DETAILED ACTION
Response to Arguments
Applicant's arguments filed 11/17/2025 have been fully considered but they are not persuasive.
Applicant argues that the prior art of record does not teach or disclose the mass spectrometer monitoring the MS scan is performed without fragmenting incoming sample ions received by the tandem mass spectrometer and to direct the mass spectrometer to switch to a group of at least one MS/MS scan associated with the sentinel ion to fragment the incoming sample ions into product ions. Examiner disagrees as Lemoine discloses a common approach to perform detection (e.g. targeted approach) where the mass spectrometer records the signal associated called a transition where a precursor ion (corresponding to the whole substance) is filtered in a first quadrupole then fragmented in quadrupole 2 and one or more product ions are filtered into the quadrupole 3 (see col. 1, lines 44-57). Furthermore, Lemoine discloses detecting a precursor ion for a series, tandem mass spectrometer 720 selects and fragments a precursor ion and mass analyzes an entire m/z range of product ions (e.g. unfragmented precursor ion and one or more product ions of the precursor ion are detected in the full product ion spectrum, see col. 13, lines 37-50). That is, the processor 730 can select the MRM transition as the sentinel (which includes precursor ions that are not fragmented, see col. 13, lines 34-38), and when received by the processor 730, the plurality of precursor ions and/or one or more product ions are divided into two or more contiguous groups (which can include a step of fragmenting, see col. 13, lines 51-60), so that different groups can be monitored separately (processor 730 can order the plurality of precursor ions and/or one or more product ions of the precursor ion according to expected retention time, see col. 13, lines 60-63).
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.
Claims 1-18, 21, and 24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lemoine (US Pat. 10,566,178, hereinafter Lemoine).
Regarding claim 1, Lemoine discloses a high resolution tandem mass spectrometer (tandem MS, see abstract) comprising:
a mass filter (mass filter) (see col. 12, lines 17-20);
a fragmentation cell (fragmentation step) (see col. 1, lines 30-41);
a high resolution mass analyzer (tandem mass spectrometer 720, see col. 12, lines 11-15); and
a controller (processor 730) for directing operation of the mass filter, fragmentation cell, and high resolution mass analyzer (see col. 12, lines 33-39);
wherein, the controller is operative to direct the mass to spectrometer to monitor an MS scan (processor 730 is a controller which is programmable or operative to perform the claimed functions, see MPEP 2114(IV) which recites “The court held that "programmable" claim language required only that the accused product could be programmed to perform the claimed functionality”, which Lemoine has disclosed as a common approach to perform detection where the mass spectrometer records the signal associated called a transition where a precursor ion (corresponding to the whole substance) is filtered in a first quadrupole then fragmented in quadrupole 2 and one or more product ions are filtered into the quadrupole 3, see col. 1, lines 44-57), performed without fragmenting incoming sample ions received by the tandem mass spectrometer, for a sentinel ion from the incoming sample ions (processor 730 can select any of the MRM transitions of a group as the at least one sentinel, the MRM transitions can include a precursor ion for a full scan product ion spectrum of the tandem MS 720, see col. 13, lines 30-50, and after the processor receives the precursor ion, divides the plurality of product ions into two or more contiguous groups of product ions (e.g. fragmentation step is inherent in producing product ions) that can be monitored separately, see col. 13, lines 51-63; and
when the mass spectrometer detects the sentinel ion during the MS scan, the controller is operative to direct the mass spectrometer to switch to a group of at least one MS/MS scan associated with the sentinel ion to fragment the incoming sample ions into product ions, and to mass analyze the product ions resulting from fragmentation of the incoming sample ions (processor 730 detects a precursor ion, and tandem MS 720 selects and fragments a precursor ions and mass analyzes an entire m/z range of product ions, see col. 13, lines 30-50).
Regarding claim 2, Lemoine discloses when the controller (processor 730) is further operative during the group of at least one MS/MS scans to monitor a next MS scan for a next sentinel ion (see col. 12, lines 23-59); and,
when the mass spectrometer detects the next sentinel ion, the controller (processor 730) is operative to direct the mass spectrometer to switch to a next group of at least one MS/MS scans associated with the next sentinel ion (see col. 12, lines 23-59).
Regarding claim 3, Lemoine discloses the controller is further operative to switch the mass spectrometer to a next MS scan to monitor for a next sentinel ion (see col. 12, lines 40-59).
Regarding claim 4, Lemoine discloses the MS/MS scan each comprise a separate MRM of the mass spectrometer (see col. 12, lines 40-59).
Regarding claim 5, Lemoine discloses the controller (processor 730) is further operative to monitor for the sentinel ion by monitoring for at least one isotope (stop sentinel) of the sentinel ion, and wherein the mass spectrometer detects the sentinel ion by evaluating the mass accuracy of the detected sentinel ion or by evaluating the detected sentinel ion and the at least one isotope to confirm a presence of the sentinel ion (see col. 12 line 40 – col. 13 line 25).
Regarding claim 6, Lemoine discloses evaluating the detected sentinel ion and the at least one isotope (stop sentinel) comprises comparing each of the detected sentinel ion and the at least one isotope (stop sentinel) against an expected intensity threshold (see col. 12 line 40 – col. 13 line 25).
Regarding claim 7, Lemoine discloses evaluating the detected sentinel ion and the at least one isotope (stop sentinel) comprises comparing the detected sentinel ion and the at least one isotope (stop sentinel) are detected in an expected isotopic ratio (see col. 12 line 40 – col. 13 line 25).
Regarding claim 8, Lemoine discloses the sentinel ion is identified by a precursor ion stored by the mass spectrometer (see col. 14, lines 3-10).
Regarding claim 9, Lemoine discloses the controller (processor 730) is further operative to calculate a mass of at least one isotope of the sentinel ion from the precursor ion (see col. 14, lines 3-10).
Regarding claim 10, Lemoine discloses an ion source (ion source 710) operative to ionize sample delivered from a separation device (see col. 12, lines 23-32).
Regarding claim 11, Lemoine discloses a sample introduction sample (sample mixture) for introducing the sample to the mass spectrometer (see col. 12, lines 5-11).
Regarding claim 12, Lemoine discloses the mass spectrometer is operative to monitor the MS scan of precursor ions for a plurality of different sentinel ions (sentinel ions), and wherein the controller (processor 730) is operative to direct the mass spectrometer to monitor the MS scan for each sentinel ion based on an expected order of delivery (see col. 12 lines 40 – col. 13 line 25).
Regarding claim 13, Lemoine discloses the sample is delivered by elution from a chromatography column (see col. 12, lines 1-11), and wherein the controller (processor 730) is operative to order the sentinel ions based on an expected elution order from the chromatography column (see col. 7, lines 34-41).
Regarding claim 14, Lemoine discloses the expected elution order is provided as a list stored by the mass spectrometer (see col. 8, lines 17-25).
Regarding claim 15, Lemoine discloses the mass spectrometer is operative to monitor the MS scan ions for a plurality of different sentinel ions (sentinel ions) and to switch to a corresponding plurality of groups of at least one MS/MS scan each group associated with a corresponding sentinel ion, and wherein the controller (processor 730) is operative to direct the mass spectrometer to overlap MS/MS scans when switching to a next group upon detection of a next sentinel ion in order to ensure correct peak definition (see col. 12 line 40 – col. 13 line 25).
Regarding claim 16, Lemoine discloses the controller (processor 730) is operative to select a stop MS/MS scan (stop sentinel) for each group, and when a stop MS/MS scan (stop sentinel) is detected, the controller (processor 730) is operative to direct the mass spectrometer to either switch to a next MS scan to monitor for a next sentinel ion or to switch to a next group of MS/MS scan modes (see col. 13, lines 9-15).
Regarding claim 17, Lemoine discloses at least one MS/MS scan includes an MS scan of a next sentinel (see col. 12, lines 54-59).
Regarding claim 18, Lemoine discloses the mass spectrometer is operative to detect a product ion during each MS/MS scan without using a time window for that MS/MS scan mode (see col. 13, lines 16-25).
Regarding claim 21, Lemoine discloses a method for mass spectrometry, comprising a tandem mass spectrometer (tandem mass spectrometer, see abstract):
receiving an ion beam of sample ions (ion beam from ion source 710, see col. 12, lines 11-16);
monitoring an MS scan performed on the ion beam without fragmenting the received sample ions of the ion beam for a sentinel ion (processor 730 can select any of the MRM transitions of a group as the at least one sentinel, the MRM transitions can include a precursor ion (e.g. not fragmented) for a full scan product ion spectrum of the tandem MS 720, see col. 13, lines 30-50);
directing the sentinel ion during the MS scan (processor 730 detects a precursor ion and mass analyzes an entire m/z range of ions, see col. 13, lines 47-50);
triggering a group of at least one MS/MS scan associated with the sentinel ion, and for each of the at least one MS/MS scan (processor 730 detects a precursor ion, and tandem MS 720 selects and fragments a precursor ions and mass analyzes an entire m/z range of product ions, see col. 13, lines 37-50):
fragmenting the ion beam of the sample ions into product ions (tandem MS 720 selects and fragments a precursor ion into product ions, see col. 13, lines 40-45); and
mass analyzing the product ions resulting from fragmenting the ion beam of the sample ions (unfragmented precursor ion and one or more product ions of the precursor ion are detected in the full product ion spectrum, see col. 13, lines 30-50).
Regarding claim 24, Lemoine discloses a system for triggering a group of precursor ion to full product ion spectrum MS/MS scans from a series of contiguous groups when an accurate mass of at least one sentinel MS/MS scan of the group is detected during a MS scan (processor 730 can select any of the MRM transitions of a group as the at least one sentinel, the MRM transitions can include a precursor ion for a full scan product ion spectrum of the tandem MS 720, see col. 13, lines 30-50), comprising:
a tandem mass spectrometer that receives an ion beam (ion beam from ion source 710, see col. 12, lines 11-16) and for each cycle of a plurality of cycles executes on the ion beam an MS scan, performed without fragmenting ions of the ion beam by the tandem MS (processor 730 can select any of the MRM transitions of a group as the at least one sentinel, see col. 13 lines 34-36, the MRM transitions can include a precursor, see col. 13, lines 37-40; unfragmented precursor ion is detected in the full ion spectrum, see col. 13 lines 47-50), followed by a series of MS/MS scans read from a list, wherein for each MS/MS scan of the series, if an accurate mass of a sentinel precursor ion of the each MS/MS scan is found within a mass threshold from the MS scan, the tandem mass spectrometer selects and fragments the ions of the ion beam (processor 730 detects a precursor ion, and tandem MS 720 selects and fragments a precursor ions and one or more product ions and mass analyzes an entire m/z range of product ions, see col. 13, lines 30-50), and
a processor in communication with the tandem mass spectrometer that (processor 730 and tandem mass spectrometer 720, see col. 13, lines 30-50):
receives a plurality of MS/MS scans that each includes a precursor ion accurate mass (processor 730 can select any of the MRM transitions of the group as the at least one sentinel, see col.13, lines 30-35),
divides the plurality of MS/MS scans into two or more contiguous groups so that different groups can be executed separately during the plurality of cycles (the mass spectrometer records the signal associated called a transition where a precursor ion (corresponding to the whole substance) is filtered in a first quadrupole then fragmented in quadrupole 2 and one or more product ions are filtered into the quadrupole 3, see col. 1, lines 44-57),
selects at least one sentinel MS/MS scan in each preceding group of the two or more contiguous groups that identifies a next group of the two or more contiguous groups that is to be executed (processor 730 detects a precursor ion, and tandem MS 720 selects and fragments a precursor ions and mass analyzes an entire m/z range of product ions, see col. 13, lines 30-50),
places a first group of the two or more contiguous groups on the list of the tandem mass spectrometer (the mass spectrometer records the signal associated called a transition where a precursor ion (corresponding to the whole substance) is filtered in a first quadrupole then fragmented in quadrupole 2, see col. 1, lines 44-57), and
when a precursor ion accurate mass of a sentinel MS/MS scan of the first group is detected by the tandem mass spectrometer within the mass threshold during an MS scan performed with fragmenting the ions of the ion beam, places a next group of the two or more contiguous groups identified by the sentinel MS/MS scan on the list (the precursor ion and/or one or more product ions of the precursor ion are detected in the full product ion spectrum, see col. 13, lines 43-50).
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HANWAY CHANG whose telephone number is (571)270-5766. The examiner can normally be reached Monday - Friday 7:30 AM - 4:00 PM EST.
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Hanway Chang
/HC/ Examiner, Art Unit 2881
/MICHAEL J LOGIE/ Primary Examiner, Art Unit 2881