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 .
Election/Restrictions
Applicant's election with traverse of Group I (claims 1-3, 10-15, and 20-25) in the reply filed on 07/13/2026 is acknowledged. The traversal is on the ground(s) that groups are directed to a common general inventive concept. This is not found persuasive. The identified subcombinations do not overlap in scope merely because each is combined with the common linking subject matter of claims 1,3, 10-15, and 20-25. The separately claimed subcombinatoins do not overlap in scope and are not obvious variants: Group 1 - claims 2 concerns ion-trap accumulation control; Group 2 - claim 8 concerns MR-ToF operating modes; Group 3 - claim 9 concerns a detector; Group 4 - claims 16-19 concern coordinated operation of multiple mass analyzers; and Group 5 - claims 4-7 concern particular operating and component parameters. These subcombinatoins perform different functions, require materially different structures or operations, and are separately usable, even though they may be combined in one analytical instrument.
The requirement is still deemed proper and is therefore made FINAL.
Claims 4-9 and 16-19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claim Objections
Claim 24 is objected to because of the following informalities:
Claim 24 recites “an ion current obtained using first configured” appears missing a noun or other identifiable referent.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2, 11-12, 15,20, and 22 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 2, 15, 20, and 22 each recites limitations using “preferably” and/or “optionally”. It is unclear whether these recited features are required limitations or merely nonlimited preferred embodiment. The specification likewise presents their features as optional implementations rather than requirements. Accordingly, it is unclear whether the preferred feature limits the claims.
Claim 11 recites “The method of claim 10 when the selecting comprises applying one or more filtering criteria.” It is unclear whether the “when” language of claim 11 affirmatively requires the filtering alternative or merely imposes the subsequent limitation if filtering happens to occur. Under the latter interpretation, an algorithm/graph/mathematical model/ML model-only method within claim 10 would be performed without the condition occurring and therefore without performing the filtering limitations of claim 11.
Claim 12 is vague and indefinite by virtue of its dependency on rejected claim 11.
Claim Rejections - 35 USC § 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 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.
Claims 1-3, 10-15, and 23-25 are rejected under 35 U.S.C. 103 as being unpatentable over US 2014/0361158 A1 [hereinafter Remes] in view of Horai, H., et al., (2010). MassBank: a public repository for sharing mass spectral data for life sciences. Journal of Mass Spectrometry, 45(7), 703–714. [hereinafter Horai].
Regarding Claim 1:
Remes teaches a method of controlling a first analytical instrument (para. [0002]: “This invention relates to methods for controlling ion population in a mass spectrometer”), the method comprising:
configuring the first analytical instrument to be controlled according to one or more first operating parameters (para. [0036]: performs dependent acquisitions in a mass spectrometer (“first analytical instrument”) using “a different set of instrumental parameters or a different pathway (or both) than used for the survey acquisition”, i.e., “first operating parameters”); and
controlling the configured first analytical instrument based on an estimated ion current (paras. [0036-0037]: controls the dependent acquisition by setting its accumulation time based on estimated ion current, where “a time required to collect…an optimal population of ions in the mass spectrometer systems is calculated.” “If the efficiency as a function of mass offset from an isolation center mass is known, then the actual ion flux in the dependent scans can be estimated with increased accuracy),
wherein the ion current is estimated by:
selecting at least one signal from stored data (paras. [0035, 0041]: performs a survey acquisition to produce multiple detected ion-intensity signals, for each signal “ion intensities are measured using a first set of instrumental parameters or a first ion pathway through the mass spectrometer system or both”, i.e., the “second operating parameters,” selects the relevant signals by limiting the calculation to survey centroids associated with the dependent isolation window),
wherein each signal of the plurality of signals is representative of an ion current obtained using the first analytical instrument configured according to the respective associated one or more second operating parameters (para. [0035]: during survey acquisition, the “ion pathway will direct the ions to a particular mass analyzer and its associated detector, from which the one or more intensities are measured,” and these intensities represent the ion flux/current attributable to the corresponding ions) or using a second analytical instrument configured according to the respective associated one or more second operating parameters (para. [0035]: “…If the pathway is one of two or more alternative pathways, then the alternative pathways may be associated with different mass analyzers and detectors”), and
wherein the at least one signal is selected based on the one or more first operating parameters (paras. [0040]: “a more accurate estimation of ion flux through the QMF can be estimated from the survey scan if the survey scan centroid peaks are convolved with the appropriate, scaled, transmission profile…” and “the estimated TIC [uses] the sum of survey scan centroids within the isolation window.” Accordingly, the isolation parameters, e.g., isolation center and isolation width, determined which signal (representative of recorded survey peaks) are included and/or their transmission weights); and
using the at least one selected signal to estimate the ion current (paras. [0006, 0040]: predict an ion flux for the dependent acquisition based on previous survey scan data. “I (c., w) is total estimated intensity for isolation center mass c and isolation width w” and calculated according to equation 9, and the estimated TIC/ion flux is then used in step 515 to calculate the accumulation time).
However, Remes does not expressly teach the stored data comprising a plurality of signals and a respective one or more second operating parameters associated with each of the plurality of signals.
Horai teaches a stored database “stores the mass spectra data in text format” and “[e]ach record contains one mass spectrum attributable to one chemical compound”. Specifically, Horai teaches the stored data comprising a plurality of signals and a respective one or more second operating parameters associated with each of the plurality of signals (Pages 1 and 3: “MassBank users can access either all of the MassBank data or a subset of the data by specifying one or more experimental conditions”. Each record includes “analytical and spectral section,” where the analytical section “describes the instrument types and analytical parameters used for mass spectrometry, including the instrument manufacturer…the method of ionization, the type of ion analyzer, ionization voltage… and the collision induced dissociation (CID) conditions” accordingly, each stored spectrum is associated in its record with the operating parameters (“second operating parameters”) under which it was acquired).
Therefore, it would have been obvious for an ordinary skilled person of art, before the effective time of filing, to store Remes’ survey-scan signals and their associated acquisition parameters in a catalogued database as taught by Horai, since Horai states that organizing each mass spectrum together with its instrument type and analytical parameters permits users to access and select spectral data obtained under specified experimental conditions, and thus applying this known data-storage arrangement to Remes would have facilitated organized retrieval of the measured intensities signals together with the condition under which they were obtained, thereby enabling the appropriate signals and associated parameters to e reliably used in Reems’ ion-flux estimation and accumulation-time control.
Regarding Claim 23:
Remes in view of Horai teaches a controller (one or more computing/processing devices shown on Figs. 3-5 of Remes) configured to perform steps as recited in claim 1.
Regarding Claim 24:
Remes in view of Horai teaches a computer program comprising instructions which, when executed by a computer (one or more computing/processing devices shown on Figs. 3-5 of Remes), cause the computer to perform steps as recited in claim 1.
Regarding Claim 25:
Remes in view of Horai teaches a system (a mass spectrometer system as shown in Fig. 3 of Remes) comprising a first analytical instrument (Fig. 3- mass analyzer 206 of Remes), the controller of claim 23 (Fig.3- computing devices of Remes) and a database (Fig.3- computing devices with storage of Remes) in communication with the first analytical instrument, the database comprising stored data.
Regarding Claim 2:
Remes in view of Horai teaches the method of claim 1. Remes further teaches:
wherein the first analytical instrument comprises an ion trap, wherein the method further comprises accumulating a batch of ions in the ion trap (paras. [0036]: teaches “the optimal ion population is collected within the mass spectrometer system,” e.g., an Orbitrap), and
wherein controlling the configured first analytical instrument based on the estimated ion current comprises regulating a number of ions in the batch of ions accumulated in the ion trap based on the estimated ion current (para. [0005]: “The dependent scans use the abundance information from the Survey scan to estimate the ion flux, so that the ion accumulation time can be set appropriately for a target ion population size”),
wherein regulating the number of ions preferably comprises controlling a fill time of the ions into the ion trap (paras. [0003]: “the time required to fill a mass spectrometer component, such as an ion trap, to its optimal ion population level is estimated from a prior measurement of ion flux into the component”).
Regarding Claim 3:
Remes in view of Horai teaches the method of claim 1. Remes further teaches:
analysing ions during a time period (para. [0036]: “a time required to collect, during a dependent acquisition… is calculated”), and
wherein controlling the configured first analytical instrument based on the estimated ion current comprises regulating a duration of the time period based on the estimated ion current (para. [0036]: “a time required to collect, during a dependent acquisition… is calculated …This calculation is performed using the ion transfer efficiencies or analyzer ratio transfer functions…as well as the detected intensities measured in Step 510”); and/or
wherein controlling the configured first analytical instrument based on the estimated ion current comprises adjusting, based on the estimated ion current, a target number of ions, an ion accumulation time and/or a mass-to-charge ratio (m/z) range (paras. [0006,0036]: “the optimal ion population is collected … by collecting ions for the calculated time …” The instrument parameters for the dependent acquisition may include “a wide range of mass-to-charge”).
Regarding Claim 10:
Remes in view of Horai teaches the method of claim 1.
Horai further teaches wherein the selecting comprises applying one or more filtering criteria to the stored data to obtain a subset of data the subset of data comprising the at least one signal and its respective associated one or more second operating parameters (Page 1: “MassBank users can access either all of the MassBank data or a subset of the data by specifying one or more experimental conditions”).
Remes further teaches the selecting comprises using an algorithm, a graph, a mathematical model, or a machine learning model to select the at least one signal (para. [0040]: Remes teaches selecting and weighing the relevant survey signals using a mathematical model – Eq. 9 for calculating total estimated intensity according to isolation center, isolation width, survey-peak m/z, and transmission efficiency).
Regarding Claim 11:
Remes in view of Horai teaches the method of claim 10. Horai further teaches:
when the selecting comprises applying one or more filtering criteria to the stored data, wherein the one or more filtering criteria comprises at least one of the one or more first operating parameters and at least one of the respective one or more second operating parameters being the same, sufficiently similar or most similar (Pages 5 and 9: “To obtain suitable search results, users should specify search conditions using the Search Parameter Setting applet before their first search… the users select the instrument type identical with or similar to the type of the query mass spectrum and the ionization mode.” “Via the Search Parameter Setting interface, MassBank allows users to select datasets obtained with different analytical methods as the search target”); and/or
wherein the one or more filtering criteria are based on one or more of: at least one of the one or more first operating parameters, at least one of the respective one or more second operating parameters, a number of detected ions, a time duration since obtaining a signal of the plurality of signals, a retention time duration, an underfill indication and an overfill indication (Page 5: The filtering criteria are based on operating parameters, including instrument type and ionization mode).
Regarding Claim 12:
Remes in view of Horai teaches the method of claim 11. Horai further teaches wherein the one or more filtering criteria comprises one or more of: the number of detected ions being greater or less than a threshold number of detected ions (page 5: “To obtain suitable search results… users should first specify the search tolerance, that is …the cutoff threshold for lower intensity peaks and the precursor ion by the m/z value…”), a target number of ions being within a threshold tolerance of the detected number of ions, a time duration since obtaining the at least one signal being less than a threshold time duration, and a retention time duration being less than a threshold retention time duration.
Regarding Claim 13:
Remes in view of Horai teaches the method of claim 1.
Remes further teaches wherein the controlling comprises measuring a further signal representative of the ion current and (para. [0041]: “First a Survey scan at very wide isolation width is performed…Then, dependent scans are taken at a series of isolation widths. For each isolation width, the actual total ion current (TIC) is recorded”).
Horai further teaches stores the mass spectral data and each record consists of analytical (e.g., operating parameters) and spectral section.
As such, the combined references teach “subsequent to the controlling, including the further signal and the one or more first operating parameters in the stored data.” In the modified method, after Remes produced and recorded actual TIC constitutes a further signal representative of the ion current, and the corresponding isolation width constitutes a first operating parameter, Horai would store the newly provided mass-spectral signals and their associated analytical parameters together as records in a relational database to further update the database.
Regarding Claim 14:
Remes in view of Horai teaches the method of claim 1. Remes further teaches wherein the at least one signal comprises more than one signal and the estimating further comprises weighting the more than one signals to estimate the ion current (paras. [0040-0041]: convolving each peak intensity with its corresponding transmission value (“weighing”) to estimate ion current).
Regarding Claim 15:
Remes in view of Horai teaches the method of claim 1. Horai further teaches:
wherein the stored data further comprises, for one or more of the plurality of signals, one or more of: scan data, pre-scan data, one or more electrometer measurements, LC detector data, and data from one or more previous experiments (Page 3: “The database layer stores the mass spectral data…”),
wherein the scan data preferably comprises one or more of: one or more acquired mass spectra, information regarding one or more detected peaks, an m/z range and ion accumulation time (Page 3: “Each record contains one mass spectrum attributable to one chemical compound… each record consists of …spectral section… lists peak data with m/z and intensity and relative intensity values in integral or real numbers...”),
wherein the information regarding the one or more detected peaks optionally comprises an intensity and/or resolution of the peaks (Page 3: “The spectral section… lists peak data with m/z and intensity and relative intensity values in integral or real numbers”).
Claims 20-22 are rejected under 35 U.S.C. 103 as being unpatentable over Remes in view of Horai, further in view of US 2017/0147639A1 [hereinafter Lee].
Regarding Claim 20:
Remes in view of Horai teaches the method of claim 1. However, the combined references do not expressly teach in response to receiving additional data after a storage threshold of the stored data is reached, deleting or overwriting one or more data entries in the stored data to include the additional data in the stored data, wherein the storage threshold preferably corresponds to a maximum number of data entries and/or a maximum storage capacity.
Lee teaches in response to receiving additional data after a storage threshold of the stored data is reached, deleting or overwriting one or more data entries in the stored data to include the additional data in the stored data, wherein the storage threshold preferably corresponds to a maximum number of data entries and/or a maximum storage capacity (para. [0023]: “If the plan cache 140 containing stored query plans exceeds a threshold size, one or more of the query plans may be discarded to make room for new query plans amount, the oldest event data is overwritten with the newest event data”).
Therefore, it would have been obvious for an ordinary skilled person in the art, before the effective time of filing, to apply the capacity-based deletion technique of Lee to Horai’s spectral database so that, upon reaching a predetermined maximum storage size, an existing removable entry is selected to make room for newly acquired spectral data, to allow the database to continue receiving and storing new measurement results while maintaining its storage usage within the available capacity.
Regarding Claim 21:
Remes in view of Horai and Lee teaches the method of claim 20. Lee further teaches wherein the stored data comprises a set of editable data and a set of non-editable data and the deleting or overwriting comprises deleting one or more data entries in the set of editable data (paras. [0023, 0037]: “hints may be pinned and unpinned to a query using a system command.” “removing query plans from the plan cache may be referred to as eviction of the query plans…query plans that include one or more hints may not be evicted… if the plan cache reached a threshold maximum size, then the query plan without the hint may be selected to be discarded to make space in the plan cache. In this way, query plans that include hints may be protected from eviction”).
Regarding Claim 22:
Remes in view of Horai and Lee teaches the method of claim 20. Horai teaches stores the analytical method and scan-related conditions associated with each spectral records, while Remes distinguish survey and dependent scan types. As such, the modified method would designate or “pin” selected Horai records based on their scan type or other criterion associated with their criticality. Routine record would remain unpinned and removed; records from selected scan types or otherwise important would be protected from eviction, as recited in claim 22.
It would have been obvious to apply the pinned-entry database management technique as taught by Lee to Horai’s stored spectral records and to pin records from selected scan types, to preserve analytically important or less readily replaceable scan data while permitting ordinary database entries to be removed when the database reaches its storage limit,
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JING WANG whose telephone number is (571)272-2504. The examiner can normally be reached M-F 7:30-17:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert Kim can be reached at 571-272-2293. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JING WANG/Examiner, Art Unit 2881
/WYATT A STOFFA/Primary Examiner, Art Unit 2881
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