DETAILED ACTION
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 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) 1, 2, 3, 4, 5, 6, 7, 11, 12, 15, 16, 17, 18, 19, 20, 21, and 22 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Baba U.S. PGPUB No. 2019/0378703.
Regarding claim 1, Baba discloses an electron capture dissociation device (ECD) (“Methods and systems are provided herein for selectively removing product ions resulting from an ECD dissociation event” [Abstract]) for use in a mass spectrometer (“an exemplary ECD/PTR mass spectrometer system” [0022]), comprising: a first set of L-shaped electrodes 411 (“the electrodes 411a-d are instead in the form of continuous L-shaped electrodes” [0050] – this is believed to be a typographical error, as figure 4 clearly illustrates only electrodes 411a and 411b, and not electrodes 411c and 411d; this is consistent with the remainder of the description of paragraph [0050]) arranged in a multipole configuration (“By this arrangement and with the proper application of RF voltages (e.g., a sinusoidal RF potential with the phase of each adjacent electrode within and between sets 411a,b being opposite to one another), a quadrupole field can be generated in each of the axial and transverse passages” [0050]), a second set of L-shaped electrodes 412 (as illustrated in figure 4) arranged in a multipole configuration (“By this arrangement and with the proper application of RF voltages (e.g., a sinusoidal RF potential with the phase of each adjacent electrode within and between sets 411a,b being opposite to one another), a quadrupole field can be generated in each of the axial and transverse passages” [0050]), said first and second electrode sets 411 and 412 being positioned relative to one another so as to provide a first channel extending along a longitudinal axis and having a proximal section comprising an inlet (on the left side of figure 4) for receiving a plurality of precursor ions and having a distal section comprising an outlet (on the right side of figure 4) through which ions can exit the first channel (“a first ion optical element disposed adjacent the inlet end of the first set of electrodes and a second ion optical element disposed adjacent the outlet end of the second set of electrodes can be provided” [0019]), and a second channel extending along a transverse axis and intersecting the first channel in an electron-ion interaction region (illustrated in figure 4) in which the precursor ions can interact with the electron beam to generate a plurality of product ions (“introducing electrons into an interaction region of the ion processing device such that the electrons interact with precursor ions within said interaction region to form product ions via electron capture dissociation” [0009]), at least one RF power source for application of one or more RF voltages to said first and second electrode sets (“By this arrangement and with the proper application of RF voltages (e.g., a sinusoidal RF potential with the phase of each adjacent electrode within and between sets 411a,b being opposite to one another), a quadrupole field can be generated in each of the axial and transverse passages” [0050]) for providing a radial confinement electromagnetic field for providing radial confinement of the ions (“RF signals applied thereto (for radial focusing along the central longitudinal axis or transverse axis)” [0046]), one or more auxiliary electrodes 420a, 420b, 420c, 420d (“As above [with respect to the description of figure 3A], lens 420a can function as an ion injection port through which ions can enter the ECD cell 410, while lens 420c and lens 420d can be biased (e.g., via application of an appropriate DC voltage) to block the exit of the ions within the transverse pathway” [0051]) positioned relative to said first and second channels (as illustrated in figure 4) to which DC voltages can be applied for guiding the product ions into any of said proximal and distal sections of the first channel and trapping said product and precursor ions therein (“DC potentials can be applied to the various lenses 320a-d for controlling the movement of ions within the ECD cell 310. For example, as discussed in more detail below, various RF and/or DC signals can be applied to lenses 320a and 320b during various phases of ion processing to facilitate axial trapping of the ions within portions of the space between the electrodes or to facilitate the injection and ejection of ions into and out of the ECD cell 310” [0044] – it is clear from the description of paragraph [0051] that the lenses 420a-d function in the same manner as the lenses 320a-d of figure 3A), and an AC excitation signal source (“electrodes of the first and second sets of electrodes are L-shaped electrodes… applying an auxiliary AC signal to the first and second sets of electrodes so as to selectively reduce the charge of the product ions” [0019]) for applying a dipole AC excitation (the AC excitation described in paragraph [0019] is a dipole excitation since paragraph [0050] identifies that “the phase of each adjacent electrode within and between sets 411a,b being opposite to one another” [0050]) to at least one of said first and second electrode sets so as to resonantly excite at least a portion of a plurality of precursor ions trapped in any of the proximal and distal sections to enter said electron-ion interaction ([0019]).
Regarding claim 2, Baba discloses a system for introducing a gas into any of said longitudinal and transverse ion traps and said electron-ion interaction region (“the ECD cell 310 can be housed within a vacuum chamber (e.g., at sub-atmospheric pressures), with a gas such as helium (He) or nitrogen (N.sub.2) being added to slow the precursor ions' movement within the ECD cell so as to lengthen the interaction time between the precursor ions and the electrons within the interaction region” [0041]).
Regarding claim 3, Baba discloses at least one electron beam source positioned relative to an inlet of said transverse channel for introduction of an electron beam into said transverse channel (“The system can also include an electron source disposed proximate to one of the first and second axial ends of the second pathway for introducing a plurality of electrons along the second central axis such that said electrons travel through said transverse pathway toward said intersection region” [0015]).
Regarding claim 4, Baba discloses that at least electron beam source comprises at least one magnet for generating a magnetic field for guiding the electron beam into said transverse channel (“It will be appreciated that the electron source 106 can, in some aspects, additionally be associated with a magnetic field generator (e.g., a permanent neodymium magnet or an electromagnet, not shown) to control the path of the electrons within the ECD reaction cell” [0033]).
Regarding claim 5, Baba discloses a controller for switching said electron beam source between an ON and an OFF state (“upon termination of the ECD reaction period (e.g., electron source turned off…” [0049]).
Regarding claim 6, Baba discloses that said first and second channels are substantially orthogonal relative to one another (as illustrated in figure 4).
Regarding claim 7, Baba discloses that said dipole AC excitation signal is off-resonance relative to said product ions so as not to cause transfer of said product ions from any of said proximal and distal sections into said electron-ion interaction region (the AC excitation signal causes charge reduction (“electrodes of the first and second sets of electrodes are L-shaped electrodes… applying an auxiliary AC signal to the first and second sets of electrodes so as to selectively reduce the charge of the product ions” [0019]), and not transfer of product ions, which is performed by lenses 320a-d (“DC potentials can be applied to the various lenses 320a-d for controlling the movement of ions within the ECD cell 310. For example, as discussed in more detail below, various RF and/or DC signals can be applied to lenses 320a and 320b during various phases of ion processing to facilitate axial trapping of the ions within portions of the space between the electrodes or to facilitate the injection and ejection of ions into and out of the ECD cell 310” [0044]), which are equivalent to lenses 420a-d in figure 4 (“As above [with respect to the description of figure 3A], lens 420a can function as an ion injection port through which ions can enter the ECD cell 410, while lens 420c and lens 420d can be biased (e.g., via application of an appropriate DC voltage) to block the exit of the ions within the transverse pathway” [0051])).
Regarding claim 11, Baba discloses a controller in communication with said RF, AC, and DC signal sources for controlling operation thereof (the controller is further configured to control at least one of DC and RF voltages… while applying an auxiliary AC signal to the first and second sets of electrodes so as to selectively reduce the charge of the product ions” [0019]).
Regarding claim 12, Baba discloses a DC voltage source for applying a DC voltage to any of said first and second pairs of auxiliary electrodes (“various RF and/or DC signals can be applied to lenses 320a and 320b during various phases of ion processing to facilitate axial trapping of the ions within portions of the space between the electrodes or to facilitate the injection and ejection of ions into and out of the ECD cell 310. Similarly, 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” [0044]).
Regarding claim 15, Baba discloses a mass spectrometer (“an exemplary ECD/PTR mass spectrometer system” [0022]), comprising: an ion guide for receiving a plurality of precursor ions (“the mass spectrometer system 100 can include one or more additional elements upstream therefrom (e.g., an RF-only focusing ion guide Q0…” [0037]), and an electron capture (ECD) device positioned downstream of said ion guide for receiving at least a portion of the ions exiting said ion guide (“the step 202 can comprise trapping the precursor cations within the ECD cell prior to the precursor ions being subject to ECD” [0037]), said ECD device comprising: a first set of L-shaped electrodes 411 (“the electrodes 411a-d are instead in the form of continuous L-shaped electrodes” [0050] – this is believed to be a typographical error, as figure 4 clearly illustrates only electrodes 411a and 411b, and not electrodes 411c and 411d; this is consistent with the remainder of the description of paragraph [0050]) arranged in a multipole configuration (“By this arrangement and with the proper application of RF voltages (e.g., a sinusoidal RF potential with the phase of each adjacent electrode within and between sets 411a,b being opposite to one another), a quadrupole field can be generated in each of the axial and transverse passages” [0050]), a second set of L-shaped electrodes 412 (as illustrated in figure 4) arranged in a multiple configuration (as illustrated in figure 4), said first and second electrode sets 411 and 412 being positioned relative to one another so as to provide a first channel having a proximal section comprising an inlet (on the left side of figure 4) for receiving a plurality of precursor ions and having a distal section comprising an outlet (on the right side of figure 4) through which ions can exit the first channel (“a first ion optical element disposed adjacent the inlet end of the first set of electrodes and a second ion optical element disposed adjacent the outlet end of the second set of electrodes can be provided” [0019]), and a second channel intersecting the first channel in an electron-ion interaction region (illustrated in figure 4) in which the precursor ions can interact with the electron beam to generate a plurality of product ions (“introducing electrons into an interaction region of the ion processing device such that the electrons interact with precursor ions within said interaction region to form product ions via electron capture dissociation” [0009]), at least one RF power source for application of one or more RF voltages to said first and second electrode sets (“By this arrangement and with the proper application of RF voltages (e.g., a sinusoidal RF potential with the phase of each adjacent electrode within and between sets 411a,b being opposite to one another), a quadrupole field can be generated in each of the axial and transverse passages” [0050]) for providing a radial confinement electromagnetic field for providing radial confinement of the ions (“RF signals applied thereto (for radial focusing along the central longitudinal axis or transverse axis)” [0046]), one or more auxiliary electrodes 420a, 420b, 420c, 420d (“As above [with respect to the description of figure 3A], lens 420a can function as an ion injection port through which ions can enter the ECD cell 410, while lens 420c and lens 420d can be biased (e.g., via application of an appropriate DC voltage) to block the exit of the ions within the transverse pathway” [0051]) positioned relative to said first and second channels (as illustrated in figure 4) to which DC voltages can be applied for guiding the product ions into any of said proximal and distal sections of the first channel and trapping said product and precursor ions therein (“DC potentials can be applied to the various lenses 320a-d for controlling the movement of ions within the ECD cell 310. For example, as discussed in more detail below, various RF and/or DC signals can be applied to lenses 320a and 320b during various phases of ion processing to facilitate axial trapping of the ions within portions of the space between the electrodes or to facilitate the injection and ejection of ions into and out of the ECD cell 310” [0044] – it is clear from the description of paragraph [0051] that the lenses 420a-d function in the same manner as the lenses 320a-d of figure 3A), and an AC excitation signal source (“electrodes of the first and second sets of electrodes are L-shaped electrodes… applying an auxiliary AC signal to the first and second sets of electrodes so as to selectively reduce the charge of the product ions” [0019]) for applying an AC excitation to at least one of said first and second electrode sets so as to resonantly excite at least a portion of a plurality of precursor ions trapped in any of the proximal and distal sections to enter said electron-ion interaction ([0019]).
Regarding claim 16, Baba discloses a system for introducing a gas into any of said longitudinal and transverse ion traps and said electron-ion interaction region (“the ECD cell 310 can be housed within a vacuum chamber (e.g., at sub-atmospheric pressures), with a gas such as helium (He) or nitrogen (N.sub.2) being added to slow the precursor ions' movement within the ECD cell so as to lengthen the interaction time between the precursor ions and the electrons within the interaction region” [0041]).
Regarding claim 17, Baba discloses at least one electron beam source positioned relative to an inlet of said transverse channel for introduction of an electron beam into said transverse channel (“The system can also include an electron source disposed proximate to one of the first and second axial ends of the second pathway for introducing a plurality of electrons along the second central axis such that said electrons travel through said transverse pathway toward said intersection region” [0015]).
Regarding claim 18, Baba discloses a controller for switching said electron beam source between an ON and an OFF state (“upon termination of the ECD reaction period (e.g., electron source turned off…” [0049]).
Regarding claim 19, Baba discloses that said first and second channels are substantially orthogonal relative to one another (as illustrated in figure 4).
Regarding claim 20, Baba discloses a DC voltage source for applying a DC voltage to any of said first and second pairs of auxiliary electrodes (“various RF and/or DC signals can be applied to lenses 320a and 320b during various phases of ion processing to facilitate axial trapping of the ions within portions of the space between the electrodes or to facilitate the injection and ejection of ions into and out of the ECD cell 310. Similarly, 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” [0044]).
Regarding claim 21, Baba discloses a mass analyzer positioned downstream of said ECD device for generating a mass spectrum of said product ions (“Reagent ions generated by the charged species source can trapped within the ion processing device for interacting with the product ions removed from the interaction region or can be transmitted through the ion processing device into a downstream mass analyzer for interacting with the product ions so as to concentrate the product ions at a lower charge state” [0014]).
Regarding claim 22, Baba discloses a controller in communication with said RF, AC, and DC signal sources for controlling operation thereof (the controller is further configured to control at least one of DC and RF voltages… while applying an auxiliary AC signal to the first and second sets of electrodes so as to selectively reduce the charge of the product ions” [0019]).
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) 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Baba U.S. PGPUB No. 2019/0378703 in view of Hager et al. U.S. PGPUB No. 2014/0353491.
Regarding claim 8, Baba discloses auxiliary electrode lenses 320a-d (“DC potentials can be applied to the various lenses 320a-d for controlling the movement of ions within the ECD cell 310. For example, as discussed in more detail below, various RF and/or DC signals can be applied to lenses 320a and 320b during various phases of ion processing to facilitate axial trapping of the ions within portions of the space between the electrodes or to facilitate the injection and ejection of ions into and out of the ECD cell 310” [0044]), which are equivalent to lenses 420a-d in figure 4 (“As above [with respect to the description of figure 3A], lens 420a can function as an ion injection port through which ions can enter the ECD cell 410, while lens 420c and lens 420d can be biased (e.g., via application of an appropriate DC voltage) to block the exit of the ions within the transverse pathway” [0051]), but Baba does not disclose that said auxiliary electrodes have a T-shaped structure having a stem portion extending from a base portion.
Hager discloses a quadrupolar configuration (“the quadrupole rod set comprises Q3” [0015]) of an ECD reaction cell (“various dissociation techniques such as… electron capture dissociation (ECD)… have been examined” [0004]), including “T-shaped electrodes” [0051], as illustrated in figures 3A and 3B.
It would have been obvious to one possessing ordinary skill in the art before the effective filing date of the claimed invention to have modified Baba with the T-shaped electrodes of Hager in order to define a sub-volume in a quadrupole in which ions of one polarity can be trapped and through which ions of the opposite polarity can be passed one or more times via the application of various potentials thereby improving selectivity of ions for downstream analysis.
Claim(s) 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Baba U.S. PGPUB No. 2019/0378703.
Regarding claim 13, Baba discloses that “the first auxiliary AC signal applied to the second sets of electrodes exhibits a frequency corresponding to the secular frequency of the precursor ions” [claim 3] and discloses that “a small amplitude auxiliary AC field” [0008]. However, Baba does not explicitly disclose that said AC voltage has a frequency in a range of about 5 to about 500 kHz, or wherein said AC voltage has an amplitude in a range of about 0.1 volts and 10 volts. It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to set the voltage to the claimed frequency and amplitude since it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. One would have been motivated to set the voltage to the claimed frequency and amplitude for the purpose of ensuring a desired amount of ion reaction in an ECD cell so as to maximize the number of fragments of ions for downstream analysis. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235.
Allowable Subject Matter
Claim 9 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Regarding claim 9; Baba U.S. PGPUB No. 2019/0378703 discloses an electron capture dissociation device (ECD) (“Methods and systems are provided herein for selectively removing product ions resulting from an ECD dissociation event” [Abstract]) for use in a mass spectrometer (“an exemplary ECD/PTR mass spectrometer system” [0022]), comprising: a first set of L-shaped electrodes 411 (“the electrodes 411a-d are instead in the form of continuous L-shaped electrodes” [0050] – this is believed to be a typographical error, as figure 4 clearly illustrates only electrodes 411a and 411b, and not electrodes 411c and 411d; this is consistent with the remainder of the description of paragraph [0050]) arranged in a multipole configuration (“By this arrangement and with the proper application of RF voltages (e.g., a sinusoidal RF potential with the phase of each adjacent electrode within and between sets 411a,b being opposite to one another), a quadrupole field can be generated in each of the axial and transverse passages” [0050]), a second set of L-shaped electrodes 412 (as illustrated in figure 4) arranged in a multipole configuration (“By this arrangement and with the proper application of RF voltages (e.g., a sinusoidal RF potential with the phase of each adjacent electrode within and between sets 411a,b being opposite to one another), a quadrupole field can be generated in each of the axial and transverse passages” [0050]), said first and second electrode sets 411 and 412 being positioned relative to one another so as to provide a first channel extending along a longitudinal axis and having a proximal section comprising an inlet (on the left side of figure 4) for receiving a plurality of precursor ions and having a distal section comprising an outlet (on the right side of figure 4) through which ions can exit the first channel (“a first ion optical element disposed adjacent the inlet end of the first set of electrodes and a second ion optical element disposed adjacent the outlet end of the second set of electrodes can be provided” [0019]), and a second channel extending along a transverse axis and intersecting the first channel in an electron-ion interaction region (illustrated in figure 4) in which the precursor ions can interact with the electron beam to generate a plurality of product ions (“introducing electrons into an interaction region of the ion processing device such that the electrons interact with precursor ions within said interaction region to form product ions via electron capture dissociation” [0009]), at least one RF power source for application of one or more RF voltages to said first and second electrode sets (“By this arrangement and with the proper application of RF voltages (e.g., a sinusoidal RF potential with the phase of each adjacent electrode within and between sets 411a,b being opposite to one another), a quadrupole field can be generated in each of the axial and transverse passages” [0050]) for providing a radial confinement electromagnetic field for providing radial confinement of the ions (“RF signals applied thereto (for radial focusing along the central longitudinal axis or transverse axis)” [0046]), one or more auxiliary electrodes 420a, 420b, 420c, 420d (“As above [with respect to the description of figure 3A], lens 420a can function as an ion injection port through which ions can enter the ECD cell 410, while lens 420c and lens 420d can be biased (e.g., via application of an appropriate DC voltage) to block the exit of the ions within the transverse pathway” [0051]) positioned relative to said first and second channels (as illustrated in figure 4) to which DC voltages can be applied for guiding the product ions into any of said proximal and distal sections of the first channel and trapping said product and precursor ions therein (“DC potentials can be applied to the various lenses 320a-d for controlling the movement of ions within the ECD cell 310. For example, as discussed in more detail below, various RF and/or DC signals can be applied to lenses 320a and 320b during various phases of ion processing to facilitate axial trapping of the ions within portions of the space between the electrodes or to facilitate the injection and ejection of ions into and out of the ECD cell 310” [0044] – it is clear from the description of paragraph [0051] that the lenses 420a-d function in the same manner as the lenses 320a-d of figure 3A), and an AC excitation signal source (“electrodes of the first and second sets of electrodes are L-shaped electrodes… applying an auxiliary AC signal to the first and second sets of electrodes so as to selectively reduce the charge of the product ions” [0019]) for applying a dipole AC excitation (the AC excitation described in paragraph [0019] is a dipole excitation since paragraph [0050] identifies that “the phase of each adjacent electrode within and between sets 411a,b being opposite to one another” [0050]) to at least one of said first and second electrode sets so as to resonantly excite at least a portion of a plurality of precursor ions trapped in any of the proximal and distal sections to enter said electron-ion interaction ([0019]). However, Baba does not disclose that said auxiliary electrodes have a T-shaped structure having a stem portion extending from a base portion.
Hager et al. U.S. PGPUB No. 2014/0353491 discloses a quadrupolar configuration (“the quadrupole rod set comprises Q3” [0015]) of an ECD reaction cell (“various dissociation techniques such as… electron capture dissociation (ECD)… have been examined” [0004]), including “T-shaped electrodes” [0051], as illustrated in figures 3A and 3B. However, there is no explicit disclosure that said auxiliary electrodes are positioned on opposed sides of a first channel with their stem portions extending to proximity of a longitudinal axis that has a proximal section comprising an inlet for receiving a plurality of precursor ions and having a distal section comprising an outlet through which ions can exit the first channel, or wherein a second pair of said auxiliary electrodes are positioned on opposed sides of a second channel with their stem portions extending to proximity of a transverse axis intersecting the first channel in an electron-ion interaction region in which the precursor ions can interact with the electron beam to generate a plurality of product ions.
The prior art fails to teach or reasonably suggest, in combination with the other claim limitations, an electron capture dissociation device (ECD) for use in a mass spectrometer, comprising: auxiliary electrodes that are positioned on opposed sides of a first channel with their stem portions extending to proximity of a longitudinal axis that has a proximal section comprising an inlet for receiving a plurality of precursor ions and having a distal section comprising an outlet through which ions can exit the first channel, or wherein a second pair of said auxiliary electrodes are positioned on opposed sides of a second channel with their stem portions extending to proximity of a transverse axis intersecting the first channel in an electron-ion interaction region in which the precursor ions can interact with the electron beam to generate a plurality of product ions.
Conclusion
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/JASON L MCCORMACK/Examiner, Art Unit 2881