DETAILED ACTION
This Office action is in response to the amendment filed on July 1st, 2026. Claims 1-20 are pending.
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over ‘Waters Quattro micro API Mass Spectrometer Operator’s Guide’ (the guide).
Regarding claim 1, the guide discloses a method comprising:
receiving an analysis of a sample compound from a mass spectrometry (MS) apparatus, the analysis associated with a plurality of mass peaks (‘A mass spectrum of a reference compound (a calibration file) is acquired’ p. 5-2);
receiving a set of mass peaks of a reference compound (‘a table of the expected masses of the peaks in the reference compound which are stored as a reference file.’ P. 5-2);
mapping a subset of the plurality of mass peaks of the sample compound to a corresponding subset of peaks of the reference compound (‘A mass spectrum of a reference compound (a calibration file) is acquired and matched against a table of the expected masses of the peaks in the reference compound’ p. 5-2), by defining a predetermined window of masses based on a mass-to-charge ratio of the first peak of the reference compound, the predetermined window of masses encompassing a group of candidate peaks in the sample compound, and automatically selecting a peak from the group of candidate peak (“The Peak Match parameters determine the limits within which the acquired data must lie for the software to recognise the calibration masses and result in a successful calibration. The default values are shown.” P. 5-3);
presenting a group of candidate peaks on a display (‘An expanded region can be displayed by clicking and dragging with the left mouse button. In this way, the less intense peaks in the spectrum can be examined to check that the correct peaks have been matched.’ p. 5-21);
overriding the mapping by performing at least one of: matching the first peak of the reference compound to a second peak of the sample compound, or matching the first peak of the reference compound to no peak in the sample compound (‘If an incorrect peak has been matched in the calibration process, this peak can be excluded manually from within the on-screen calibration report. … If the true reference peak is present, this can be included in the calibration by the same procedure:’ P. 5-24);
and defining a scaling factor based on the mapping to define a calibrating adjustment, the scaling factor scaling the peaks as a function of at least one of a mass value, a charge value, an intensity value, or a time value (‘The mass differences between the reference peaks and calibration peaks are the calibration points. A calibration curve is fitted through the calibration points.’ p. 5-2).
The guide does not directly disclose defining a predetermined window of time after the sample compound was injected into the MS apparatus, defining a predetermined window of masses instead. However, defining a predetermined window of time is functionally equivalent to defining a predetermined window of masses because the time required for an ion to traverse the drift tube or the mass spectrometer is dependent on the mass to charge ratio. If a predetermined window of time is known, the corresponding window of masses can be easily calculated, given the settings of the device. In fact, the only way a group of mass peaks could reasonably be identified as lying in a time window is if the equivalent mass window was calculated and the peaks grouped by mass, since the “set of mass peaks” includes data about masses but not times, the mass peaks being intensity counts measured over time, not individually time stamped detector blimps. Hence, defining a predetermined window of time is functionally equivalent to defining a predetermined window of masses.
The guide further does not disclose limiting the display of candidate peaks to the those within the predetermined window of time. It would have been obvious to a person having ordinary skill in the art at the time the application was filed to modify the method to limit the display and editing of the peak matching to this predefined mass window to ensure the user does not degrade the quality of the calibration by adding clearly erroneous matches.
The guide does not disclose that the analysis received is from a mass spectrometry (MS) apparatus having a drift tube with an effective length of at least 20 cm that allows molecules to travel in a cyclic pattern and to be selectively ejected to a detector during each cycle. However, the form of the mass separator used to form the mass spectrum has does not appear to have any effect on the method, since only the detected masses are received and manipulated. Therefore, this is considered non-limiting.
Alternatively, mass spectrometry (MS) apparatuses having a drift tube with an effective length of at least 20 cm that allows molecules to travel in a cyclic pattern and to be selectively ejected to a detector during each cycle are known in the art, and it would have been obvious to a person having ordinary skill in the art at the time the application was filed to apply the method of the guide to a mass spectrum received from such an apparatus in order to calibrate the spectrum.
Regarding claim 2, the guide discloses the claimed invention except for the MS apparatus being an ion mobility apparatus. However, as discussed above, the form of the ion separator used to form the mass spectrum has does not appear to have any effect on the method. Therefore, this is considered non-limiting.
Alternatively, ion mobility mass spectrometers are well known in the art, and it would have been obvious to a person having ordinary skill in the art at the time the application was filed to apply the method to mass spectra obtained using such an apparatus because calibration will be required of all mass spectrometers, including ion mobility mass spectrometers.
Regarding claim 3, the guide discloses the method of claim 1, wherein the reference compound is a custom reference compound received from a user (‘Selecting the appropriate reference file for the reference sample to be used.’ p. 5-4).
Regarding claim 4, the guide discloses the method of claim 1, further comprising:
displaying the corresponding subset of peaks of the reference compound in a reference compound interface on a display (‘The calibration report contains four displays: … the reference spectrum’ p. 5-21);
receiving a selection of the first peak of the reference compound (‘An expanded region can be displayed by clicking and dragging with the left mouse button. In this way, the less intense peaks in the spectrum can be examined to check that the correct peaks have been matched.’ p. 5-21); and
displaying, in a sample compound interface on the display, a plurality of peaks of the sample compound that fall within a window of masses around the first peak of the reference compound, the plurality of peaks comprising the first peak of the sample compound and the second peak of the sample compound (‘An expanded region can be displayed by clicking and dragging with the left mouse button. In this way, the less intense peaks in the spectrum can be examined to check that the correct peaks have been matched.’ p. 5-21).
Regarding claim 5, the guide discloses the method of claim 4, wherein overriding the mapping comprises receiving a selection of the second peak of the sample compound in the sample compound interface (‘If the true reference peak is present, this can be included in the calibration by the same procedure: Place the cursor over the required peak and click with the right mouse button. The peak is matched with the closest peak in the reference spectrum.’ p. 5-24).
Regarding claim 6, the guide discloses the method of claim 1, further comprising:
for each of the plurality of mass peaks of the sample compound mapped to corresponding peaks of the reference compound, calculating a residual value by calculating a difference between each mapped pair of peaks (‘The vertical distance of each calibration point from the curve is calculated. This distance represents the remaining (or residual) mass difference after calibration.’ p. 5-2);
displaying the residual values in a residual interface on the display (‘The calibration report contains four displays: … a plot of residual against mass’ p. 5-21);
receiving a selection of one of the residual values, the selected residual value corresponding to a pair of matched peaks from the reference compound and the sample compound (‘An expanded region can be displayed by clicking and dragging with the left mouse button. In this way, the less intense peaks in the spectrum can be examined to check that the correct peaks have been matched.’ p. 5-21);
removing the mapping between the pair of matched peaks (‘If an incorrect peak has been matched in the calibration process, this peak can be excluded manually from within the on-screen calibration report.’ p. 5-24); and
recalculating the calibrating adjustment (inherent, the calibrating adjustment is based on the matching and changing the matching will change the points being fitting to the curve).
Regarding claim 7, the guide discloses the method of claim 1, wherein the calibrating adjustment is based on a plurality of points fitted with a regression line, and further comprising:
displaying the plurality of points and the regression line in a model fit interface on the display (‘The calibration report contains four displays: … a plot of mass difference against mass (the calibration curve)’ p. 5-21);
receiving a selection of one of the points, the selected point corresponding to a pair of matched peaks from the reference compound and the sample compound (‘An expanded region can be displayed by clicking and dragging with the left mouse button.’ p. 5-21);
removing the mapping between the pair of matched peaks (‘If an incorrect peak has been matched in the calibration process, this peak can be excluded manually from within the on-screen calibration report. … If the true reference peak is present, this can be included in the calibration by the same procedure:’ p. 5-24); and
recalculating the calibrating adjustment with the selected point removed from the plurality of points (inherent, the calibrating adjustment is based on the matching and removing the matching will change the points being fitting to the curve).
Regarding claim 8, the guide discloses a non-transitory computer-readable storage medium, the computer-readable storage medium including instructions that when executed by a computer (‘The MassLynx™ software’ p. 1-3), cause the computer to:
receive an analysis of a sample compound from a mass spectrometry (MS) apparatus the analysis associated with a plurality of mass peaks (‘A mass spectrum of a reference compound (a calibration file) is acquired’ p. 5-2);
receive a set of mass peaks of a reference compound (‘a table of the expected masses of the peaks in the reference compound which are stored as a reference file.’ p. 5-2);
map a subset of the plurality of mass peaks of the sample compound to a corresponding subset of peaks of the reference compound, the mapping matching a first peak of the reference compound to a first peak of the sample compound (‘A mass spectrum of a reference compound (a calibration file) is acquired and matched against a table of the expected masses of the peaks in the reference compound’ p. 5-2) by defining a predetermined window of masses based on a mass-to-charge ratio of the first peak of the reference compound, the predetermined window of masses encompassing a group of candidate peaks in the sample compound, and automatically selecting a peak from the group of candidate peak (“The Peak Match parameters determine the limits within which the acquired data must lie for the software to recognise the calibration masses and result in a successful calibration. The default values are shown.” P. 5-3);
present a group of candidate peaks on a display (‘An expanded region can be displayed by clicking and dragging with the left mouse button. In this way, the less intense peaks in the spectrum can be examined to check that the correct peaks have been matched.’ p. 5-21);
override the mapping by performing at least one of: match the first peak of the reference compound to a second peak of the sample compound, or match the first peak of the reference compound to no peak in the sample compound (‘If an incorrect peak has been matched in the calibration process, this peak can be excluded manually from within the on-screen calibration report. … If the true reference peak is present, this can be included in the calibration by the same procedure:’ P. 5-24); and
define a scaling factor based on the mapping to define a calibrating adjustment, the scaling factor scaling the peaks as a function of at least one of a mass value, a charge value, an intensity value, or a time value (‘The mass differences between the reference peaks and calibration peaks are the calibration points. A calibration curve is fitted through the calibration points.’ p. 5-2).
The guide does not directly disclose defining a predetermined window of time after the sample compound was injected into the MS apparatus, defining a predetermined window of masses instead. However, defining a predetermined window of time is functionally equivalent to defining a predetermined window of masses because the time required for an ion to traverse the drift tube or the mass spectrometer is dependent on the mass to charge ratio. If a predetermined window of time is known, the corresponding window of masses can be easily calculated, given the settings of the device. In fact, the only way a group of mass peaks could reasonably be identified as lying in a time window is if the equivalent mass window was calculated and the peaks grouped by mass, since the “set of mass peaks” includes data about masses but not times, the mass peaks being intensity counts measured over time, not individually time stamped detector blimps. Hence, defining a predetermined window of time is functionally equivalent to defining a predetermined window of masses.
The guide does not disclose limiting the display of candidate peaks or overriding options to the specific group of candidate peaks in the predetermined window of time. It would have been obvious to a person having ordinary skill in the art at the time the application was filed to modify the software to limit the display and editing of the peak matching to this predefined mass window to ensure the user does not degrade the quality of the calibration by adding clearly erroneous matches.
The guide does not disclose that the analysis received is from a mass spectrometry (MS) apparatus having a drift tube with an effective length of at least 20 cm that allows molecules to travel in a cyclic pattern and to be selectively ejected to a detector during each cycle. However, the form of the mass separator used to form the mass spectrum has does not appear to have any effect on the instructions, since only the detected masses are received and manipulated. Therefore, this is considered non-limiting.
Alternatively, mass spectrometry (MS) apparatuses having a drift tube with an effective length of at least 20 cm that allows molecules to travel in a cyclic pattern and to be selectively ejected to a detector during each cycle are known in the art, and it would have been obvious to a person having ordinary skill in the art at the time the application was filed to apply the method of the guide to a mass spectrum received from such an apparatus in order to calibrate the spectrum.
Regarding claims 9-14, see analysis of claims 2-7.
Regarding claim 15, the guide discloses a computing apparatus comprising:
a processor (‘host computer’); and
a memory storing instructions that (‘The MassLynx™ software’ p. 1-3), when executed by the processor, configure the apparatus to:
receive an analysis of a sample compound from a mass spectrometry (MS) apparatus the analysis associated with a plurality of mass peaks (‘A mass spectrum of a reference compound (a calibration file) is acquired’ p. 5-2);
receive a set of mass peaks of a reference compound (‘a table of the expected masses of the peaks in the reference compound which are stored as a reference file.’ p. 5-2);
map a subset of the plurality of mass peaks of the sample compound to a corresponding subset of peaks of the reference compound, the mapping matching a first peak of the reference compound to a first peak of the sample compound (‘A mass spectrum of a reference compound (a calibration file) is acquired and matched against a table of the expected masses of the peaks in the reference compound’ p. 5-2) by defining a predetermined window of masses based on a mass-to-charge ratio of the first peak of the reference compound, the predetermined window of masses encompassing a group of candidate peaks in the sample compound, and automatically selecting a peak from the group of candidate peak (“The Peak Match parameters determine the limits within which the acquired data must lie for the software to recognise the calibration masses and result in a successful calibration. The default values are shown.” P. 5-3);
present a group of candidate peaks on a display (‘An expanded region can be displayed by clicking and dragging with the left mouse button. In this way, the less intense peaks in the spectrum can be examined to check that the correct peaks have been matched.’ p. 5-21)
override the mapping by performing at least one of: match the first peak of the reference compound to a second peak of the sample compound, or match the first peak of the reference compound to no peak in the sample compound (‘If an incorrect peak has been matched in the calibration process, this peak can be excluded manually from within the on-screen calibration report. … If the true reference peak is present, this can be included in the calibration by the same procedure:’ P. 5-24); and
define a scaling factor based on the mapping to define a calibrating adjustment, the scaling factor scaling the peaks as a function of at least one of a mass value, a charge value, an intensity value, or a time value (‘The mass differences between the reference peaks and calibration peaks are the calibration points. A calibration curve is fitted through the calibration points.’ p. 5-2).
The guide does not directly disclose defining a predetermined window of time after the sample compound was injected into the MS apparatus, defining a predetermined window of masses instead. However, defining a predetermined window of time is functionally equivalent to defining a predetermined window of masses because the time required for an ion to traverse the drift tube or the mass spectrometer is dependent on the mass to charge ratio. If a predetermined window of time is known, the corresponding window of masses can be easily calculated, given the settings of the device. In fact, the only way a group of mass peaks could reasonably be identified as lying in a time window is if the equivalent mass window was calculated and the peaks grouped by mass, since the “set of mass peaks” includes data about masses but not times, the mass peaks being intensity counts measured over time, not individually time stamped detector blimps. Hence, defining a predetermined window of time is functionally equivalent to defining a predetermined window of masses.
The guide does not disclose limiting the display of candidate peaks or overriding options to the specific group of candidate peaks in the predetermined window of time. It would have been obvious to a person having ordinary skill in the art at the time the application was filed to modify the software to limit the display and editing of the peak matching to this predefined mass window to ensure the user does not degrade the quality of the calibration by adding clearly erroneous matches.
The guide does not disclose that the analysis received is from a mass spectrometry (MS) apparatus having a drift tube with an effective length of at least 20 cm that allows molecules to travel in a cyclic pattern and to be selectively ejected to a detector during each cycle. However, the form of the mass separator used to form the mass spectrum has does not appear to have any effect on the instructions, since only the detected masses are received and manipulated. Therefore, this is considered non-limiting.
Alternatively, mass spectrometry (MS) apparatuses having a drift tube with an effective length of at least 20 cm that allows molecules to travel in a cyclic pattern and to be selectively ejected to a detector during each cycle are known in the art, and it would have been obvious to a person having ordinary skill in the art at the time the application was filed to apply the method of the guide to a mass spectrum received from such an apparatus in order to calibrate the spectrum.
Regarding claims 16-20, see analysis of claims 2 and 4-7.
Response to Arguments
Applicant's arguments filed July 1st, 2026 have been fully considered but they are not persuasive.
Regarding the 112 rejections, applicant notes that examiner’s rejection appears to be incomplete.
Examiner apologizes for the confusion. It appears, for reasons unknown to examiner, that a portion of the rejection failed to save or was otherwise removed before mailing. The missing portion simply further elaborated on the idea that the only way a group of mass peaks could reasonably be identified as lying in a time window is if the equivalent mass window was calculated as an intermediary step, since the “set of mass peaks” includes data about masses but not times, the mass peaks being intensity counts measured over time, not individually time stamped detector blimps. Therefore, examiner was assuming this was the method used, in which case a showing that the mass window is found is functionally equivalent.
Based on applicant’s response it appears examiner tentative interpretation that the pre-defined time window is able to identify a group of candidate peaks via calculation of the equivalent mass window is correct (see remarks, “The predetermined time window recited in the claim reflects a window or range of time that one can reasonably expect to elapse after injection until the molecule impacts on the sensor. That range of times depends on the mass-to-charge ratio.”) so examiner has moved the explanation of why a mass window and time window are equivalent to the main rejection and withdrawn the 112 rejections.
Regarding the 103 rejections, applicant argues that the peak window of the guide’s peak window is a threshold for determining whether a calibration succeeded, not a tool for identifying and presenting alternative candidates to the user, based on the quote that the acquired data must lie within the limits for the software to recognize the calibration matches and result in successful calibration.
The window is indeed a threshold but not for determining whether a calibration succeeded. It is the threshold in order for software to recognize a match. This is identical to applicant’s using the window to, as applicant say in their remarks, “automatically select{} as the initial match”. Regarding presenting alternative candidates to the user, examiner has admitted that the Guide does not use the peak window for this purpose, and cites the mass window as being functionally equivalent to a time window for identifying a group of candidate peaks and automatically selecting a peak from that group of peaks as the first peak (the initial matching step).
Applicant argues that the Guide’s peak window is a gating criterion applied after matching to see if the calibration passes, rather than a mechanism for identifying or matching peaks.
The guide very clearly uses the peak window for the peak matching. The mass window is defined as a “peak match parameter” and selected in a dialog box for parameters for “perform(ing) auto peak matching”. The guide also states that “Increasing the Peak window and the Initial error gives a greater chance of incorrect peak matching.” In order for a larger mass window to result in a greater chance of matching the wrong peak, the mass window must be used in the peak matching.
Applicant argues that examiner’s stated motivation does not support the combination because the guide does not present candidate peaks to the user at all.
Examiner strongly disagrees that the Guide does not present candidate peaks to the user at all and if applicant believes this examiner asks that applicant state why they believe the portions of the Guide examiner cites for this are not adequate. Applicant’s remarks do not address those parts of the rejection, only the peak matching parts, so examiner does not know why applicant feels the Guide does not disclose this.
Applicant argues that the calibration curve of the Guide is not used to produce a data scaling factor but hardware settings. Applicant cites portions of the Guide that discuss applying the calibration factor to future data and defining a model or function that maps the sample compounds to their expected drift times or m/z ratios.
Examiner does not see how the quoted passages show that the calibration curve is used to produce hardware settings. They simply show that the calibration curve is used with future data sets. A calibration curve, by its very nature, is a software setting and not a hardware setting. Regardless of whether the calibration curve could be used in some hardware setting application, a calibration curve is fundamentally a data scaling, and there is no question that the calibration curve scales the peaks as a function of the mass value since it is literally defined as the curve that maps (or scales) the reference and calibration peaks by mass.
Applicant argues that the calibration procedure of the Guide is fundamentally different as it describes calibration as adjusting the physical parameters of a quadrupole analyzer – specifically static and scanning settings, and states that the calibration curve is an intermediate computational step that drives the new instrument hardware settings.
Applicant presents no evidence that the calibration curve is an intermediate computational step that drives new instrument hardware settings. The guide does include a section on tuning that describes tuning the physical parameters of the hardware but this is not related to the calibration curve and is in an entirely different chapter (chapter 3) than the portions examiner relies upon (chapter 5). Regarding the static and scanning calibrations, these are software settings. The static calibration results in a calibration curve that is used to calibrate data acquired in static mode, and the scanning calibration results in a calibration curve that is used to calibrate data acquired in scanning mode. In either case the calibration outputs a calibration curve that is used to calibrate data, not change a hardware setting.
Applicant argues that the cyclic drift tube limitation is limiting because the cyclic drift tube creates a specific and substantial technical problem which applicant’s method solves.
This merely shows that the invention is useful, it does not show why a data analysis method is limited by the source of the data. Applicant must show that the peak mapping method would proceed differently in some way because the peaks were measured with a detector placed in a cyclic drift tube in order for the cyclic tube to be limiting on the method. Furthermore, examiner has provided a back-up line of reasoning for obviousness in the case that the cyclic drift tube is considered limiting.
Applicant argues that the cyclic drift tube limitation is limiting because the type of MS apparatus directly affects the structure and complexity of the data received, and therefore form the mapping algorithm required.
Applicant does not elaborate on how the type of MS apparatus directly affects the structure and complexity of the data received, and examiner does not see how the peak data would be structurally any different. The data would still consist of a list of m/z ratios and the intensity or number of counts at each one. The basic form and structure of the data would appear to be identical, so the steps which use those values would also proceed identically, and applicant has not provided any evidence or line of reasoning for why the data would be structurally different.
Conclusion
THIS ACTION IS MADE FINAL. 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 ELIZA W OSENBAUGH-STEWART whose telephone number is (571)270-5782. The examiner can normally be reached 10am - 6pm Pacific Time M-F.
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, 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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/ELIZA W OSENBAUGH-STEWART/Primary Examiner, Art Unit 2881
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