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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 03/06/2026 has been entered.
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, 14, 27 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hench, L. et al., US 20060115804 A1 (hereinafter Hench), in view of Xiaolu, S. e t al., US7545493B2, (hereinafter Xiaolu), in view of Zhao, W. et al., CN 109211873 A (hereinafter Zhao), and further in view WO 2010016267 A1 (hereinafter Kawata).
Regarding claim 1, Hench teaches a non-transitory computer-accessible medium having stored thereon computer-executable instructions for determining phenotypic information for at least one cell, wherein, when a computing arrangement executes the instructions, the computing arrangement is configured to perform procedures comprising: (a) generating spectral information of the at least one cell (the spectra are shown in Fig. 6) using a Raman spectroscopy procedure (para [0013] first sentence) that is based on at least one vibrational probe (para [0009] last sentence); and (b) determining the phenotypic information based on the spectral information (para [0013] last para; para [0046]; claim 18); wherein the Raman spectroscopy procedure is a single-cell spontaneous Raman spectroscopy procedure (para [0107] lines 1-5; Fig. 6 shows the cells are one kind, which are MLE-12 cells); wherein the single-cell spontaneous Raman spectroscopy procedure is performed using a whole-cell confocal micro-Raman spectrometer (para [0107] lines 1-5; Fig. 6 shows the cells are whole MLE-12 cells; para [0063]).
Hench fails to teach wherein the whole-cell confocal micro-Raman spectrometer has or provides an illumination spot size from about 5µm to about 10µm, or from about 10 µm to about 100 µm; and wherein the whole-cell confocal micro-Raman spectrometer has or provides a pinhole size from about 200 µm to about 400 µm, or from about 400 µm to about 1000 µm, wherein the Raman spectroscopy procedure optically integrates the Raman signal over the entire cell without subcellular resolution.
Xiaolu, from the same field of endeavor as Hench, teaches wherein the whole-cell confocal micro-Raman spectrometer has or provides an illumination spot size from about 5µm to about 10µm, or from about 10 µm to about 100 µm (col 4 lines 25-31; the spot size corresponds to the diameter of the fiber 112 in fig. 1).
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 Xiaolu to Hench to have wherein the whole-cell confocal micro-Raman spectrometer has or provides an illumination spot size from about 5µm to about 10µm, or from about 10 µm to about 100 µm in order to maintain the beam’s spatial brightness (col 4 lines 25-31).
Hench, when modified by Xiaolu, does not teach wherein the whole-cell confocal micro-Raman spectrometer has or provides a pinhole size from about 200 µm to about 400 µm, or from about 400 µm to about 1000 µm, and wherein the Raman spectroscopy procedure optically integrates the Raman signal over the entire cell without subcellular resolution.
Zhao, from the same field of endeavor as Hench, teaches wherein the whole-cell confocal micro-Raman spectrometer has or provides a pinhole size from about 200 µm to about 400 µm (p. 2 para 5 lines 1-4), or from about 400 µm to about 1000 µm.
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 Zhao to Hench, when modified by Xiaolu, to have wherein the whole-cell confocal micro-Raman spectrometer has or provides a pinhole size from about 200 µm to about 400 µm (p. 2 para 5 lines 1-4), or from about 400 µm to about 1000 µm in order to reduce the energy loss of the Raman, improve the detection intensity in the Raman spectrum (p. 2 para 5 lines 1-4).
Hench, when modified by Xiaolu and Zhao, does not teach wherein the Raman spectroscopy procedure optically integrates the Raman signal over the entire cell without subcellular resolution (this limitation pertains to para [0049] of the specification).
Kawata, from the same field of endeavor as Hench, teaches wherein the Raman spectroscopy procedure optically integrates the Raman signal over the entire cell without subcellular resolution (fig. 27 and fig. 13 show images of the entire cell without external scanning, p. 12 para 2; the “without external scanning” means without scanning part of the sample at a subcellular resolution).
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 Kawata to Hench, when modified by Xiaolu and Zhao, to have wherein the Raman spectroscopy procedure optically integrates the Raman signal over the entire cell without subcellular resolution in order to detect with high sensitivity, high speed, and high spatial resolution, the distribution of a microscopic sample, such as a molecule inside a living cell (Abstract lines 1-3).
Regarding claim 14, Hench teaches a system for determining phenotypic information for at least one cell, comprising: a computer hardware arrangement (the Raman spectrum was processed by the computer) configured to: (a) generate spectral information of the at least one cell (the spectra are shown in Fig. 6) using a Raman spectroscopy procedure (para [0013] first sentence) that is based on at least one vibrational probe (para [0009] last sentence); and (b) determine the phenotypic information based on the spectral information (para [0013] last para; para [0046]; claim 18); wherein the Raman spectroscopy procedure is a single-cell spontaneous Raman spectroscopy procedure(para [0107] lines 1-5; Fig. 6 shows the cells are one kind, which are MLE-12 cells); wherein the single-cell spontaneous Raman spectroscopy procedure is performed using a whole-cell confocal micro-Raman spectrometer (para [0107] lines 1-5; Fig. 6 shows the cells are whole MLE-12 cells; para [0063]).
Hench fails to teach wherein the whole-cell confocal micro-Raman spectrometer has or provides an illumination spot size from about 5µm to about 10µm, or from about 10 µm to about 100 µm; and wherein the whole-cell confocal micro-Raman spectrometer has or provides a pinhole size from about 200 µm to about 400 µm, or from about 400 µm to about 1000 µm, and wherein the Raman spectroscopy procedure optically integrates the Raman signal over the entire cell without subcellular resolution.
Xiaolu, from the same field of endeavor as Hench, teaches wherein the whole-cell confocal micro-Raman spectrometer has or provides an illumination spot size from about 5µm to about 10µm, or from about 10 µm to about 100 µm (col 4 lines 25-31; the spot size corresponds to the diameter of the fiber 112 in fig. 1).
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 Xiaolu to Hench to have wherein the whole-cell confocal micro-Raman spectrometer has or provides an illumination spot size from about 5µm to about 10µm, or from about 10 µm to about 100 µm in order to maintain the beam’s spatial brightness (col 4 lines 25-31).
Hench, when modified by Xiaolu, does not teach wherein the whole-cell confocal micro-Raman spectrometer has or provides a pinhole size from about 200 µm to about 400 µm, or from about 400 µm to about 1000 µm and wherein the Raman spectroscopy procedure optically integrates the Raman signal over the entire cell without subcellular resolution.
Zhao, from the same field of endeavor as Hench, teaches wherein the whole-cell confocal micro-Raman spectrometer has or provides a pinhole size from about 200 µm to about 400 µm (p. 2 para 5 lines 1-4), or from about 400 µm to about 1000 µm.
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 Zhao to Hench, when modified by Xiaolu, to have wherein the whole-cell confocal micro-Raman spectrometer has or provides a pinhole size from about 200 µm to about 400 µm (p. 2 para 5 lines 1-4), or from about 400 µm to about 1000 µm in order to reduce the energy loss of the Raman, improve the detection intensity in the Raman spectrum (p. 2 para 5 lines 1-4).
Kawata, from the same field of endeavor as Hench, teaches wherein the Raman spectroscopy procedure optically integrates the Raman signal over the entire cell without subcellular resolution (fig. 27 and fig. 13 show images of the entire cell without external scanning, p. 12 para 2; the “without external scanning” means without scanning part of the sample at a subcellular resolution).
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 Kawata to Hench, when modified by Xiaolu and Zhao, to have wherein the Raman spectroscopy procedure optically integrates the Raman signal over the entire cell without subcellular resolution in order to detect with high sensitivity, high speed, and high spatial resolution, the distribution of a microscopic sample, such as a molecule inside a living cell (Abstract lines 1-3).
Regarding claim 27, Hench teaches a method for determining phenotypic information for at least one cell, comprising: (a) generating spectral information of the at least one cell (the spectra are shown in Fig. 6) using a Raman spectroscopy procedure (para [0013] first sentence) that is based on at least one vibrational probe (para [0009] last sentence); (b) by “using a computer hardware arrangement, determining the phenotypic information based on the spectral information” (para [0013] last para; para [0046]; claim 18); wherein the Raman spectroscopy procedure is a single-cell spontaneous Raman spectroscopy procedure(para [0107] lines 1-5; Fig. 6 shows the cells are one kind, which are MLE-12 cells); wherein the single-cell spontaneous Raman spectroscopy procedure is performed using a whole-cell confocal micro-Raman spectrometer (para [0107] lines 1-5; Fig. 6 shows the cells are whole MLE-12 cells; para [0063]).
Hench fails to teach wherein the whole-cell confocal micro-Raman spectrometer has or provides an illumination spot size from about 5µm to about 10µm, or from about 10 µm to about 100 µm; and wherein the whole-cell confocal micro-Raman spectrometer has or provides a pinhole size from about 200 µm to about 400 µm, or from about 400 µm to about 1000 µm, and wherein the Raman spectroscopy procedure optically integrates the Raman signal over the entire cell without subcellular resolution.
Xiaolu, from the same field of endeavor as Hench, teaches wherein the whole-cell confocal micro-Raman spectrometer has or provides an illumination spot size from about 5µm to about 10µm, or from about 10 µm to about 100 µm (col 4 lines 25-31; the spot size corresponds to the diameter of the fiber 112 in fig. 1).
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 Xiaolu to Hench to have wherein the whole-cell confocal micro-Raman spectrometer has or provides an illumination spot size from about 5µm to about 10µm, or from about 10 µm to about 100 µm in order to maintain the beam’s spatial brightness (col 4 lines 25-31).
Hench, when modified by Xiaolu, does not teach wherein the whole-cell confocal micro-Raman spectrometer has or provides a pinhole size from about 200 µm to about 400 µm, or from about 400 µm to about 1000 µm, and wherein the Raman spectroscopy procedure optically integrates the Raman signal over the entire cell without subcellular resolution.
Zhao, from the same field of endeavor as Hench, teaches wherein the whole-cell confocal micro-Raman spectrometer has or provides a pinhole size from about 200 µm to about 400 µm (p. 2 para 5 lines 1-4), or from about 400 µm to about 1000 µm.
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 Zhao to Hench, when modified by Xiaolu, to have wherein the whole-cell confocal micro-Raman spectrometer has or provides a pinhole size from about 200 µm to about 400 µm (p. 2 para 5 lines 1-4), or from about 400 µm to about 1000 µm in order to reduce the energy loss of the Raman, improve the detection intensity in the Raman spectrum (p. 2 para 5 lines 1-4).
Kawata, from the same field of endeavor as Hench, teaches wherein the Raman spectroscopy procedure optically integrates the Raman signal over the entire cell without subcellular resolution (fig. 27 and fig. 13 show images of the entire cell without external scanning, p. 12 para 2; the “without external scanning” means without scanning part of the sample at a subcellular resolution).
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 Kawata to Hench, when modified by Xiaolu and Zhao, to have wherein the Raman spectroscopy procedure optically integrates the Raman signal over the entire cell without subcellular resolution in order to detect with high sensitivity, high speed, and high spatial resolution, the distribution of a microscopic sample, such as a molecule inside a living cell (Abstract lines 1-3).
Claim(s) 6, 7, 8, 9, 10, 19, 20, 21, 22, 23, 32, 33, 34, 35, 36 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hench, Xiaolu, Zhao, and Kawata as applied to claims 1, 14, 27 above, and in view of Min, W. et al., US 20160243261 A1 (hereinafter Min).
Regarding claim 6, Hench does not teach the computer-accessible medium of claim 1, wherein the at least one vibrational probe includes one of (i) at least one Deuterium-labeled branched-chain amino acid, or (ii) at least one deuterium-labeled palmitic acid.
Min, from the same field of endeavor as Hench, teaches the computer-accessible medium of claim 1, wherein the at least one vibrational probe includes one of (i) at least one Deuterium-labeled branched-chain amino acid (para [0023]), or (ii) at least one deuterium-labeled palmitic acid.
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 Min to Hench to have the computer-accessible medium of claim 1, wherein the at least one vibrational probe includes one of (i) at least one Deuterium-labeled branched-chain amino acid, or (ii) at least one deuterium-labeled palmitic acid in order for the sample to be stable and in order to trace and quantify proteome dynamics (para [0008] lines 1-3).
Regarding claim 7, Hench does not teach the computer-accessible medium of claim 1, wherein the at least one vibrational probe includes or provides at least one metabolite molecule that is used by a living organism for biosynthesis.
Min, from the same field of endeavor as Hench, teaches the computer-accessible medium of claim 1, wherein the at least one vibrational probe includes or provides at least one metabolite molecule that is used by a living organism for biosynthesis (para [0044] lines 4-8).
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 Min to Hench to have the computer-accessible medium of claim 1, wherein the at least one vibrational probe includes or provides at least one metabolite molecule that is used by a living organism for biosynthesis in order to optimize the sensitivity, specificity, and compatibility with dynamics of live cells and animals (para [0268] lines 4-6).
Regarding claim 8, Hench does not teach the computer-accessible medium of claim 1, wherein the at least one vibrational probe includes at least one of (i) natural perdeuterated amino acids, (ii) partially deuterated amino acids, (iii) palmitic acid, (iv) oleic acid, (v) deuterated cholesterol, (vi) heavy water, (vii) deuterated glucose, (viii) deuterated acetate, (ix) alkyne bearing amino acids, (x) l-homopropargylglycine, (xi) alkyne bearing fatty acids, (xii) 17-octadecynoic acid, (xiii) alkyne bearing nucleic acids, (xiv) 5-ethynyl-2′-deoxyuridine, (xv) 5-ethynyl uridine, (xvi) propargylcholine, (xvii) 3-O-propargyl-D-glucose, (xviii) Carbow orgenell dyes, (xix) Carbow-Mito, (xx) Carbow-Lyso, (xxi) Carbow-ER, (xxii) at least one drug, (xxiii) erlotinib, (xxiv) rhabduscin, (xxv) terbinafine, (xxvi) or carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone.
Min, from the same field of endeavor as Hench, teaches the computer-accessible medium of claim 1, wherein the at least one vibrational probe includes at least one of (i) natural perdeuterated amino acids, (ii) partially deuterated amino acids, (iii) palmitic acid, (iv) oleic acid, (v) deuterated cholesterol, (vi) heavy water, (vii) deuterated glucose (fig. 29 para [0082]), (viii) deuterated acetate, (ix) alkyne bearing amino acids, (x) l-homopropargylglycine, (xi) alkyne bearing fatty acids, (xii) 17-octadecynoic acid, (xiii) alkyne bearing nucleic acids, (xiv) 5-ethynyl-2′-deoxyuridine, (xv) 5-ethynyl uridine, (xvi) propargylcholine, (xvii) 3-O-propargyl-D-glucose, (xviii) Carbow orgenell dyes, (xix) Carbow-Mito, (xx) Carbow-Lyso, (xxi) Carbow-ER, (xxii) at least one drug, (xxiii) erlotinib, (xxiv) rhabduscin, (xxv) terbinafine, (xxvi) or carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone.
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 Min to Hench to have the computer-accessible medium of claim 1, wherein the at least one vibrational probe includes at least one of (i) natural perdeuterated amino acids, (ii) partially deuterated amino acids, (iii) palmitic acid, (iv) oleic acid, (v) deuterated cholesterol, (vi) heavy water, (vii) deuterated glucose, (viii) deuterated acetate, (ix) alkyne bearing amino acids, (x) l-homopropargylglycine, (xi) alkyne bearing fatty acids, (xii) 17-octadecynoic acid, (xiii) alkyne bearing nucleic acids, (xiv) 5-ethynyl-2′-deoxyuridine, (xv) 5-ethynyl uridine, (xvi) propargylcholine, (xvii) 3-O-propargyl-D-glucose, (xviii) Carbow orgenell dyes, (xix) Carbow-Mito, (xx) Carbow-Lyso, (xxi) Carbow-ER, (xxii) at least one drug, (xxiii) erlotinib, (xxiv) rhabduscin, (xxv) terbinafine, (xxvi) or carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone in order to optimize the sensitivity, specificity, and compatibility with dynamics of live cells and animals (para [0268] lines 4-6) in order to achieve much higher deuterium labeling efficiency, and improve imaging sensitivity, and speed of the device (para [0173] lines 4-7).
Regarding claim 9, Hench does not teach the computer-accessible medium of claim 1, wherein the at least one vibrational probe has or provides at least one Raman peak in a cell-silent spectral region.
Min, from the same field of endeavor as Hench, teaches the computer-accessible medium of claim 1, wherein the at least one vibrational probe has or provides at least one Raman peak in a cell-silent spectral region (para [0260] lines 1-4).
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 Min to Hench to have the computer-accessible medium of claim 1, wherein the at least one vibrational probe has or provides at least one Raman peak in a cell-silent spectral region in order to enable high specificity and sensitivity signals (para [0218] last sentence).
Regarding claim 10, Hench does not teach the computer-accessible medium of claim 9, wherein the cell-silent spectral region is between 1800 cm-1 and 2800 cm-1.
Min, from the same field of endeavor as Hench, teaches the computer-accessible medium of claim 9, wherein the cell-silent spectral region is between 1800 cm-1 and 2800 cm-1 (this is shown in fig. 10a).
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 Min to Hench to have the computer-accessible medium of claim 9, wherein the cell-silent spectral region is between 1800 cm-1 and 2800 cm-1 in order to enable high specificity and sensitivity signals (para [0218] last sentence).
Regarding claim 19, Hench does not teach the system of claim 14, wherein the at least one vibrational probe includes one of (i) at least one Deuterium-labeled branched-chain amino acid, or (ii) at least one deuterium-labeled palmitic acid.
Min, from the same field of endeavor as Hench, teaches the system of claim 14, wherein the at least one vibrational probe includes one of (i) at least one Deuterium-labeled branched-chain amino acid (para [0023]), or (ii) at least one deuterium-labeled palmitic acid.
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 Min to Hench to have the system of claim 14, wherein the at least one vibrational probe includes one of (i) at least one Deuterium-labeled branched-chain amino acid, or (ii) at least one deuterium-labeled palmitic acid in order for the sample to be stable and in order to trace and quantify proteome dynamics (para [0008] lines 1-3).
Regarding claim 20, Hench does not teach the system of claim 14, wherein the at least one vibrational probe includes or provides at least one metabolite molecule that is used by a living organism for biosynthesis.
Min, from the same field of endeavor as Hench, teaches the system of claim 14, wherein the at least one vibrational probe includes or provides at least one metabolite molecule that is used by a living organism for biosynthesis (para [0044] lines 4-8).
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 Min to Hench to have the system of claim 14, wherein the at least one vibrational probe includes or provides at least one metabolite molecule that is used by a living organism for biosynthesis in order to optimize the sensitivity, specificity, and compatibility with dynamics of live cells and animals (para [0268] lines 4-6).
Regarding claim 21, Hench does not teach the system of claim 14, wherein the at least one vibrational probe includes at least one of (i) natural perdeuterated amino acids, (ii) partially deuterated amino acids, (iii) palmitic acid, (iv) oleic acid, (v) deuterated cholesterol, (vi) heavy water, (vii) deuterated glucose, (viii) deuterated acetate, (ix) alkyne bearing amino acids, (x) l-homopropargylglycine, (xi) alkyne bearing fatty acids, (xii) 17-octadecynoic acid, (xiii) alkyne bearing nucleic acids, (xiv) 5-ethynyl-2′-deoxyuridine, (xv) 5-ethynyl uridine, (xvi) propargylcholine, (xvii) 3-O-propargyl-D-glucose, (xviii) Carbow orgenell dyes, (xix) Carbow-Mito, (xx) Carbow-Lyso, (xxi) Carbow-ER, (xxii) at least one drug, (xxiii) erlotinib, (xxiv) rhabduscin, (xxv) terbinafine, (xxvi) or carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone.
Min, from the same field of endeavor as Hench, teaches the system of claim 14, wherein the at least one vibrational probe includes at least one of (i) natural perdeuterated amino acids, (ii) partially deuterated amino acids, (iii) palmitic acid, (iv) oleic acid, (v) deuterated cholesterol, (vi) heavy water, (vii) deuterated glucose (fig. 29 para [0082]), (viii) deuterated acetate, (ix) alkyne bearing amino acids, (x) l-homopropargylglycine, (xi) alkyne bearing fatty acids, (xii) 17-octadecynoic acid, (xiii) alkyne bearing nucleic acids, (xiv) 5-ethynyl-2′-deoxyuridine, (xv) 5-ethynyl uridine, (xvi) propargylcholine, (xvii) 3-O-propargyl-D-glucose, (xviii) Carbow orgenell dyes, (xix) Carbow-Mito, (xx) Carbow-Lyso, (xxi) Carbow-ER, (xxii) at least one drug, (xxiii) erlotinib, (xxiv) rhabduscin, (xxv) terbinafine, (xxvi) or carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone.
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 Min to Hench to have the system of claim 14, wherein the at least one vibrational probe includes at least one of (i) natural perdeuterated amino acids, (ii) partially deuterated amino acids, (iii) palmitic acid, (iv) oleic acid, (v) deuterated cholesterol, (vi) heavy water, (vii) deuterated glucose, (viii) deuterated acetate, (ix) alkyne bearing amino acids, (x) l-homopropargylglycine, (xi) alkyne bearing fatty acids, (xii) 17-octadecynoic acid, (xiii) alkyne bearing nucleic acids, (xiv) 5-ethynyl-2′-deoxyuridine, (xv) 5-ethynyl uridine, (xvi) propargylcholine, (xvii) 3-O-propargyl-D-glucose, (xviii) Carbow orgenell dyes, (xix) Carbow-Mito, (xx) Carbow-Lyso, (xxi) Carbow-ER, (xxii) at least one drug, (xxiii) erlotinib, (xxiv) rhabduscin, (xxv) terbinafine, (xxvi) or carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone in order to achieve much higher deuterium labeling efficiency, and improve imaging sensitivity, and speed of the device (para [0173] lines 4-7).
Regarding claim 22, Hench does not teach the system of claim 14, wherein the at least one vibrational probe has or provides at least one Raman peak in a cell-silent spectral region.
Min, from the same field of endeavor as Hench, teaches the system of claim 14, wherein the at least one vibrational probe has or provides at least one Raman peak in a cell-silent spectral region (para [0260] lines 1-4).
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 Min to Hench to have the system of claim 14, wherein the at least one vibrational probe has or provides at least one Raman peak in a cell-silent spectral region in order to enable high specificity and sensitivity signals (para [0218] last sentence).
Regarding claim 23, Hench does not teach the system of claim 22, wherein the cell-silent spectral region is between 1800 cm-1 and 2800 cm-1.
Min, from the same field of endeavor as Hench, teaches the system of claim 22, wherein the cell-silent spectral region is between 1800 cm-1 and 2800 cm-1 (this is shown in fig. 10a).
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 Min to Hench to have the system of claim 22, wherein the cell-silent spectral region is between 1800 cm-1 and 2800 cm-1 in order to enable high specificity and sensitivity signals (para [0218] last sentence).
Regarding claim 32, Hench does not teach the method of claim 27, wherein the at least one vibrational probe includes one of (i) at least one Deuterium-labeled branched-chain amino acid, or (ii) at least one deuterium-labeled palmitic acid.
Min, from the same field of endeavor as Hench, teaches the method of claim 27, wherein the at least one vibrational probe includes one of (i) at least one Deuterium-labeled branched-chain amino acid (para [0023]), or (ii) at least one deuterium-labeled palmitic acid.
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 Min to Hench to have the method of claim 27, wherein the at least one vibrational probe includes one of (i) at least one Deuterium-labeled branched-chain amino acid, or (ii) at least one deuterium-labeled palmitic acid in order for the sample to be stable and in order to trace and quantify proteome dynamics (para [0008] lines 1-3).
Regarding claim 33, Hench does not teach the method of claim 27, wherein the at least one vibrational probe includes or provides at least one metabolite molecule that is used by a living organism for biosynthesis.
Min, from the same field of endeavor as Hench, teaches the method of claim 27, wherein the at least one vibrational probe includes or provides at least one metabolite molecule that is used by a living organism for biosynthesis (para [0044] lines 4-8).
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 Min to Hench to have the method of claim 27, wherein the at least one vibrational probe includes or provides at least one metabolite molecule that is used by a living organism for biosynthesis in order to optimize the sensitivity, specificity, and compatibility with dynamics of live cells and animals (para [0268] lines 4-6).
Regarding claim 34, Hench does not teach the method of claim 27, wherein the at least one vibrational probe includes at least one of (i) natural perdeuterated amino acids, (ii) partially deuterated amino acids, (iii) palmitic acid, (iv) oleic acid, (v) deuterated cholesterol, (vi) heavy water, (vii) deuterated glucose, (viii) deuterated acetate, (ix) alkyne bearing amino acids, (x) l-homopropargylglycine, (xi) alkyne bearing fatty acids, (xii) 17-octadecynoic acid, (xiii) alkyne bearing nucleic acids, (xiv) 5-ethynyl-2′-deoxyuridine, (xv) 5-ethynyl uridine, (xvi) propargylcholine, (xvii) 3-O-propargyl-D-glucose, (xviii) Carbow orgenell dyes, (xix) Carbow-Mito, (xx) Carbow-Lyso, (xxi) Carbow-ER, (xxii) at least one drug, (xxiii) erlotinib, (xxiv) rhabduscin, (xxv) terbinafine, (xxvi) or carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone.
Min, from the same field of endeavor as Hench, teaches the method of claim 27, wherein the at least one vibrational probe includes at least one of (i) natural perdeuterated amino acids, (ii) partially deuterated amino acids, (iii) palmitic acid, (iv) oleic acid, (v) deuterated cholesterol, (vi) heavy water, (vii) deuterated glucose (fig. 29 para [0082]), (viii) deuterated acetate, (ix) alkyne bearing amino acids, (x) l-homopropargylglycine, (xi) alkyne bearing fatty acids, (xii) 17-octadecynoic acid, (xiii) alkyne bearing nucleic acids, (xiv) 5-ethynyl-2′-deoxyuridine, (xv) 5-ethynyl uridine, (xvi) propargylcholine, (xvii) 3-O-propargyl-D-glucose, (xviii) Carbow orgenell dyes, (xix) Carbow-Mito, (xx) Carbow-Lyso, (xxi) Carbow-ER, (xxii) at least one drug, (xxiii) erlotinib, (xxiv) rhabduscin, (xxv) terbinafine, (xxvi) or carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone.
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 Min to Hench to have the method of claim 27, wherein the at least one vibrational probe includes at least one of (i) natural perdeuterated amino acids, (ii) partially deuterated amino acids, (iii) palmitic acid, (iv) oleic acid, (v) deuterated cholesterol, (vi) heavy water, (vii) deuterated glucose, (viii) deuterated acetate, (ix) alkyne bearing amino acids, (x) l-homopropargylglycine, (xi) alkyne bearing fatty acids, (xii) 17-octadecynoic acid, (xiii) alkyne bearing nucleic acids, (xiv) 5-ethynyl-2′-deoxyuridine, (xv) 5-ethynyl uridine, (xvi) propargylcholine, (xvii) 3-O-propargyl-D-glucose, (xviii) Carbow orgenell dyes, (xix) Carbow-Mito, (xx) Carbow-Lyso, (xxi) Carbow-ER, (xxii) at least one drug, (xxiii) erlotinib, (xxiv) rhabduscin, (xxv) terbinafine, (xxvi) or carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone in order to achieve much higher deuterium labeling efficiency, and improve imaging sensitivity, and speed of the device (para [0173] lines 4-7).
Regarding claim 35, Hench does not teach the method of claim 27, wherein the at least one vibrational probe has or provides at least one Raman peak in a cell-silent spectral region.
Min, from the same field of endeavor as Hench, teaches the method of claim 27, wherein the at least one vibrational probe has or provides at least one Raman peak in a cell-silent spectral region (para [0260] lines 1-4).
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 Min to Hench to have the method of claim 27, wherein the at least one vibrational probe has or provides at least one Raman peak in a cell-silent spectral region in order to enable high specificity and sensitivity signals (para [0218] last sentence).
Regarding claim 36, Hench does not teach the method of claim 35, wherein the cell-silent spectral region is between 1800 cm-1 and 2800 cm-1.
Min, from the same field of endeavor as Hench, teaches the method of claim 35, wherein the cell-silent spectral region is between 1800 cm-1 and 2800 cm-1 (this is shown in fig. 10a).
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 Min to Hench to have the method of claim 35, wherein the cell-silent spectral region is between 1800 cm-1 and 2800 cm-1 in order to enable high specificity and sensitivity signals (para [0218] last sentence).
Claim(s) 11, 12, 24, 25, 37, 38 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hench, Xiaolu, Zhao, and Kawata as applied to claims 1, 14, 27 above, and in view of Nie, Shuming, and Steven R. Emory. "Probing single molecules and single nanoparticles by surface-enhanced Raman scattering." science 275.5303 (1997): 1102-1106 (hereinafter Nie).
Regarding claim 11, Hench does not teach the computer-accessible medium of claim 1, wherein the at least one vibrational probe includes at least one Raman-active nanoparticle. Regarding claim 12, Hench does not teach the computer-accessible medium of claim 11, wherein the at least one Raman-active nanoparticle has a size of between 10 nanometer and 500 nanometer.
Nie, from the same field of endeavor as Hench, teaches the computer-accessible medium of claim 1, wherein the at least one vibrational probe includes at least one Raman-active nanoparticle (Fig. 4 shows active Ag nanoparticle with R6G molecules) and the computer-accessible medium of claim 11, wherein the at least one Raman-active nanoparticle has a size of between 10 nanometer and 500 nanometer (p. 2 col 1 para 2 lines 16-22).
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 Nie to Hench to have the computer-accessible medium of claim 1, wherein the at least one vibrational probe includes at least one Raman-active nanoparticle and the computer-accessible medium of claim 11, wherein the at least one Raman-active nanoparticle has a size of between 10 nanometer and 500 nanometer in order to increase the Raman signal (Abstract lines 5-8).
Regarding claim 24, Hench does not teach the system of claim 14, wherein the at least one vibrational probe includes at least one Raman-active nanoparticle. Regarding claim 25, Hench does not teach the system of claim 24, wherein the at least one Raman-active nanoparticle has a size of between 10 nanometer and 500 nanometer.
Nie, from the same field of endeavor as Hench, teaches the system of claim 14, wherein the at least one vibrational probe includes at least one Raman-active nanoparticle (Fig. 4 shows active Ag nanoparticle with R6G molecules) and the system of claim 24, wherein the at least one Raman-active nanoparticle has a size of between 10 nanometer and 500 nanometer (p. 2 col 1 para 2 lines 16-22).
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 Nie to Hench to have the system of claim 14, wherein the at least one vibrational probe includes at least one Raman-active nanoparticle and the system of claim 24, wherein the at least one Raman-active nanoparticle has a size of between 10 nanometer and 500 nanometer in order to increase the Raman signal (Abstract lines 5-8).
Regarding claim 37, Hench does not teach the method of claim 27, wherein the at least one vibrational probe includes at least one Raman-active nanoparticle. Regarding claim 38, Hench does not teach the method of claim 37, wherein the at least one Raman-active nanoparticle has a size of between 10 nanometer and 500 nanometer.
Nie, from the same field of endeavor as Hench, teaches the method of claim 27, wherein the at least one vibrational probe includes at least one Raman-active nanoparticle (Fig. 4 shows active Ag nanoparticle with R6G molecules) and the method of claim 37, wherein the at least one Raman-active nanoparticle has a size of between 10 nanometer and 500 nanometer (p. 2 col 1 para 2 lines 16-22).
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 Nie to Hench to have the method of claim 27, wherein the at least one vibrational probe includes at least one Raman-active nanoparticle and the method of claim 37, wherein the at least one Raman-active nanoparticle has a size of between 10 nanometer and 500 nanometer in order to increase the Raman signal (Abstract lines 5-8).
Claim(s) 13, 26, 39 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hench, Xiaolu, Zhao, Kawata, and Nie as applied to claims 11, 25, 37 above, and in view of Hodges, Matthew D., et al. "Combining immunolabeling and surface-enhanced Raman spectroscopy on cell membranes." ACS nano 5.12 (2011): 9535-9541 (hereinafter Hodges).
Regarding claim 13, the modified device of Hench does not teach the computer-accessible medium of claim 11, wherein the at least one Raman-active nanoparticle has a Raman peak that is distinguishable from at least one of Raman peaks of the at least one cell.
Hodges, from the same field of endeavor as Hench, teaches the computer-accessible medium of claim 11, wherein the at least one Raman-active nanoparticle has a Raman peak that is distinguishable from at least one of Raman peaks of the at least one cell (this is shown in fig. 3, the blue spectrum has the highest density of nanoparticles and blue has the lowest).
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 Hodges to the modified device of Hench to have the computer-accessible medium of claim 11, wherein the at least one Raman-active nanoparticle has a Raman peak that is distinguishable from at least one of Raman peaks of the at least one cell in order to maximize the SERS signals (p. 5 col 1 para 3 lines 4-7).
Regarding claim 26, the modified device of Hench does not teach the system of claim 25, wherein the at least one Raman-active nanoparticle has a Raman peak that is distinguishable from at least one of Raman peaks of the at least one cell.
Hodges, from the same field of endeavor as Hench, teaches the system of claim 25, wherein the at least one Raman-active nanoparticle has a Raman peak that is distinguishable from at least one of Raman peaks of the at least one cell (this is shown in fig. 3 , the blue spectrum has the highest density of nanoparticles and blue has the lowest).
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 Hodges to the modified device of Hench to have the system of claim 25, wherein the at least one Raman-active nanoparticle has a Raman peak that is distinguishable from at least one of Raman peaks of the at least one cell in order to maximize the SERS signals (p. 5 col 1 para 3 lines 4-7).
Regarding claim 39, the modified device of Hench does not teach the method of claim 37, wherein the at least one Raman-active nanoparticle has a Raman peak that is distinguishable from at least one of Raman peaks of the at least one cell.
Hodges, from the same field of endeavor as Hench, teaches the method of claim 37, wherein the at least one Raman-active nanoparticle has a Raman peak that is distinguishable from at least one of Raman peaks of the at least one cell (this is shown in fig. 3, the blue spectrum has the highest density of nanoparticles and red has the lowest).
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 Hodges to the modified device of Hench to have the method of claim 37, wherein the at least one Raman-active nanoparticle has a Raman peak that is distinguishable from at least one of Raman peaks of the at least one cell in order to maximize the SERS signals (p. 5 col 1 para 3 lines 4-7).
Claim(s) 43, 44, 45 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hench, Xiaolu, Zhao, and Kawata as applied to claims 1, 14, 27 above, and in view of Gibson, E. et al., US20110207207A1 (hereinafter Gibson).
Regarding claim 43, Hench does not teach the computer-accessible medium of claim 1, wherein the Raman spectroscopy procedure acquires Raman spectra from at least 6000 cells in an hour in a fully automatic manner. Regarding claim 44, Hench does not teach the computer-accessible medium of claim 14, wherein the Raman spectroscopy procedure acquires Raman spectra from at least 6000 cells in an hour in a fully automatic manner. Regarding claim 45, Hench does not teach the computer-accessible medium of claim 27, wherein the Raman spectroscopy procedure acquires Raman spectra from at least 6000 cells in an hour in a fully automatic manner.
Gibson, from the same field of endeavor as Hench, teaches wherein the Raman spectroscopy procedure acquires Raman spectra from at least 6000 cells in an hour in a fully automatic manner (p. 6 claim 11, note that the system implements Raman measurements).
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 Gibson to Hench to have wherein the Raman spectroscopy procedure acquires Raman spectra from at least 6000 cells in an hour in a fully automatic manner in order to identify the target cell based on the spectrum signal and generates the cell sorting control signal based on the identity of the target cell (Abstract last sentence).
Claim(s) 46, 47, 48 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hench, Xiaolu, Zhao, and Kawata as applied to claims 1, 14, 27 above, and in view of Piredda, Paola, et al. "Subcellular Raman microspectroscopy imaging of nucleic acids and tryptophan for distinction of normal human skin cells and tumorigenic keratinocytes." Analytical chemistry 87.13 (2015): 6778-6785 (hereinafter Piredda).
Regarding claim 46, Hench does not teach the system of claim 1, wherein the cells comprise skin cancer cells, cervical cancer cells or breast cancer cells. Regarding claim 47, Hench does not teach the system of claim 14, wherein the cells comprise skin cancer cells, cervical cancer cells or breast cancer cells. Regarding claim 48, Hench does not teach system of claim 27, wherein the cells comprise skin cancer cells, cervical cancer cells or breast cancer cells.
Piredda, from the same field of endeavor as Hench, teaches wherein the cells comprise skin cancer cells (this is shown in fig. 1), cervical cancer cells or breast cancer cells (this is shown in fig. 1).
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 Piredda to Hench to have wherein the cells comprise skin cancer cells, cervical cancer cells or breast cancer cells in order to clearly discriminate between normal and tumor cells (p. 6 conclusion section para 1 last sentence).
Claim(s) 49, 50, 51 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hench, Xiaolu, Zhao, and Kawata as applied to claims 1, 14, 27 above, and in view of Zhang, Yong, et al. "Anti-cancer drug sensitivity assay with quantitative heterogeneity testing using single-cell Raman spectroscopy." Molecules 23.11 (2018): 2903 (hereinafter Zhang).
Regarding claim 49, Hench does not teach the computer-accessible medium of claim 1, wherein the phenotypic information is phenotypic response to a chemotherapy reagent. Regarding claim 50, Hench does not teach the computer-accessible medium of claim 14, wherein the phenotypic information is phenotypic response to a chemotherapy reagent. Regarding claim 51, Hench does not teach the computer-accessible medium of claim 27, wherein the phenotypic information is phenotypic response to a chemotherapy reagent.
Zhang, from the same field of endeavor as Hench, teaches wherein the phenotypic information is phenotypic response to a chemotherapy reagent (p. 3 para 2 lines 1-3).
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 Hench to have wherein the phenotypic information is phenotypic response to a chemotherapy reagent in order to show another method for the sensitivity testing of targeted anti-cancer drugs (p. 3 para 2 lines 9-12).
Conclusion
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/ROBERTO FABIAN JR/Examiner, Art Unit 2877
/Kara E. Geisel/Supervisory Patent Examiner, Art Unit 2877
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