DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Arguments
Applicant’s arguments filed on 2/20/26 have been considered but are moot because the arguments do not apply to any of the references being used in the current rejection. The amendment necessitates the new ground(s) of rejection presented due to the added language in the independent claim(s).
Status of the Application
Claim(s) 1-25 is/are pending.
Claim(s) 6-9, 13-15, 16-17, 19-20, 24-25 is/are withdrawn.
Claim(s) 1-5, 10-12, 16-25 is/are rejected.
Election by Original Presentation
Newly amended claims 16 and 19 (and 17, 20, 24-25) are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons:
Original Group I covers separation of analyte ions and reporter/complementary ions, where the reporter/complementary ion TOF path length is longer than that for the analyte ions. However, the analyte ions need not have higher m/z than the reporter/complimentary ions. It is classified in e.g. H01J 49/0031,427,282,406,45, C07B2200/05, G01N2458/00,15.
New Group II* covers separation of two m/z ranges of ions, where the first group of ions has a wider m/z range than a narrow second group, and the second group has a longer TOF path length than the first group. However, the groups cover ranges constructed for any reason, including tagged or untagged ions, unrelated ranges of ions, ions having the same m/z but in different constructively defined ranges/sub-ranges of ions, etc. It is classified in e.g. H01J 49/0031, G01N30/8682, etc.
Inventions I and II are related as combination and subcombination. Inventions in this relationship are distinct if it can be shown that (1) the combination as claimed does not require the particulars of the subcombination as claimed for patentability, and (2) that the subcombination has utility by itself or in other combinations (MPEP § 806.05(c)). In the instant case, the combination as claimed does not require the particulars of the subcombination as claimed because the reporter/complementary ions do not need to be the narrower range of ions. The subcombination has separate utility such as for untagged mass spectrometry (e.g. of different inorganics, direct measurement without pre-processing, etc).
The examiner has required restriction between combination and subcombination inventions. Where applicant elects a subcombination, and claims thereto are subsequently found allowable, any claim(s) depending from or otherwise requiring all the limitations of the allowable subcombination will be examined for patentability in accordance with 37 CFR 1.104. See MPEP § 821.04(a). Applicant is advised that if any claim presented in a continuation or divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 16-17, 19-20, 24-25 is/are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
In view of the 112(b) issues and broadest reasonable interpretation of the claims, these claims have been interpreted broadly in a manner that continues to read on the references of the prior rejection. Accordingly, to expedite prosecution, a 103 rejection is set forth in view of this interpretation, but it is noted that in the future, clarification along the lines of the Group II* construction will be interpreted as falling under amendments to a non-elected group of claims.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Claim Rejections – 35 U.S.C. § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
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The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
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Claim(s) 16-17, 19-20, 24-25 is/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 pre-AIA the applicant regards as the invention.
Claims 16 and 19 recite “the first ions are ions having m/z within a first relatively broad range, and the second ions are ions having m/z within a second different relatively narrow range” but it is unclear to what degree a range is relatively broad or narrow a range. The limitation is read to mean they are broader and narrow relative to each other.
Claims 17, 20, 24-25 are rejected due to their dependency from claims 16 or 19.
Claim Rejections – 35 U.S.C. § 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:
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Claim(s) 1-3, 18 is/are rejected under 35 U.S.C. § 103 as being unpatentable over Grinfield et al. (US 20160005580 A1) [hereinafter Grinfield] in view of Thompson (US 20180362416 A1).
Regarding claim 1, Grinfield teaches a method of analysing analyte molecules labelled with chemical or isobaric tags, wherein each tag comprises a reporter region and a balancer region, the method comprising:
ionising
fragmenting (see e.g. fig. 13, [0134]) the
analysing the analyte fragment ions (all the ions) using a time-of-flight mass analyser (see e.g. figs 13, [0002]) operating in a first mode of operation (e.g. reading out from induced signal current from detector, [0137-38]), wherein in the first mode of operation ions are caused to travel along a flight path having a first length (length of path so far as the ions pass by the induced current detector) (note generally selecting number of oscillations, [0118-19, 124]); and
analysing
Grinfield may fail to explicitly disclose the ions being labelled analyte ions; and fragmenting to additionally produce reporter ions or complementary ions, wherein a reporter ion is an ion of a reporter region and wherein a complementary ion is an ion of a combined balancer region and analyte molecule.
However, the use of tagged ions, and analyzing fragmented tagged ions was well known in the art at the time the application was effectively filed. For example, Thompson a wide range of isobaric mass tags to enable the ability to improve quantitative analysis of biomolecules by mass spectrometry (see Thompson, [0002-03]), including providing higher multiplexing rates (see [0011-12]), wherein labelled analyte ions are used for and fragmenting to produce analyte fragment ions and reporter ions (see e.g. abstract, [0088]) or analyte fragment ions and complementary ions, wherein a reporter ion is an ion of a reporter region (see abstract, claim 1) and wherein a complementary ion is an ion of a combined balancer region and analyte molecule. It would have been obvious to a person having ordinary skill in the art at the time the application was effectively filed to combine the teachings of Thompson in the system of the prior art, because a skilled artisan would have been motivated to improve quantitative analysis of biomolecules, and provide flexible selection of tags to enable higher multiplexing rates, in the manner taught by Thompson.
Regarding claim 2, the combined teaching of Grinfield and Thompson teaches the time-of-flight mass analyser comprises one or more ion reflectors (see e.g. Grinfield, fig 13: 71, 72); in the first mode of operation ions are caused to make n reflection(s) in the one or more ion reflectors (induced current read out on every pass, reflection, see [0137]), wherein n is an integer > 0; and in the second mode of operation ions are caused to make m reflection(s) in the one or more ion reflectors, wherein m is an integer > n (additional reflections before impinging on detector, see [0138]).
Regarding claim 3, the combined teaching of Grinfield and Thompson teaches the time-of-flight mass analyser is a multi-reflection time-of-flight (MR-ToF) mass analyser (see Grinfield, abstract) comprising: two ion mirrors (see e.g. fig 13: 71-1, 72-1) spaced apart and opposing each other in a first direction X (see X), each mirror elongated generally along a drift direction Y (see Y) between a first end and a second end (see fig 13), the drift direction Y being orthogonal to the first direction X (see fig 13); an ion injector (see e.g. 111, 114, 124, etc) for injecting ions into a space between the ion mirrors (see fig 13), the ion injector located in proximity with the first end of the ion mirrors (see fig 13); and a detector (see e.g. 117) for detecting ions after they have completed a plurality of reflections between the ion mirrors (see [0138]; note selection of e.g. low or high resolution mode, [0143]), the detector located in proximity with the first end of the ion mirrors (see fig 13); wherein analysing analyte fragment ions using the analyser operating in the first mode of operation comprises: injecting analyte fragment ions from the ion injector into the space between the ion mirrors (see fig 13), wherein the ions follow a zigzag ion path having plural reflections between the ion mirrors in the direction X (see fig 13) whilst: (a) drifting along the drift direction Y towards the second end of the ion mirrors (see fig 13), (b) reversing drift direction velocity in proximity with the second end of the ion mirrors (see fig 13), and (c) drifting back along the drift direction Y to the first end of the ion mirrors (see fig 13); and then causing the ions to travel to the detector for detection (see 117, [0138]).
Regarding claim 18, Grinfield teaches an analytical instrument, comprising:
an ion source (required for operation of system, see e.g. [0143]);
a fragmentation device (see e.g. fig 17: 171);
a time-of-flight (ToF) mass analyser (see fig 17, abstract) operable in a first mode of operation (e.g. reading out from induced signal current from detector, [0137-38]) in which ions are caused to travel along a flight path having a first length (length of path so far as the ions pass by the induced current detector) (note generally selecting number of oscillations, [0118-19, 124]), and a second different mode of operation (direct detector impingement, see [0138]) (note generally also e.g. high resolution mode, low resolution mode, self-diagnostic mode, [0143]) in which ions are caused to travel along a flight path having a second length (see [0137-38], full path of the ions before impinging on detector; see generally [0143]), wherein the second length is greater than the first length (greater than flight path before impinging on detector); and
a control system (required for intended operation of system) configured, when the instrument is being used to analyse molecules
cause the fragmentation device to fragment the
cause the time-of-flight mass analyser to analyse the analyte fragment ions using the first mode of operation (see [0137-38]); and
cause the time-of-flight mass analyser to analyse the reporter ions or the complementary ions using the second mode of operation (see [0137-38]).
Grinfield may fail to explicitly disclose the ions being labelled analyte ions, labelled with chemical or isobaric tags, wherein each tag comprises a reporter region and a balancer region; and fragmenting to additionally produce reporter ions or complementary ions, wherein a reporter ion is an ion of a reporter region and wherein a complementary ion is an ion of a combined balancer region and analyte molecule.
However, the use of tagged ions, and analyzing fragmented tagged ions was well known in the art at the time the application was effectively filed. For example, Thompson a wide range of isobaric mass tags to enable the ability to improve quantitative analysis of biomolecules by mass spectrometry (see Thompson, [0002-03]), including providing higher multiplexing rates (see [0011-12]), wherein labelled analyte ions are used for and fragmenting to produce analyte fragment ions and reporter ions (see e.g. abstract, [0088]) or analyte fragment ions and complementary ions, wherein a reporter ion is an ion of a reporter region (see abstract, claim 1) and wherein a complementary ion is an ion of a combined balancer region and analyte molecule. It would have been obvious to a person having ordinary skill in the art at the time the application was effectively filed to combine the teachings of Thompson in the system of the prior art, because a skilled artisan would have been motivated to improve quantitative analysis of biomolecules, and provide flexible selection of tags to enable higher multiplexing rates, in the manner taught by Thompson.
Claim(s) 4-5, 10-12, 21-23 is/are rejected under 35 U.S.C. § 103 as being unpatentable over Grinfield and Thompson, as applied to claim 1 above, and further in view of (and/or as evidenced by) Makarov (US 7829842 B2) (incorporated by reference in Grinfield, [0144]).
Regarding claim 4, the combined teaching of Grinfield and Thompson teaches analysing reporter ions or complementary ions using the analyser operating in the second mode of operation comprises: (i) injecting reporter ions or complementary ion from the ion injector into the space between the ion mirrors (see Grinfield, fig 13), wherein the ions complete a first cycle in which the ions follow a zigzag ion path having plural reflections between the ion mirrors in the direction X (see fig 13) whilst: (a) drifting along the drift direction Y towards the second end of the ion mirrors (see fig 13), (b) reversing drift direction velocity in proximity with the second end of the ion mirrors (see fig 13), and (c) drifting back along the drift direction Y towards the first end of the ion mirrors (see fig 13); (ii) reversing the drift direction velocity of the ions in proximity with the first end of the ion mirrors such that the ions are caused to complete a further cycle in which the ions follow a zigzag ion path having plural reflections between the ion mirrors in the direction X (see fig 13; see repeated oscillation between 130-1, 130-2, [0136]) whilst: (a) drifting along the drift direction Y towards the second end of the ion mirrors (see fig 13), (b) reversing drift direction velocity in proximity with the second end of the ion mirrors (see fig 13), and (c) drifting back along the drift direction Y towards the first end of the ion mirrors (see fig 13); and then (iii) causing the ions to travel to the detector for detection (see 117, [0138]).
The combined teaching of Grinfield and Thompson may fail to explicitly disclose subsequently reversing the drift direction velocity of the ions in proximity with the first end of the ion mirrors. However, in a different embodiment, Grinfield teaches using deflection to operate the system for MSn analysis of ions through repeated selection and fragmentation of ions (see Grinfield, [0144]), which provides subsequently reversing the drift direction velocity of the ions in proximity with the first end of the ion mirrors (see generally, fig 17, around 124). Furthermore, Makarov (which Grinfield incorporates by reference to explain MSn operation, [0144]) teaches operating the fragmentation cell in a passthrough mode to provide the optional ability to better accumulate ions, store lower abundance ions, reduce energy spread, and/or improve control over subsequent fragmentations (see Makarov, col 4, lines 31-59). It would have been obvious to a person having ordinary skill in the art at the time the application was effectively filed to combine the use of passthrough repetition system of Grinfield and Makarov in the system of the prior art, because a skilled artisan would have been motivated to look for ways to improve control over the system, including improving accumulation, storage, energy spread, and/or preparation for subsequent fragmentation, in the manner taught by Grinfield and Makarov.
Regarding claim 5, the combined teaching of Grinfield and Thompson teaches a deflector (see Grinfield, e.g. fig 13: 124, etc) or lens located in proximity with the first end of the ion mirrors (see fig 13); and analysing reporter ions or complementary ions using the analyser operating in the second mode of operation comprises: (i) injecting reporter ions or complementary ions from the ion injector into the space between the ion mirrors (see fig 13), wherein the ions complete a first cycle in which the ions follow a zigzag ion path having plural reflections between the ion mirrors in the direction X (see fig 13) whilst: (a) drifting along the drift direction Y from the deflector or lens towards the second end of the ion mirrors (see fig 13), (b) reversing drift direction velocity in proximity with the second end of the ion mirrors (see fig 13), and (c) drifting back along the drift direction Y to the deflector or lens (see fig 13); (ii)
The combined teaching of Grinfield and Thompson may fail to explicitly disclose using the deflector or lens to reverse the drift direction velocity. However, in a different embodiment, Grinfield teaches using deflection to operate the system for MSn analysis of ions through repeated selection and fragmentation of ions (see Grinfield, [0144]), which provides subsequently reversing the drift direction velocity of the ions in proximity with the first end of the ion mirrors (see generally, fig 17, around 124), wherein the deflector or lens reverses the drift direction velocity (see fig 17). Furthermore, Makarov (which Grinfield incorporates by reference to explain MSn operation, [0144]) teaches operating the fragmentation cell in a passthrough mode to provide the optional ability to better accumulate ions, store lower abundance ions, reduce energy spread, and/or improve control over subsequent fragmentations (see Makarov, col 4, lines 31-59). It would have been obvious to a person having ordinary skill in the art at the time the application was effectively filed to combine the use of passthrough repetition system of Grinfield and Makarov in the system of the prior art, because a skilled artisan would have been motivated to look for ways to improve control over the system, including improving accumulation, storage, energy spread, and/or preparation for subsequent fragmentation, in the manner taught by Grinfield and Makarov.
Regarding claim 10, the combined teaching of Grinfield and Thompson may fail to explicitly disclose the steps of analysing the analyte fragment ions and analysing the reporter ions or the complementary ions comprises analysing one or more single packets of ions. It is unclear whether the ions and injected continuously or in packets. However, the use of ion packets was notoriously well known in the art. Further, Makarov (incorporated by reference in Grinfield, [0144]), explicitly teaches using ion packets (see Makarov, e.g. col 8, lines 55-57). It would have been obvious to a person having ordinary skill in the art at the time the application was effectively filed to use the system with ion packets to enable the intended operation of the system.
Regarding claim 11, the combined teaching of Grinfield, Thompson, and Makarov teaches an ion path comprising a cyclic segment (see Grinfield, fig 13); an ion injector (see e.g. 111, 114, 124, etc) for injecting ions into the ion path; at least one ion reflector (see 71, 72) arranged along the ion path; and a detector (see e.g. 117) arranged at the end of the ion path (see fig 13); wherein the method comprises: (i) injecting a packet of ions comprising analyte fragment ions and reporter ions or complementary ions from the ion injector into the ion path (see fig 13) such that the analyte fragment ions and the reporter ions or the complementary ions travel along the ion path to the ion reflector (see fig 13); (ii) causing the analyte fragment ions to travel from the ion reflector to the detector for detection (see fig 13); (iii) using the ion reflector to cause the reporter ions or the complementary ions to complete one or more cycles along the cyclic segment of the ion path (see fig 13); and then (iv) causing the reporter ions or the complementary ions to travel from the ion reflector to the detector for detection (see fig 13).
Regarding claim 12, the combined teaching of Grinfield, Thompson, and Makarov teaches the time-of-flight mass analyser is a multi- reflection time-of-flight (MR-ToF) mass analyser (see Grinfield, abstract) comprising: two ion mirrors (see e.g. fig 13: 71-1, 72-1) spaced apart and opposing each other in a first direction X (see fig 13), each mirror elongated generally along a drift direction Y between a first end and a second end (see fig 13), the drift direction Y being orthogonal to the first direction X (see fig 13); an ion injector (see e.g. 111, 114, 124, etc) for injecting ions into a space between the ion mirrors, the ion injector located in proximity with the first end of the ion mirrors (see fig 13); a deflector or lens (see e.g. 161, 124, etc) located in proximity with the first end of the ion mirrors (see fig 13); and a detector (see e.g. 117) for detecting ions after they have completed a plurality of reflections between the ion mirrors (see fig 13), the detector located in proximity with the first end of the ion mirrors (see fig 13); and wherein the method further comprises: (i) injecting a packet of ions comprising analyte fragment ions and reporter ions or complementary ions from the ion injector into the space between the ion mirrors (see fig 13), wherein the ions complete a first cycle in which the ions follow a zigzag ion path having plural reflections between the ion mirrors in the direction X (see fig 13) whilst: (a) drifting along the drift direction Y from the deflector or lens towards the second end of the ion mirrors (see fig 13), (b) reversing drift direction velocity in proximity with the second end of the ion mirrors (see fig 13), and (c) drifting back along the drift direction Y to the deflector or lens (see fig 13); (ii) causing the analyte fragment ions to travel from the deflector or lens to the detector for detection (see fig 13); (iii) using the deflector or lens to reverse the drift direction velocity of the reporter ions or the complementary ions such that these ions are caused to complete a further cycle in which these ions follow a zigzag ion path having plural reflections between the ion mirrors in the direction X (see fig 13) whilst: (a) drifting along the drift direction Y from the deflector or lens towards the second end of the ion mirrors (see fig 13), (b) reversing drift direction velocity in proximity with the second end of the ion mirrors (see fig 13), and (c) drifting back along the drift direction Y to the deflector or lens (see fig 13); and then (iv) causing the reporter ions or the complementary ions to travel from the deflector or lens to the detector for detection (see fig 13).
Regarding claim 21, the combined teaching of Grinfield, Thompson, and Makarov teaches repeating step (ii) one or more times before causing the second ions to travel from the deflector or lens to the detector for detection (see Grinfield, [0144]; see also indefinite trapping, [0136]).
Regarding claim 22, the combined teaching of Grinfield, Thompson, and Makarov teaches repeating step (ii) one or more times before causing the ions to travel from the deflector or lens to the detector for detection (see Grinfield, [0144]; see also indefinite trapping, [0136]).
Regarding claim 23, the combined teaching of Grinfield, Thompson, and Makarov teaches repeating step (iii) one or more times before causing the reporter ions or the complimentary ions to travel from the deflector or lens to the detector for detection (see Grinfield, [0144]; see also indefinite trapping, [0136]).
Claim(s) 16-17, 19-20, 24-25 is/are rejected under 35 U.S.C. § 103 as being unpatentable over Grinfield et al. (US 20160005580 A1) [hereinafter Grinfield] in view of (and/or as evidenced by) Makarov (US 7829842 B2) (incorporated by reference in Grinfield, [0144]).
Regarding claim 16, Grinfield teaches a method of operating a time-of-flight (ToF) mass analyser that comprises:
an ion path comprising a cyclic segment (see e.g. fig 13);
an ion injector (= see e.g. 111, 114, 124, etc) for injecting ions into the ion path (see figs 13);
at least one ion reflector (see 71,72) arranged along the ion path; and
a detector (see 117) arranged at the end of the ion path (see figs 13);
the method comprising:
(i) injecting a
(ii) causing the first ions to travel from the ion reflector to the detector for detection (see fig 13);
(iii) using the ion reflector to cause the second ions to complete one or more cycles along the cyclic segment of the ion path (see fig 13); and then
(iv) causing the second ions to travel from the ion reflector to the detector for detection (see fig 13);
wherein before arriving at the ion reflector, the first and second ions follow the same ion path (all ions, see fig 13); and then, the first ions (all ions) are caused to travel from the ion reflector to the detector for detection, while the ion reflector is used to cause only the second ions to complete one or more cycles along the cyclic segment of the ion path before they are caused to travel from the ion reflector to the detector for detection.
It is unclear whether the ions and injected continuously or in packets. However, the use of ion packets was notoriously well known in the art. Further, Makarov (incorporated by reference in Grinfield, [0144]), explicitly teaches using ion packets (see Makarov, e.g. col 8, lines 55-57). It would have been obvious to a person having ordinary skill in the art at the time the application was effectively filed to use the system with ion packets to enable the intended operation of the system.
The combined teaching of Grinfield and Makarov may fail to explicitly disclose the first ions are caused to travel from the ion reflector to the detector for detection, while the ion reflector is used to cause only the second ions to complete one or more cycles along the cyclic segment of the ion path before they are caused to travel from the ion reflector to the detector for detection.
However, in different embodiments, Grinfield teaches that multiple mesh detectors may be used to monitor beam ion quantity during the experiment and detect spatial location of the beams (see Grinfield, [0035]). It would have been obvious to a person having ordinary skill in the art at the time the application was effectively filed to combine the embodiments of Grinfield to use additional mesh detectors to enable the ability to learn more about the beam location and current. Therefore, the combined teaching of Grinfield and Makarov teaches the first ions are caused to travel from the ion reflector to the detector for detection (defining as mesh detector formed at specified location at end of beam path, [0035]), while the ion reflector is used to cause only the second ions to complete one or more cycles along the cyclic segment of the ion path before they are caused to travel from the ion reflector to the detector for detection (after repeatedly traversing the TOF, see [0136], detected again).
Regarding claim 17, the combined teaching of Grinfield and Makarov teaches the time-of-flight (ToF) mass analyser is a multi- reflection time-of-flight (MR-ToF) mass analyser (see Grinfield, abstract) that comprises: two ion mirrors (see e.g. fig 13: 71, 72) spaced apart and opposing each other in a first direction X (see fig 13), each mirror elongated generally along a drift direction Y between a first end and a second end (see fig 13), the drift direction Y being orthogonal to the first direction X (see fig 13); wherein the ion injector is configured to inject ions into a space between the ion mirrors (see figs 13), and the ion injector is located in proximity with the first end of the ion mirrors (see fig 13); wherein the detector (see 117) is configured to detect ions after they have completed a plurality of reflections between the ion mirrors (see fig 13), and the detector is located in proximity with the first end of the ion mirrors (see fig 13); and wherein the ion reflector comprises a deflector (see 124) or lens located in proximity with the first end of the ion mirrors (see fig 13); wherein the method comprises: (i) injecting a packet of ions comprising first ions and second ions from the ion injector into the space between the ion mirrors (see fig 13), wherein the ions complete a first cycle in which the ions follow a zigzag ion path having plural reflections between the ion mirrors in the direction X (see fig 13) whilst: (a) drifting along the drift direction Y from the deflector or lens towards the second end of the ion mirrors (see fig 13), (b) reversing drift direction velocity in proximity with the second end of the ion mirrors (see fig 13), and (c) drifting back along the drift direction Y to the deflector or lens (see fig 13); (ii) causing the first ions to travel from the deflector or lens to the detector for detection (see fig 13); (iii)
The combined teaching of Grinfield and Thompson may fail to explicitly disclose using the deflector or lens to reverse the drift direction velocity. However, in a different embodiment, Grinfield teaches using deflection to operate the system for MSn analysis of ions through repeated selection and fragmentation of ions (see Grinfield, [0144]), which provides subsequently reversing the drift direction velocity of the ions in proximity with the first end of the ion mirrors (see generally, fig 17, around 124), wherein the deflector or lens reverses the drift direction velocity (see fig 17). Furthermore, Makarov (which Grinfield incorporates by reference to explain MSn operation, [0144]) teaches operating the fragmentation cell in a passthrough mode to provide the optional ability to better accumulate ions, store lower abundance ions, reduce energy spread, and/or improve control over subsequent fragmentations (see Makarov, col 4, lines 31-59). It would have been obvious to a person having ordinary skill in the art at the time the application was effectively filed to combine the use of passthrough repetition system of Grinfield and Makarov in the system of the prior art, because a skilled artisan would have been motivated to look for ways to improve control over the system, including improving accumulation, storage, energy spread, and/or preparation for subsequent fragmentation, in the manner taught by Grinfield and Makarov.
Regarding claim 19, Grinfield teaches a time-of-flight (ToF) mass analyser comprising:
an ion path comprising a cyclic segment (see e.g. fig 13);
an ion injector (see e.g. 111, 114, 124, etc) for injecting ions into the ion path (see figs 13);
at least one ion reflector (see 71,72) arranged along the ion path; and
a detector (see 117) arranged at the end of the ion path (see figs 13);
wherein the analyser is configured to analyse ions by:
(i) injecting a
(ii) causing the first ions to travel from the ion reflector to the detector for detection (see fig 13);
(iii) using the ion reflector to cause the second ions to complete one or more cycles along the cyclic segment of the ion path (see fig 13); and then
(iv) causing the second ions to travel from the ion reflector to the detector for detection (see fig 13);
wherein before arriving at the ion reflector, the first and second ions follow the same ion path (all ions, see fig 13); and then, the first ions (all ions) are caused to travel from the ion reflector to the detector for detection, while the ion reflector is used to cause only the second ions to complete one or more cycles along the cyclic segment of the ion path before they are caused to travel from the ion reflector to the detector for detection.
The combined teaching of Grinfield and Makarov may fail to explicitly disclose the first ions are caused to travel from the ion reflector to the detector for detection, while the ion reflector is used to cause only the second ions to complete one or more cycles along the cyclic segment of the ion path before they are caused to travel from the ion reflector to the detector for detection.
However, in different embodiments, Grinfield teaches that multiple mesh detectors may be used to monitor beam ion quantity during the experiment and detect spatial location of the beams (see Grinfield, [0035]). It would have been obvious to a person having ordinary skill in the art at the time the application was effectively filed to combine the embodiments of Grinfield to use additional mesh detectors to enable the ability to learn more about the beam location and current. Therefore, the combined teaching of Grinfield and Makarov teaches the first ions are caused to travel from the ion reflector to the detector for detection (defining as mesh detector formed at specified location at end of beam path, [0035]), while the ion reflector is used to cause only the second ions to complete one or more cycles along the cyclic segment of the ion path before they are caused to travel from the ion reflector to the detector for detection (after repeatedly traversing the TOF, see [0136], detected again).
Regarding claim 20, the combined teaching of Grinfield, Thompson, and Makarov teaches the time-of-flight (ToF) mass analyser is a multi-reflection time-of-flight (MR-ToF) mass analyser (see Grinfield, abstract) that comprises two ion mirrors (see e.g. fig 13: 71, 72) spaced apart and opposing each other in a first direction X (see fig 13), each mirror elongated generally along a drift direction Y between a first end and a second end (see fig 13), the drift direction Y being orthogonal to the first direction X (see fig 13); the ion injector is configured to inject ions into a space between the ion mirrors (see fig 13), and the ion injector is located in proximity with the first end of the ion mirrors (see fig 13); the detector (see 117, see also [0035]) is configured to detect ions after they have completed a plurality of reflections between the ion mirrors (see fig 13), and the detector is located in proximity with the first end of the ion mirrors (see fig 13); and the ion reflector (see 71, 72, etc) is a deflector or lens located in proximity with the first end of the ion mirrors (see fig 13); wherein the analyser is configured to analyse ions by: (i) injecting a packet of ions comprising first ions and second ions from the ion injector into the space between the ion mirrors (see fig 13), wherein the ions complete a first cycle in which the ions follow a zigzag ion path having plural reflections between the ion mirrors in the direction X (see fig 13) whilst: (a) drifting along the drift direction Y from the deflector or lens towards the second end of the ion mirrors (see fig 13), (b) reversing drift direction velocity in proximity with the second end of the ion mirrors (see fig 13), and (c) drifting back along the drift direction Y to the deflector or lens (see fig 13); (ii) causing the first ions to travel from the deflector or lens to the detector for detection (see fig 13); (iii)
The combined teaching of Grinfield and Thompson may fail to explicitly disclose subsequently reversing the drift direction velocity of the ions in proximity with the first end of the ion mirrors. However, in a different embodiment, Grinfield teaches using deflection to operate the system for MSn analysis of ions through repeated selection and fragmentation of ions (see Grinfield, [0144]), which provides subsequently reversing the drift direction velocity of the ions in proximity with the first end of the ion mirrors (see generally, fig 17, around 124). Furthermore, Makarov (which Grinfield incorporates by reference to explain MSn operation, [0144]) teaches operating the fragmentation cell in a passthrough mode to provide the optional ability to better accumulate ions, store lower abundance ions, reduce energy spread, and/or improve control over subsequent fragmentations (see Makarov, col 4, lines 31-59). It would have been obvious to a person having ordinary skill in the art at the time the application was effectively filed to combine the use of passthrough repetition system of Grinfield and Makarov in the system of the prior art, because a skilled artisan would have been motivated to look for ways to improve control over the system, including improving accumulation, storage, energy spread, and/or preparation for subsequent fragmentation, in the manner taught by Grinfield and Makarov.
Regarding claim 24, the combined teaching of Grinfield and Makarov teaches repeating step (ii) one or more times before causing the second ions to travel from the deflector or lens to the detector for detection (see Grinfield, [0144]; see also indefinite trapping, [0136]).
Regarding claim 25, the combined teaching of Grinfield and Makarov teaches repeating step (iii) one or more times before causing the second ions to travel from the deflector or lens to the detector for detection (see Grinfield, [0144]; see also indefinite trapping, [0136]).
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 extension fee 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.
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/JAMES CHOI/Examiner, Art Unit 2878
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