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 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) 19 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by McAlister U.S. PGPUB No. 2022/0093378.
Regarding claim 19, McAlister discloses a method of performing data-dependent tandem mass spectrometry (“a method of data dependent analysis 400” [0060]), the method comprising: acquiring, by a mass spectrometer, an MS1 mass spectrum of ions produced from a sample (“a mass analyzer used to collect the MS1 spectrum” [0065]); determining, by the mass spectrometer and based on the MS1 mass spectrum, a set of observed precursor ions (“theoretical fragments of the precursor compound identified by the spectral search” [0065]); determining, by the mass spectrometer, expected fragment ions for the set of observed precursor ions (“the exclusion list can include peaks found in… theoretical fragments of the precursor compound identified by the spectral search” [0065]); and acquiring, by the mass spectrometer, one or more MS2 mass spectra for select ions observed in the MS1 mass spectrum (“the MS2 analysis can be performed on the selected peak” [0063]), wherein the expected fragment ions are excluded from being selected for MS2 analysis (“the exclusion list can be further based on the mass accuracy or resolution of a mass analyzer used to collect the MS1 spectrum, such as by including a mass range determined by the theoretical exact mass and the mass accuracy or resolution of the mass analyzer” [0065]).
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, 5, 10, 16, 17, and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over McAlister U.S. PGPUB No. 2022/0093378 in view of Tate U.S. PGPUB No. 2020/0013609.
Regarding claim 1, McAlister discloses a system for performing data-dependent tandem mass spectrometry (“a method of data dependent analysis 400” [0060]), performing a method to: direct a mass spectrometer to acquire an MS1 mass spectrum of ions produced from a sample (“a mass analyzer used to collect the MS1 spectrum” [0065]); determine, based on the MS1 mass spectrum, a set of observed precursor ions (“At 402, a survey scan can be performed. The survey scan can be used to identified precursor ions for further analysis” [0060]); determine expected fragment ions for the set of observed precursor ions (“theoretical fragments of the precursor compound identified by the spectral search” [0065]); add the expected fragment ions to an exclusion list (“the exclusion list can include peaks found in… theoretical fragments of the precursor compound identified by the spectral search” [0065]); and direct the mass spectrometer to perform an MS2 analysis for select ions observed in the MS1 mass spectrum (“the MS2 analysis can be performed on the selected peak” [0063]), wherein the exclusion list is used to exclude one or more ions observed in the MS1 mass spectrum from being selected for the MS2 analysis (“the exclusion list can be further based on the mass accuracy or resolution of a mass analyzer used to collect the MS1 spectrum, such as by including a mass range determined by the theoretical exact mass and the mass accuracy or resolution of the mass analyzer” [0065]). However, although McAlister discloses that “the data analyzer 504 and the spectral library 506 can reside locally with the mass spectrometer 502, such as on a computer system controlling the mass spectrometer 502” [0069], there is no explicit disclosure that the system comprises: a memory storing instructions; and a processor communicatively coupled to the memory.
Tate ‘609 discloses a computer system (“A system, method, and computer program product are disclosed for identifying precursor ions originating from an ion source device using a scanning sequential windowed precursor ion selection and mass analysis survey scan” [0064]) controlling a mass spectrometer (“controlling a mass spectrometer to perform a precursor ion survey scan that filters out fragments or adducts of precursor ions” [0002]), wherein the system comprises: a memory storing instructions (“Computer system 100 also includes a memory 106, which can be a random access memory (RAM) or other dynamic storage device, coupled to bus 102 for storing instructions to be executed by processor 104” [0090]), and a processor (“The processor instructs the mass analyzer” [0067]) communicatively coupled to the memory (“Computer system 100 also includes a memory 106… coupled to bus 102 for storing instructions to be executed by processor 104” [0090]).
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 McAlister with the computer controller of Tate ‘609 in order to utilize a commercially available computer that is designed for controlling the operations of a mass spectrometer to embody the generic computer controller broadly described in McAlister.
Regarding claim 2, McAlister discloses determining that a signal for an ion observed in the MS1 mass spectrum satisfies MS2 analysis criteria; and exclude the ion observed in the MS1 mass spectrum from being selected for the MS2 analysis based on the exclusion list (“In various embodiments, the exclusion list can include peaks found in the MS2 spectra and/or theoretical fragments of the precursor compound identified by the spectral search, including theoretical fragments not found in the MS2 spectra” [0065]).
Regarding claim 3, McAlister discloses that the MS2 analysis criteria comprise at least one of an intensity threshold (“During a typical data-dependent method the mass spectrometer will trigger MS2 spectra on these product ions if they meet all the standard method filters (e.g., the product ion is abundant enough in the MS1 scan to satisfy an intensity filter)” [0052]), a charge state requirement, or an expected isotope distribution (the charge state requirement and expected isotope distribution are referenced in the alternative to the intensity threshold and McAlister teaches at least the intensity threshold, as in paragraph [0052]).
Regarding claim 5, McAlister discloses accessing, from a dataset, data indicating the expected fragment ions for the set of observed precursor ions (“the exclusion list can include… theoretical fragments of the precursor compound identified by the spectral search” [0065]).
Regarding claim 10, McAlister discloses refining the exclusion list based on fragment ions observed in the MS2 analysis (“the fragments can include fragments in the MS2 spectra… the identified fragments can be added to an exclusion list” [0065]).
Regarding claim 16, McAlister discloses a system to: direct a mass spectrometer to acquire an MS1 mass spectrum of ions produced from a sample (“a mass analyzer used to collect the MS1 spectrum” [0065]); determine, based on the MS1 mass spectrum, a set of observed precursor ions (“At 402, a survey scan can be performed. The survey scan can be used to identified precursor ions for further analysis” [0060]); determine expected fragment ions for the set of observed precursor ions (“theoretical fragments of the precursor compound identified by the spectral search” [0065]); add the expected fragment ions to an exclusion list (“the exclusion list can include peaks found in… theoretical fragments of the precursor compound identified by the spectral search” [0065]); and direct the mass spectrometer to perform an MS2 analysis for select ions observed in the MS1 mass spectrum (“the MS2 analysis can be performed on the selected peak” [0063]), wherein the exclusion list is used to exclude one or more ions observed in the MS1 mass spectrum from being selected for the MS2 analysis (“the exclusion list can be further based on the mass accuracy or resolution of a mass analyzer used to collect the MS1 spectrum, such as by including a mass range determined by the theoretical exact mass and the mass accuracy or resolution of the mass analyzer” [0065]). However, although McAlister discloses that “the data analyzer 504 and the spectral library 506 can reside locally with the mass spectrometer 502, such as on a computer system controlling the mass spectrometer 502” [0069], there is no explicit disclosure that the system comprises: a memory storing instructions; and a processor communicatively coupled to the memory.
Tate ‘609 discloses a computer system (“A system, method, and computer program product are disclosed for identifying precursor ions originating from an ion source device using a scanning sequential windowed precursor ion selection and mass analysis survey scan” [0064]) controlling a mass spectrometer (“controlling a mass spectrometer to perform a precursor ion survey scan that filters out fragments or adducts of precursor ions” [0002]), wherein the system comprises: a memory storing instructions (“Computer system 100 also includes a memory 106, which can be a random access memory (RAM) or other dynamic storage device, coupled to bus 102 for storing instructions to be executed by processor 104” [0090]), and a processor (“The processor instructs the mass analyzer” [0067]) communicatively coupled to the memory (“Computer system 100 also includes a memory 106… coupled to bus 102 for storing instructions to be executed by processor 104” [0090]).
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 McAlister with the computer controller of Tate ‘609 in order to utilize a commercially available computer that is designed for controlling the operations of a mass spectrometer to embody the generic computer controller broadly described in McAlister.
Regarding claim 17, McAlister discloses acquiring an MS2 mass spectrum based on the MS2 analysis of one of the select ions observed in the MS1 mass spectrum (“peaks can be identified in the survey scan… a peak can be selected for analysis. In various embodiments, a precursor ion with the highest abundance can be selected. In other embodiments, precursors may be selected at least in part based on an inclusion list. The inclusion list can include mass-to-charge ratios or m/z ranges of particular interest, and when ions are detected within those ranges, they can be selected for MS2 analysis. In further embodiments, an exclusion list can be used to avoid listed precursor ions, such as a precursor ion that was previously analyzed or fragments thereof” [0061-0062]); and refine the exclusion list based on observed fragment ions observed in the MS2 analysis (“In various embodiments, the exclusion list can include peaks found in the MS2 spectra and/or theoretical fragments of the precursor compound identified by the spectral search, including theoretical fragments not found in the MS2 spectra” [0065]).
Regarding claim 18, McAlister discloses determining that a signal for an ion observed in the MS1 mass spectrum satisfies MS2 analysis criteria; and exclude the ion observed in the MS1 mass spectrum from being selected for the MS2 analysis based on the exclusion list (“In various embodiments, the exclusion list can include peaks found in the MS2 spectra and/or theoretical fragments of the precursor compound identified by the spectral search, including theoretical fragments not found in the MS2 spectra” [0065]).
Claim(s) 4 is/are rejected under 35 U.S.C. 103 as being unpatentable over McAlister U.S. PGPUB No. 2022/0093378 in view of Tate U.S. PGPUB No. 2020/0013609 in further view of Coon et al. U.S. PGPUB No. 2014/0336951.
Regarding claim 4, although McAlister discloses comparing ions observed in the MS2 mass spectrum against a dataset of expected precursor ions associated with the sample and designating ions observed in the MS2 mass spectrum that have matches in the dataset to be the set of observed precursor ions (“matching the experimentally observed MS2 spectra against a database or using an algorithm using de novo analysis to identify the precursor ion” [0056]), there is no explicit disclosure of comparing ions observed in the MS1 mass spectrum against a dataset of expected precursor ions associated with the sample; and designating ions observed in the MS1 mass spectrum that have matches in the dataset to be the set of observed precursor ions.
Coon ‘951 discloses comparing ions observed in the MS1 mass spectrum against a dataset of expected precursor ions associated with the sample; and designating ions observed in the MS1 mass spectrum that have matches in the dataset to be the set of observed precursor ions (“The charge state and peptide mass are obtained from the first mass spectrum while the fragmentation pattern is recorded in the second mass spectrum. With this information it is possible to identify the peptide and protein of origin, e.g., by comparison to peptide fragmentation patterns stored in a database” [0002]).
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 McAlister with the method of comparing ions observed in an MS1 mass spectrum, as in Coon ‘951, in order to provide additional analysis of a sample specimen so as to acquire the most information possible in identifying a sample composition, instead of merely comparing ions observed in the MS2 spectrum.
Claim(s) 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over McAlister U.S. PGPUB No. 2022/0093378 in view of Tate U.S. PGPUB No. 2020/0013609 in further view of Coon et al. U.S. PGPUB No. 2012/0261568.
Regarding claim 6, McAlister discloses accessing, from a dataset, data indicating the expected fragment ions for the set of observed precursor ions (“the exclusion list can include… theoretical fragments of the precursor compound identified by the spectral search” [0065]). However, McAlister does not disclose that the dataset is generated based on a spectral library before acquisition of the MS1 mass spectrum.
Coon ‘568 discloses accessing, from a dataset, data indicating the expected fragment ions for the set of observed precursor ions (“optimize analyte identification or quantitation during data acquisition by comparing the precursor analyte ion mass spectrometry data to the list of target analytes, target analyte precursor ion information and landmark precursor ion signal information” [0132]), wherein the dataset is generated based on a spectral library before acquisition of the MS1 mass spectrum (“Target lists were loaded into the instrument's firmware for instant access during acquisition. Peptide lists were stored in an internal database and sorted based on their precursor mass for fast look ups using a binary search algorithm” [0419]) and wherein “performing the MS1 scan comprises generating a distribution of precursor analyte ions from the sample and measuring mass-to-charge ratios of at least a portion of the product ions in a mass analyzer, thereby generating one or more analyte ion peaks” [Claim 25].
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 McAlister with the dataset of Coon ‘568 in order to utilize a premade database of standards against which spectral identification may be made, thereby reducing the amount of time required to form a new database.
Claim(s) 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over McAlister U.S. PGPUB No. 2022/0093378 in view of Tate U.S. PGPUB No. 2020/0013609 in further view of Nishimura et al. U.S. PGPUB No. 2011/0111443.
Regarding claim 7, McAlister discloses accessing, from a dataset, data indicating the expected fragment ions for the set of observed precursor ions (“the exclusion list can include… theoretical fragments of the precursor compound identified by the spectral search” [0065]). However, McAlister does not disclose that the dataset is generated using a spectral simulation algorithm to simulate theoretical fragmentation spectra for the set of observed precursor ions.
Nishimura discloses accessing, from a dataset, data indicating the expected fragment ions for the set of observed precursor ions, wherein the dataset is generated using a spectral simulation algorithm to simulate theoretical fragmentation spectra for the set of observed precursor ions (“In this method, the spectrum pattern of actually observed fragment ions and the calculated database of the fragment ions obtained by a theoretical simulation based on the characteristics of the disintegration behavior of the sugar chain, are automatically collated, and from the homologousness, a candidate structure is speculated” [0473]).
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 McAlister with the dataset of Nishimura in order to ensure accurate identification of ions in mass analysis as compared to expected values for the ions in the mass analysis.
Claim(s) 14 and 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over McAlister U.S. PGPUB No. 2022/0093378 in view of Tate U.S. PGPUB No. 2020/0013609 in further view of Tate et al. U.S. PGPUB No. 2018/0166263.
Regarding claim 14, McAlister discloses the claimed invention except that while McAlister discloses that “an exclusion list can be used to avoid listed precursor ions, such as a precursor ion that was previously analyzed or fragments thereof” [0062], there is no explicit disclosure of determining, by the mass spectrometer and based on a scoring algorithm, a fragment-ion-likelihood score for an ion observed in the MS1 mass spectrum; and excluding, by the mass spectrometer, the ion observed in the MS1 mass spectrum from being selected for the MS2 analysis based on the fragment-ion-likelihood score.
Tate ‘263 discloses determining, by a mass spectrometer and based on a scoring algorithm, a fragment-ion-likelihood score for an ion observed in the MS1 mass spectrum (“a mass spectrometry (MS) survey scan step that produces a precursor ion mass spectrum, a peak list step that ranks the peaks of the precursor ion mass spectrum by intensity” [Claim 1]); and excluding, by the mass spectrometer, the ion observed in the MS1 mass spectrum from being selected for the MS2 analysis based on the fragment-ion-likelihood score (“a filtering step that excludes from the peak list precursor ions that were fragmented in a previous cycle and selects a subset of peaks from the peak list with the highest intensities producing a filtered peak list, and a mass spectrometry/mass spectrometry step (MS/MS) step during which an MS/MS scan is performed on each precursor ion on the filtered peak list producing a product ion spectrum for each MS/MS scan” [Claim 1]).
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 McAlister with the likelihood scoring of Tate ‘263 in order to generate an accurate threshold by which certain precursors are determined from mass spectral data, so as to properly correlate the mass spectral data with the specific precursor species desired to be excluded from further scanning.
Regarding claim 15, McAlister discloses the claimed invention except that while McAlister discloses that “an exclusion list can be used to avoid listed precursor ions, such as a precursor ion that was previously analyzed or fragments thereof” [0062], there is no explicit disclosure of determining, based on a scoring algorithm, fragment-ion-likelihood scores for ions observed in the MS1 mass spectrum; and select a subset of the ions observed in the MS1 mass spectrum for MS2 analysis, wherein ions in the subset are selected in order from lowest to highest fragment-ion-likelihood scores.
Tate ‘263 discloses determining, based on a scoring algorithm, fragment-ion-likelihood scores for ions observed in the MS1 mass spectrum (“a precursor ion MS survey scan… A peak list is generated by ranking the mass-to charge ratio (m/z) peaks of the MS survey scan spectrum from highest intensity to lowest intensity” [0045]); and select a subset of the ions observed in the MS1 mass spectrum for MS2 analysis “an MS/MS scan is performed on each precursor ion on the filtered peak list, producing a product ion spectrum for each MS/MS scan” [0019], wherein ions in the subset are selected in order from lowest to highest fragment-ion-likelihood scores (“a precursor ion MS survey scan… A peak list is generated by ranking the mass-to charge ratio (m/z) peaks of the MS survey scan spectrum from highest intensity to lowest intensity” [0045]).
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 McAlister with the likelihood scoring of Tate ‘263 in order to generate an accurate threshold by which certain precursors are determined from mass spectral data, so as to properly correlate the mass spectral data with the specific precursor species desired to be excluded from further scanning.
Claim(s) 20, 21, and 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over McAlister U.S. PGPUB No. 2022/0093378 in view of Tate et al. U.S. PGPUB No. 2018/0166263.
Regarding claim 20, McAlister discloses the claimed invention except that while McAlister discloses that “an exclusion list can be used to avoid listed precursor ions, such as a precursor ion that was previously analyzed or fragments thereof” [0062], there is no explicit disclosure of determining, by the mass spectrometer and based on a scoring algorithm, a fragment-ion-likelihood score for an ion observed in the MS1 mass spectrum; and excluding, by the mass spectrometer, the ion observed in the MS1 mass spectrum from being selected for the MS2 analysis based on the fragment-ion-likelihood score.
Tate ‘263 discloses determining, by a mass spectrometer and based on a scoring algorithm, a fragment-ion-likelihood score for an ion observed in the MS1 mass spectrum (“a mass spectrometry (MS) survey scan step that produces a precursor ion mass spectrum, a peak list step that ranks the peaks of the precursor ion mass spectrum by intensity” [Claim 1]); and excluding, by the mass spectrometer, the ion observed in the MS1 mass spectrum from being selected for the MS2 analysis based on the fragment-ion-likelihood score (“a filtering step that excludes from the peak list precursor ions that were fragmented in a previous cycle and selects a subset of peaks from the peak list with the highest intensities producing a filtered peak list, and a mass spectrometry/mass spectrometry step (MS/MS) step during which an MS/MS scan is performed on each precursor ion on the filtered peak list producing a product ion spectrum for each MS/MS scan” [Claim 1]).
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 McAlister with the likelihood scoring of Tate ‘263 in order to generate an accurate threshold by which certain precursors are determined from mass spectral data, so as to properly correlate the mass spectral data with the specific precursor species desired to be excluded from further scanning.
Regarding claim 21, McAlister discloses the claimed invention except that while McAlister discloses that “an exclusion list can be used to avoid listed precursor ions, such as a precursor ion that was previously analyzed or fragments thereof” [0062], there is no explicit disclosure of determining that a fragment-ion-likelihood score for an ion observed in an MS1 mass spectrum satisfies a threshold; wherein the excluding the ion from being selected for MS2 analysis is based on the determining that the fragment-ion-likelihood score for the ion observed in the MS1 mass spectrum satisfies a threshold.
Tate ‘263 discloses determining, by a mass spectrometer and based on a scoring algorithm, a fragment-ion-likelihood score for an ion observed in the MS1 mass spectrum (“a precursor ion MS survey scan… A peak list is generated by ranking the mass-to charge ratio (m/z) peaks of the MS survey scan spectrum from highest intensity to lowest intensity” [0045]); and excluding, by the mass spectrometer, the ion observed in the MS1 mass spectrum from being selected for the MS2 analysis based on the fragment-ion-likelihood score (“For example, any precursor ions that were fragmented in an earlier cycle are excluded from the precursor ion peak list. Also, precursor ions on the peak list that are within a certain m/z threshold or tolerance of a precursor ion that was previously fragmented are also excluded from the precursor ion list” [0046] – “an MS/MS scan is performed on each precursor ion on the filtered peak list, producing a product ion spectrum for each MS/MS scan” [0019]); wherein determining that the fragment-ion-likelihood score for the ion observed in the MS1 mass spectrum satisfies a threshold (“precursor ions on the peak list that are within a certain m/z threshold or tolerance of a precursor ion that was previously fragmented are also excluded from the precursor ion list” [0046]); wherein the excluding the ion from being selected for the MS2 analysis is based on the determining that the fragment-ion-likelihood score for the ion observed in the MS1 mass spectrum satisfies a threshold (“precursor ions on the peak list that are within a certain m/z threshold or tolerance of a precursor ion that was previously fragmented are also excluded from the precursor ion list” [0046]).
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 McAlister with the likelihood scoring of Tate ‘263 in order to generate an accurate threshold by which certain precursors are determined from mass spectral data, so as to properly correlate the mass spectral data with the specific precursor species desired to be excluded from further scanning.
Regarding claim 22, McAlister discloses defining the threshold based on user input received by way of a user interface of the mass spectrometer (“Or it may involve more complex filtering such as a dynamic exclusion list where ions previously selected for MSn analysis are excluded form additional MSn analysis for a user defined period of time” [0004]).
Allowable Subject Matter
Claims 8, 9, 11, 12, and 13 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 8; McAlister U.S. PGPUB No. 2022/0093378 discloses a method of performing data-dependent tandem mass spectrometry (“a method of data dependent analysis 400” [0060]), the method comprising: acquiring, by a mass spectrometer, an MS1 mass spectrum of ions produced from a sample (“a mass analyzer used to collect the MS1 spectrum” [0065]); determining, by the mass spectrometer and based on the MS1 mass spectrum, a set of observed precursor ions (“theoretical fragments of the precursor compound identified by the spectral search” [0065]); determining, by the mass spectrometer, expected fragment ions for the set of observed precursor ions (“the exclusion list can include peaks found in… theoretical fragments of the precursor compound identified by the spectral search” [0065]); and acquiring, by the mass spectrometer, one or more MS2 mass spectra for select ions observed in the MS1 mass spectrum (“the MS2 analysis can be performed on the selected peak” [0063]), wherein the expected fragment ions are excluded from being selected for MS2 analysis (“the exclusion list can be further based on the mass accuracy or resolution of a mass analyzer used to collect the MS1 spectrum, such as by including a mass range determined by the theoretical exact mass and the mass accuracy or resolution of the mass analyzer” [0065]). McAlister discloses accessing, from a dataset, data indicating the expected fragment ions for the set of observed precursor ions (“the exclusion list can include… theoretical fragments of the precursor compound identified by the spectral search” [0065]). However, there is no explicit disclosure that filtering the data of the dataset based on one or more of a precursor ion m/z, a precursor ion charge, a mass analyzer mass accuracy, a fragment ion m/z, or a fragment ion charge.
The prior art fails to teach or reasonably suggest, in combination with the other claim limitations, a system for performing data-dependent tandem mass spectrometry, the system comprising: a memory storing instructions; and a processor communicatively coupled to the memory and configured to execute the instructions to: direct a mass spectrometer to acquire an MS1 mass spectrum of ions produced from a sample; determine, based on the MS1 mass spectrum, a set of observed precursor ions by accessing, from a dataset, data indicating the expected fragment ions for the set of observed precursor ions; and filtering the data of the dataset based on one or more of a precursor ion m/z, a precursor ion charge, a mass analyzer mass accuracy, a fragment ion m/z, or a fragment ion charge.
Regarding claim 9; McAlister U.S. PGPUB No. 2022/0093378 discloses a method of performing data-dependent tandem mass spectrometry (“a method of data dependent analysis 400” [0060]), the method comprising: acquiring, by a mass spectrometer, an MS1 mass spectrum of ions produced from a sample (“a mass analyzer used to collect the MS1 spectrum” [0065]); determining, by the mass spectrometer and based on the MS1 mass spectrum, a set of observed precursor ions (“theoretical fragments of the precursor compound identified by the spectral search” [0065]); determining, by the mass spectrometer, expected fragment ions for the set of observed precursor ions (“the exclusion list can include peaks found in… theoretical fragments of the precursor compound identified by the spectral search” [0065]); and acquiring, by the mass spectrometer, one or more MS2 mass spectra for select ions observed in the MS1 mass spectrum (“the MS2 analysis can be performed on the selected peak” [0063]), wherein the expected fragment ions are excluded from being selected for MS2 analysis (“the exclusion list can be further based on the mass accuracy or resolution of a mass analyzer used to collect the MS1 spectrum, such as by including a mass range determined by the theoretical exact mass and the mass accuracy or resolution of the mass analyzer” [0065]). McAlister discloses accessing, from a dataset, data indicating the expected fragment ions for the set of observed precursor ions (“the exclusion list can include… theoretical fragments of the precursor compound identified by the spectral search” [0065]). However, there is no explicit disclosure of determining a preliminary set of expected fragment ions for the set of observed precursor ions; determining frequencies with which ions occur in the preliminary set of expected fragment ions; filtering the preliminary set of expected fragment ions based on the frequencies to obtain a filtered set of expected fragment ions; and designating the expected fragment ions in the filtered set of expected fragment ions to be the expected fragment ions for the set of observed precursor ions.
The prior art fails to teach or reasonably suggest, in combination with the other claim limitations, a system for performing data-dependent tandem mass spectrometry, the system comprising: determine, based on the MS1 mass spectrum, a set of observed precursor ions; a memory storing instructions; and a processor communicatively coupled to the memory and configured to execute the instructions to: determining a preliminary set of expected fragment ions for the set of observed precursor ions; determining frequencies with which ions occur in the preliminary set of expected fragment ions; filtering the preliminary set of expected fragment ions based on the frequencies to obtain a filtered set of expected fragment ions; and designating the expected fragment ions in the filtered set of expected fragment ions to be the expected fragment ions for the set of observed precursor ions.
Regarding claim 11; McAlister U.S. PGPUB No. 2022/0093378 discloses a method of performing data-dependent tandem mass spectrometry (“a method of data dependent analysis 400” [0060]), the method comprising: acquiring, by a mass spectrometer, an MS1 mass spectrum of ions produced from a sample (“a mass analyzer used to collect the MS1 spectrum” [0065]); determining, by the mass spectrometer and based on the MS1 mass spectrum, a set of observed precursor ions (“theoretical fragments of the precursor compound identified by the spectral search” [0065]); determining, by the mass spectrometer, expected fragment ions for the set of observed precursor ions (“the exclusion list can include peaks found in… theoretical fragments of the precursor compound identified by the spectral search” [0065]); and acquiring, by the mass spectrometer, one or more MS2 mass spectra for select ions observed in the MS1 mass spectrum (“the MS2 analysis can be performed on the selected peak” [0063]), wherein the expected fragment ions are excluded from being selected for MS2 analysis (“the exclusion list can be further based on the mass accuracy or resolution of a mass analyzer used to collect the MS1 spectrum, such as by including a mass range determined by the theoretical exact mass and the mass accuracy or resolution of the mass analyzer” [0065]). McAlister discloses accessing, from a dataset, data indicating the expected fragment ions for the set of observed precursor ions (“the exclusion list can include… theoretical fragments of the precursor compound identified by the spectral search” [0065]). However, although McAlister discloses that “compounds can be removed from the exclusion list periodically, such as based on the expected chromatographic elution time or peak width” [0065], McAlister does not disclose replacing, in the exclusion list, the expected fragment ions with the observed fragment ions observed in the MS2 analysis.
The prior art fails to teach or reasonably suggest, in combination with the other claim limitations, a system for performing data-dependent tandem mass spectrometry, the system comprising: a memory storing instructions; and a processor communicatively coupled to the memory and configured to execute the instructions to: add expected fragment ions determined from a set of observed precursor ions determined from an MS1 mass spectrum to an exclusion list; and direct a mass spectrometer to perform an MS2 analysis for select ions observed in the MS1 mass spectrum, wherein the exclusion list is used to exclude one or more ions observed in the MS1 mass spectrum from being selected for the MS2 analysis; and refining the exclusion list based on fragment ions observed in the MS2 analysis; replacing, in the exclusion list, the expected fragment ions with the observed fragment ions observed in the MS2 analysis.
Regarding claim 12; McAlister U.S. PGPUB No. 2022/0093378 discloses a method of performing data-dependent tandem mass spectrometry (“a method of data dependent analysis 400” [0060]), the method comprising: acquiring, by a mass spectrometer, an MS1 mass spectrum of ions produced from a sample (“a mass analyzer used to collect the MS1 spectrum” [0065]); determining, by the mass spectrometer and based on the MS1 mass spectrum, a set of observed precursor ions (“theoretical fragments of the precursor compound identified by the spectral search” [0065]); determining, by the mass spectrometer, expected fragment ions for the set of observed precursor ions (“the exclusion list can include peaks found in… theoretical fragments of the precursor compound identified by the spectral search” [0065]); and acquiring, by the mass spectrometer, one or more MS2 mass spectra for select ions observed in the MS1 mass spectrum (“the MS2 analysis can be performed on the selected peak” [0063]), wherein the expected fragment ions are excluded from being selected for MS2 analysis (“the exclusion list can be further based on the mass accuracy or resolution of a mass analyzer used to collect the MS1 spectrum, such as by including a mass range determined by the theoretical exact mass and the mass accuracy or resolution of the mass analyzer” [0065]). McAlister discloses accessing, from a dataset, data indicating the expected fragment ions for the set of observed precursor ions (“the exclusion list can include… theoretical fragments of the precursor compound identified by the spectral search” [0065]). However, although McAlister discloses that “compounds can be removed from the exclusion list periodically, such as based on the expected chromatographic elution time or peak width” [0065], McAlister does not disclose adding, to the exclusion list, any of the observed fragment ions that are not duplicative of the expected fragment ions in the exclusion list.
The prior art fails to teach or reasonably suggest, in combination with the other claim limitations, a system for performing data-dependent tandem mass spectrometry, the system comprising: a memory storing instructions; and a processor communicatively coupled to the memory and configured to execute the instructions to: add expected fragment ions determined from a set of observed precursor ions determined from an MS1 mass spectrum to an exclusion list; and direct a mass spectrometer to perform an MS2 analysis for select ions observed in the MS1 mass spectrum, wherein the exclusion list is used to exclude one or more ions observed in the MS1 mass spectrum from being selected for the MS2 analysis; and refining the exclusion list based on fragment ions observed in the MS2 analysis; adding, to the exclusion list, any of the observed fragment ions that are not duplicative of the expected fragment ions in the exclusion list.
Regarding claim 13; McAlister U.S. PGPUB No. 2022/0093378 discloses a method of performing data-dependent tandem mass spectrometry (“a method of data dependent analysis 400” [0060]), the method comprising: acquiring, by a mass spectrometer, an MS1 mass spectrum of ions produced from a sample (“a mass analyzer used to collect the MS1 spectrum” [0065]); determining, by the mass spectrometer and based on the MS1 mass spectrum, a set of observed precursor ions (“theoretical fragments of the precursor compound identified by the spectral search” [0065]); determining, by the mass spectrometer, expected fragment ions for the set of observed precursor ions (“the exclusion list can include peaks found in… theoretical fragments of the precursor compound identified by the spectral search” [0065]); and acquiring, by the mass spectrometer, one or more MS2 mass spectra for select ions observed in the MS1 mass spectrum (“the MS2 analysis can be performed on the selected peak” [0063]), wherein the expected fragment ions are excluded from being selected for MS2 analysis (“the exclusion list can be further based on the mass accuracy or resolution of a mass analyzer used to collect the MS1 spectrum, such as by including a mass range determined by the theoretical exact mass and the mass accuracy or resolution of the mass analyzer” [0065]). McAlister discloses accessing, from a dataset, data indicating the expected fragment ions for the set of observed precursor ions (“the exclusion list can include… theoretical fragments of the precursor compound identified by the spectral search” [0065]). However, although McAlister discloses that “compounds can be removed from the exclusion list periodically, such as based on the expected chromatographic elution time or peak width” [0065], McAlister does not disclose removing, from the exclusion list, any of the expected fragment ions that are not among the fragment ions observed in the MS2 analysis.
The prior art fails to teach or reasonably suggest, in combination with the other claim limitations, a system for performing data-dependent tandem mass spectrometry, the system comprising: a memory storing instructions; and a processor communicatively coupled to the memory and configured to execute the instructions to: add expected fragment ions determined from a set of observed precursor ions determined from an MS1 mass spectrum to an exclusion list; and direct a mass spectrometer to perform an MS2 analysis for select ions observed in the MS1 mass spectrum, wherein the exclusion list is used to exclude one or more ions observed in the MS1 mass spectrum from being selected for the MS2 analysis; and refining the exclusion list based on fragment ions observed in the MS2 analysis; removing, from the exclusion list, any of the expected fragment ions that are not among the fragment ions observed in the MS2 analysis.
Conclusion
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/JASON L MCCORMACK/Examiner, Art Unit 2881
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