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
Claims 1-14 as filed on 1/29/2026 are pending and under examination in the instant office action.
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.
Claims 1, 2, 4, 5, 7, 8 and 14 remain rejected under 35 U.S.C. 102 (a) (1) as being anticipated by Tamer et al (“Gold-Coated Iron Composite Nanospheres Targeted the Detection of Escherichia coli”. Int. J. Mol. Sci. 2013, 14, pages 6223-6240).
The cited reference by Tamer teaches a method of monitoring and detecting “biological target species” or bacterial cells belonging to Escherichia coli (E.coli) in a liquid by using SERS (surface enhanced Raman scattering), wherein the method comprises steps of:
disposing metallic nanoparticles in the liquid, wherein the nanoparticles are treated or modified with a surfactant including 3–mercaptophenylboronic acid (3-MBA), 1-decanethiol (1–DT) and/or hexadecyltrimetylammonium bromide (CTAB) for capturing and/or conjugating bacterial cells of E. coli in the liquid (see abstract; see sections 3.6 and 3.8 on pages 6234-6235);
illuminating the liquid with Raman pump light (see page 6232, figure 7, see section “instrumentation” page 6236);
observing Raman-scattered light from the liquid, wherein the Raman-scattered light is scattered by the “selected species” (such as bacterial cells belonging to E.coli) in an interaction that is surface-enhanced by the metallic nanoparticles (see figure 7, see figures S3-S6).
Thus, the cited document anticipates claims 1, 7, 8 and 14.
As applied to claim 2: bacterial cells inherently possess negative charge; and surfactants provide for positive charge cations for being amphoteric (1-D) or cationic (CBTA).
As applied to claim 4: in the cited method the electrostatic attraction between the nanoparticles and bacterial cells is considered to be “label-free” because no dyes or no fluorophores are used.
As applied to claim 5: the observing Raman-scattered light from the liquid is performed continuously in real time for a viewing duration within the broadest meaning of the claims.
Thus, the cited document by Tamer anticipates the claimed invention.
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.
Claims 1-8 and 14 remain rejected under 35 U.S.C. 103 as being unpatentable over Tamer et al (“Gold-Coated Iron Composite Nanospheres Targeted the Detection of Escherichia coli”. Int. J. Mol. Sci. 2013, 14, pages 6223-6240), Liu et al (“Label and label-free based surface-enhanced Raman scattering for pathogen bacteria detection: A review”. Biosensors and Bioelectronics. 2017, 94, pages 131-140) and Ma et al (Frontiers in Immunology, 2017, Vol. 8, Article 1513, pages 1-11).
The cited reference by Tamer is relied upon as explained above for the disclosure of a method of monitoring and detecting biological target species or bacterial cells belonging to Escherichia coli (E.coli) in a liquid by using SERS (surface enhanced Raman scattering), wherein the capture of bacterial cells on nanoparticles is based on electrostatic interaction/attraction between negatively charged bacteria and positively charged ions of surfancts(s) that are used for treating/modifying nanoparticles.
In particular, in the method of the cited reference by Tamer a test liquid is a suspension of bacterial cells in PBS. But Tamer clearly recognizes that SERS techniques and substrates enable detection of biological cells present in any biofluids (see page 6225 par. 3); thus, in clinical samples including plasma, blood, etc as encompassed by claim 6.
The cited reference by Tamer does not explicitly recognize importance of electrostatic interaction of nanoparticles-based SERS strategies.
However, the prior art recognizes the importance of electrostatic interaction of nanoparticles-based SERS strategies; for example: see Liu at table 4. The reference by Lui also teaches that the main goal for nanoparticles-based SERS is to make nanoparticles come into contact with bacterial surface at many points and close as possible (see sentence bridging pages 135 and 136), that outer membranes of bacterial cells are charged positively due to liposaccharides and teichoic acid (page 136, col.1, par. 2); and, further, that SERS spectra of whole cells are found to originate from interior or exterior including membrane proteins (page 134, col. 2, par. 2). It is known in the prior art that peripheral membrane of biological cells also contain positively charged motifs (see reference by Ma page 2, col. 2, lines 9-10). Thus, it is a logical and clearly obvious to provide a negatively charged nanoparticle surface for a positively charged biological cell surface to capture biological cell, thereby, providing for proper electrostatic interaction of nanoparticles-based SERS strategies.
Therefore, it would have been obvious to one having ordinary skill in the art at the time the claimed invention was filed to modify surface charge of nanoparticles depending on the charge of biological species to be captured as based on electrostatic interaction and/or attraction with a reasonable expectation of success in detecting biological species by the nanoparticles-based SERS.
Thus, the claimed invention as a whole was clearly prima facie obvious, especially in the absence of evidence to the contrary.
The claimed subject matter fails to patentably distinguish over the state art as represented be the cited references. Therefore, the claims are properly rejected under 35 USC § 103.
Claims 1-14 remain rejected under 35 U.S.C. 103 as being unpatentable over Tamer et al (“Gold-Coated Iron Composite Nanospheres Targeted the Detection of Escherichia coli”. Int. J. Mol. Sci. 2013, 14, pages 6223-6240), Liu et al (“Label and label-free based surface-enhanced Raman scattering for pathogen bacteria detection: A review”. Biosensors and Bioelectronics. 2017, 94, pages 131-140) and Ma et al (Frontiers in Immunology, 2017, Vol. 8, Article 1513, pages 1-11) as applied to claims 1-8 and 14 above, and further in view of Chang et al (“Antibiotic Susceptibility Test with Surface-Enhanced Raman Scattering in a Microfluidic System”. Analytical Chemistry, 2019, 91, pages 10988-10995) and Wu et al (IDS reference; ACS Applied Materials and Interfaces. 2015, 7, pages 9965-9971).
The cited reference by Tamer is relied upon as explained above.
But it is silent with regard to methods/assays of monitoring biological species by SERS techniques for performing antibiotic susceptibility assays and for performing detection and assays for mammalian cells including cancer cells and their interactions with drugs.
However, the reference by Chang clearly teaches and/or suggest antibiotic susceptibility testing of bacterial cells with SERS (see abstract). The reference by WU clearly teaches detecting and testing mammalian cancer cells from blood samples by applying SERS techniques (see abstract).
Therefore, it would have been obvious to one having ordinary skill in the art at the time the claimed invention was filed to modify the Tamer’s method of monitoring and detecting biological target species in a liquid by using SERS (surface enhanced Raman scattering) for antibiotic susceptibility assays and/or for performing detection and assays for mammalian cells including cancer cells with a reasonable expectation of success in detecting biological species including bacterial cells and mammalian cells by the nanoparticles-based SERS because the SERS based observations are applicable for various bacterial species including bacteria and mammalian cells including their reactions to drugs including antibiotics.
Thus, the claimed invention as a whole was clearly prima facie obvious, especially in the absence of evidence to the contrary.
The claimed subject matter fails to patentably distinguish over the state art as represented be the cited references. Therefore, the claims are properly rejected under 35 USC § 103.
Response to Arguments
Applicant's arguments filed on 1/29/2026 have been fully considered but they are not persuasive.
With regard to claim rejection under 35 U.S.C. 102 (a) (1) as being anticipated by Tamer et al (“Gold-Coated Iron Composite Nanospheres Targeted the Detection of Escherichia coli”. Int. J. Mol. Sci. 2013, 14, pages 6223-6240) Applicants argue that the disclosure by cited reference is missing a claimed element that is “electrostatic attraction” between nanoparticles and target bacterial cells.
This argument is not found persuasive because claim-recited “electrostatic attraction” is an intended mechanism of action but not a structural element. The structural elements in the cited method and in the claimed method are the same including nanoparticles, surfactant (for example: hexadecyltrimetylammonium bromide or CTAB) and bacterial cells. The CTAB is a recognized cationic surfactant for carrying a positive charge. The bacterial cells of E.coli have been chosen by Tamer for having glucosides moieties on surface (page 6229, section 2.2, lines 10-11); and the glucoside moieties on bacterial surface including lipopolysaccharides (LPS) and teichoic acids (Tas) are predominantly negatively charged under physiological conditions (as evidenced by the cited Liu at page 136, col. 1, par. 2, lines 3-5). Thus, the opposite charges of structural elements in the cited method of Tamer are drawn together by electrostatic attraction regardless whether or not Tamer explicitly recognizes it.
Applicants also argue that Tamer describes washing nanoparticles with ethanolamine to avoid “non-specific interaction” (page 6235, lines 4-5), presuming that it encompasses exclusion of electrostatic interaction. However, this particular manipulation is done in the absence of CTAB for the other nanoparticles that are treated solely with mostly “neutral” compounds 3–mercaptophenylboronic acid (3-MBA) and 1-decanethiol (1–DT).
Thus, as a whole the disclosure by Tamer is neither missing claimed structural elements not it is a teaching away.
With regard to claim rejection under 35 U.S.C. 103 Applicants’ arguments are mostly based on the disclosure by Tamer and are the same as above. Applicants argue that the secondary references cannot be combined with the teaching by Tamer due to contradictory teaching by Tamer.
This argument with regard to the teaching by Tamer is not found persuasive for the reasons above. Moreover, CTAB surfactant, which is taught/used by Tamer, is the same surfactant that is used in the instant application (par. 0050 of published application).
Further, the argument about a combination of the cited references is not found persuasive because the cited references are in the same field of endeavor (such as applying surface-enhanced Raman scattering substrates for detection of biological targets) and they seek to solve the same problems as the instant application and claims (such as label-free based surface-enhanced Raman scattering substrates for detection of biological targets), and one of skill in the art is free to select components available in the prior art, In re Winslow, 151 USPQ 48 (CCPA, 1966).
No claims are allowed.
Conclusion
THIS ACTION IS MADE FINAL. 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.
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Vera Afremova
March 11, 2026
/VERA AFREMOVA/ Primary Examiner, Art Unit 1653