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 .
Status of Claims
Currently, claims 1, 3, 5, 6, and 12-26 are pending in the instant application. Claims 17-26 are withdrawn from consideration as being drawn to a non-elected invention. Claims 1, 3, 5, 6, and 12-16 are currently under examination. All the amendments and arguments have been thoroughly reviewed but are deemed insufficient to place this application in condition for allowance. The following rejections are either newly applied, as necessitated by amendment, or are reiterated. They constitute the complete set being presently applied to the instant Application. Response to Applicant's arguments follow. This action is FINAL.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Any rejection not reiterated is withdrawn in view of the amendments to the claims.
Claim Rejections - 35 USC § 112
The rejection of claim 16, under 35 USC 112(b) is incorporated from the previous office action and maintained herein because claim 16 continues to recite “the single DAPA based …”. It is additionally noted that the terms lack sufficient antecedent basis.
Claim Rejections - 35 USC § 103
Claims 1, 3, 5, 6, 12 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of Sim (Sim et al; KR20200019585; published February 24, 2024; as cited in the IDS dated 6/4/2025; machine translation included) and Seow (Seow et al; Scientific Reports, 5:18293, DOI:10.1038; pages 1-5; 2015; as cited in the IDS dated 6/4/2025), in view of Ma (Ma et al; Nature Communications, DOI: 10.1038, pages 1-8; 2016).
Sim teaches a biosensor platform comprising a substrate (“1-5: sNPS platform configuration), a nanostructure, and a measuring device to measure surface plasmon resonance of Au nanoparticles (Raleigh scattering, see whole document). Sim teaches the nanostructure in the biosensor is comprised of two Au-bridged nanoparticles via dsDNA after single stranded DNA hybridization (see “1-4: Synthesis-with-direction of nanostructures”; AuNS-1ssDNA1 with AuNS-1ssDNA2 to form AuNS-dsDNA-AuNS).
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Sim teaches that the bridged nanoparticles are conjugated with MutS (capture probe), to detect SNPs (target DNA). Sim teaches the bridged nanoparticles comprise a gap (see figures), comprising about 2 nm. Sim teaches conjugation of AuNS with ssDNA (section 1-3) as well as synthesis with direction of the nanostructures (section 1-4). Particularly, Sim teaches the gold precursor, HAuCl4 and reducing agent NH2OH.HCL were dissolved in water and the pH of each solution was adjusted by slowly adding NaOH. Sim teaches seeds for DNA induced synthesis were prepared in the form of AuNS-dsDNA-AuNS via hybridization of the ssDNA on each AuNS.
Sim does not teach a biosensor comprising a metal nanostructure comprising three nanospheres (nanoseeds) conjugated with single stranded DNA and bridged to one another, where the biosensor comprises at least one nanosphere conjugated with one single stranded DNA (1sDNA) and at least one metal nanosphere conjugated with two single stranded DNAs at a ratio of 2:1, however Seow teaches a nanostructure comprising a single gold (Au) nanosphere conjugated with 2 single stranded DNA strands, each on one side of the nanosphere, as well as two gold nanospheres each conjugated with one single stranded DNA (see figure 5).
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Seow teaches the metal is gold (Au) (see whole document). Although Seow teaches that the nanospheres are assembled to each other via an external bridging ssDNA, it would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date, to have substituted the assembly of the nanostructure taught by Seow with a metal nanostructure with 2 ssDNA sequences, each complementary to a ssDNA on a metal nanostructure as taught by Sim as this is considered the substitution of one known element for another with predictable results. Both Sim and Seow teach the ability to detect targets via Raleigh scattering with the assembled DNA nanostructures. It would have further been prima facie obvious to one of ordinary skill in the art prior to the effective filing date to have conjugated a DNA capture probe to the biosensor, as opposed to MutS as the hybridization of DNA probes to targets was known to be highly specific to particular targets as exemplified by the teachings of Seow.
Sim and Seow do not teach that the nanostructure comprises a first, second, third, or fourth crystal structure, each crystal structure grown from a surface of one of the metal nanospheres toward the double stranded DNA between each metal nanosphere and surrounds an end of the double stranded DNA, however Ma teaches that crystal structures surrounding the bridged DNA are present under the conditions of nanostructure formation taught by Sim (see page 2, col 2). Ma teaches:
Gold precursor (HAuCl4, 0.03%) and reductant (NH2OH·HCl, 1 mM) were separately dissolved in water and the pH of each solution was adjusted to be 5 (±0.1) by gradually adding NaOH under nitrogen environment. After the HAuCl4 aqueous solution was stirred and stabilized for 7 days at 4 °C, 250 μl of 2 nM linear DNA-conjugated AuNS or 0.5 nM plasmid DNA-conjugated AuNS was mixed with 100 μl of NH2OH solution and 57 μl of HAuCl4 solution, and a colour change was observed within one minute. After 15 min, the synthesized particles were rinsed by repeated centrifugation and re-suspension in water. By varying the amounts of gold precursor (3.8 μl, 9.4 μl, 28.3 μl) and reductant solution (6.7 μl, 16.6 μl, 50.0 μl, respectively), the size of the nanocrystals was controlled during the course of DNA-directed nanocrystal synthesis.
Further, Ma teaches “This study reports a utility of DNA as a molecular regulator of nanocrystal growth in a sequence-independent manner, enabling synthesis of metallic nanocrystals of desired shapes (synthesis-with-design) for a number of applications in biomedical imaging, optical antennas and biomolecular sensors.”
Therefore it would have been prima obvious to one of ordinary skill in the art prior to the effective filing date to have arrived at the metal nanostructure comprising three metal nanoseeds and double stranded DNA between each of the metal nanoseeds, as taught by Sim and Seow, to include metal crystal structure as recited in the claims in view of the teachings of Ma, with a reasonable expectation of success.
Claims 13-15 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of Sim and Seow in view of Ma as applied to claims 1, 3, 5, 6, 12 and 16 above, and further in view of Yin (Yin et al; BioMed Research International; 2020, Article ID 8891876; doi:10.1155; pages 1-14).
The teachings of Sim and Seow in view of Ma are set forth above and incorporated herein. Although Sim and Seow in view of Ma do not teach a DNA capture probe conjugated to the assembled nanospheres for detection of miR361, Yin teaches expression analysis of mir361 using RT-PCR (see pages 2-3). Therefore, it would have been prima facie obvious to the ordinary artisan prior to the effective filing date to have detecting miR361 as taught by Yin, using a biosensor assembly as suggested by Sim and Seow in view of Ma for the purpose of detecting miR361 as taught by Yin.
Conclusion
No claims are allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to examiner Jehanne Sitton whose telephone number is (571) 272-0752. The examiner is a hoteling examiner and can normally be reached Mondays-Fridays from 8:00 AM to 2:00 PM Eastern Time Zone.
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/JEHANNE S SITTON/Primary Examiner, Art Unit 1682
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