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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 02/09/2026 has been entered.
Response to Arguments
Applicant’s arguments with respect to claim(s) 1-20 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Claim Rejections - 35 USC § 103
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 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.
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.
Claim(s) 1, 2, 3, 4, 6, 7, 8, 9, 10, 12, 17, 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Nam, Wonil, et al. "Refractive-index-insensitive nanolaminated SERS substrates for label-free Raman profiling and classification of living cancer cells." Nano letters 19.10 (2019): 7273-7281 (hereinafter Nam), in view in view of KR 102177560 B1 (hereinafter Wook), and further in view of Liu, Dongyue, et al. "Investigation of wavenumber calibration for Raman spectroscopy using a polymer reference." Optical Sensing and Detection V. Vol. 10680. SPIE, 2018 (Dongyue).
Regarding claim 1, Nam teaches a method for label-free surface-enhanced Raman spectroscopy of cells comprising: providing a sample system (Fig. 1 shows the SERS substrates is attaches to cell membrane); wherein the sample system comprises a nanolaminated surface-enhanced Raman spectroscopy (SERS) substrate (Fig. 1 has a nanolaminated SERS substrates); and wherein a plurality of cells are adherent to at least one surface of the nanolaminated SERS substrate (this is explicitly shown in Fig. 4b); obtaining a dataset comprising SERS signals over a dataset mapping area (Fig. 4D and 4G, p. 6 col 2 para 1 lines 11-23).
Nam fails to teach obtaining plasmonically enhanced electronic Raman scattering (ERS) signals of the substrate over the dataset mapping area; normalizing the SERS signals using the ERS signals to create a calibrated dataset; and subjecting the calibrated dataset to multivariate analysis, wherein the calibrated dataset is generated by (a) per-pixel, concurrent acquisition of a broadband ERS continuum originating from layers of the nanolaminated surface-enhanced Raman spectroscopy substrate;(b) per-pixel normalization of the SERS signals using the broadband ERS continuum; and(c) wherein the broadband ERS continuum is not a molecular vibrational band.
Wook, from the same field of endeavor as Nam, teaches “obtaining plasmonically enhanced electronic Raman scattering (ERS) signals of the substrate over the dataset mapping area; normalizing the SERS signals using the ERS signals to create a calibrated dataset” (p. 4 last para to p. 5 para 1; fig. 15 shows the calibrated dataset, p. 7 para 7); “wherein the calibrated dataset is generated by (a) concurrent acquisition of a broadband ERS continuum originating from layers of the nanolaminated surface-enhanced Raman spectroscopy substrate;(b) normalization of the SERS signals using the broadband ERS continuum; and(c) wherein the broadband ERS continuum is not a molecular vibrational band” (p. 4 last para, p. 7 para 7; the ERS originating from the substrate comprises a nanoporous dielectric/metal film and this ERS is not coming from the molecular vibrational band).
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the invention to apply the teaching of Wook to Nam to have obtaining plasmonically enhanced electronic Raman scattering (ERS) signals of the substrate over the dataset mapping area; normalizing the SERS signals using the ERS signals to create a calibrated dataset; “wherein the calibrated dataset is generated by (a) concurrent acquisition of a broadband ERS continuum originating from layers of the nanolaminated surface-enhanced Raman spectroscopy substrate;(b) normalization of the SERS signals using the broadband ERS continuum; and(c) wherein the broadband ERS continuum is not a molecular vibrational band” in order to increase the accuracy for quantifying the concentration of the sample (p. 4 last para).
Nam, when modified by Wook, does not teach explicitly wherein the calibrated dataset is generated by per pixel.
Dongyue, from the same field of endeavor as Nam, teaches wherein the calibrated dataset is generated by per pixel (p. 6 para 2 last sentence).
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the invention to apply the teaching of Liu to Nam, when modified by Wook, to have wherein the calibrated dataset is generated by per pixel in order to increase the accuracy of the wavenumber calibration.
Regarding claim 2, the modified device of Nam does not teach the method of claim 1, wherein the nanolaminated surface- enhanced Raman spectroscopy substrate comprises vertically stacked metal-insulator- metal (MIM) nanostructures and wherein the broadband ERS continuum originates from metallic layers of the vertically stacked MTM nanostructures.
However, Wook discloses wherein the nanolaminated surface- enhanced Raman spectroscopy substrate comprises vertically stacked gold film and SiO2 nanostructures (fig. 1) and wherein the broadband ERS continuum originates from metallic layers of the vertically stacked gold film and SiO2 nanostructures (figs. 1-2).
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the invention to try to apply the teaching of Wook to Nam, which means the ERS is originating from the MIM nanostructures of fig. 1, in order to increase the accuracy of the measurements.
Regarding claim 3, Nam teaches the method of claim 2, wherein the vertically stacked MIM nanostructures comprise gold (p. 6 col 1 last para lines 10-17).
Regarding claim 4, Nam teaches the method of claim 3, wherein vertically stacked MIM nanostructures have a RI-insensitive SERS enhancement factor greater than or equal to about 1 x 107 (Abstract “5 x 107”).
Regarding claim 6, Nam teaches the method claim 1, wherein the SERS measurements are obtained after near-infrared excitation (Fig. 4A “785 nm”) over the dataset mapping area (Fig. 4D and 4G).
Regarding claim 7, Nam teaches the method of claim 6, wherein the near-infrared excitation is carried out using a laser (p. 6 col 1 last para lines 7-10).
Regarding claim 8, Nam teaches the method of claim 7, wherein the near-infrared excitation is carried using a wavelength of about 700-800 nm (Fig. 4A “785 nm”).
Regarding claim 9, Nam teaches the method of claim 1, wherein the multivariate analysis comprises a supervised machine learning method (Fig. 5 “LDA” is a supervised machine learning method).
Regarding claim 10, Nam teaches the method of claim 9, wherein the supervised machine learning method comprise PCA-LDA (this is shown in Fig. 5).
Regarding claim 12, Nam teaches the method of claim 1, wherein the plurality of cells comprises a cancer cell (fig. 4B).
Regarding claim 17, Nam teaches the method of claim 2, wherein vertically stacked MIM nanostructures have a RI- insensitive SERS enhancement factor greater than or equal to about 1 x 107 (Abstract “5 x 107”).
Regarding claim 18, Nam teaches the method of claim 6, wherein the near-infrared excitation is carried using a wavelength of about 700-800 nm (Fig. 4A).
Claim 5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Nam, Wook, and Dongyue as applied to claim 1 above, and further in view of Zhang; X., et al., US 20110058164 A1 (hereinafter Zhang).
Regarding claim 5, the modified device of Nam teaches the method of claim 1, wherein the dataset mapping area is an area of about 100 μm x 100 μm (p. 6 col 2 para 1 lines 11-16).
Nam fails to disclose containing about 20 pixels x 20 pixels.
Zhang, from the same field of endeavor as Nam, teaches containing about 20 pixels x 20 pixels (para [0027] last sentence; this means the minimum grid is 20 pixels x 20 pixels).
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the invention to apply the teaching of Zhang to the modified device of Nam to have containing about 20 pixels x 20 pixels in order to detect and localize Raman signals to specific locations on a chip or grid.
Claim 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Nam, Wook, and Dongyue as applied to claim 9 above, and further in view of Liu, Wenjing, et al. "Raman spectroscopy in colorectal cancer diagnostics: comparison of PCA‐LDA and PLS‐DA models." Journal of Spectroscopy 2016.1 (2016): 1603609 (hereinafter Liu).
Regarding claim 11, the modified device of Nam does not teach the method of claim 9, wherein the supervised machine learning method comprises PLS-DA.
Liu, from the same field of endeavor as Nam, teaches the method of claim 9, wherein the supervised machine learning method comprises PLS-DA (Abstract lines 6-12; this is a general teaching).
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the invention to apply the teaching of Liu to the modified device of Nam to have the method of claim 9, wherein the supervised machine learning method comprises PLS-DA in order to yielded a diagnostic accuracy.
Claim 13, 14, 15, 16, 19, 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Nam, Wook, and Dongyue as applied to claim 9 above, and further in view of Vicario, A. N. N. A. L. I. S. A., et al. "Surface-enhanced Raman spectroscopy of the anti-cancer drug irinotecan in presence of human serum albumin." Colloids and Surfaces B: Biointerfaces 127 (2015): 41-46 (hereinafter Vicario).
Regarding claim 13, Nam teaches the method of claim 1, wherein the method is carried out on a first plurality of cells (Fig. 4B “Breast normal cells”); and wherein the method is carried out on a second plurality of cells (Fig. 4B “Breast cancer cells”).
The modified device of Nam fails to disclose “which have been treated with an exogenous material or stimuli”. Regarding claim 14, the modified device of Nam does not teach the method of claim 13, wherein the exogeneous material is a drug. Regarding claim 15, the modified device of Nam does not teach the method of claim 14, wherein the drug is an anti-cancer drug.
Vicario, from the same field of endeavor as Nam, teaches “which have been treated with an exogenous material or stimuli” (the exogenous material is anticancer drug, irinotecan (CPT-11), Abstract lines 7-12), the method of claim 13, wherein the exogeneous material is a drug (Abstract lines 7-12), and the method of claim 14, wherein the drug is an anti-cancer drug (Abstract lines 7-12).
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the invention to apply the teaching of Vicario to the modified device of Nam to have “which have been treated with an exogenous material or stimuli”, the method of claim 13, wherein the exogeneous material is a drug, and the method of claim 14, wherein the drug is an anti-cancer drug in order to provide the basis for the development of an innovative methodology for therapeutic drug monitoring in cancer patients.
Regarding claim 16, the modified device of Nam does not teach the method of claim 13, further comprising at least two iterations of carrying out the method on a first plurality of cells and on a second plurality of cells; “wherein the first iteration comprises treatment with the exogenous material at a first concentration; and wherein the second iteration comprises treatment with the exogenous material at a second concentration”.
Vicario, from the same field of endeavor as Nam, teaches the method of claim 13, further comprising at least two iterations of carrying out the method on a first plurality of cells (the cells of albumin in Fig. 4(a)) and on a second plurality of cells (the cells of albumin in Fig. 4(b)); “wherein the first iteration comprises treatment with the exogenous material at a first concentration; and wherein the second iteration comprises treatment with the exogenous material at a second concentration” (this entire limitation is shown in Fig. 4a and 4b, where two concentrations of CPT-11 in albumin solution).
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the invention to apply the teaching of Vicario to Nam to have the method of claim 13, further comprising at least two iterations of carrying out the method on a first plurality of cells and on a second plurality of cells; “wherein the first iteration comprises treatment with the exogenous material at a first concentration; and wherein the second iteration comprises treatment with the exogenous material at a second concentration” in order to provide the basis for the development of an innovative methodology for therapeutic drug monitoring in cancer patients.
Regarding claim 19, the modified device of Nam does not teach the method of claim 14, further comprising at least two iterations of carrying out the method on a first plurality of cells and on a second plurality of cells; wherein the first iteration comprises treatment with the exogenous material at a first concentration; and wherein the second iteration comprises treatment with the exogenous material at a second concentration.
Vicario, from the same field of endeavor as Nam, teaches the method of claim 14, further comprising at least two iterations of carrying out the method on a first plurality of cells (the cells of albumin in Fig. 4(a)) and on a second plurality of cells (the cells of albumin in Fig. 4(b)); “wherein the first iteration comprises treatment with the exogenous material at a first concentration; and wherein the second iteration comprises treatment with the exogenous material at a second concentration” (this entire limitation is shown in Fig. 4a and 4b, where two concentrations of CPT-11 in albumin solution).
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the invention to apply the teaching of Vicario to the modified device of Nam to have the method of claim 14, further comprising at least two iterations of carrying out the method on a first plurality of cells and on a second plurality of cells; wherein the first iteration comprises treatment with the exogenous material at a first concentration; and wherein the second iteration comprises treatment with the exogenous material at a second concentration in order to provide the basis for the development of an innovative methodology for therapeutic drug monitoring in cancer patients.
Regarding claim 20, the modified device of Nam does not teach the method of claim 15, further comprising at least two iterations of carrying out the method on a first plurality of cells and on a second plurality of cells; wherein the first iteration comprises treatment with the exogenous material at a first concentration; and wherein the second iteration comprises treatment with the exogenous material at a second concentration.
Vicario, from the same field of endeavor as Nam, teaches the method of claim 15, further comprising at least two iterations of carrying out the method on a first plurality of cells (the cells of albumin in Fig. 4(a)) and on a second plurality of cells (the cells of albumin in Fig. 4(b)); “wherein the first iteration comprises treatment with the exogenous material at a first concentration; and wherein the second iteration comprises treatment with the exogenous material at a second concentration” (this entire limitation is shown in Fig. 4a and 4b, where two concentrations of CPT-11 in albumin solution).
Therefore, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the invention to apply the teaching of Vicario to the modified device of Nam to have the method of claim 15, further comprising at least two iterations of carrying out the method on a first plurality of cells and on a second plurality of cells; wherein the first iteration comprises treatment with the exogenous material at a first concentration; and wherein the second iteration comprises treatment with the exogenous material at a second concentration in order to provide the basis for the development of an innovative methodology for therapeutic drug monitoring in cancer patients.
Conclusion
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/ROBERTO FABIAN JR/Examiner, Art Unit 2877
/Kara E. Geisel/Supervisory Patent Examiner, Art Unit 2877