DETAILED ACTION
Response to Arguments
Applicant's arguments filed 06 March 2026 have been fully considered but they are not persuasive.
Page 10 of the remarks take the position that axis along arrow “B” cannot be interpreted as the claimed central axis because the axis along “B” is the axis along which electrons from the electron source travel. This has been found unpersuasive. Specifically, the claim does not require the ion source to be positioned along the claimed central axis, only that the central axis is “for receiving ions from an ion source”. Baba teaches in paragraph [0044] recites “lens 320c and lens 320d can be biased (e.g., via application of an appropriate DC voltage) to block the exit of the ions within the transverse pathway 316”. That is, because the ions exist within the transverse pathway 316, they are received from the ion source. In otherwords, in order for 320c and 320d to block exit of ions within 316 (figure 3A), the ions are within the 314/313 as seen in figure 3a
Therefore, because the claim does not require any positional relationship between the ion source and the central axis and Baba suggests an axis that receives ions (i.e. generated from an ion source), the claim is not distinguished from Baba.
By amendment, a new grounds rejection is necessitated over Schoen in view of Baba, discussed below.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 5-9 and 13-14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Baba (WO 2017/221151) (copy of publication submitted herewith).
Regarding claim 1, Baba teaches a method of performing mass spectrometry (fig. 2), comprising:
ionizing a sample to generate a plurality of precursor ions (201, [0037]),
passing said precursor ions through a mass filter to select at least one subset of said ions ([0037] teaches one or more mass analyzers upstream from ECD (step 202) operated as a conventional mass filter to select a range of precursor cations of interest for transmission therethrough),
introducing said selected ions into a branched radiofrequency (RF) ion trap (step 202, figure 3A shows branched ECD cell, paragraph [0037] last sentence teaches trapping the precursor cations within the ECD cell prior to being subject to ECD (i.e. ECD cell acts as an ion trap)) and
subjecting at least a portion of said selected precursor ions to fragmentation within said ion trap so as to generate a first plurality of fragment ions (step 203 ECD is a dissociation technique resulting in fragmentation of ions),
isolating at least a portion of said first plurality of fragment ions ([0038] teaches extracting/removing product ions having a higher m/z ratio (product ions) by operating the ECD as a high-pass filter, see additional discussion in paragraphs [0053]-[0054] of extracting higher m/z product ions from ECD, thus isolating a portion of product ions (i.e. fragments) in the ECD or isolating a portion by extracting to Q2),
releasing at least a portion of said isolated ions ([0039] product ions trapped in PTR cell after ECD, paragraph [0045] transmitting ions from ECD cell to Q2 operated as a cell for PTR or CID) and subjecting at least a portion thereof to fragmentation so as to generate a second plurality of fragment ions ([0045] transmitting ions from ECD to Q2 operated as a cell for CID)
wherein said branched RF ion trap comprises an axial section (313/314 in figure 3a) characterized by a central axis (316) for receiving ions from an ion source ([0044] teaches ions within transverse pathway 316 thus receiving ions from the ion source) and having a trap center and four branches extending from the trap center (four branches extending from center of ECD cell in figure 4a which acts as a trap as discussed above, therefore the center is interpreted as the trap center)
wherein two of said branches are positioned transverse to said central axis (branches 315a/315b are orthogonal to 313/314)
wherein said step of isolating at least a portion of said first plurality of fragment ions comprises causing said at least a portion of said first plurality of fragment ions to enter at least one of said transverse branches (in passage to Q2 product ions pass through 315b when interpreting portion to be the filtered portion of product ions removed from EDC).
Regarding claim 5, Baba teaches wherein said step of causing said at least a portion of said first plurality of fragment ions to enter one of said transverse branches comprises applying a DC voltage to an isolation electrode positioned in proximity of said branches ([0053] applying a DC offset to Q2a to attract cations and product ions having a m/z greater than precursor ions, thus portion of fragment ions enter the branch along 315b (see figures 3a and 4)).
Regarding claim 6, Baba teaches wherein said isolation electrode extends from said proximal end to said distal end of the axial section (Q2a in figure 4 extends along the axis 315 of figure 3A, interpreting its extent to be the proximal and distal end of the axial section the limitation is met).
Regarding claim 7, Baba teaches removing unwanted fragment ions from the fragment ions in said at least one transverse branch by applying a resolving DC voltage to said at least one transverse branch (interpreting Q2a to be part of the transverse branch 412a/412b the DC offset is interpreted to be the claimed resolving DC voltage to remove unwanted fragment ions (i.e. product ions that do not need to undergo additional EDC) see paragraph [0053]).
Regarding claim 8, Baba teaches wherein said step of releasing said selected isolated ions comprises adjusting a DC voltage applied to said isolation electrode ([0053] teaches adjusting DC offset resulting in high pass filter mode).
Regarding claim 9, Baba teaches wherein said released ions undergo said second fragmentation in vicinity of said trap center (as seen in figure 3a ECD occurs at intersection between 315 and 317).
Regarding claim 13, Baba teaches wherein said precursor ions are fragmented using any of collision induced dissociation (CID) and electron activation dissociation (EAD) ([0045] ECD and CID (note as evidenced by Zhang US pgPub 2024/0404646 ECD is a type of EAD see paragraph [0036])).
Regarding claim 14, Baba teaches wherein said first plurality of fragment ions are fragmented using any of CID and EAD ([0045] teaches ECD and collision induced dissociation (i.e. CID)).
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 10-12 are rejected under 35 U.S.C. 103 as being unpatentable over Baba as evidenced by Zhang (US pgPub 2024/0404646) in view of Baba (US pgPub 2018/005810).
Regarding claim 10, Baba teaches wherein any of said precursor ions and said first plurality of fragment ions are dissociated via electron activation dissociation using an electron beam (electron beam seen in figure 3A, ECD is a type of EAD as evidenced by Zhang see paragraph [0036]).
Baba fails to disclose the energy of the electron beam.
However, Baba teaches ECD using an electron beam having an energy in a range of about 0 eV to about 50 eV ([0004] ECD 0-3 eV).
Baba modifies Baba by suggesting an appropriate electron beam energy for ECD.
Since both inventions are directed towards ECD, it would have been obvious to one of ordinary skill in the art to use the electron beam energy of Baba in the primary Baba method because it would resolve the problem of what beam energy would be appropriate to initiated electron capture dissociation.
Regarding claim 11, Baba teaches passing said second plurality of fragment ions through a mass analyzer so as to generate a mass spectrum thereof (implicit after CID in order to generate MS2 [0045]).
Regarding claim 12, Baba teaches wherein said mass analyzer comprises a time-of- flight mass analyzer (140 in figure 1 see paragraph [0034]).
Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over Schoen et al. (US pgPub 2009/0090853) in view of Baba.
Regarding claim 1, Schoen teaches a method of performing mass spectrometry (inherent to the apparatus of figure 1A/B), comprising:
ionizing a sample to generate a plurality of precursor ions (via ionization source 1, [0029]),
passing said precursor ions through a mass filter (mass filter Q1 or element 18 see paragraph [0031]) to select at least one subset of said ions ([0031] teaches Q1 is configured to select ions having m/z within a narrow range of values),
introducing said selected ions into a branched radiofrequency (RF) ion trap (Q2 comprising 42/45 and 48 and 12-14 see paragraph [0031] collisional cell requires trapping to cause fragmentation) and subjecting at least a portion of said selected precursor ions to fragmentation within said ion trap so as to generate a first plurality of fragment ions ([0031] “the branched ion transfer device 15 may incorporate one or more collision cells 42/45/48 for the fragmentation of the selected ions”),
isolating at least a portion of said first plurality of fragment ions (via 30 which is a mass filter see paragraph [0031] “he resultant product ions are then directed to a selected one of a mass analyzer 30 (also labeled Q.sub.3,1) in the first branch, which may take the form of a quadrupole mass filter, and an ion trap mass analyzer 33 (also labeled IT.sub.3,2) in the second branch in a manner more fully described below”),
releasing at least a portion of said isolated ions (to additional stages QN see paragraph [0038] and figure 1a-b)
wherein said branched RF ion trap comprises an axial section (along 42) characterized by a central axis for receiving ions from an ion source (central axis along 42 receives ions from source 1) and having a trap center (center of 42) and four branches extending from the trap center ([0056] envisioned additional third and fourth stages, thus while only two branches shown, there could be four),
wherein two of said branches are positioned transverse to said central axis (two branches transverse to center of 42), and wherein isolating at least a portion of said first plurality of fragment ions comprises causing said at least a portion of said first plurality of fragment ions to enter at least one of said transverse branches (see discussion with respect to paragraph [0031] above).
While Schoen teaches additional stages after mass filtering, Schoen fails to teach subjecting at least a portion thereof to fragmentation so as to generate a second plurality of fragment ions.
However, Baba teaches at least a portion thereof to fragmentation so as to generate a second plurality of fragment ions ([0045] and figure 3A show a quadrupole Q2 for performing CID on product ions exiting the first cell).
Baba modifies Schoen by suggesting an additional CID cell downstream of the first fragmentation cell.
Since Schoen suggests additional stages after mass filtering after fragmentation and Baba suggests an additional fragmentation stage, it would have been obvious to one of ordinary skill in the art to add an additional fragmentation step of the fragment ions so as to facilitate MS2 analysis allowing for more structural information about the sample.
Relevant art
US20160126076 and US 20160322208 to Baba also teaches fragmentation and isolation of ions within the trap.
US20130026360 teaches fragmentation in a traverse section of an ion trap see figure 11 and associated text.
US2018/0005810 to Baba teaches in paragraph [0058] “it will be appreciated that the ion reaction devices described herein can be inserted in series in between two quadrupole filters, for example, between a quadrupole filter (Q1) upstream of the ion reaction device 600 (and disposed between the ion source and the ion reaction device), serves to trap/guide/etc. ions and provides a source of ions at the entrance of the device 600, and a downstream quadrupole (Q2), which can receive product ions and unreacted ions and either trap/guide/etc. in the quadrupole for further analysis or processing”
Satake et al. (US 2011/0204221) see figure 5 ECD by substituting 42 with an electron source ([0049]) and downstream CID 6.
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