DETAILED ACTION
Response to Arguments
Applicant's arguments filed 29 June 2026 have been fully considered but they are not persuasive.
Rejections under 35 USC 102: Yamaguchi
The remark have been persuasive, by amendment Yamaguchi fails to disclose the claimed MR-TOF, therefore fails to anticipate claim 1. The rejection is herein withdrawn.
Rejections under 35 USC § 103: Wildgoose in view of Yamaguchi
The remarks take the position that Wildgoose teaches two modes of operation a first mode in which reflector 22 is activated and a second mode in which reflector 22 is inactivated. When activated, ions are reflected back again to perform another pass/cycle. When inactivated, ions are allowed to hit the detector. The examiner agrees. In the first mode 20 is in a deactivated state and ions are detected ([0088]). In the second mode when 20 is activated, the ions continue on their flight path of multiple reflections. Paragraph [0088] teaches this may be just one return cycle or multiple return cycles if longer ion flight paths are desired. That is, the number of passes is interpreted to be the number of times the ions travel along the z direction in figure 2 (i.e. each time from left to right and from right to left). Therefore, in the first mode when 20 is deactivated the ions perform k reflections and a single pass. In the second mode, 20 is activated and the ions are reflected back to the second end of the mass analyzer 8 rather than striking detector and from the second end reflected back towards the detector along the z direction ([0088]). That is, in the second mode the ions travel three or more passes. Since the number of passes is three or more times in the second mode the single pass in the first mode, the number of K reflections between mirrors when following the zig-zag ion path is three times more in the second mode than in the first mode.
There is no requirement that wherein altering the second path length in the second mode of operation comprises altering the number K of reflections for each N passes that ions made between the ion mirrors when following the zigzag ion path. Instead, the claim only requires altered K reflections in the second mode of operation. As discussed above, paragraph [0088] is clearly evident that the number of K reflections is more in the activated state of ion mirror.
Applicant is reminded that although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Here, there is no requirement that the reflections per pass are different in the second mode, therefore under the broadest reasonable interpretation of the claim as long as there are more or less reflections in the second mode than in the first mode the limitation is met.
Therefore, the amendment is insufficient to overcome the prior art.
The remarks point to paragraph 0091 and suggest Wildgoose teaches away from altering the number of reflections. This has not been found persuasive, paragraph [0091] appears to suggest that number of reflections in the z-dimension should be the same, however it does not suggest that the number of reflections in the second mode (i.e. activated state of reflector 20) should not be different from the first mode. Indeed, this is clearly the case as discussed in paragraph [0088].
Therefore, the remarks have been found unpersuasive and the rejection stands as reiterated herein below.
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.
Claims 1, 3-5, 7, 9, 14-23 and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Wildgoose (US pgPub 2024/0339314) in view of Yamaguchi as evidenced by ‘747.
Regarding claim 1, Wildgose teaches a method of operating an analytical instrument (inherent to the apparatus of figure 3) that comprises an ion analyser (inherent) configured to analyse ions by determining drift times of ions along an ion path ([0088]), the ion path comprising at least a first segment (14), and a cyclic segment (ion mirrors 10), wherein the ion path is configured such that ions make a single pass of the first segment (14 is an accelerator) and make one or more passes of the cyclic segment ([0088]); the method comprising:
operating the analyser in a first mode of operation, wherein in the first mode of operation ([0088] detecting at detector 16 when 22 is deactivated) (i) a first electric potential is provided along the first segment of the ion path (potential applied to accelerator 14 to pulse packets ([0087]), paragraph [0065] describes this as a first/second mode), (ii) a second electric potential is provided along the cyclic segment of the ion path (voltages applied to ion mirrors), (iii) the first segment of the ion path has a first path length (inherent to accelerator), and (iv) the cyclic segment of the ion path has a second path length (from first end of mirror to second end of mirror and returning to ion detector 16 [0087]-[0087]), and analysing ions by determining drift times of ions along the ion path so as to obtain a first set of ion data (inherent to TOF MS);
operating the analyser in a second mode of operation (activating reflector 20 so as to reflect ions back towards the second end of mass analzyer 8, see paragraph [0088]) by altering at least one of the second path length (activating reflector 20 to increase the flight path see paragraph [0088]), and analysing ions by determining drift times of ions along the ion path so as to obtain a second set of ion data (by deactivating deflector 20 to detect data)
wherein the ion analyser is a time-of-flight (ToF) mass analyser, and wherein the physicochemical property is mass to charge ratio (m/z) ([0086])
wherein the time-of-flight mass analyser is a multi-reflection time-of-flight (MR-ToF) mass analyser (fig. 3) comprising:
two ion mirrors (10) spaced apart and opposing each other in a first direction X (fig. 3, 10 spaced apart in the x direction), each mirror elongated generally along a drift direction Y between a first end and a second end (fig. 3, shows mirrors 10 elongated along a drift direction), the drift direction Y being orthogonal to the first direction X (x (between mirrors) is orthogonal to y direction along mirrors);
an ion injector (accelerator 14) for injecting ions into a space between the ion mirrors (as seen in figure 3), the ion injector located in proximity with the first end of the ion mirrors (located in proximity to the left end of mirrors best seen in figure 3); and
a detector (16) for detecting ions after they have completed N passes between the ion mirrors ([0088] either a single pass in first mode or multiple passes in second mode), wherein in each pass the ions follow a zigzag ion path having plural K reflections between the ion mirrors in the direction X (as seen in figure 3); and
wherein altering the second path length in the second mode of operation comprises altering the number K of reflections that ions make between the ion mirrors when following the zigzag ion path ([0088] which teaches either detecting ions when they return to 16 (first mode) by deactivating reflector 20 or continue back towards 22 for additional flight distance by oscillations between mirrors 10, thus altering the number of reflections between ion mirrors over the three or more passes as compared to the single pass of the first mode. See further discussion in response to arguments section above).
Wildgoose fails to disclose comparing the first set of ion data to the second set of ion data, and identifying a first ion peak in the first set of ion data that corresponds to a second ion peak in the second set of ion data; determining the number N of passes of the cyclic segment of the ion path taken by ions associated with the corresponding first and second ion peaks; and using the determined number of passes N to determine a value of a m/z of the ions associated with the corresponding first and second ion peaks.
However, Yamaguchi teaches comparing the first set of ion data to the second set of ion data ([0055] of Yamaguchi comparing the two flight time spectra obtained through the first round of measurement and second round of measurement ), and identifying a first ion peak in the first set of ion data that corresponds to a second ion peak in the second set of ion data ([0057]);
determining the number N of passes of the cyclic segment of the ion path taken by ions associated with the corresponding first and second ion peaks ([0059]); and
using the determined number of passes N to determine a value of a m/z of the ions associated with the corresponding first and second ion peaks ([0059] with the number of turns, data processor recalculates the exact m/z of each ion on the basis of the flight time calculated using the number of turns, wherein the number of turns is determined by the corresponds of the beams of two flight time spectrums.).
Yamaguchi modifies Wildgoose by suggesting the use of the data from two different modes of operation with different flight paths (abstract, [0065]) to improve identify all peaks even in situations of samples containing may components.
Since both inventions are directed towards TOF-MS and operating in two modes (note Wildgoose describes the operation of paragraph [0088] as a first and second mode see paragraph [0065]), it would have been obvious to one of ordinary skill in the art to use the data analysis suggested in Yamaguchi in the method of Wildgoose because it would improve identification of all peaks in situations of samples containing many components (abstract). Note, Yamaguchi suggested the method is applicable to any changes in flight distance ([0065]), thus suitable for the device of Wildgoose.
Regarding claim 3, Wildgoose teaches the detector located in proximity with the first end of the ion mirrors (16 is in proximity with the same left side of mirrors 10).
Regarding claim 4, Wildgoose teaches wherein the analyser is configured to analyse ions by: (i) injecting ions from the ion injector into the space between the ion mirrors (via accelerator 14), wherein the ions complete a first cycle in which the ions follow a zigzag ion path (from 14 to 22, see paragraph [0087]) between the ion mirrors in the direction X whilst (reflection between mirror 10 thus x direction):
(a) drifting along the drift direction Y towards the second end of the ion mirrors (drifting from 20 to 22 as seen in figure 3),
(b) reversing drift direction velocity in proximity with the second end of the ion mirrors (reversing by reversing deflector 22 back to first end see paragraph [0087], since the direction is reversed, the direction velocity is reversed),
and (c) drifting back along the drift direction Y towards the first end of the ion mirrors ([0087])
(ii) reversing the drift direction velocity of the ions in proximity with the first end of the ion mirrors (fig. 3, 20 via activating reflector 20 ions are reflected back towards the second end of mass analyzer 8 ([0088]), which comprises to ion mirrors 10) such that the ions are caused to complete a further cycle in which the ions follow a zigzag ion path having plural K reflections between the ion mirrors in the direction X (fig. 3 shows zigzag ion path, [0088], x direction interpreted to be between ion mirrors 10) whilst: (a) drifting along the drift direction Y towards the second end of the ion mirrors (y direction is from 20 to 22 see paragraph [0088] for reflection between mirrors in the above described mirror, paragraph [0087] teaches reflecting between mirrors as they drift in the z direction (i.e. equivalent to the claimed y direction)), (b) reversing drift direction velocity in proximity with the second end of the ion mirrors ([0088] repeating the manner disclosed in paragraph [0087], which requires in part ions are reflected at the second end of the mass analyzer by the second reflector back towards the first end. That is, requiring reversing the drift direction velocity because velocity is a vector, thus any reversal of direction is a reversal of velocity), and (c) drifting back along the drift direction Y towards the first end of the ion mirrors (reversal drift the same manner as in the first direction, see paragraph [0087]-[0088]);(iii) repeating step (ii) one or more times ([0088] suggests either deactivate detector to allow detection or maintain in active state for additional cycle); and then (iv) causing the ions to travel to the detector for detection ([0088]).
Claim 5 further requires the use of a deflector in proximity with the first end of the ion mirrors to perform the claimed reversal to complete additional cycles. Wildgoose suggests using a deflector (reflector 20) in proximity with the first end (left side of mirrors 10 in figure 3) for additional cycles as discussed above in claim 4.
Regarding claim 7, Wildgoose teaches wherein the number K of reflections that ions make between the ion mirrors when following the zigzag ion path is altered by altering a voltage applied to the deflector ([0088], activating or deactivating reflector. Paragraph [0089] teach voltages are applied to reflectors 20/22).
Regarding claim 9, Wildgoose teaches wherein the deflector is a first deflector (20) and the analyzer comprising a second deflector (22) located in proximity with the second end of the mirrors (as seen in figure 2), wherein the second deflector is configured to cause the ions to reverse their drift direction velocity in proximity with the second end of the ion mirrors and drift back along the drift direction towards the deflector ([0088]).
Regarding claim 14, Wildgoose in view of Yamaguchi teaches wherein determining the number N of passes of the cyclic segment of the ion path taken by ions associated with the corresponding first and second ion peaks comprises: measuring a drift time difference between first and second ion peaks (Yamaguchi, [0059] flight time difference); and using the measured drift time difference to estimate the number N of passes of the cyclic segment of the ion path taken by ions associated with the corresponding first and second ion peaks (the flight time difference is used to approximate m/z to determine number of turns. Since the m/z value is approximate, the number of turns is an estimate).
Regarding claim 15, Wildgoose fails to disclose how the MR-TOF is controlled,
However, Yamaguchi teaches a non-transitory computer readable storage medium storing computer software code which when executed on a processor performs the method of claim 1 (figure 2, data processor 7, see paragraph [0057]- [0059]).
Yamaguchi modifies Wildgoose by suggesting a data processor to control the MS system.
Since both inventions are directed towards complicated analysis systems, it would have been obvious to one of ordinary skill in the art to automate with a programed computer as it would simplify the operation of mass spectrometry.
Regarding claim 16, Wildgoose in view of Yamaguchi teaches a control system for an analytical instrument, the control system configured to cause the analytical instrument to perform the method of claim 1 (Wildgoose teaches control circuitry to control the activation of reflector 20/22 as modified by Yamaguchi control system claim 15 above).
Claim 17 is a combination of claims 1 and 16 and is obvious as discussed herein above.
Claim 19 is a combination of claims 3 and 4 and is taught as in the citations herein above.
Regarding claim 20, Wildgoose teaches a deflector located in proximity with the first end of the ion mirrors and wherein reversing the drift direction velocity of the ions includes using the deflector to reverse the drift velocity of the ion ([0088]-[0099]).
Regarding claim 21, Wildgoose wherein the number K of reflections that ions make between the ion mirrors when following the zigzag ion path is altered by altering a voltage applied to the deflector ([0088]).
Regarding claim 23, Wildgoose teaches wherein the deflector is a first deflector (20) and the analyzer comprising a second deflector (22) located in proximity with the second end of the mirrors (as seen in figure 2), wherein the second deflector is configured to cause the ions to reverse their drift direction velocity in proximity with the second end of the ion mirrors and drift back along the drift direction towards the deflector ([0088]).
Regarding claim 24, Wildgoose in view of Yamaguchi teaches wherein determining the number N of passes of the cyclic segment of the ion path taken by ions associated with the corresponding first and second ion peaks comprises: measuring a drift time difference between first and second ion peaks (Yamaguchi, [0059] flight time difference); and using the measured drift time difference to estimate the number N of passes of the cyclic segment of the ion path taken by ions associated with the corresponding first and second ion peaks (the flight time difference is used to approximate m/z to determine number of turns. Since the m/z value is approximate, the number of turns is an estimate).
Claims 1, 16-17, 25 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Brown (US pgPub 2021/0193451) in view of Yamaguchi(US pgPub 2006/0219890) as evidenced by ‘747 (JP2006012747 submitted with the office action of 19 March 2026).
Regarding claim 1, Brown teaches a method of operating an analytical instrument (inherent to the apparatus of figures 1-2b) that comprises an ion analyser (figs. 2a and 2b) configured to analyse ions by determining drift times of ions along an ion path (MR-TOF measures drift times), the ion path comprising at least a first segment (accelerator 6), and a cyclic segment (ion mirrors 2), wherein the ion path is configured such that ions make a single pass of the first segment (14 is an accelerator) and make one or more passes of the cyclic segment (a single pass in figure 2a or in figure 2b); the method comprising:
operating the analyser in a first mode of operation, wherein in the first mode of operation ([0090] first mode) (i) a first electric potential is provided along the first segment of the ion path ([0095] ions pass through the accelerator 6 in the first mode, paragraph [0034] taches a voltage applied to the accelerator), (ii) a second electric potential is provided along the cyclic segment of the ion path (voltages applied to ion mirrors), (iii) the first segment of the ion path has a first path length (inherent to accelerator), and (iv) the cyclic segment of the ion path has a second path length ([0090]), and analysing ions by determining drift times of ions along the ion path so as to obtain a first set of ion data (inherent to TOF MS);
operating the analyser in a second mode of operation ([0098]) by altering at least one of the second path length (as seen in figure 2b lower number of reflections as compared to the path in figure 2a), and analysing ions by determining drift times of ions along the ion path so as to obtain a second set of ion data (detecting at detector 8)
wherein the ion analyser is a time-of-flight (ToF) mass analyser, and wherein the physicochemical property is mass to charge ratio (m/z) ([0093] teaches MRTOF and paragraph [0094] teaches separate according to the mass to charge)
wherein the time-of-flight mass analyser is a multi-reflection time-of-flight (MR-ToF) mass analyser (figs. 1-2b) comprising:
two ion mirrors (2) spaced apart and opposing each other in a first direction X (fig. 2, 2 spaced apart in the x direction), each mirror elongated generally along a drift direction Y between a first end and a second end (fig. 2, shows mirrors 2 elongated along a drift direction), the drift direction Y being orthogonal to the first direction X (x (between mirrors) is orthogonal to y direction along mirrors);
an ion injector (accelerator 6) for injecting ions into a space between the ion mirrors (as seen in figures 1-2b), the ion injector located in proximity with the first end of the ion mirrors (located in proximity to the left end of mirrors best seen in figure 2a-2b); and
a detector (8) for detecting ions after they have completed N passes between the between the ion mirrors (as seen in figures 2a-2b, in each figure a single pass), wherein in each pass the ions follow a zig-zag ion path having plural k reflections between the ion mirrors in the x direction (as seen in figure 2a-2b),
altering the second path length in the second mode of operation by altering the number K of reflections that ions make between the ion mirrors when following the zigzag ion path (as seen comparing figures 2a-2b, see also paragraph [0090] and paragraph [0114]).
Brown fails to disclose comparing the first set of ion data to the second set of ion data, and identifying a first ion peak in the first set of ion data that corresponds to a second ion peak in the second set of ion data; determining the number N of passes of the cyclic segment of the ion path taken by ions associated with the corresponding first and second ion peaks; and using the determined number of passes N to determine a value of a m/z of the ions associated with the corresponding first and second ion peaks.
However, Yamaguchi teaches comparing the first set of ion data to the second set of ion data ([0055] of Yamaguchi comparing the two flight time spectra obtained through the first round of measurement and second round of measurement ), and identifying a first ion peak in the first set of ion data that corresponds to a second ion peak in the second set of ion data ([0057]);
determining the number N of passes of the cyclic segment of the ion path taken by ions associated with the corresponding first and second ion peaks ([0059]); and
using the determined number of passes N to determine a value of a m/z of the ions associated with the corresponding first and second ion peaks ([0059] with the number of turns, data processor recalculates the exact m/z of each ion on the basis of the flight time calculated using the number of turns, wherein the number of turns is determined by the corresponds of the beams of two flight time spectrums.).
Yamaguchi modifies Brown by suggesting the use of the data from two different modes of operation with different flight paths (abstract, [0065]) to improve identify all peaks even in situations of samples containing may components.
Since both inventions are directed towards TOF-MS and operating in two modes (note Brown describes the operation of paragraph [0090] as a first and second mode), it would have been obvious to one of ordinary skill in the art to use the data analysis suggested in Yamaguchi in the method of Brown because it would improve identification of all peaks in situations of samples containing many components (abstract). Note, Yamaguchi suggested the method is applicable to any changes in flight distance ([0065]), thus suitable for the device of Brown.
Regarding claim 16, Brown in view of Yamaguchi teaches a control system for an analytical instrument, the control system configured to cause the analytical instrument to perform the method of claim 1 (Brown teaches control of the reflections as modified by Yamaguchi control system claim 15 above).
Claim 17 is a combination of claims 1 and 16 and is obvious as discussed herein above.
Regarding claims 24 and 25, Brown teaches wherein altering the number K of reflections that ions make between the ion mirrors when following the zigzag ion path comprises altering the number K of reflections by 1 ([0027]-[0028] teaches the first number of times that ions are reflected may be 5 and the second number of times ions are reflected may be 4, thus envisioning altering the number of reflections by 1. See also paragraph [0113] for progressively decreasing number of ion mirror reflections over several modes of operation).
Claims 8 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Wildgoose (US pgPub 2024/0339314) in view of Yamaguchi and further in view of Grinfled (USPN 9,136,101).
Regarding claim 8, Wildgoose in view of Yamaguchi fails to disclose wherein the ion mirrors are a non-constant distance from each other in the X direction along at least a portion of their lengths in the drift direction Y, wherein the drift direction velocity of ions towards the second end of the ion mirrors is opposed by an electric field resulting from the non-constant distance of the two mirrors from each other, and wherein the electric field causes the ions to reverse their drift direction velocity in proximity with the second end of the ion mirrors and drift back along the drift direction towards the deflector.
However, Grinfeld teaches wherein the ion mirrors (fig. 3, 31/32) are a non-constant distance from each other in the X direction along at least a portion of their lengths in the drift direction Y (see separation distances between 31/32 in x direction along the y direction), wherein the drift direction velocity of ions towards the second end of the ion mirrors is opposed by an electric field resulting from the non-constant distance of the two mirrors from each other (col. 23, lines 42-47 teaches field causes ion to reverse their direction and travel back toward injector thus field opposes drift direction velocity), and wherein the electric field causes the ions to reverse their drift direction velocity in proximity with the second end of the ion mirrors and drift back along the drift direction towards the deflector (col. 23, lines 42-47 and figure 3 shows ions reversing near the second end of the ion mirrors). Note: alternatively see non-constant distances between ion mirrors in figures 7a-7b and 9
Grinfeld modifies the combined device by suggesting a non-constant separation distance between ion mirrors.
Since both inventions are directed towards MR-TOF, it would have been obvious to one of ordinary skill in the art to adopt the non-constant separation distance between mirrors suggested in Grinfeld in the combined device because it would facilitate both an extended flight path and spatial focusing without additional components (col. 24, lines 17-20), therefore simplifying the device of Grinfeld by removing the need for additional periodic lenses 12 to achieve spatial focusing, thus simplifying the device.
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 MICHAEL J LOGIE whose telephone number is (571)270-1616. The examiner can normally be reached M-F: 7:00AM-3:00PM.
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/MICHAEL J LOGIE/Primary Examiner, Art Unit 2881
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