DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
This Office action is in response to correspondence received March 12, 2026.
Claims 1-8 are amended. Claims 9 and 10 are newly added. Claims 1-10 are pending and have been examined.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1-4 and 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bloomfield et al., US PGPUB 20160268111 A1 (“Bloomfield”) in view of Wildgoose, CN-106463331-A (2017) (“Wildgoose”).
Per claims 1 and 8, which are similar in scope, Bloomfield teaches A method for processing mass spectrometry data, comprising steps of in par 049: “As described above, sequential windowed acquisition (SWATH) is a tandem mass spectrometry technique that allows a mass range to be scanned within a time interval using multiple precursor ion scans of adjacent or overlapping precursor mass windows. A first mass analyzer selects each precursor mass window for fragmentation. A high resolution second mass analyzer is then used to detect the product ions produced from the fragmentation of each precursor mass window. SWATH allows the sensitivity of precursor ion scans to be increased without the traditional loss in specificity.” This teaches processing mass spectroscopy data because scanning a mass range within a time interval is processing data from mass spectroscopy.
Bloomfield then teaches obtaining data of a plurality of MS/MS spectra for a compound contained in a sample by performing an MS/MS scan measurement in par 070, experiment of using 40 eV across a peptide of 829.5303 Da. See also par 068, experimental results, using energy of 10 eV, teaches performing an MS/MS scan measurement. See also par 002: “Tandem mass spectrometry or mass spectrometry/mass spectrometry (MS/MS) is a method that can provide both qualitative and quantitative information.”
Bloomfield then teaches using a plurality of different kinds of precursor ions originating from the compound using a mass spectrometer, in par 051: “Transmission window 210 transmits precursor ions with masses between M.sub.1 and M.sub.2, has set mass, or center mass, 215, and has sharp vertical edges 220 and 230. The SWATH precursor window size is M.sub.2−M.sub.1. The rate at which transmission window 210 transmits precursor ion is constant with respect to precursor mass.” Precursor ions plural are between M_1 and M_2 which teaches a plurality as each ion would have a mass and here there are ions between two Mass values. They are specifically identified as precursor ions.
Bloomfield then teaches where each of the plurality of MS/MS spectra corresponds to one of the plurality of different kinds of precursor ions in par 053: “Essentially, when the intensities of product ions produced from precursor ions filtered by the overlapping transmission windows are plotted as a function of the transmission window moving across the precursor mass range, each product ion has an intensity for the same precursor mass range that its precursor ion has been transmitted. In other words, for a rectangular transmission window (such as transmission window 210 of FIG. 2) that transmits precursor ions at a constant rate with respect to precursor mass, the edges (such as edges 220 and 230 of FIG. 2) define a unique boundary of both precursor ion transmission and product ion intensity as the transmission is stepped across the precursor mass range.” This teaches a plurality of spectra because the spectra are “overlapping transmission windows.” As explained, for a transmission window, the edges define a precursor ion and product ion. Then it is stepped across the precursor mass range which clarifies what is taught: that as the mass increases, there are different transmission windows with different (corresponding) product ions. See also par 057: “In various embodiments, the accuracy of the correlation is improved by combining product ion spectra from successive groups of the overlapping rectangular precursor ion transmission windows. Product ion spectra from successive groups are combined by successively summing the intensities of the product ions in the product ion spectra.” Product ion spectra is taught which is plural, this teaches each of the plurality of MS/MS spectra as it is plural. That it corresponds to one of the plurality of different kinds of precursor ions is because the transmission windows correspond to product ions of different masses: “One skilled in the art can appreciate that the intensities of the product ions produced by the overlapping windows can be plotted as function of the precursor mass based on any parameter of transmission window 310 including, but not limited to, trailing edge 340, set mass, or leading edge 330.”
Bloomfield then teaches and creating data of a merged MS/MS spectrum for the compound by merging the data of the plurality of MS/MS spectra acquired by the MS/MS scan measurements for the plurality of kinds of precursor ions originating from the compound in par 057: “In various embodiments, the accuracy of the correlation is improved by combining product ion spectra from successive groups of the overlapping rectangular precursor ion transmission windows. Product ion spectra from successive groups are combined by successively summing the intensities of the product ions in the product ion spectra. This summing produces a function that can have a shape that is non-constant with precursor mass. The shape can be a triangle, for example. The shape describes product ion intensity as a function of precursor mass.” Here combining teaches merged because product ion spectra (plural) are combined with the successive precursor ions. It is the plurality of precursor ions because it is as a function of precursor mass, mass being a variable. See also Fig 4 and pars 059-060: “FIG. 4 is diagram 400 showing how product ion spectra from successive groups of the overlapping rectangular precursor ion transmission windows are summed to produce a triangular function that describes product ion intensity as a function of precursor mass, in accordance with various embodiments. Plot 410 shows that there is a precursor ion 420 at mass 430. Overlapping rectangular precursor ion transmission windows 440 are stepped across a mass range producing a plurality of product ion spectrum. Essentially, a product ion spectrum (not shown) is produced for each window 440.
Successive groups 450 of windows 440 are selected. The product ion intensities from spectra (not shown) from the successive groups 450 of windows 440 are summed. This summing produces plot 460. Plot 460 shows that a product ion of precursor ion 420 acquires a triangular shaped function 470 of product ion intensity with respect to precursor mass. Plot 460 also shows that the apex or center of gravity of function 470 points to mass 430 of precursor ion 420.” The sum is stepped across a mass range which as shown in Fig 4 is precursor mass, which is a plurality of precursor ions (plurality of kinds of ions taught by plurality of masses of ions).
Bloomfield then teaches wherein the plurality kinds of precursor ions generated from the compound are selected by a first mass filter based on an MS spectrum obtained by performing an MS scan measurement in par 073-075: “FIG. 8 is a schematic diagram showing a system 800 for identifying a precursor ion of a product ion in a tandem mass spectrometry experiment, in accordance with various embodiments. System 800 includes mass filter 810, fragmentation device 820, mass analyzer 830, and processor 840. In system 800, the mass filter, the fragmentation device, and the mass analyzer are shown as different stages of a quadrupole, for example. One of ordinary skill in the art can appreciate that the mass filter, the fragmentation device, and the mass analyzer can include, but are not limited to, one or more of an ion trap, orbitrap, an ion mobility device, or a time-of-flight (TOF) device.
Processor 840 can be, but is not limited to, a computer, microprocessor, or any device capable of sending and receiving control signals and data from a tandem mass spectrometer and processing data. Processor 840 is in communication with mass filter 810 and mass analyzer 830.
Mass filter 810 steps a transmission window across a mass range. The transmission window has a constant rate of precursor ion transmission for each precursor ion. Stepping the transmission window produces a series of overlapping transmission windows across the mass range.”
Note that Mass filter steps across a mass range that therefore transmits precursor ions for each precursor ion, teaching a plurality.
Bloomfield then teaches and wherein the data of the plurality of MS/MS spectra is obtained by detecting product ions see par 070: “In the second experiment, a higher collision energy of 40 eV was used. In this experiment, a calibration peptide of 829.5303 Da and its product ion and isotopes were compared.” Product ion and isotopes were compared teaches obtaining by detecting product ions as the experiment starts with a certain peptide and then results with product ions being detected, as shown in par 071, the intensities are found, which teaches the amount of ions being detected.
Bloomfield then teaches wherein the each of the plurality of MS/MS spectra corresponds to one of the plurality of kinds of precursor ions in par 071: “FIG. 7 is an exemplary plot 700 of the product ion intensities as a function of precursor mass of the three most intense product ions and three first isotopes of those product ions produced by a high energy collision experiment performed on a calibration peptide of 829.5303 Da, where rectangular precursor transmission windows were summed to produce the effect of triangular transmission windows, in accordance with various embodiments. Traces 710, 720, and 730 are for product ions that have TOF masses 494.334, 607.417, and 724.497, respectively. Traces 715, 725, and 735 are for product ion first isotopes that have TOF masses 495.338, 608.423, and 725.501, respectively. When traces 710, 720, and 730 are centroided and calibrated, they indicate precursor mass values of 829.48, 829.39, and 829.27, respectively. When traces 715, 725, and 735 are centroided and calibrated, they indicate precursor isotope mass values of 830.53, 830.30, and 830.15, respectively.” Each trace, 715, 724, and 735, indicate one of the plurality of kinds of precursor ions. They are each a trace (each a spectrum) of the intensity of product ions.
Bloomfield does not teach and wherein the data of the plurality of MS/MS spectra is obtained by detecting product ions separated according to mass-to-charge ratios of the product ions.
Wildgoose teaches DDA and tandem mass spectroscopy techniques. See page 2, background technology.
Wildgoose teaches and wherein the data of the plurality of MS/MS spectra is obtained by detecting product ions separated according to mass-to-charge ratios of the product ions, in page 19 of the pdf: “In the two methods, the acquisition system to generate two dimensions are m/z of a two-dimensional data set, and another one-dimensional precursor m/z-fragment ion m/z. allows effectively reproduces the precursor ion mass spectrometry fragment ion data from the orthogonal relationship between the precursor ion m/z and fragment ion m/z.” Because the data set has m/z of precursor and fragment (product) both, Wildgoose teaches detecting product ions according to m/z (mass to charge).
It would have been obvious to one ordinarily skilled in the art before the effective filing date of the claimed invention to modify the merged spectra teaching of Bloomfield with the separating according to m/z teaching of Wildgoose because Wildgoose teaches (in the same teaching) that “effectively reproduces the precursor ion mass spectrometry fragment ion data from the orthogonal relationship between the precursor ion m/z and fragment ion m/z.” This effective reproduction in two dimensions allows for easy discernment of which fragment ion m/z came from which precursor ion m/z, which is comprehensible and facilitates understanding the makeup of a compound. For these reasons one would be motivated to modify Bloomfield with Wildgoose.
Per claim 2, Bloomfield and Wildgoose teach the limitations of claim 1, above. Bloomfield further teaches processing mass spectrometry data according to claim 1, further comprising a step of identifying the compound by estimating a partial structure of the compound corresponding to a mass peak included in the data of the merged MS/MS spectrum, based on a mass-to-charge ratio of the mass peak.
In par 002: “The product ion spectrum can be used to identify a molecule of interest. The intensity of one or more product ions can be used to quantitate the amount of the compound present in a sample.” And par 062: “Usually for quantitation, at least eight measurements are needed across a liquid chromatography (LC) peak, for example. Since a single scan takes about one second, it is difficult to get quantitative information on a fast LC elution. A fast LC elution occurs, for example, in the case of small molecules. In contrast, LC elutions in the proteomics case take on the order of tens of seconds. In a fast LC elution, the peak is rising and falling rapidly but it is still possible to detect this behavior within a scan of an overlapped transmission window. If, for example, a window width is 200 DA and a 900 Da mass range is scanned at 1.5 ms per step with overlapping windows, the scan takes 1.35 seconds, but each ion within the range is present in 200 scans and its behavior is observed for 300 ms out of each 1350 ms. As a result, the elution profile can be reconstructed by fitting an elution profile to the fragment ions observed from the overlapping windows.”
See also pars 059-061: “FIG. 4 is diagram 400 showing how product ion spectra from successive groups of the overlapping rectangular precursor ion transmission windows are summed to produce a triangular function that describes product ion intensity as a function of precursor mass, in accordance with various embodiments. Plot 410 shows that there is a precursor ion 420 at mass 430. Overlapping rectangular precursor ion transmission windows 440 are stepped across a mass range producing a plurality of product ion spectrum. Essentially, a product ion spectrum (not shown) is produced for each window 440.
In par 060: “Successive groups 450 of windows 440 are selected. The product ion intensities from spectra (not shown) from the successive groups 450 of windows 440 are summed. This summing produces plot 460. Plot 460 shows that a product ion of precursor ion 420 acquires a triangular shaped function 470 of product ion intensity with respect to precursor mass. Plot 460 also shows that the apex or center of gravity of function 470 points to mass 430 of precursor ion 420.”
See par 061: “The methods and systems described above involve a single scan across a mass range using overlapping precursor ion transmission windows. In various embodiments, additional information is obtained by performing two or more scans across a mass range using overlapping precursor ion transmission windows.”
See also par 071 for teaching masses: “Traces 710, 720, and 730 are for product ions that have TOF masses 494.334, 607.417, and 724.497, respectively. Traces 715, 725, and 735 are for product ion first isotopes that have TOF masses 495.338, 608.423, and 725.501, respectively. When traces 710, 720, and 730 are centroided and calibrated, they indicate precursor mass values of 829.48, 829.39, and 829.27, respectively. When traces 715, 725, and 735 are centroided and calibrated, they indicate precursor isotope mass values of 830.53, 830.30, and 830.15, respectively.”
Per claim 3, Bloomfield and Wildgoose teach the limitations of claim 1, above. Bloomfield further teaches wherein the data of the plurality of MS/MS spectra are data acquired by MS/MS scan measurements of the compound isolated by a column of a chromatograph. In par 067: “One skilled in the art can appreciate that although reconstructing an elution profile from multiple scans across a mass range is described first and identifying a precursor ion from a product ion selected from multiple scans across a mass range is described second, these actions can be performed in the reverse order. For example, a precursor ion can be identified from multiple scans across a mass range first, and then the elution profile of that precursor ion can be reconstructed from the same multiple scans across a mass range.”
Per claim 4, Bloomfield and Wildgoose teach the limitations of claim 3, above. Bloomfield further teaches the data of the merged MS/MS spectrum is created by collecting a mass peak having a highest intensity from among mass peaks having a common mass-to-charge ratio in the data of the plurality of MS/MS spectra in par 058: “For example, if a triangle is used, the apex or center of gravity can be used to point to the precursor mass. In other words, if the intensities of the product ions are successively selected and summed to produce a triangular function of intensity with respect to precursor mass, for example, the apex or center of gravity of the function for each product ion points to the precursor ion mass. The apex or center of gravity of the function is less dependent on the accuracy of the measurements at the edges of the actual transmission window. Of course, product ions that are the result of more than one precursor ion may still be difficult to discern.”
Claim(s) 5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bloomfield et al., US PGPUB 20160268111 A1 (“Bloomfield”) in view of Wildgoose, CN-106463331-A (2017) (“Wildgoose”), further in view of Jones et al., US PGPUB 20210109069 A1 (“Jones”).
Per claim 5, Bloomfield and Wildgoose teaches the limitations of claim 3, above. Bloomfield does not teach the data of the plurality of MS/MS spectra are data acquired by DDA which includes repeating a process of performing the MS scan measurement of the compound isolated by the column to detect an ion having an intensity exceeding a previously determined threshold and perform the MS/MS scan measurement using the detected ion as a precursor ion.
Jones teaches determining if intensity threshold as been met or exceeded and if not then repeating with second sample. See abstract.
Jones teaches the data of the plurality of MS/MS spectra are data acquired by DDA which includes repeating a process of performing the MS scan measurement of the compound isolated by the column to detect an ion having an intensity exceeding a previously determined threshold and perform the MS/MS scan measurement using the detected ion as a precursor ion in par 0136: “As can be seen from FIG. 3, the absolute amount of signal (i.e. the total number of ions emitted or ejected per ejection) can vary considerably dependent upon the sample. For example, with reference to FIG. 3, sample #7 produced a signal which was approximately ×6 times higher than the signal produced by sample #1. If a spectral quality threshold based on the total number of ions produced is utilised then it can be seen that sample #7 would require approximately ×6 times fewer ejections to meet this threshold than sample #1.” See sample 7 for a mass peak of an intensity exceeding a previously determined threshold. For performing an MS/MS scan using the detected ion as a precursor see par 0138: “According to various embodiments the quality threshold may correspond with the quality of an ion mobility peak. In the particular example shown in FIG. 4, although the average ion mobility could be determined from the ion mobility peak as shown, the peak shape is somewhat irregular. Accordingly, sample may continue to be ejected from a sample well until a corresponding ion mobility peak is obtained which is determined to have an acceptable peak shape. For example, the ion mobility peak may have a smoother more regular peak shape and may have a standard deviation σ in the range σ≤0.1, 0.1-0.2, 0.2-0.3, 0.3-0.4, 0.4-0.5, 0.5-0.6, 0.6-0.7, 0.7-0.8, 0.8-0.9, 0.9-1.0 or ≥1.0.” See also pars 0139-0140: “FIG. 5 shows four mass spectra and is an example of a MS/MS experiment which was conducted at multiple different collision energies. Precursor or parent ions having a nominal mass to charge ratio of 281 were selected by a mass filter. The selected parent ions were then fragmented at a range of different collision energies. The principal fragments and the optimum collision energy for each fragmentation pathway may then be determined.
From FIG. 5 it is apparent that parent ions remain largely unfragmented at a collision energy of 10V i.e. when parent ions are caused to enter a collision cell filled with a collision gas for fragmentation and wherein there is a potential difference of 10V between the ion optics immediately upstream of the collision cell and the entrance to the collision cell.”
It would have been obvious to one ordinarily skilled in the art before the effective filing date of the claimed invention to modify the merging of plurality of precursors and parent ions teaching of Bloomfield with the scanning until a threshold is reached and using an ion as a precursor ion teaching of Jones because Jones teaches in pars 09-010 that: “one problem with the current approach of analysing samples using Acoustic Mist Ionisation is that time may be wasted acquiring unnecessary data. Furthermore, some samples may also need to be reanalysed due to insufficient data quality. It is therefore desired to provide an improved method of analysing samples.” Jones’ teaching avoids wasting time acquiring unnecessary data. Scans that have to be reanalyzed due to poor data quality is inefficient and one would be motivated to combine Jones with Bloomfield in order to run fewer scans because of improved data collection. For these reasons, one would be motivated to modify Bloomfield with Jones.
Claim(s) 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bloomfield et al., US PGPUB 20160268111 A1 (“Bloomfield”) in view of Wildgoose, CN-106463331-A (2017) (“Wildgoose”), further in view of Jones et al., US PGPUB 20210109069 A1 (“Jones”), further in view of Ryumin et al., US PGPUB 20220093377 A1 (“Ryumin”).
Per claim 6, Bloomfield, Wildgoose, and Jones teach the limitations of claim 5, above. Bloomfield does not teach wherein the data of the merged MS/MS spectrum are created by merging data of a plurality of MS/MS spectra acquired by MS/MS scan measurements using precursor ions which are identical in mass number and different in number of charges.
Ryumin teaches using different charge states for protein analysis. See par 004.
Ryumin teaches wherein the data of the merged MS/MS spectrum are created by merging data of a plurality of MS/MS spectra acquired by MS/MS scan measurements using precursor ions which are identical in mass number and different in number of charges in pars 069-070: “In various embodiments, ions are measured and then separated according to charge state using a single analog-to-digital converter (ADC) detector. As described above, the number of primary electrons generated in a conventional electron multiplier ADC detector depends on the charge state of the incident ions. Therefore, highly charged ions generate more primary electrons resulting in a more intense electron signal digitized by the ADC detector. This results in substantially different responses for individual ions having different charge states.
It is, therefore, possible to sort the signals during or after acquisition based on their detector signal response. Specifically, ions with different charge states are separated or sorted into different spectra.”
It would have been obvious to one ordinarily skilled in the art before the effective filing date of the claimed invention to modify the mass spectroscopy merging teaching of Bloomfield with the using ions of different charges teaching of Ryumin because Ryumin teaches in par 066: “As described above, in some mass spectrometry analysis methods, such as top-down protein analysis, overlapping of mass or m/z peaks in a mass spectrum is a significant problem. In addition, the overlap can be so extensive that even mass spectrometers with the highest mass resolution cannot deconvolve such overlapped peaks.” Ryumin’s teaching of the problem of overlapping peaks is solved by the teachings of Ryumin, above. As one would be motivated by the problem of overlapping peaks, particularly in measuring proteins, one would be motivated to combine Bloomfield and Ryumin for Ryumin’s problem teaching above, so that one would be able to resolve peaks. For this reason one would be motivated to modify Bloomfield with Ryumin.
Claim(s) 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bloomfield et al., US PGPUB 20160268111 A1 (“Bloomfield”) in view of Wildgoose, CN-106463331-A (2017) (“Wildgoose”), further in view of Ryumin et al., US PGPUB 20220093377 A1 (“Ryumin”).
Per claim 7, Bloomfield and Wildgoose teach the limitations of claim 3, above. Bloomfield does not teach displaying, on a screen, a chromatogram and the merged MS/MS spectrum for each compound contained in the sample.
Ryumin teaches displaying, on a screen, a chromatogram and the merged MS/MS spectrum for each compound contained in the sample in par 058 where a display is taught, “Computer system 100 may be coupled via bus 102 to a display 112, such as a cathode ray tube (CRT) or liquid crystal display (LCD), for displaying information to a computer user. An input device 114, including alphanumeric and other keys, is coupled to bus 102 for communicating information and command selections to processor 104. Another type of user input device is cursor control 116, such as a mouse, a trackball or cursor direction keys for communicating direction information and command selections to processor 104 and for controlling cursor movement on display 112. This input device typically has two degrees of freedom in two axes, a first axis (i.e., x) and a second axis (i.e., y), that allows the device to specify positions in a plane.”
And the spectrum for each compound is taught in pars 080-081: “FIG. 8 is a series of plots 800 showing how ion peak overlap is reduced in mass spectra by separating single ion arrival pulses with similar intensities into separate data sets and creating a mass spectrum for each of the separate data sets, in accordance with various embodiments. Plot 810 of FIG. 8 shows a portion of a mass spectrum where all ion arrival pulses are conventionally combined to generate a single mass spectrum. The mass spectrum of plot 810 includes considerable ion peak overlap.
Plot 820, in contrast, shows eight separate mass spectra all plotted on the same scale and also plotted on the same scale as the mass spectrum of plot 810. Each of the mass spectra of plot 820 represents combined ion peaks for single arrival pulses with similar intensities. In other words, the eight different mass spectra of plot 820 represent ions with eight different charge state ranges. A comparison of the eight different mass spectra in plot 820 shows that a large amount of ion peak overlap is reduced by separating the ions into these different mass spectra. Note that many peaks in the eight different mass spectra in plot 820 that have the same m/z value.”
It would have been obvious to one ordinarily skilled in the art before the effective filing date of the claimed invention to modify the mass spectroscopy merging teaching of Bloomfield with the using ions of different charges teaching of Ryumin because Ryumin teaches in par 066: “As described above, in some mass spectrometry analysis methods, such as top-down protein analysis, overlapping of mass or m/z peaks in a mass spectrum is a significant problem. In addition, the overlap can be so extensive that even mass spectrometers with the highest mass resolution cannot deconvolve such overlapped peaks.” Ryumin’s teaching of the problem of overlapping peaks is solved by the teachings of Ryumin, above. As one would be motivated by the problem of overlapping peaks, particularly in measuring proteins, one would be motivated to combine Bloomfield and Ryumin for Ryumin’s problem teaching above, so that one would be able to resolve peaks. For this reason one would be motivated to modify Bloomfield with Ryumin.
Claim(s) 9 and 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bloomfield et al., US PGPUB 20160268111 A1 (“Bloomfield”) in view of Wildgoose, CN-106463331-A (2017) (“Wildgoose”), further in view of Yamamura et al., US PGPUB 20190234916 A1 (“Yamamura”).
Per claims 9 and 10, which are similar in scope, Bloomfield and Wildgoose teach the limitations of claims 1 and 8, above. Bloomfield does not teach comprising extracting a mass peak present in the merged MS/MS spectrum, determining a fragment ion corresponding to the mass peak, and identifying the compound based on the fragment ion.
Yamamura teaches a database which stores mass spec data about compounds plus their names and other information. See abstract.
Yamamura teaches comprising extracting a mass peak present in the merged MS/MS spectrum in par 051: “Alternatively, the mass spectrum creator 24 may create the mass spectrum data by averaging a plurality of pieces of mass spectrum data acquired within a predetermined time width centered on the retention time of the peak top in a direction of the time axis.” This teaches merged MS/MS spectrum. Then for extracting the mass peak see par 052: “When mass spectrum data is generated from the three-dimensional data under each of the mass spectrometry conditions, the mass peak extractor 25 extracts a mass peak (a base peak denoted as “BP” in FIG. 2) having the highest intensity in each piece of mass spectrum data.”
Yamamura then teaches determining a fragment ion corresponding to the mass peak That it is a fragment ion is taught in par 047 where the measurement is of the product ions, see par 047: “In the collision cell, the precursor ion is fragmented into product ions, and the rear mass separator performs mass scanning to measure the product ions. The above process is performed under each of the 20 mass spectrometry conditions, which allows the three-dimensional data to be obtained under each of the mass spectrometry conditions. FIG. 3 shows an example of the three-dimensional data.” That it determines the fragment ion is taught in par 052: “The mass spectrum data to which this flag has been given is registered on the compound database 21 (denoted as “DB” in FIG. 2) together with the compound name and the mass spectrometry condition by the database registration unit 31 (step S52). Mass spectrum data (FIG. 5 (b)) having a base peak whose intensity is equal to or less than the threshold (NO in step S51) is not registered on the compound database 21. The mass spectrum data to which the peak intensity flag has been given and stored in the compound database 21 is used for pattern matching to identify, for example, an unknown component contained in the sample.” And Fig 3 where each peak corresponds to an ion (mass to charge ratio). See also par 053: “This integrated mass spectrum data corresponds to mass spectrum data exhaustively including respective mass peaks of ions generated from the target compound.” See also par 003: “The triple quadrupole mass spectrometer is a mass spectrometer including front and rear mass separators with a collision cell interposed between the front and rear mass separators, and is capable of obtaining a product ion spectrum (MS.sup.2 spectrum) by selecting an ion (precursor ion) having a specific mass-to-charge ratio from ions originating from the components in the sample and performing mass scanning to measure product ions generated through fragmentation of the precursor ion. Furthermore, the IT-TOF mass spectrometer is a mass spectrometer including an ion trap and a time-of-flight mass separator, and is capable of obtaining an MS.sup.n spectrum (n is an integer equal to or greater than 2) by performing mass scanning to measure product ions generated after performing selection and fragmentation of a precursor ion one or more times.”
Yamamura then teaches and identifying the compound based on the fragment ion in par 005: “First, a compound to be registered on the database is introduced into the chromatograph mass spectrometer, and mass scanning is repeatedly performed during a time when the compound is flowing out from the chromatograph to measure ions originating from the compound, whereby a mass spectrum at each time point is acquired. Then, intensities of all ions of the mass spectrum at each time point are summed up and plotted in a direction of the time axis, so that a total ion chromatogram is constructed. The mass spectrum described above may be various types of mass spectrum such as the above-described MS.sup.1 spectrum and MS.sup.n spectrum, a precursor ion spectrum, and a neutral loss spectrum, and a plurality of types of mass spectra are usually acquired for one compound stored in the database.” As the spectra in par 005 are described in par 003, they are the product ion spectra. See also par 014: “c) a database registration unit that registers, on the database, mass spectrum data determined to include the mass peak satisfying the predetermined criterion or mass spectrum data based on the mass spectrum data determined to include the mass peak satisfying the predetermined criterion together with a compound name and a mass spectrometry condition.”
It would have been obvious to one ordinarily skilled in the art before the effective filing date of the claimed invention to modify the precursor/fragment ion and merged MS/MS spectra teaching of Bloomfield with the database of compounds and mass peak analysis teaching of Yamamura because Yamamura teaches a technical problem in pars 009-010 that there is a lot of time and labor required to check mass spec one by one, and the solution is that there is a database and determination unit, see par 011-014. This saves time in making determinations of what a compound is based on the spectra and therefore one would be motivated to combine Bloomfield with Yamamura because it would help identify compounds more quickly.
Therefore, claims 1-10 are rejected under 35 USC 103.
Prior Art Made of Record
The following prior art is considered relevant to the Applicant’s disclosure but is not relied upon in the rejection.
Harvey, General Theory of Column Chromatography. Libretexts, archived on Jan 21, 2022, available at: < https://web.archive.org/web/20220121175731/https://chem.libretexts.org/Bookshelves/Analytical_Chemistry/Analytical_Chemistry_2.1_(Harvey)/12%3A_Chromatographic_and_Electrophoretic_Methods/12.02%3A_General_Theory_of_Column_Chromatography >
Teaches liquid solid column chromatography.
Response to arguments
Priority acknowledged on Summary sheet (PTO-326).
Applicant has amended the claims requiring further search and consideration, based on this new art is applied and the arguments are moot.
The 101 is overcome based on actual performing of MS/MS scan and not mere data analysis. The actual scan performance is not mere data gathering as it is a specific kind of analysis performed. Therefore the 101 is overcome.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RICHARD W. CRANDALL whose telephone number is (313)446-6562. The examiner can normally be reached M - F, 8:00 AM - 5:00 PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anita Coupe can be reached at (571) 270-3614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/RICHARD W. CRANDALL/ Primary Examiner, Art Unit 3619
Prosecution Insights