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 .
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Specification
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Rejections - 35 USC § 102/103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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.
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, 7-9, 13 and 20-21 is/are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over US 20110315866 to Mitchell.
Regarding Claim 1, Mitchell discloses a method of mass analysing a single analytical sample (Figs. 2-3 and 6-10, quadrupole mass spectrometer 10 with hybrid of a m/z 50-250 full scan and a m/z 117, 183 single ion monitoring (SIM) experiment; ¶¶ [0015]-[0017], [0027]-[0029], [0032]-[0053]), comprising: i) transmitting different species of ions through a mass spectrometer (Figs. 2-3 and 6-10, quadrupole mass spectrometer 10 with hybrid of a m/z 50-250 full scan and a m/z 117, 183 single ion monitoring (SIM) experiment; ¶¶ [0015]-[0017], [0027]-[0029], [0032]-[0053]); ii) sequentially mass analysing, or otherwise detecting, said different species of ions in a particular sequential order (Figs. 2-3 and 6-10, m/z 50-250 full forward scan and a m/z 117, 183 single ion monitoring (SIM) experiment; ¶¶ [0015]-[0017], [0027]-[0029], [0032]-[0053]); and then iii) repeating steps i) and ii), wherein the sequential order in which said different species of ions are mass analysed, or otherwise detected, is different when step ii) is repeated (Figs. 2-3 and 6-10, m/z 50-250 full reverse scan and a m/z 117, 183 single ion monitoring (SIM) experiment; ¶¶ [0015]-[0017], [0027]-[0029], [0032]-[0053]).
Regarding Claim 7, Mitchell discloses each time step ii) is performed, it comprises mass filtering said different species of ions using a mass filter such that only a single species of ion is transmitted to an ion detector at any one time (Figs. 2-3 and 6-10, quadrupole mass spectrometer 10 (filter) with hybrid of a m/z 50-250 full scan and a m/z 117, 183 single ion monitoring (SIM) experiment; ¶¶ [0015]-[0017], [0027]-[0029], [0032]-[0053]), and wherein the mass filter is controlled so as to change the species of ion that is transmitted to the detector at different times, thereby defining said sequential order in which the different species of ions are mass analysed (Figs. 2-3 and 6-10, quadrupole mass spectrometer 10 (filter) with controller 20 setting RF and DC amplitudes for forward and reverse scanning of hybrid of a m/z 50-250 full scan and a m/z 117, 183 single ion monitoring (SIM) experiment; ¶¶ [0015]-[0017], [0027]-[0029], [0032]-[0053]).
Regarding Claim 8, Mitchell discloses a first time that step ii) is performed, the mass filter transmits only a first of said different species of ions to the detector at a first time, and subsequently transmits only a second of the different species of ions to the detector at a second, subsequent time (Figs. 2-3 and 6-10, quadrupole mass spectrometer 10 (filter) with controller 20 setting RF and DC amplitudes for forward scanning of hybrid of a m/z 50-250 full scan and a m/z 117, 183 single ion monitoring (SIM) experiment; ¶¶ [0015]-[0017], [0027]-[0029], [0032]-[0053]); and wherein a subsequent time that step ii) is performed, the mass filter transmits only the second of said different species of ions to the detector at one time, and subsequently transmits only the first of the different species of ions to the detector at a later time (Figs. 2-3 and 6-10, quadrupole mass spectrometer 10 (filter) with controller 20 setting RF and DC amplitudes for reverse scanning of hybrid of a m/z 50-250 full scan and a m/z 117, 183 single ion monitoring (SIM) experiment; ¶¶ [0015]-[0017], [0027]-[0029], [0032]-[0053]).
Regarding Claim 9, Mitchell discloses step iii) comprises performing an analytical sequence that consists of repeating steps i) and ii) a plurality of times, wherein the sequential order in which said different species of ions are mass analysed, or otherwise detected, during these plurality of times is different each and every time step ii) is performed within the analytical sequence (Figs. 2-3 and 6-10, quadrupole mass spectrometer 10 (filter) with controller 20 setting RF and DC amplitudes for forward and reverse (a plurality of 2) scanning of hybrid of a m/z 50-250 full scan and a m/z 117, 183 single ion monitoring (SIM) experiment; ¶¶ [0015]-[0017], [0027]-[0029], [0032]-[0053]).
Regarding Claim 13, Mitchell discloses all of the steps are performed within a single experimental run (Figs. 2-3 and 6-10, quadrupole mass spectrometer 10 (filter) with controller 20 for forward and reverse scanning of hybrid of a m/z 50-250 full scan and a m/z 117, 183 single ion monitoring (SIM) experiment; ¶¶ [0015]-[0017], [0027]-[0029], [0032]-[0053]).
Regarding Claim 20, Mitchell discloses step iii) comprises repeating step ii) in a manner such that the first species of ion mass analysed, or otherwise detected, any given time that step ii) is performed differs from the last species of ion that was mass analysed, or otherwise detected, the preceding time that step ii) was performed (Figs. 2-3 and 6-10, quadrupole mass spectrometer 10 with controller 20 for forward and reverse scanning of hybrid of a m/z 50-250 full scan and a m/z 117, 183 single ion monitoring (SIM) experiment; ¶¶ [0015]-[0017], [0027]-[0029], [0032]-[0053]).
Regarding Claim 21, Mitchell discloses a mass spectrometer (Figs. 2-3 and 6-10, quadrupole mass spectrometer 10; ¶¶ [0015]-[0021], [0027]-[0029], [0032]-[0053]).comprising: a mass analyser (Figs. 2-3 and 6-10, quadrupole mass spectrometer 10 (filter) with mass analyzer 14; ¶¶ [0015]-[0021], [0027]-[0029], [0032]-[0053]); and a controller having electronic circuitry (Figs. 2-3 and 6-10, quadrupole mass spectrometer 10 with controller 20 for RF electronics 19 and DC electronics 22; ¶¶ [0015]-[0021], [0027]-[0029], [0032]-[0053]) configured to control the spectrometer to: i) transmit different species of ions through the mass spectrometer(Figs. 2-3 and 6-10, quadrupole mass spectrometer 10 with hybrid of a m/z 50-250 full scan and a m/z 117, 183 single ion monitoring (SIM) experiment; ¶¶ [0015]-[0017], [0027]-[0029], [0032]-[0053]); ii) sequentially mass analyse, or otherwise detect, said different species of ions in a particular sequential order (Figs. 2-3 and 6-10, m/z 50-250 full forward scan and a m/z 117, 183 single ion monitoring (SIM) experiment; ¶¶ [0015]-[0017], [0027]-[0029], [0032]-[0053]); and then iii) repeat steps i) and ii), wherein the sequential order in which said different species of ions are mass analysed, or otherwise detected, is different when step ii) is repeated (Figs. 2-3 and 6-10, m/z 50-250 full reverse scan and a m/z 117, 183 single ion monitoring (SIM) experiment; ¶¶ [0015]-[0017], [0027]-[0029], [0032]-[0053]).
Claim(s) 2-6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mitchell as applied to claim 1 above, and further in view of US 20160118235 to Fujita.
Regarding Claim 2, Mitchell discloses the method of claim 1, however, although Mitchell discloses adjusting the performance using RF electronics 19 and DC electronics 22, Mitchell does not explicitly disclose the sensitivity with which the mass spectrometer is able to detect ions varies for a period of time, and wherein step ii) and iii) are performed during said period of time. Fujita discloses the sensitivity with which the mass spectrometer is able to detect ions varies for a period of time (Figs. 1-4, peak intensity gradually decreasing with time, or with the repetition of the measurement; ¶¶ [0005], [0019], [0025]-[0027], [0049], [0056]-[0057]) and Mitchell discloses step ii) and iii) are performed during said period of time (Figs. 2-3 and 6-10, forward and reverse scanning (i.e., repetition of the measurement) of hybrid of a m/z 50-250 full scan and a m/z 117, 183 single ion monitoring (SIM) experiment; ¶¶ [0015]-[0017], [0027]-[0029], [0032]-[0053]). It would have been obvious to one of ordinary skill in the art before the effective filing of the application to modify the invention of Mitchell by providing the sensitivity with which the mass spectrometer is able to detect ions varies for a period of time, and wherein step ii) and iii) are performed during said period of time as in Fujita and Mitchell in order to provide for greater accuracy by accounting for contaminants or other substances attached to the surface of the pre-quadrupole mass filter.
Regarding Claim 3, Fujita discloses varying the operation of the mass spectrometer in a manner that causes the sensitivity with which the spectrometer is able to detect ions to vary for said period of time (Figs. 1-5, peak intensity gradually decreasing with time, or with the repetition of the measurement and polarity of the voltage applied to pre-quadrupole mass filter 12 reversed; ¶¶ [0005], [0019], [0025]-[0027], [0050]-[0064]).
Regarding Claim 4, Fujita discloses said step of varying the operation of the mass spectrometer comprises switching the voltage applied to at least one electrode of the mass spectrometer that controls the transmission of ions therethrough to a different voltage; and wherein step i) comprises subsequently transmitting said different species of ions through the spectrometer and passed said at least one of said electrodes (Figs. 1-5, voltage -V1 applied to pre-quadrupole mass filter 12 followed by -V2 to transmitted three mass-to-charge ratios M1, M2 and M3 are selected as the measurement target; ¶¶ [0005], [0019], [0025]-[0027], [0048]-[0064])..
Regarding Claim 5, Fujita discloses said step of varying the operation of the mass spectrometer comprises switching the polarity of the voltage to a different polarity (Figs. 1-5, peak intensity gradually decreasing with time, or with the repetition of the measurement and polarity of the voltage -V1 applied to pre-quadrupole mass filter 12 reversed to +V1; ¶¶ [0005], [0019], [0025]-[0027], [0050]-[0064]).
Regarding Claim 6, Fujita discloses the step of varying the operation of the mass spectrometer comprises alternating the mass spectrometer between a first mode of operation in which it generates and transmits positive ions and a second mode of operation in which it generates and transmits negative ions, and/or vice versa (Figs. 1-5, positive and negative ions alternately subjected to measurement; ¶¶ [0025]-[0027], [0050]-[0064]).
Claim(s) 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mitchell in view of US 20150051843 to Wang.
Regarding Claim 11, Mitchell discloses the method of claim 1, but is silent regarding comparing the ion signal detected for one of said different species of ions with the ion signal detected for another of said different species of ions. Wang discloses comparing the ion signal detected for one of said different species of ions with the ion signal detected for another of said different species of ions (Figs. 16-19, comparing signals of the first peak (x) and the second peak (y0; ¶ [0093]-[0102]). It would have been obvious to one of ordinary skill in the art before the effective filing of the application to modify the invention of Mitchell by providing comparing the ion signal detected for one of said different species of ions with the ion signal detected for another of said different species of ions as in Wang in order to provide for greater accuracy in grouping related ions.
Claim(s) 12 and 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mitchell in view of US 20100084552 to Kawana.
Regarding Claim 12, Mitchell discloses the method of claim 1, but is silent regarding the spectrometer comprises a user interface and, prior to step ii), the method comprises selecting the species of ions that are to be said different species of ions and inputting these selected species of ions into the user interface so that the mass spectrometer performs steps ii) and iii) on these ions. Kawana discloses a user interface (Fig. 1, control section 10 connected with input section 11 for allowing a user or operator to perform an input operation therethrough; ¶¶ [0005], [0015], [0039]-[0049]) and, prior to step ii), the method comprises selecting the species of ions that are to be said different species of ions and inputting these selected species of ions into the user interface so that the mass spectrometer performs steps ii) and iii) on these ions (Fig. 1, user uses input section 11 to input and designate, as analysis conditions, a plurality of mass values in one cycle, and an interval span Ta which is a duration of one cycle; ¶¶ [0005], [0015], [0039]-[0049]). It would have been obvious to one of ordinary skill in the art before the effective filing of the application to modify the invention of Mitchell by providing the spectrometer comprises a user interface and, prior to step ii), the method comprises selecting the species of ions that are to be said different species of ions and inputting these selected species of ions into the user interface so that the mass spectrometer performs steps ii) and iii) on these ions as in Kawana in order to provide for greater accuracy in designating ions of interest.
Regarding Claim 22, Mitchell discloses the mass spectrometer of claim 21, but is silent regarding a user interface for inputting the species of ions that are to be said different species of ions into the mass spectrometer, and wherein the mass spectrometer is configured to perform steps ii) and iii) on these inputted species of ions. Kawana discloses a user interface for inputting the species of ions that are to be said different species of ions into the mass spectrometer, and wherein the mass spectrometer is configured to perform steps ii) and iii) on these inputted species of ions (Fig. 1, user uses input section 11 to input and designate, as analysis conditions, a plurality of mass values in one cycle, and an interval span Ta which is a duration of one cycle; ¶¶ [0005], [0015], [0039]-[0049]). It would have been obvious to one of ordinary skill in the art before the effective filing of the application to modify the invention of Mitchell by providing a user interface for inputting the species of ions that are to be said different species of ions into the mass spectrometer, and wherein the mass spectrometer is configured to perform steps ii) and iii) on these inputted species of ions as in Kawana in order to provide for greater accuracy in designating ions of interest.
Claim(s) 16-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mitchell as applied to claim 1 above, and further in view of WO 2020031703 to Hashimoto (citations to English translation in US 20210313159).
Regarding Claim 16, Mitchell discloses the method of claim 1, and further discloses chromatography and an ion source in general. However, Mitchell does not explicitly disclose separating a sample that comprises a plurality of different analytes of interest using a chromatography device such that said different analytes of interest elute from the chromatography device over different respective time periods, and ionising the sample eluting from the chromatography device so as to provide ions of said analytes of interest. Hashimoto discloses separating a sample that comprises a plurality of different analytes of interest using a chromatography device such that said different analytes of interest elute from the chromatography device over different respective time periods (Figs. 1-2, various components in sample are separated in time in chromatograph 11; ¶¶ [0005]-[0006], [0038]-[0045]), and ionising the sample eluting from the chromatography device so as to provide ions of said analytes of interest (Figs. 1-2, solution (measurement sample) sent from liquid chromatograph device 11 is ionized by ion source 6 such as an electrospray ion source; ¶¶ [0005]-[0006], [0038]-[0045]). It would have been obvious to one of ordinary skill in the art before the effective filing of the application to modify the invention of Mitchell by providing separating a sample that comprises a plurality of different analytes of interest using a chromatography device such that said different analytes of interest elute from the chromatography device over different respective time periods, and ionising the sample eluting from the chromatography device so as to provide ions of said analytes of interest as in Hashimoto in order to provide for a well-known alternative device for providing samples/analytes to a mass spectrometry unit. See, e.g., "substitution of art-recognized equivalents" as discussed in MPEP 2144.06II "An express suggestion to substitute one equivalent component or process for another is not necessary to render such substitution obvious. In re Fout, 675 F.2d 297, 213 USPQ 532 (CCPA 1982)."
Regarding Claim 17, Mitchell discloses steps i) to iii) are performed during each time period that each analyte of interest is expected (Figs. 2-3 and 6-10, quadrupole mass spectrometer 10 with controller 20 for forward and reverse scanning of hybrid of a m/z 50-250 full scan and a m/z 117, 183 single ion monitoring (SIM) experiment; ¶¶ [0015]-[0017], [0027]-[0029], [0032]-[0053]) and Hashimoto discloses each analyte of interest is eluted from the chromatograph device (Figs. 1-2, various components in sample are separated in time in chromatograph 11; ¶¶ 0005]-[0006], [0038]-[0045]).
Claim(s) 18-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mitchell in view of Hashimoto as applied to claim 17 above, and further in view of Wang.
Regarding Claim 18, Mitchell in view of Hashimoto discloses the method of claim 17, and Hashimoto further discloses comprising performing steps i) to iii) over the period that an analyte of interest elutes from the chromatography device (Figs. 1-2, various components in sample are separated in time in chromatograph 11; ¶¶ [0005]-[0008], [0038]-[0045]), so as to obtain the intensity of the ion signal detected for one of said different species of ions for each time that the steps are repeated (Figs. 1-2, various components in sample are separated in time in chromatograph 11 with ion intensity signals derived from different compounds obtained by executing the SIM measurement mode or the MRM measurement mode for ions having different mass-to-charge ratios one after another; ¶¶ [0005]-[0008], [0038]-[0045]); producing a first set of data that comprises the intensity of the ion signal as a function of detection time (Figs. 1-2, various components in sample are separated in time in chromatograph 11 with ion intensity signals derived from different compounds obtained by executing the SIM measurement mode or the MRM measurement mode for ions having different mass-to-charge ratios one after another; ¶¶ [0005]-[0008], [0038]-[0045]); processing the first set of data so as to obtain a second set of processed data and determining if maintenance of the spectrometer is required based on a comparison of the first and second sets of data (Figs. 1-3, signal variance evaluation unit 105 evaluating data for determining maintenance requirement, Steps S1-S5; ¶¶ [0044]-[0065]). However, although Hashimoto discloses determining a signal variation from a signal average value and standard deviation, Mitchell in view of Hashimoto do not explicitly disclose smoothing the first set of data so as to obtain a second set of smoothed data. Wang discloses smoothing the first set of data so as to obtain a second set of smoothed data (Figs. 4-6, comparing smoothed data to raw data; ¶¶ [0025]-[0035], [0041], [0051]). It would have been obvious to one of ordinary skill in the art before the effective filing of the application to modify the invention of Mitchell in view of Hashimoto by providing smoothing the first set of data so as to obtain a second set of smoothed data as in Wang as an alternative to the signal variance process of Hashimoto and/or to provide greater accuracy through minimizing interference/noise.
Regarding Claim 19, Hashimoto discloses controlling a display screen to indicate that maintenance of the spectrometer is required if the first and second sets of data do not match or differ by a predetermined or threshold amount (Figs. 1-3, signal variance evaluation unit 105 with display unit 20 maintenance requirement, Steps S1-S5; ¶¶ [0044]-[0065]).
Claim(s) 24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hashimoto in view of Wang.
Regarding Claim 24, Hashimoto discloses a mass spectrometer (Figs. 1-2, liquid chromatograph mass spectrometry apparatus 100; ¶¶ [0005]-[0006], [0037]-[0045]); comprising: a separation device for separating ions, or analytes (Figs. 1-2, various components in sample are separated in time in chromatograph 11; ¶¶ [0005]-[0006], [0038]-[0045]); a mass analyser (Figs. 1-2, mass spectrometry unit 8 with mass separation unit 7 and detector; ¶¶ [0037]-[0045]); and a controller having electronic circuitry configured to control the mass spectrometer (Figs. 1-2, liquid chromatograph mass spectrometry apparatus 100 with controller 10; ¶¶ [0037]-[0045]) to: i) operate during a period of time in which the sensitivity with which the mass analyser is able to detect ions varies (Figs. 1-6, liquid chromatograph mass spectrometry apparatus 100 with controller 10 operating while ion source 6 is stable or unstable (varying sensitivity); ¶¶ [0037]-[0057]); ii) determine the intensity of the ion signal of an ion of interest detected by the mass analyser within said period of time (Figs. 1-6, liquid chromatograph mass spectrometry apparatus 100 with controller 10 determining chromatography peaks 1 in MRM measurement, the (m/z) to be measured; ¶¶ [0005]-[0008], [0037]-[0057]); iii) repeat steps i) and ii) as the ion of interest, or an analyte from which it is derived, elutes from the separation device (Figs. 1-7, when the signal variance evaluation unit 105 evaluates as unstable, the operation control unit 106 changes the conditions (ion generation conditions) such as the voltage applied to the ion source 6, a position, the gas flow rate used for spraying and heating, and the temperature of the ion source 6 (step S7), and performs the measurement again (step S1); ¶¶ [0037]-[0057], [0071]-[0075]); wherein when step ii) is repeated, it is performed at different times after said period of time begins (Figs. 1-7, time width of each small section 5 in each channel; ¶¶ [0037]-[0062]); iv) produce a first set of data that comprises the intensity of the ion signal as a function of detection time (Figs. 1-6, controller 10 determining chromatography peaks 1 in MRM/SIM measurement, the (m/z) to be measured; ¶¶ [0005]-[0008], [0025]-[0026], [0037]-[0057]); v) process the first set of data so as to obtain a second set of processed data and determine if maintenance of the spectrometer is required based on a comparison of the first and second sets of data (Figs. 1-3, signal variance evaluation unit 105 evaluating data for determining maintenance requirement, Steps S1-S5; ¶¶ [0044]-[0065]). However, although Hashimoto discloses determining a signal variation from a signal average value and standard deviation, Hashimoto does not explicitly disclose smoothing the first set of data so as to obtain a second set of smoothed data. Wang discloses smoothing the first set of data so as to obtain a second set of smoothed data (Figs. 4-6, comparing smoothed data to raw data; ¶¶ [0025]-[0035], [0041], [0051]). It would have been obvious to one of ordinary skill in the art before the effective filing of the application to modify the invention of Hashimoto by providing smoothing the first set of data so as to obtain a second set of smoothed data as in Wang as an alternative to the signal variance process of Hashimoto and/or to provide greater accuracy through minimizing interference/noise.
Conclusion
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/DAVID J BOLDUC/Primary Examiner, Art Unit 2852