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 .
Claim Interpretation
In the claims, the term “sample matrix” is defined at paragraph [0115] of the specification of the immediate application: “The sample matrix is a medium in which one or more analytes are analyzed, for example plant-based sample matrix, microbes-based sample matrix, mammalian sample matrix (cells, tissues, urine etc.) or any other synthetic/purified analyte in a solvent’s matrix”.
In the claims, the term “fingerprint” is given the exemplary definition at paragraph [0082] of the specification of the immediate application: “The MS fingerprints according to the present disclosure may comprise extracted spectral features indicative of the presence or absence of analyte”. This definition agrees with the definition of the term “fingerprint” understood from the art, where Darrach et al. U.S. PGPUB No. 2005/0170523, for example, defines a “fingerprint” as “a characteristic… ion spectrum (“fingerprint”) of the target molecule which is analyzed by a subsequent mass spectrometer” [0028].
If Applicant disagrees with the interpretations of the claim language, Applicant is invited to provide specific citation to the specification of the immediate application or to references within the art, specifically defining the terms of the claims.
Claim Rejections - 35 USC § 112
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.
Claims 17 and 18 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.
Claim 17 recites the limitation "to search the analyte library…" in claim 11. There is insufficient antecedent basis for this limitation in the claim. Although claim 15 defines a step to search the analyte library, claim 17 does not depend on claim 15, and claim 11, upon which claim 17 depends, does not include any step of searching a library.
Claim 18 recites the limitation "to search the analyte library…" in claim 11. There is insufficient antecedent basis for this limitation in the claim. Although claim 15 defines a step to search the analyte library, claim 18 does not depend on claim 15, and claim 11, upon which claim 18 depends, does not include any step of searching a library.
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.
Claim(s) 15 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Smoot et al. U.S. PGPUB No. 2021/0096138.
Regarding claim 15, Smoot discloses a system for using an analyte library to identify at least one analyte (“identifying at least one condition related to the sample from the comparison of the at least one identified related compound to the one or more known inflammatory bowel disease and/or lymphoma profiles” [Abstract]), the system comprising: at least one processing device (“a computer system or computing device may include one or more processors and storage devices (e.g., memory and disk drives)” [0145]); and at least one memory device (“a computer system or computing device may include one or more processors and storage devices (e.g., memory and disk drives)” [0145]) storing instructions that, when executed by the at least one processing device, cause the system to (“The mass spectrometry system may include a processor configured to execute computer-executable instructions and a computer-readable storage medium (e.g., memory and/or additional hardware storage) storing computer-executable instructions configured to perform various steps, methods, and/or functionality in accordance with aspects of the present invention” [0145]): receive mass spectrum data from analysis of a sample using mass spectrometry (“Obtaining a mass spectrometric proteomic profile from the sample” [0040]), the mass spectrum data including a mass spectrum (“The proteomic profile may include all or part of the information, for example, mass spectrometric data, such as m/z values of peaks in the mass spectrum” [0021]) and a sample matrix (“Within HGMS, multiple annotated areas of a tissue sample may be analyzed” [0046] – where paragraph [0115] of the specification of the immediate application identifies “tissues” as an example of a sample matrix, and Smoot identifies in paragraph [0037] that “matrix effects” a present in the MALDI-TOF mass spectrometry data), and the sample including the at least one analyte (“determining a distribution of the one or more analytes in the tissue sample” [0122]); identify peaks in the mass spectrum (“The proteomic profile may include all or part of the information, for example, mass spectrometric data, such as m/z values of peaks in the mass spectrum” [0021] – “A characteristic proteomic profile may, for example, be characterized by the pattern formed by the combination of spectral amplitudes at given m/z vales” [0074]); assign at least one ion type to the peaks (“if the proteomic profile is presented in the form of a mass spectrum, the proteomic signature may be a peak or a combination of peaks that differ, qualitatively or quantitatively, from the mass spectrum of a corresponding reference sample” [0073] – “Obtaining a mass spectrometric proteomic profile from the sample may comprise experimentally measuring the mass to charge ratios of ions to obtain an experimental value corresponding to the mass to charge ratio of each of the ions and distinguishing candidate ions having substantially the same mass to charge ratio” [0040]); annotate the peaks for the analyte based on the sample matrix (“The subset of peaks from spectra is used as a fingerprint for a diagnosis. Each new spectrum from a new sample is compared to these fingerprints and matched to the one to which it is more similar. All other peaks and parts of the spectra are ignored. Within HGMS, multiple annotated areas of a tissue sample may be analyzed for unique diagnostic information related to the individual areas of cells, which when combined and analyzed together may help provide a more accurate diagnosis for the sample and patient as a whole” [0046]); extract an ion fingerprint for the analyte based on the annotated peaks (“The subset of peaks from spectra is used as a fingerprint for a diagnosis. Each new spectrum from a new sample is compared to these fingerprints and matched to the one to which it is more similar. All other peaks and parts of the spectra are ignored. Within HGMS, multiple annotated areas of a tissue sample may be analyzed for unique diagnostic information related to the individual areas of cells, which when combined and analyzed together may help provide a more accurate diagnosis for the sample and patient as a whole” [0046]); search the analyte library for at least one match of the sample by comparing the ion fingerprint with stored ion fingerprints in the analyte library (“The subset of peaks from spectra is used as a fingerprint for a diagnosis. Each new spectrum from a new sample is compared to these fingerprints and matched to the one to which it is more similar. All other peaks and parts of the spectra are ignored. Within HGMS, multiple annotated areas of a tissue sample may be analyzed for unique diagnostic information related to the individual areas of cells, which when combined and analyzed together may help provide a more accurate diagnosis for the sample and patient as a whole” [0046]); and provide the at least one match (“the substantial identity of two proteomic profiles, may be determined by matching the proteomic profile of a tissue sample with the proteomic profile of a reference sample using an appropriate algorithm” [0074]).
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.
Claim(s) 1, 2, 3, 4, 5, 7, 9, 10, 11, 12, 13, 16, 17, and 23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Smoot et al. U.S. PGPUB No. 2021/0096138 in view of Grothe, Jr. et al. U.S. PGPUB No. 2014/0138537.
Regarding claim 1, Smoot discloses a system for building an analyte library (described in paragraph [0041]), the system comprising: at least one processing device (“a computer system or computing device may include one or more processors and storage devices (e.g., memory and disk drives)” [0145]); and at least one memory device (“a computer system or computing device may include one or more processors and storage devices (e.g., memory and disk drives)” [0145]) storing instructions that, when executed by the at least one processing device, cause the system to (“The mass spectrometry system may include a processor configured to execute computer-executable instructions and a computer-readable storage medium (e.g., memory and/or additional hardware storage) storing computer-executable instructions configured to perform various steps, methods, and/or functionality in accordance with aspects of the present invention” [0145]): receive mass spectrum data from analysis of a sample using mass spectrometry (“Obtaining a mass spectrometric proteomic profile from the sample” [0040]), the mass spectrum data including a mass spectrum (“The proteomic profile may include all or part of the information, for example, mass spectrometric data, such as m/z values of peaks in the mass spectrum” [0021]) and a sample matrix (“Within HGMS, multiple annotated areas of a tissue sample may be analyzed” [0046] – where paragraph [0115] of the specification of the immediate application identifies “tissues” as an example of a sample matrix, and Smoot identifies in paragraph [0037] that “matrix effects” a present in the MALDI-TOF mass spectrometry data), and the sample including an analyte (“determining a distribution of the one or more analytes in the tissue sample” [0122]); identify peaks in the mass spectrum (“The proteomic profile may include all or part of the information, for example, mass spectrometric data, such as m/z values of peaks in the mass spectrum” [0021] – “A characteristic proteomic profile may, for example, be characterized by the pattern formed by the combination of spectral amplitudes at given m/z vales” [0074]); assign at least one ion type to the peaks (“if the proteomic profile is presented in the form of a mass spectrum, the proteomic signature may be a peak or a combination of peaks that differ, qualitatively or quantitatively, from the mass spectrum of a corresponding reference sample” [0073] – “Obtaining a mass spectrometric proteomic profile from the sample may comprise experimentally measuring the mass to charge ratios of ions to obtain an experimental value corresponding to the mass to charge ratio of each of the ions and distinguishing candidate ions having substantially the same mass to charge ratio” [0040]); annotate the peaks for the analyte based on the sample matrix (“The subset of peaks from spectra is used as a fingerprint for a diagnosis. Each new spectrum from a new sample is compared to these fingerprints and matched to the one to which it is more similar. All other peaks and parts of the spectra are ignored. Within HGMS, multiple annotated areas of a tissue sample may be analyzed for unique diagnostic information related to the individual areas of cells, which when combined and analyzed together may help provide a more accurate diagnosis for the sample and patient as a whole” [0046]); extract an ion fingerprint for the analyte based on the annotated peaks (“The subset of peaks from spectra is used as a fingerprint for a diagnosis. Each new spectrum from a new sample is compared to these fingerprints and matched to the one to which it is more similar. All other peaks and parts of the spectra are ignored. Within HGMS, multiple annotated areas of a tissue sample may be analyzed for unique diagnostic information related to the individual areas of cells, which when combined and analyzed together may help provide a more accurate diagnosis for the sample and patient as a whole” [0046]). Smoot discloses the claimed invention except that while Smoot identifies an analyte (“identifying at least one inflammatory bowel disease and/or lymphoma related compound in the sample from results from the mass spectrometer, comparing the at least one identified related compound in the sample to one or more known inflammatory bowel disease and/or lymphoma profiles” [Abstract] – “determining a distribution of the one or more analytes within the feline tissue sample” [0118]), based on an ion fingerprint (“The subset of peaks from spectra is used as a fingerprint for a diagnosis. Each new spectrum from a new sample is compared to these fingerprints and matched to the one to which it is more similar” [0046]), and the operation is generally performed on a storage device (“The mass spectrometry system may include a processor configured to execute computer-executable instructions and a computer-readable storage medium (e.g., memory and/or additional hardware storage) storing computer-executable instructions configured to perform various steps, methods, and/or functionality in accordance with aspects of the present invention” [0145]), there is no explicit disclosure of a step to store an analyte identification entry including the ion fingerprint for the analyte.
Grothe discloses “A method of acquiring and compiling data obtained on a mass spectrometer system, comprises… storing at least one new entry in the mass-spectral library relating to the recognized additional contribution” [Abstract] wherein “A resulting product spectrum exhibits a set of fragmentation peaks (a fragment set) which, in many instances, may be used as a fingerprint to derive structural information relating to the parent peptide or protein” [0003].
It would have been obvious to one possessing ordinary skill in the art before the effective filing date of the claimed invention to have modified Smoot with the storing step of Grothe in order to generate a history of identified samples in a library that can be utilized to improve the speed of identifying additional, future samples to be analyzed.
Regarding claim 2, Smoot discloses the claimed invention except that while Smoot discloses “In ESI tandem mass spectrometry (ESI/MS/MS), analysis of both precursor ions and product ions is possible, thereby monitoring a single precursor product reaction and producing a signal only when the desired precursor ion is present” [0035], there is no explicit disclosure of extracting at least one precursor ion from the mass spectrum data, wherein the analyte identification entry further includes the at least one precursor ion.
Grothe discloses “A method of acquiring and compiling data obtained on a mass spectrometer system, comprises… storing at least one new entry in the mass-spectral library relating to the recognized additional contribution” [Abstract] wherein “various ions are analyzed and detected by the mass spectrometer together with its detector 35 and, as a result, appropriately identified according to their various mass-to-charge ratios” [0042]. Grothe discloses extracting at least one precursor ion from the mass spectrum data, wherein the analyte identification entry further includes the at least one precursor ion (“reading a plurality of tandem mass spectra previously obtained using the mass spectrometer system, each tandem mass spectrum comprising detected intensity data for a precursor ion type having a respective precursor-ion mass-to-charge (m/z) ratio and an MS2 spectrum comprising detected intensity data for one or more product ion types formed by fragmentation of the precursor ion type and having respective product-ion m/z ratios; (b) sorting the tandem mass spectra according to the precursor-ion m/z ratios; (c) assigning each tandem mass spectrum to one of a plurality of library segments according to its respective precursor-ion m/z ratio, each library segment representing a respective range of precursor-ion m/z ratios; (d) assigning each of the product ion types within each library segment to one of a plurality of bins defined for the library segment, each bin representing a respective range of product-ion m/z ratios” [0024]).
It would have been obvious to one possessing ordinary skill in the art before the effective filing date of the claimed invention to have modified Smoot with the precursor identification step of Grothe in order to improve the accuracy of identifying an analyte by analyzing as much information as possible about the sample to be analyzed.
Regarding claim 3, Smoot discloses the claimed invention except that while Smoot discloses “In ESI tandem mass spectrometry (ESI/MS/MS), analysis of both precursor ions and product ions is possible, thereby monitoring a single precursor product reaction and producing a signal only when the desired precursor ion is present” [0035], there is no explicit disclosure of compiling precursor metadata for the sample, wherein the analyte identification entry further includes the precursor metadata wherein the precursor metadata is complied with tandem mass spectrometry (MS/MS) data.
Grothe discloses “A method of acquiring and compiling data obtained on a mass spectrometer system, comprises… storing at least one new entry in the mass-spectral library relating to the recognized additional contribution” [Abstract] wherein “various ions are analyzed and detected by the mass spectrometer together with its detector 35 and, as a result, appropriately identified according to their various mass-to-charge ratios” [0042]. Grothe discloses compiling precursor metadata for the sample, wherein the analyte identification entry further includes the precursor metadata wherein the precursor metadata is complied with tandem mass spectrometry (MS/MS) data (“reading a plurality of tandem mass spectra previously obtained using the mass spectrometer system, each tandem mass spectrum comprising detected intensity data for a precursor ion type having a respective precursor-ion mass-to-charge (m/z) ratio and an MS2 spectrum comprising detected intensity data for one or more product ion types formed by fragmentation of the precursor ion type and having respective product-ion m/z ratios; (b) sorting the tandem mass spectra according to the precursor-ion m/z ratios; (c) assigning each tandem mass spectrum to one of a plurality of library segments according to its respective precursor-ion m/z ratio, each library segment representing a respective range of precursor-ion m/z ratios; (d) assigning each of the product ion types within each library segment to one of a plurality of bins defined for the library segment, each bin representing a respective range of product-ion m/z ratios” [0024]).
It would have been obvious to one possessing ordinary skill in the art before the effective filing date of the claimed invention to have modified Smoot with the precursor identification step of Grothe in order to improve the accuracy of identifying an analyte by analyzing as much information as possible about the sample to be analyzed.
Regarding claim 4, Smoot discloses the claimed invention except that while Smoot discloses “In ESI tandem mass spectrometry (ESI/MS/MS), analysis of both precursor ions and product ions is possible, thereby monitoring a single precursor product reaction and producing a signal only when the desired precursor ion is present” [0035], there is no explicit disclosure of compiling precursor metadata for the sample, wherein the analyte identification entry further includes the precursor metadata wherein the precursor metadata is complied with tandem mass spectrometry (MS/MS) data.
Grothe discloses “A method of acquiring and compiling data obtained on a mass spectrometer system, comprises… storing at least one new entry in the mass-spectral library relating to the recognized additional contribution” [Abstract] wherein “various ions are analyzed and detected by the mass spectrometer together with its detector 35 and, as a result, appropriately identified according to their various mass-to-charge ratios” [0042]. Grothe discloses compiling precursor metadata for the sample, wherein the analyte identification entry further includes the precursor metadata wherein the precursor metadata is complied with tandem mass spectrometry (MS/MS) data (“reading a plurality of tandem mass spectra previously obtained using the mass spectrometer system, each tandem mass spectrum comprising detected intensity data for a precursor ion type having a respective precursor-ion mass-to-charge (m/z) ratio and an MS2 spectrum comprising detected intensity data for one or more product ion types formed by fragmentation of the precursor ion type and having respective product-ion m/z ratios; (b) sorting the tandem mass spectra according to the precursor-ion m/z ratios; (c) assigning each tandem mass spectrum to one of a plurality of library segments according to its respective precursor-ion m/z ratio, each library segment representing a respective range of precursor-ion m/z ratios; (d) assigning each of the product ion types within each library segment to one of a plurality of bins defined for the library segment, each bin representing a respective range of product-ion m/z ratios” [0024]).
It would have been obvious to one possessing ordinary skill in the art before the effective filing date of the claimed invention to have modified Smoot with the precursor identification step of Grothe in order to improve the accuracy of identifying an analyte by analyzing as much information as possible about the sample to be analyzed.
Regarding claim 5, Smoot discloses that the analyte library is indexed to search based on the ion fingerprint (“The subset of peaks from spectra is used as a fingerprint for a diagnosis. Each new spectrum from a new sample is compared to these fingerprints and matched to the one to which it is more similar” [0046]), and wherein the analyte identification entry further includes the mass spectrum data including the mass spectrum and the sample matrix (“Within HGMS, multiple annotated areas of a tissue sample may be analyzed for unique diagnostic information related to the individual areas of cells, which when combined and analyzed together may help provide a more accurate diagnosis for the sample and patient as a whole” [0046]).
Regarding claim 7, Smoot discloses that the mass spectrum data includes at least one of tandem mass spectrometry (MS/MS) data (“In ESI tandem mass spectrometry (ESI/MS/MS), analysis of both precursor ions and product ions is possible” [0035]) and sequential mass spectrometry (MSn) data.
Regarding claim 9, Smoot discloses that the instructions further cause the system to: process the mass spectrum data by grouping the peaks in the mass spectrum based on a relationship among the peaks to identify at least one analyte in the sample (“A genetic algorithm is a machine-learning algorithm that is similar to classical genetics. Initially, peaks from the spectra may be formed into groups (individuals) and evaluated for how well they may differentiate between the phenotypes (benign and malignant)” [0044]).
Regarding claim 10, Smoot discloses that the instructions further cause the system to: filter noise from the mass spectrum data by identifying peaks in the mass spectrum data which do not have a relationship to other peaks in the mass spectrum data (“The subset of peaks from spectra is used as a fingerprint for a diagnosis. Each new spectrum from a new sample is compared to these fingerprints and matched to the one to which it is more similar. All other peaks and parts of the spectra are ignored” [0046]).
Regarding claim 11, Smoot discloses that the mass spectrum data is measured using at least one of:(1) liquid chromatography mass spectroscopy (LC/MS); (2) flow injection mass spectrometry; (3) capillary electrophoresis mass spectrometry (CEMS); (4) gas chromatographic mass spectrometry (GCMS); (5) ion mobility mass spectrometry; (6) direct infusion mass spectrometry; (7) open port interface (OPI) mass spectrometry; and (8) matrix-assisted laser desorption ionization (MALDI) mass spectrometry (“The use of matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI) to assay feline tissue samples is described” [Abstract]).
Regarding claim 12, Smoot discloses that analyte identification entries stored in the analyte library are used to train at least one machine learning model for analyte identification (“A linear discriminant analysis is a machine-learning algorithm that may be used to dimensionally reduce a dataset onto a lower-dimensional space. In a linear discriminant analysis, the computer program is taught to recognize a subset of peaks from the IBD samples and the SCL samples. The subset of peaks from spectra is used as a fingerprint for a diagnosis. Each new spectrum from a new sample is compared to these fingerprints and matched to the one to which it is more similar. All other peaks and parts of the spectra are ignored. Within HGMS, multiple annotated areas of a tissue sample may be analyzed for unique diagnostic information related to the individual areas of cells, which when combined and analyzed together may help provide a more accurate diagnosis for the sample and patient as a whole” [0044]).
Regarding claim 13, Smoot discloses that to annotate the peaks for the analyte is further based on experimental conditions (“Annotation of the sample may occur after part of or the entire sample has been subjected to mass spectrometry such that selection of the areas of interest is performed post-acquisition of mass spectral data. In this example, the analyzed sample may be stained, and the digital microscopy image annotated for regions of interest; these regions of interest can be superimposed onto the image of the sample use in the mass spectrometry analysis to isolate their components of the spectral data file. In another example, a serial section of the sample may be stained, and the digital microscopy image annotated for regions of interest; these regions of interest can be superimposed onto the image of the sample used in the mass spectrometry analysis to isolate their components of the spectral data file. In another example, the sample may be annotated using the same sample that was subjected to mass spectrometry and staining that same sample for conversion to a digital image for annotation” [0049]).
Regarding claim 16, Smoot discloses the claimed invention except that while Smoot discloses “In ESI tandem mass spectrometry (ESI/MS/MS), analysis of both precursor ions and product ions is possible, thereby monitoring a single precursor product reaction and producing a signal only when the desired precursor ion is present” [0035], there is no explicit disclosure of extracting at least one precursor ion from the mass spectrum data, wherein to search the analyte library further includes comparing the at least one precursor ion with stored precursor ions in the analyte library.
Grothe discloses “A method of acquiring and compiling data obtained on a mass spectrometer system, comprises… storing at least one new entry in the mass-spectral library relating to the recognized additional contribution” [Abstract] wherein “various ions are analyzed and detected by the mass spectrometer together with its detector 35 and, as a result, appropriately identified according to their various mass-to-charge ratios” [0042]. Grothe discloses extracting at least one precursor ion from the mass spectrum data, wherein to search the analyte library further includes comparing the at least one precursor ion with stored precursor ions in the analyte library (“reading a plurality of tandem mass spectra previously obtained using the mass spectrometer system, each tandem mass spectrum comprising detected intensity data for a precursor ion type having a respective precursor-ion mass-to-charge (m/z) ratio and an MS2 spectrum comprising detected intensity data for one or more product ion types formed by fragmentation of the precursor ion type and having respective product-ion m/z ratios; (b) sorting the tandem mass spectra according to the precursor-ion m/z ratios; (c) assigning each tandem mass spectrum to one of a plurality of library segments according to its respective precursor-ion m/z ratio, each library segment representing a respective range of precursor-ion m/z ratios; (d) assigning each of the product ion types within each library segment to one of a plurality of bins defined for the library segment, each bin representing a respective range of product-ion m/z ratios” [0024]).
It would have been obvious to one possessing ordinary skill in the art before the effective filing date of the claimed invention to have modified Smoot with the precursor identification step of Grothe in order to improve the accuracy of identifying an analyte by analyzing as much information as possible about the sample to be analyzed.
Regarding claim 17, Smoot discloses the claimed invention except that while Smoot discloses “In ESI tandem mass spectrometry (ESI/MS/MS), analysis of both precursor ions and product ions is possible, thereby monitoring a single precursor product reaction and producing a signal only when the desired precursor ion is present” [0035], there is no explicit disclosure of compiling precursor metadata for the sample, wherein to search the analyte library is further based on the precursor metadata.
Grothe discloses “A method of acquiring and compiling data obtained on a mass spectrometer system, comprises… storing at least one new entry in the mass-spectral library relating to the recognized additional contribution” [Abstract] wherein “various ions are analyzed and detected by the mass spectrometer together with its detector 35 and, as a result, appropriately identified according to their various mass-to-charge ratios” [0042]. Grothe discloses compiling precursor metadata for the sample, wherein to search the analyte library is further based on the precursor metadata (“reading a plurality of tandem mass spectra previously obtained using the mass spectrometer system, each tandem mass spectrum comprising detected intensity data for a precursor ion type having a respective precursor-ion mass-to-charge (m/z) ratio and an MS2 spectrum comprising detected intensity data for one or more product ion types formed by fragmentation of the precursor ion type and having respective product-ion m/z ratios; (b) sorting the tandem mass spectra according to the precursor-ion m/z ratios; (c) assigning each tandem mass spectrum to one of a plurality of library segments according to its respective precursor-ion m/z ratio, each library segment representing a respective range of precursor-ion m/z ratios; (d) assigning each of the product ion types within each library segment to one of a plurality of bins defined for the library segment, each bin representing a respective range of product-ion m/z ratios” [0024]).
It would have been obvious to one possessing ordinary skill in the art before the effective filing date of the claimed invention to have modified Smoot with the precursor identification step of Grothe in order to improve the accuracy of identifying an analyte by analyzing as much information as possible about the sample to be analyzed.
Regarding claim 23, Smoot discloses a method for building an analyte library (described in paragraph [0041]), the method comprising: receiving mass spectrum data from analysis of a sample using mass spectrometry (“Obtaining a mass spectrometric proteomic profile from the sample” [0040]), mass spectrum data including a mass spectrum (“The proteomic profile may include all or part of the information, for example, mass spectrometric data, such as m/z values of peaks in the mass spectrum” [0021]) and a sample matrix (“Within HGMS, multiple annotated areas of a tissue sample may be analyzed” [0046] – where paragraph [0115] of the specification of the immediate application identifies “tissues” as an example of a sample matrix, and Smoot identifies in paragraph [0037] that “matrix effects” a present in the MALDI-TOF mass spectrometry data), and the sample including an analyte (“determining a distribution of the one or more analytes in the tissue sample” [0122]); identifying peaks in the mass spectrum (“The proteomic profile may include all or part of the information, for example, mass spectrometric data, such as m/z values of peaks in the mass spectrum” [0021] – “A characteristic proteomic profile may, for example, be characterized by the pattern formed by the combination of spectral amplitudes at given m/z vales” [0074]); assigning at least one ion type to the peaks (“if the proteomic profile is presented in the form of a mass spectrum, the proteomic signature may be a peak or a combination of peaks that differ, qualitatively or quantitatively, from the mass spectrum of a corresponding reference sample” [0073] – “Obtaining a mass spectrometric proteomic profile from the sample may comprise experimentally measuring the mass to charge ratios of ions to obtain an experimental value corresponding to the mass to charge ratio of each of the ions and distinguishing candidate ions having substantially the same mass to charge ratio” [0040]); annotating the peaks for the analyte based on the sample matrix (“The subset of peaks from spectra is used as a fingerprint for a diagnosis. Each new spectrum from a new sample is compared to these fingerprints and matched to the one to which it is more similar. All other peaks and parts of the spectra are ignored. Within HGMS, multiple annotated areas of a tissue sample may be analyzed for unique diagnostic information related to the individual areas of cells, which when combined and analyzed together may help provide a more accurate diagnosis for the sample and patient as a whole” [0046]); extracting an ion fingerprint for the analyte based on the annotated peaks (“The subset of peaks from spectra is used as a fingerprint for a diagnosis. Each new spectrum from a new sample is compared to these fingerprints and matched to the one to which it is more similar. All other peaks and parts of the spectra are ignored. Within HGMS, multiple annotated areas of a tissue sample may be analyzed for unique diagnostic information related to the individual areas of cells, which when combined and analyzed together may help provide a more accurate diagnosis for the sample and patient as a whole” [0046]). Smoot discloses the claimed invention except that while Smoot identifies an analyte (“identifying at least one inflammatory bowel disease and/or lymphoma related compound in the sample from results from the mass spectrometer, comparing the at least one identified related compound in the sample to one or more known inflammatory bowel disease and/or lymphoma profiles” [Abstract] – “determining a distribution of the one or more analytes within the feline tissue sample” [0118]), based on an ion fingerprint (“The subset of peaks from spectra is used as a fingerprint for a diagnosis. Each new spectrum from a new sample is compared to these fingerprints and matched to the one to which it is more similar” [0046]), and the operation is generally performed on a storage device (“The mass spectrometry system may include a processor configured to execute computer-executable instructions and a computer-readable storage medium (e.g., memory and/or additional hardware storage) storing computer-executable instructions configured to perform various steps, methods, and/or functionality in accordance with aspects of the present invention” [0145]), there is no explicit disclosure of a step to store an analyte identification entry including the ion fingerprint for the analyte.
Grothe discloses “A method of acquiring and compiling data obtained on a mass spectrometer system, comprises… storing at least one new entry in the mass-spectral library relating to the recognized additional contribution” [Abstract] wherein “A resulting product spectrum exhibits a set of fragmentation peaks (a fragment set) which, in many instances, may be used as a fingerprint to derive structural information relating to the parent peptide or protein” [0003].
It would have been obvious to one possessing ordinary skill in the art before the effective filing date of the claimed invention to have modified Smoot with the storing step of Grothe in order to generate a history of identified samples in a library that can be utilized to improve the speed of identifying additional, future samples to be analyzed.
Claim(s) 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Smoot et al. U.S. PGPUB No. 2021/0096138 in view of Grothe, Jr. et al. U.S. PGPUB No. 2014/0138537 in further view of Geromanos et al. U.S. PGPUB No. 2018/0144918.
Regarding claim 18, Smoot discloses the claimed invention except that while Smoot discloses “In ESI tandem mass spectrometry (ESI/MS/MS), analysis of both precursor ions and product ions is possible, thereby monitoring a single precursor product reaction and producing a signal only when the desired precursor ion is present” [0035], there is no explicit disclosure that to search the analyte library further includes searching for the at least one match in the analyte library based on the at least one match being within a precursor tolerance of the sample.
Geromanos discloses a method of tandem mass spectrometry (“Techniques and embodiments will now be described with reference to illustrative embodiments for analyzing samples, for instance, in a system analyzing samples using an MS process, such as LC/MS/MS” [0027]) wherein “product ion spectra can also be searched using very wide precursor mass tolerances (for example, the width of the isolation window at all available charge states)” [0037].
It would have been obvious to one possessing ordinary skill in the art before the effective filing date of the claimed invention to have modified Smoot and Grothe with the precursor tolerance of Geromanos in order to enhance identification of an analyte by coordinating between precursor and fragment ion mass spectra with a specific allowance according to an expected analyte to be identified.
Allowable Subject Matter
Claims 19, 20, 21, and 22 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Regarding claim 19; Smoot et al. U.S. PGPUB No. 2021/0096138 discloses a system for building an analyte library (described in paragraph [0041]), the system comprising: at least one processing device (“a computer system or computing device may include one or more processors and storage devices (e.g., memory and disk drives)” [0145]); and at least one memory device (“a computer system or computing device may include one or more processors and storage devices (e.g., memory and disk drives)” [0145]) storing instructions that, when executed by the at least one processing device, cause the system to (“The mass spectrometry system may include a processor configured to execute computer-executable instructions and a computer-readable storage medium (e.g., memory and/or additional hardware storage) storing computer-executable instructions configured to perform various steps, methods, and/or functionality in accordance with aspects of the present invention” [0145]): receive mass spectrum data from analysis of a sample using mass spectrometry (“Obtaining a mass spectrometric proteomic profile from the sample” [0040]), the mass spectrum data including a mass spectrum (“The proteomic profile may include all or part of the information, for example, mass spectrometric data, such as m/z values of peaks in the mass spectrum” [0021]) and a sample matrix (“Within HGMS, multiple annotated areas of a tissue sample may be analyzed” [0046] – where paragraph [0115] of the specification of the immediate application identifies “tissues” as an example of a sample matrix, and Smoot identifies in paragraph [0037] that “matrix effects” a present in the MALDI-TOF mass spectrometry data), and the sample including an analyte (“determining a distribution of the one or more analytes in the tissue sample” [0122]); identify peaks in the mass spectrum (“The proteomic profile may include all or part of the information, for example, mass spectrometric data, such as m/z values of peaks in the mass spectrum” [0021] – “A characteristic proteomic profile may, for example, be characterized by the pattern formed by the combination of spectral amplitudes at given m/z vales” [0074]); assign at least one ion type to the peaks (“if the proteomic profile is presented in the form of a mass spectrum, the proteomic signature may be a peak or a combination of peaks that differ, qualitatively or quantitatively, from the mass spectrum of a corresponding reference sample” [0073] – “Obtaining a mass spectrometric proteomic profile from the sample may comprise experimentally measuring the mass to charge ratios of ions to obtain an experimental value corresponding to the mass to charge ratio of each of the ions and distinguishing candidate ions having substantially the same mass to charge ratio” [0040]); annotate the peaks for the analyte based on the sample matrix (“The subset of peaks from spectra is used as a fingerprint for a diagnosis. Each new spectrum from a new sample is compared to these fingerprints and matched to the one to which it is more similar. All other peaks and parts of the spectra are ignored. Within HGMS, multiple annotated areas of a tissue sample may be analyzed for unique diagnostic information related to the individual areas of cells, which when combined and analyzed together may help provide a more accurate diagnosis for the sample and patient as a whole” [0046]); extract an ion fingerprint for the analyte based on the annotated peaks (“The subset of peaks from spectra is used as a fingerprint for a diagnosis. Each new spectrum from a new sample is compared to these fingerprints and matched to the one to which it is more similar. All other peaks and parts of the spectra are ignored. Within HGMS, multiple annotated areas of a tissue sample may be analyzed for unique diagnostic information related to the individual areas of cells, which when combined and analyzed together may help provide a more accurate diagnosis for the sample and patient as a whole” [0046]). However, Smoot does not disclose scoring a plurality of analyte identification entries with a confidence score; and providing each of the plurality of analyte identification entries with an associated confidence score above a threshold score.
The prior art fails to teach or reasonably suggest, in combination with the other claim limitations, a system for using an analyte library to identify at least one analyte, the system comprising: at least one processing device; and at least one memory device storing instructions that, when executed by the at least one processing device, cause the system to: search the analyte library for at least one match of the sample by comparing the ion fingerprint with stored ion fingerprints in the analyte library; and provide the at least one match further including to: score a plurality of analyte identification entries with a confidence score; and provide each of the plurality of analyte identification entries with an associated confidence score above a threshold score.
Regarding claims 20, 21, and 22; these claims would be allowable at least for their dependence, either directly or indirectly, upon claim 19.
Conclusion
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/JASON L MCCORMACK/Examiner, Art Unit 2881
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