanostructures to various inorganic materials with controllable shape, size and rigidity” (see legend for Fig. 1). 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 the construct of Agarwal so as to have further coated the DOPM with an inorganic silica shell. One would have been motivated to have done so in order to have achieved the benefit set forth by Jing of providing a DNA origami structure with increased toughness / rigidity while maintaining the flexibility of the structure. Secondly, while Agarwal teaches that the one or more functional moieties extend beyond the DOPM so as to enable biding of the DNA origami structure to additional moieties, such as gold nanoparticles (AuNPs) and streptavidin-modified quantum dots (QDs; see e.g., p. 5463, col. 1), Agarwal does not teach that the one or more functional moieties also extends outside of an inorganic shell. However, Jing teaches silica coated DNA origami structures in which functional moieties extend outside the silica shell (e.g., p. 2418 and Fig. 5 and supplemental Fig. 1A). Jing exemplifies DNA origami structures having a linker or capture nucleic acid extending outside the silica shell which binds to spacer / complementary strand that is attached to a AuNR via a thiol group (e.g., p. 2418 and Fig. 5d and supplemental Fig. 1A). 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 the construct of Agarwal so that the functional moieties extended outside of the inorganic silica shell, as taught by Jing. One would have been motivated to have done so in order to have accomplished the objective that the functional moieties (extending outside of the inorganic silica shell) could be used to bind to target molecules, such as the Au nanoparticles and streptavidin-modified QDs of Agarwal. Regarding claim 2, as discussed above, modification of the construct of Agarwal would have resulted in a construct in which the inorganic shell comprises silica. Regarding claims 3 and 4, in the construct of Agarwal, the DNAO comprises DNA and the polymers comprise the cationic polymer of pLys and the nonionic amphiphilic polymer of polyethylene glycol (PEG; e.g., abstract and p. 5460, col. 2). Regarding claim 6, Agarwal teaches that the functional moiety is attached to an oligonucleotide (p. 5460, col. 2) and that the functional moiety comprises a co-polymer comprising (a) a cationic polymer that electrostatically binds to negatively charged DNAO, and (b) a nonionic amphiphilic polymer (abstract and legend for Fig. 1). Agarwal (abstract) states “we coated several different DNA origami structures with a cationic poly(ethyleneglycol)–polylysine block copolymer, which electrostatically covered the DNA nanostructures to form DNA origami polyplex micelles (DOPMs).” Further, Jing teaches that the functional moieties that extend outside of the shell comprise singled stranded oligonucleotides that are complementary to single-stranded nucleic acid extensions on a structured DNA (e.g., Fig. 5 and Supplemental Fig. 1 and p. 2416). Accordingly, modification of the construct of Agrawal as set forth above would have resulted in a construct comprising one or more functional moieties comprising an oligonucleotide that is complimentary to single-stranded nucleic acid extensions placed at one or more locations on the DNAO, and one or more functional moieties that comprise a co-polymer comprising PEG-Lys - i.e., (a) a cationic polymer that electrostatically binds to negatively charged DNAO, and (b) a nonionic amphiphilic polymer. Regarding claim 7, Agarwal teaches that the functional moiety that extends outside of the shell include thiolated oligonucleotides attached to AuNPs or biotin attached to QDs (p. 5460, col. 2) Regarding claim 14, Agarwal teaches that the construct is in a solution and thereby the product that results from modification of the construct of Agarwal is considered to be a composition comprising the construct of present claim 1 . 07-21-aia AIA 7. Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Agarwal et al (Block Copolymer Micellization as a Protection Strategy for DNA Origami. Angew. Chem. Int. Ed. 2017. 56: 5460-5464 and Supporting Information, 30 pages total) in view of Jing et al (Solidifying framework nucleic acids with silica. Nature Protocols. August 2019. 14: 2416-2436 and Supporting Information, 59 pages total), and further in view of Hawthorne et al (U.S. 20200179531) . The teachings of Agarwal and Jing are presented above. The combined references do not teach that the structured nucleic acid is bound to an inorganic core. However, Hawthorne teaches DNA origami constructs that can be used for diagnostic purposes and for the separation of target molecules (e.g., para [0183], [0221], [0229] [0526] and [0529). Hawthorne teaches particles comprising a DNA scaffold that is a DNA origami scaffold (e.g., para [0183]), wherein the DNA scaffold is bound to an inorganic core subparticle, and wherein the inorganic core comprises a magnetic material or a metal material, such as gold (e.g., para [0245]). It is disclosed that the core subparticle can aid in separating the particles comprising the DNA scaffold (and agents attached thereto) from other biomolecules in a solution (e.g., para [0191], [0529] and [0550]). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the construct of Agarwal so as to have incorporated into the construct an inorganic core subparticle bound to the structured nucleic acid. One would have been motivated to have done so for the benefits disclosed by Hawthorne that the inorganic core subparticle can aid in assembling the DNA scaffold and can facilitate the separation of the particles comprising the DNA origami scaffold from other biomolecules in a composition . 07-21-aia AIA 8. Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Agarwal et al (Block Copolymer Micellization as a Protection Strategy for DNA Origami. Angew. Chem. Int. Ed. 2017. 56: 5460-5464 and Supporting Information, 30 pages total) in view of Jing et al (Solidifying framework nucleic acids with silica. Nature Protocols. August 2019. 14: 2416-2436 and Supporting Information, 59 pages total) and further in view of Schultzaberger et al (WO 2021074087) . The teachings of Agarwal and Jing are presented above. As discussed above, the combined references teach constructs wherein the polymers that interact with nucleic acid present in the DNAO template to form the DOPM comprise: a cationic polymer that electrostatically binds to negatively charged DNAO; a nonionic amphiphilic polymer; and a functional terminal group. Further, Agarwal (p. 5462, col. 2) states “functional molecules or materials are attached to DNA origami structures by coupling them to oligonucleotides and hybridizing these to complementary strands displayed on the DNA origami.” The combined references do not teach that a DNA template to be used for amplification is bound to a functional terminal group and a primer pair is bound to the functional terminal group on the polymer, the primer pair comprising: (i) a first primer sequence complementary to either a forward strand or a reverse strand of the DNA template; and (ii) a second primer sequence complementary to a DNA strand opposite the first primer sequence; and wherein one primer in the primer pair comprises a cleavable linker. However, Schultzaberger teaches a method that uses an element comprising DNA origami to label and detect an analyte (e.g., para [0084], [0218-0219]). The reference (para [0050] states: “In some examples, the element is coupled to a DNA origami including the plurality of fluorophores. In some examples, the DNA origami includes a combination of different fluorophores. In some examples, the element is coupled to the DNA origami via copper(I)- catalyzed click reaction, strain-promoted azide-alkyne cycloaddition, hybridization of an oligonucleotide to a complementary oligonucleotide, biotin-streptavidin interaction, NTA- His-Tag interaction, or Spytag-Spycatcher interaction.” It is disclosed that the DNA origami may be used for signal amplification (para [0221-0222]). It is also disclosed that signal amplification may be achieved using primers coupled to an element to amplify one or more templates by incorporating fluorescent nucleotides into the amplification products (para [0053-0054]). Schultzaberger also teaches that the fluorophores can be subsequently detected by incorporating a cleavable linker within an oligonucleotide primer so as to permit selective cleavage of elongated strands (para [0211]). Schultzaberger (para [0210] states: “It will be appreciated that different nucleotides (or other elements) that it is desired to optically detect may have different oligonucleotide primers 1111 than one another, and thus may be hybridized to different amplification templates 1113 to which different numbers and types of fluorophores may be coupled in such a manner as to permit optically distinguishing the nucleotides or other elements from one another.” In view of the teachings of Schultzaberger, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the construct of Agarwal so as to have hybridized a first and second primer of a primer pair to the functional terminal groups that extend outside of the silica shell and to have used the primers of the primer pair for performing an amplification reaction of a DNA template. One would have been motivated to have made this modification so that the DNA origami construct of Agarwal could be used to detect the presence of a target DNA by detecting fluorophore labeled primer extension amplification products of the target DNA template. 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 incorporated a cleavable linker in at least one of the first and second primers so that incorporated fluorophore moieties would be released from the DNA origami construct and could be detected as indicative of the presence of the amplified DNA template . 07-21-aia AIA 9. Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Agarwal et al (Block Copolymer Micellization as a Protection Strategy for DNA Origami. Angew. Chem. Int. Ed. 2017. 56: 5460-5464 and Supporting Information, 30 pages total) in view of Jing et al (Solidifying framework nucleic acids with silica. Nature Protocols. August 2019. 14: 2416-2436 and Supporting Information, 59 pages total) and further in view of Rajendran et al (J. Am. Chem. Soc. 2011. 133: 14488-14491) . The teachings of Agarwal and Jing are presented above. The combined references do not teach that the DNAO is stabilized by crosslinking. However, Rajendran teaches that the thermal stability of DNA origami structures is significantly increased by photo-cross-linking 8-methoxypsoralen (which is a bifunctional molecule) in the DNA strands (abstract; p. 14488, col. 2 and p. 14491, col. 1). Rajendran teaches that cross-linking the DNA strands of the DNA origami structures permits the structures to be used at higher temperatures (p. 14488, col. 1). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have further modified the constructs of Agarwal so as to have crosslinked the DNA strands of the DNA origami structures in order to have achieved the benefit set froth by Rajendran of increasing the thermal stability of the DNA origami structures at higher temperatures. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CARLA J MYERS whose telephone number is (571)272-0747. The examiner can normally be reached M-Th 6:30-5:00 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, Wu-Cheng Winston Shen can be reached on 571-272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /CARLA J MYERS/Primary Examiner, Art Unit 1682 Application/Control Number: 18/343,768 Page 2 Art Unit: 1682 Application/Control Number: 18/343,768 Page 3 Art Unit: 1682 Application/Control Number: 18/343,768 Page 4 Art Unit: 1682 Application/Control Number: 18/343,768 Page 5 Art Unit: 1682 Application/Control Number: 18/343,768 Page 6 Art Unit: 1682 Application/Control Number: 18/343,768 Page 7 Art Unit: 1682 Application/Control Number: 18/343,768 Page 8 Art Unit: 1682 Application/Control Number: 18/343,768 Page 9 Art Unit: 1682 Application/Control Number: 18/343,768 Page 10 Art Unit: 1682 Application/Control Number: 18/343,768 Page 11 Art Unit: 1682 Application/Control Number: 18/343,768 Page 12 Art Unit: 1682
Prosecution Insights