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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 8/11/25 has been entered.
Response to Arguments
Applicant’s arguments filed on 8/11/25 have been fully considered but are found not persuasive.
The remarks argue the invention is directed to a cascaded instrument where ions exiting a charge filter are processed by the processing stage and then enter a second charge filter, but Clemmer is an IMS and does not include a charge filter instrument. However, Clemmer explicitly teaches the system using multiple ion analytical instruments disposed along the drift tubes “such that alternate and/or additional ion separation, ion conformation alteration, ion processing and/or ion analysis may be carried out within or along” the drift tubes, and can include multiple mass filters (Clemmer, [0112]). As for the limitation regarding the processing stage, the term is sufficiently broad to read on any type of processing stage between the analytical instruments, including e.g. drift tubes, filters, other analytical instruments, funnels, etc.
Examiner respectfully suggests clarifying the type of processing device is and the configuration of the cascading instrument (e.g. fig 14 of the application).
The remarks argue multipass systems are not claimed, so it is immaterial that Clemmer teaches it. However, Clemmer is relied upon to teach different systems using cascading instruments, which additionally enables the ability to perform mulitpass analysis. It is noted that "[t]he use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain.” In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968))." MPEP §2123.
The remarks argue that Westphall teaches only measuring a single charge magnitude for a packet of charged particles, not each individual charge magnitudes or charge states of each ion. However, Westphall teaches a “significant advantage of the increased sensitivity of the present methods and devices is that measurable signals associated with individual electrically charged particles may be generated from the analysis of very small samples” (Westphall, [0055]). Further the claims are broad enough to read on direct and indirect determination of charge magnitudes or charge states. Also, the claims are broad enough to read on determination of charge states generally without even requiring individual measurements of individual ions.
Status of the Application
Claim(s) 1, 5-6, 23-24, 28-29 is/are pending.
Claim(s) 29 is/are withdrawn.
Claim(s) 1, 5-6, 23-24, 28 is/are rejected.
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, 5-6 is/are rejected under 35 U.S.C. § 103 as being unpatentable over Westphall et al. (US 20040169137 A1) [hereinafter Westphall] in view of Hoyes et al. (US 20050092911 A1) [hereinafter Hoyes] and Clemmer et al. (US 20170307565 A1) [hereinafter Clemmer].
Regarding claim 1, Westphall teaches a charge filter instrument, comprising:
an electric field-free drift region (see [0035]) having an inlet end and an outlet end opposite the inlet end (see fig 1), the inlet end configured to be coupled to an ion source (see fig 1: 110) to receive a plurality of ions to drift axially through the drift region from the inlet end toward the outlet end (see fig 1, e.g. [0049]),
a plurality of spaced-apart charge detection cylinders (see fig 2a: 310, [0041,140]) disposed in the drift region and through which a plurality of ions drifting axially through the drift region pass (see fig 1),
a plurality of charge sensitive amplifiers (see 360) each coupled to at least one of the plurality of charge detection cylinders (see fig 2a) and each configured to produce a charge detection signal corresponding to a magnitude of charge of one or more of the plurality of ions passing through a respective at least one of the plurality of charge detection cylinders (see fig 1, [0058]),
one of a charge deflector having a single inlet coupled to the outlet end of the drift region and a single outlet, and a charge steering device (see deflection, [0051]) having a single inlet coupled to the outlet end of the drift region (receiving ions from downstream) and multiple outlets (see [0051]),
means for determining charge magnitudes or charge states of each of the plurality of ions drifting axially through the drift region based on the charge detection signals produced by at least some of the plurality of charge sensitive amplifiers (see fig 2a, via induced charge), and
means for controlling the one of the charge deflector and the charge steering device to pass through a corresponding one of the single outlet and a specified one of the multiple outlets only ions having a determined charge magnitude or charge state
wherein the electric field-free drift region is a first electric field-free drift region, the plurality of charge detection cylinders is a first plurality of charge detection cylinders, the plurality of charge sensitive amplifiers is a first plurality of charge sensitive amplifiers, the one of a charge deflector and a charge steering device is one of a first charge deflector and a first charge steering device, the means for determining charge magnitudes or charge states is a first means for determining charge magnitudes or charge states, the means for controlling is a first means for controlling (defining these elements as first elements),
and wherein the charge filter instrument comprising the first electric field-free drift region, the first plurality of charge detection cylinders, the first plurality of charge sensitive amplifiers, the one of the first charge deflector and the first charge steering device, the first means for determining charge magnitudes or charge states and the first means for controlling is a first charge filter instrument (defining these elements as first elements),
Westphall may fail to explicitly disclose the determined charge magnitude or charge state being equal to, or within a specified range of, a specified charge magnitude or charge state.
However, Westphall teaches the system is capable of measuring both m/z and absolute charge states which can enable measurements of absolute mass (see [0029-30]). The use of deflection/steering to remove unwanted ions outside a desired range of absolute charges or masses was well known in the art. For example, Hoyes teaches that separating/filtering ions into different streams based on charge state (see Hoyes, e.g. [0131-132, 136]) is advantageous for analysis of the ionization spectra, including in study of protein digests (see [0006, 21]). 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 Hoyes in the system of Westphall because a skilled artisan would have been motivated to look for ways to learn more information about the sample, including based on separation by charge state, in the manner taught by Hoyes.
Westphall may fail to explicitly disclose a second charge filter instrument identical to the first charge filter instrument, the second charge filter instrument comprising a second electric field-free drift region having a second inlet end and a second outlet end opposite the second inlet end, and a second plurality of charge detection cylinders disposed in the second electric field-free drift region, and at least one ion processing stage disposed between the one of the single outlet and the specified one of the multiple outlets of the corresponding one of the first charge deflector and the first charge steering device and the second inlet end of the second electric field-free drift region of the second charge filter instrument.
However, Clemmer teaches a system to enable precise steering of ions into different channels without losing ions (see Clemmer, fig 1a, [0073]), as well as use of multiple-pass drift tubes to enable the ability to more precisely separate out specific m/z ranges (see fig 1a, [0031]), a second charge filter instrument identical to the first charge filter instrument (see [0112], fig 1a,b,etc), and at least one ion processing stage (see e.g. in funnels 32_1,2, etc, [0039], or drift portion, etc) disposed between the one of the single outlet and the specified one of the multiple outlets of the corresponding one of the first charge deflector and the first charge steering device and the second inlet end of the second electric field-free drift region of the second charge filter instrument (between analyzer/charge filter instruments). 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 Clemmer, including the use of multiple-pass systems, to augment the functionality of Westphall, because a skilled artisan would have been motivated to look for ways to improve precision of the system by further separating the ions via multiple passes, and to enable the additional functionality to learn more information about the sample, including enabling the additional ability to process separated ions via fragmentation and then separate those even further, in the manner taught by Clemmer. Therefore, the combined teaching of Westphall, Hoyes, and Clemmer teaches the second charge filter instrument comprising a second electric field-free drift region (see Westphall, fig 1 duplicated) having a second inlet end and a second outlet end opposite the second inlet end (see fig 1), and a second plurality of charge detection cylinders (see 310) disposed in the second electric field-free drift region (see fig 1).
Regarding claim 5, the combined teaching of Westphall, Hoyes, and Clemmer teaches the ion source (see Westphall, fig 1: 110) including an ion generator (required for intended operation of system, see e.g. MALDI, [0065]) configured to generate the plurality of ions from a sample and to supply the generated plurality of ions (note generally the discussion of any suitable upstream source, [0056]) to the inlet of the drift region such that the generated plurality of ions drift axially through the drift region toward the ion outlet end thereof (see fig 1).
Regarding claim 6, Westphall teaches the ion source further includes one or more of (i) at least one instrument (see electrostatic sorting element, [0051]) for separating the generated ions according to at least one molecular characteristic (see [0051]), (ii) at least one dissociation stage configured to dissociate ions passing therethrough, and (iii) at least one ion trap (see [0056]) configured to trap ions therein and to selectively release trapped ions therefrom.
Claim(s) 28 is/are rejected under 35 U.S.C. § 103 as being unpatentable over Westphall et al. (US 20040169137 A1) [hereinafter Westphall] in view of Hoyes et al. (US 20050092911 A1) [hereinafter Hoyes].
Regarding claim 28, Westphall teaches a charge filter instrument, comprising:
an electric field-free drift region (see [0035]) having an inlet end and an outlet end opposite the inlet end (see fig 1), the inlet end configured to be coupled to an ion source (see fig 1: 110) to receive a plurality of ions to drift axially through the drift region from the inlet end toward the outlet end (see fig 1, e.g. [0049]),
a plurality of spaced-apart charge detection cylinders (see fig 2a: 310, [0041,140]) disposed in the drift region and through which the plurality of ions drifting axially through the drift region pass (see fig 1),
a plurality of charge sensitive amplifiers (see 360) each coupled to at least one of the plurality of charge detection cylinders (see fig 2a) and each configured to produce a charge detection signal corresponding to a magnitude of charge of one or more of the plurality of ions passing through a respective at least one of the plurality of charge detection cylinders (see fig 1, [0058]),
one of a charge deflector having a single inlet coupled to the outlet end of the drift region and a single outlet, and a charge steering device (see deflection, [0051]) having a single inlet coupled to the outlet end of the drift region (receiving ions from downstream) and multiple outlets (see [0051]),
at least one voltage source (required for intended operation of deflector, [0051]) having at least one voltage output operatively coupled to the one of the charge deflector and the charge steering device (see [0051]),
at least one processor (required for intended operation of system, see computer, [0096]), and
at least one memory (required for intended operation of system, see computer, [0096]) having instructions stored therein executable by the at least one processor to cause the at least one processor to
(a) monitor the charge detection signals produced by at least some of the plurality of charge sensitive amplifiers as the plurality of ions drift axially through the field-free drift region toward the outlet end thereof (see fig 2a, [0096]),
(b) determine charge magnitudes or charge states of each of the plurality of ions (m/z information) drifting axially through the field-free drift region based on the monitored charge detection signals (see fig 2a, via induced charge, [0019]), and
(c) control the at least one voltage output of the at least one voltage source to cause the one of the charge deflector and the charge steering device to pass through a corresponding one of the single outlet and a specified one of the multiple outlets only ions having a determined charge magnitude or charge state
Westphall may fail to explicitly disclose the determined charge magnitude or charge state being equal to, or within a specified range of, a specified charge magnitude or charge state.
However, Westphall teaches the system is capable of measuring both m/z and absolute charge states which can enable measurements of absolute mass (see [0029-30]). The use of deflection/steering to remove unwanted ions outside a desired range of absolute charges or masses was well known in the art. For example, Hoyes teaches that separating/filtering ions into different streams based on charge state (see Hoyes, e.g. [0131-132, 136]) is advantageous for analysis of the ionization spectra, including in study of protein digests (see [0006, 21]). 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 Hoyes in the system of Westphall because a skilled artisan would have been motivated to look for ways to learn more information about the sample, including based on separation by charge state, in the manner taught by Hoyes.
Conclusion
This is a RCE adding dependent claim 22 into independent claim 1. Independent claim 28 is unamended. All claims are identical to, patentably indistinct from, or have unity of invention with the invention claimed in the earlier application (that is, restriction (including lack of unity) would not be proper) and could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the earlier application. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action in this case. See MPEP § 706.07(b). 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to James Choi whose telephone number is (571) 272 – 2689. The examiner can normally be reached on 8:00 am – 5:30 pm M-T, and every other Friday.
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/JAMES CHOI/Examiner, Art Unit 2881