DETAILED ACTION
This Office action is in response to the amendment filed on June 30th, 2026. Claims 1 and 3-20 are pending.
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Objections
Claim 3 is objected to for depending on a cancelled claim. For the purposes of examination, it will be assumed applicant intended for claim 3 to depend on claim 1.
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.
Claim(s) 10-15 and 18 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2021/064558 (the ‘558 publication).
Regarding claim 10, the ‘558 publication discloses a mass spectrometer, comprising:
a branched RF ion trap comprising two sets of multipole rods positioned axially relative to one another and shaped so as to provide a central channel having an inlet for receiving a plurality of precursor ions and an outlet through which ions can exit the ion trap, said ion trap further providing a transverse channel for receiving an electron beam such that the electron beam and the received ions can interact in a region located at an intersection of said axial and said transverse channels (fig. 9, element 200),
a source for generating an electron beam (“The apparatus 200 contains two filaments, each one disposed at either the first axial end 212 or second axial end 213 of the second pathway 210.”),
an electrode positioned between said source and an inlet of said transverse channel for accelerating electrons of the electron beam to a desired kinetic energy (“Pole electrode 58 further controls the entrance of electrons 60 into the apparatus 40 and also serves to block ions and reaction products from escaping. Another pole electrode 59 is present or situated proximate to the second axial end 53 of the second pathway 50.” P 69),
a DC voltage source configured to apply a DC voltage to said electrode, and
a controller in communication with said DC voltage source and configured to control the DC voltage applied to said electrode so as to adjust an energy of said electron beam between a first energy regime and a second energy regime (“For electrons, electron energy can be controlled by the potential difference between the electron source and the intersection point between the ion pathway and the charged species pathway.” P 77),
wherein in the first energy regime electron impact excitation of ions from organics (EIEIO) fragmentation of a plurality of precursor ions introduced into the branched RF ion trap can occur (intended use, the controller is configured to achieve any energy range desired up to the maximum level of the voltage source, also “In addition, for electron associated fragmentation, Hot ECD, high energy electron ionization dissociation (HEEID), activated ions ECD (AI-ECD), Electron Impact Excitation of Ions from Organics (EIEIO), electron detachment dissociation (EDD), negative ETD, and negative ECD can be implemented.” P 48) and
in the second energy regime EIEIO fragmentation is substantially inhibited (intended use, the controller is configured to achieve any energy range desired up to the maximum level of the voltage source, including energies where EIEIO is inhibited).
Regarding claim 11, the ‘558 publication discloses the mass spectrometer of Claim 10, further comprising an ion source for receiving a sample and ionizing said sample so as to generate said plurality of precursor ions (“receiving precursor ions from an ion source.” P 19).
Regarding claim 12, the ‘558 publication discloses the mass spectrometer of Claim 10, further comprising an ion guide positioned downstream of said ion source for receiving at least a portion of said precursor ions and focusing said ions into an ion beam (“devices can be situated either before or after the apparatus in accordance with the present teachings. For example, the devices can include various ion guides,”).
Regarding claim 13, the ‘558 publication discloses the mass spectrometer of Claim 12, further comprising a first mass analyzer positioned downstream of the ion guide and upstream of said branched RF ion trap for receiving said ion beam, wherein said first mass analyzer is configured to select precursor ions having a target m/z ratio for transmission to said branched RF ion trap, wherein at least a portion of said precursor ions undergoes fragmentation in said branched RF ion trap to generate a plurality of product ions (fig. 9, element 218).
Regarding claim 14, the ‘558 publication discloses the mass spectrometer of Claim 13, further comprising a second mass analyzer positioned downstream of said branched RF ion trap for receiving at least a portion of said plurality of product ions (fig. 9, element 219).
Regarding claim 15, the ‘558 publication discloses the mass spectrometer of Claim 14, further comprising an ion detector positioned downstream of said second mass analyzer for receiving at least a portion of said product ions transmitted through said second mass analyzer and generating ion detection signals in response to detection of said product ions (“it will be appreciated that other types of devices can be situated either before or after the apparatus in accordance with the present teachings. For example, the devices can include … mass spectrometer devices”).
Regarding claim 18, the ‘558 publication discloses the mass spectrometer of Claim 10, wherein said first energy regime spans a range of about 10 eV to about 20 eV and said second energy regime spans a range of about 30 eV to about 50 eV (intended use, controller can generally apply voltages that allow for any conceivable electron energy up to the maximum of the voltage supply).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2021/064558 (the ‘558 publication).
Regarding claim 16, the ‘558 publication discloses the claimed invention except it does not explicitly recite an analysis module in communication with said ion detector to receive said ion detection signals, wherein said analysis module is configured to process said ion detection signals to generate a mass spectrum of the product ions transmitted through said second mass analyzer. Mass spectrometers routinely include analysis modules in communication with the ion detector to receive and process detection signals to generate mass spectra. It would have been obvious to a person having ordinary skill in the art at the time the application was filed to include such an analysis module in the mass spectrometer of the ‘558 publication so that the detector signals could be read out any processed into a form that is useful to the operator.
Claim(s) 17 and 19-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over the ‘558 publication as applied to claim 16 above, and further in view of US 2011/0143951 (Thompson).
Regarding claim 17, the ‘558 publication discloses the claimed invention except for the analysis module being further configured to compare a mass spectrum of the sample generated with the electron kinetic energy within said first energy regime with a mass spectrum of the sample generated with the electron kinetic energy within said second energy regime to identify mass peaks corresponding to product ions generated via said EIEIO fragmentation.
Thompson discloses an analysis module for a mass spectrometer configured to compare mass spectrum of the sample generated in a first fragmentation regime with a mass spectrum of the sample generated in a second fragmentation regime to identify mass peaks corresponding to product ions generated in the first fragmentation regime (“The spectra obtained at low collision energy and higher effective collision energy can be compared by determining a `difference spectrum`, where the low energy spectrum is subtracted from the high-energy spectrum.” P 111). It would have been obvious to a person having ordinary skill in the art at the time the application was filed to modify the mass spectrometer of the ‘558 publication to include the analysis module of Thompson so that background ions can be filtered out.
Regarding claim 19, the ‘558 publication in view of Thompson discloses the mass spectrometer of claim 17, wherein the spectral comparison is performed via spectrum subtraction resulting in subtracted spectra (Thompson “The spectra obtained at low collision energy and higher effective collision energy can be compared by determining a `difference spectrum`, where the low energy spectrum is subtracted from the high-energy spectrum.” P 111).
Regarding claim 20, the ‘558 publication in view of Thompson discloses the mass spectrometer of claim 19, wherein the subtracted spectra is further matched to a library spectra (Thompson, “The regions of the difference spectrum that match the template receive a high score while regions that do not match the template get a low or zero score.”).
Claim(s) 1-2 and 4-9 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2021/064558 (the ‘558 publication).
Regarding claim 1, the ‘558 publication discloses a method of performing mass spectrometry, comprising:
introducing a first batch of precursor ions generated via ionization of a first portion of a sample into an ion trap configured to trap said ions (“In this way, the apparatus 100 functions as an ion trap where ions that are injected are accumulated at the intersection point between the first 101 and second pathways 110.” P 72),
exposing at least a portion of said first batch of trapped precursor ions to an electron beam having a first energy so as to cause dissociation of at least a portion thereof, subsequently (“Filament 114 can then be turned on such that electrons can pass through the aperture of pole electrode 115 into the apparatus 100. Upon this, electrons may interact with the ions and undergo EID resulting in fragmentation into product ions.” P 73), and
releasing ions from said ion trap and detecting at least a portion of said released ions and generating a first mass spectrum thereof (“Once sufficient fragmentation has occurred, the filament 14 can be turned off, the potential of gate electrode 105 can be increased and the potential of gate electrode 106 can be lowered to allow the exit of product ions through the second axial end 104 as depicted in FIG. 7.” P 73),
wherein said first energy is within an energy regime in which fragmentation of the first batch of precursor ions via electron impact excitation of ions from organics (EIEIO) can occur (“In addition, for electron associated fragmentation, Hot ECD, high energy electron ionization dissociation (HEEID), activated ions ECD (AI-ECD), Electron Impact Excitation of Ions from Organics (EIEIO), electron detachment dissociation (EDD), negative ETD, and negative ECD can be implemented.” P 48).
The ‘558 publication does not disclose introducing a second batch of precursor ions generated via ionization of a second portion of the sample into the ion trap to trap said second batch of the precursor ions, exposing said second batch of trapped precursor ions to an electron beam at a second energy to cause dissociation of at least a portion thereof, and subsequently, releasing additional ions from the ion trap and detecting at least a portion of the additional released ions and generating a second mass spectrum thereof, and also does not disclose that for one of the energy regimes EIEIO is substantially inhibited.
However, this is merely repeating the method at a second energy, specifically a second energy at which EIEIO is substantially inhibited. It would have been obvious to a person having ordinary skill in the art at the time the application was filed to repeat the method at a second energy so that additional information could be obtained, potentially allowing for better identification of the sample. It would further have been obvious to select an energy regime in which EIEIO is substantially inhibited so that the information would not be the same information obtained in the EIEIO spectrum.
Regarding claim 4, the ‘558 publication discloses the claimed invention except it is silent as to whether precursor ions in said first and second batches of precursor ions are singly charged. It would have been obvious to use singly charged ions if desired, as the method would appear to work identically with singly or multiply charged ions.
Regarding claim 5, the ‘558 publication discloses the claimed invention except it is silent as to whether precursor ions in said first ands second batches of precursor ions comprise any of singly charged sodiated and potassiated ions. It would have been obvious to use singly charged ions if desired, as the method would appear to work identically with any ions.
Regarding claim 6, the ‘558 publication discloses the method of claim 1 wherein the one or said first and second energies is in a range of about 10 eV to about 20 eV (“The mechanisms for EID can include, for example, electron capture dissociation (ECD) using electrons having kinetic energies of 0 to 3 eV, Hot ECD (electrons with kinetic energy of 5 to 10 eV), and high energy electron ionization dissociation (HEEID) (electrons with kinetic energy greater than 13 eV).” P 4) within the energy regime in which fragmentation of the first or second batch of precursor ions, respectively, via EIEIO can occur (intended result, the ‘558 publication disclose both energies in this range and EIEIO, if these energy ranges overlap the method of the ‘558 will cover the overlap).
Regarding claim 7, the ‘558 publication discloses the method of claim 1 further comprising ionizing a sample to generate any of said first and said second batch of the precursor ions (inherent, the sample must be ionized for there to be sample ions).
Regarding claim 8, the ‘558 publication discloses the method of claim 1 except it is silent to whether the other one of said first and second energies is in a range of about 30eV to about 70 eV within the other energy regime which fragmentation of the first or second batch of precursor ions, respectively, via EIEIO is substantially inhibited. It would have been obvious to a person having ordinary skill in the art at the time the application was filed to use this range as a mater of routine optimization or experimentation, as applicant has not stated that this range is critical or solves any particular problem.
Regarding claim 9, the ‘558 publication discloses the method of claim 1 wherein said ion trap comprises a branched RF ion trap (element 200).
Claim(s) 3 is/are rejected under 35 U.S.C. 103 as being unpatentable over the ‘558 publication as applied to claim 2 above, and further in view of US 2011/0143951 (Thompson).
Regarding claim 3, the ‘558 publication discloses the claimed invention except for subtracting the mass peaks associated with said first mass spectrum from respective mass peaks associated with the second mass spectrum to generate a resultant mass spectrum in which EIEIO-generated fragments are more readily identifiable.
Thompson discloses a method of performing mass spectrometry comprising subtracting the mass peaks associated with a first mass spectrum with fragmentation from respective mass peaks associated with a second mass spectrum with little or no fragmentation to generate a resultant mass spectrum in which fragments are more readily identifiable (“The spectra obtained at low collision energy and higher effective collision energy can be compared by determining a `difference spectrum`, where the low energy spectrum is subtracted from the high-energy spectrum.” P 111). It would have been obvious to a person having ordinary skill in the art at the time the application was filed to modify the mass spectrometry method of the ‘558 publication to include spectrum subtraction of Thompson so that background ions can be filtered out.
Response to Arguments
Applicant's arguments filed June 30th, 2026 have been fully considered but they are not persuasive.
Regarding the rejections of claims 10-20, applicant argues that the prior art teaches controlling the potential difference between the electron source and the intersection point to control the electron energy in general but does not disclose controlling to achieve first an energy which causes EIEIO fragmentation to occur and another energy in which fragmentation is inhibited.
Whether fragmentation occurs or not is irrelevant to whether the controller is configured to control the voltage to achieve the different electron energies. If a controller can control the energy to form 10 eV electrons, it can do so regardless of whether this energy causes EIEIO in the ions present or not. All that examiner must show is that the controller can control the energy of the electrons to achieve at least two different energy levels, including energies in the general ranges needed for EIEIO fragmentation (on the order of 10 eV). Regardless, examiner does show that the prior art discloses EIEIO fragmentation, and any controller that can control energy can of course achieve energies at which such fragmentation does not occur.
As with respect to claims 10-20, applicant argues that the prior art “does not appear to mention EIEIO fragmentation at all.”
This is demonstratively false, see “In addition, for electron associated fragmentation, Hot ECD, high energy electron ionization dissociation (HEEID), activated ions ECD (AI-ECD), Electron Impact Excitation of Ions from Organics (EIEIO), electron detachment dissociation (EDD), negative ETD, and negative ECD can be implemented.”
Regarding claims 1 and 3-9, applicant argues that neither Baba nor Thompson teaches or suggests generating the specific mass spectra claimed, that being one specta in the EIEIO fragmentation regime and a second outside that energy regime. Applicant further notes that because the arts do not disclose the creation of both spectra, the references cannot provide the advantage of using the spectra for enhanced identification of fragments.
Baba does in fact disclose generating mass spectra using EIEIO fragmentation, as well as generating mass spectra in other energy regimes (see all the regimes in quote above). The only thing Baba does not specifically disclose is generating both spectra from the same sample, but a person having ordinary skill in the art could easily imagine generating multiple spectra from the same sample at various energies, as this is a fairly standard practice in the art. Only claim 3 recites any comparison of the two spectra, all that applicant claims in claims 1 and 4-9 is that the basic mass spectrometry method is run twice, with an energy change between spectra. Therefore discussion of enhanced identification through the comparison is not relevant for those claims.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELIZA W OSENBAUGH-STEWART whose telephone number is (571)270-5782. The examiner can normally be reached 10am - 6pm Pacific Time M-F.
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/ELIZA W OSENBAUGH-STEWART/Primary Examiner, Art Unit 2881
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