CTNF 18/569,781 CTNF 87462 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Claim Rejections - 35 USC § 102 07-07-aia AIA 07-07 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 – 07-08-aia AIA (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. 07-15-aia AIA 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 for controlling the DC voltage applied to said electrode so as to adjust an energy of said electron beam between a first and a second energy regime, wherein in the first energy regime EID fragmentation of a plurality of precursor ions introduced into the branched RF ion trap can occur and in the second energy regime EID fragmentation is substantially inhibited (“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). 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 07-20-aia AIA 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. 07-21-aia AIA 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 . 07-22-aia AIA 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 EID 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.”) . 07-21-aia AIA 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). 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 trapped precursor ions to an electron beam at a second energy to cause dissociation of at least a portion thereof, and subsequently, releasing ions from the ions trap and detecting at least a portion of the released ions and generating a second mass spectrum thereof, wherein fragmentation of said precursor ions via electron induced dissociation (EID) at one of said first and second energies is more probable than at the other electron energy However, this is merely repeating the method at a second energy. 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. Regarding claim 2, the ‘558 publication discloses the method of Claim 1, wherein said EID of the trapped ions can occur only at first energy (intended result of the already addressed limitation to exposing the trapped ions to different energies, hence non-limiting). Regarding claim 4, the ‘558 publication discloses the claimed invention except it is silent as to whether said 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 said precursor ions are 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 said electron energy at which said fragmentation of the precursor ions via EID is more probable is in a range of about 10 eV to about 20 eV (“high energy electron ionization dissociation (HEEID) (electrons with kinetic energy greater than 13 eV).” P 4). Regarding claim 7, the ‘558 publication discloses the method of claim 1 further comprising ionizing a sample to generate any of said first and 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 wherein said electron energy at which said fragmentation of the precursor ions is less probable is in a range of about 30 eV to about 70 eV (obvious to use this range as a matter of routine optimization or experimentation). Regarding claim 9, the ‘558 publication discloses the method of claim 1 wherein said ion trap comprises a branched RF ion trap (element 200) . 07-22-aia AIA 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 EID-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. Conclusion 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. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert Kim can be reached at 571-272-2293. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. 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If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /ELIZA W OSENBAUGH-STEWART/Primary Examiner, Art Unit 2881 Application/Control Number: 18/569,781 Page 2 Art Unit: 2881 Application/Control Number: 18/569,781 Page 3 Art Unit: 2881 Application/Control Number: 18/569,781 Page 4 Art Unit: 2881 Application/Control Number: 18/569,781 Page 5 Art Unit: 2881 Application/Control Number: 18/569,781 Page 6 Art Unit: 2881 Application/Control Number: 18/569,781 Page 7 Art Unit: 2881 Application/Control Number: 18/569,781 Page 8 Art Unit: 2881 Application/Control Number: 18/569,781 Page 9 Art Unit: 2881 Application/Control Number: 18/569,781 Page 10 Art Unit: 2881 Application/Control Number: 18/569,781 Page 11 Art Unit: 2881