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 .
Response to Arguments
Applicant’s arguments, see pages 2-7, filed 08/10/2026, with respect to the rejection(s) of claims 10-11, 13, 17, 19-20 and 22-23 under 35 U.S.C. 102(a)(1) and claims 1-5 and 21 under 35 U.S.C. 103 and have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Akihiro Sano (US 7473892 B2), hereinafter referred to as Sano in view of Ogra.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 18 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 18 is dependent on claim 17. Claim 17 recites “the processing comprises confining the first ions in the ion trap while collisionally damping the first ions with the deuterium gas”. Claim 18 later recites “processing the first ions comprises collisionally cooling the first ions”. Collisional damping refers to collisions resulting in less kinetic energy of the ions. Collisional cooling also refers to collisions resulting in less kinetic energy of the ions. Therefore, claim 18 does not further limit the processing limitation recited in claim 17.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 24 and 25 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 24 recites “wherein the deuterium gas is a background or buffer gas”. Claim 24 is dependent on claim 1 which recites “the ion trap is filled with deuterium gas to induce collisional damping of ion in the ion trap”. The specifications explain “Ion traps utilize a background or buffer gas to induce collisional damping and thus increase mass resolution and sensitivity” (para. [0006]). It is unclear how the limitation of claim 24 further limits the deuterium gas.
Claim 25 recites “wherein the deuterium gas is used as a background or buffer gas”. Claim 25 is dependent on claim 10 which recites “wherein the deuterium gas is used to induce collisional damping of ions in the ion trap”. The specifications explain “Ion traps utilize a background or buffer gas to induce collisional damping and thus increase mass resolution and sensitivity” (para. [0006]). It is unclear how the limitation of claim 25 further limits the deuterium gas.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 1-3, 5, 10-13, 16-20, and 24-25 are rejected under 35 U.S.C. 103 as being unpatentable over Sano in view of Ogra.
Regarding claim 1, An analytical instrument comprising an ion trap, wherein the ion trap is a mass analyzer (As shown in FIG. 22a, in this embodiment, an ion trap mass spectroscopy unit is provided as the mass spectroscopy unit (col. 21, lines 43-45));
and the ion trap is filled with gas (When collision induced dissociation (CID) is used as the dissociation method during tandem mass spectroscopy, the ion trap itself in which the neutral gas, such as He gas, is filled functions as a collision cell, there is no need to provide a separate collision cell (col. 21, lines 54-58)).
Sano fails to teach the ion trap is filled with deuterium gas to induce collisional damping of ion in the ion trap.
However, Ogra teaches an ion trap filled with deuterium gas to induce collisional damping of ion in the ion trap (Table 1 below).
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Ogra teaches an octopole collision cell filled with deuterium gas, wherein an octopole is a type of ion trap.
Further, Ogra teaches the use of deuterium for collisional damping. Collisional damping refers to collisions resulting in less kinetic energy of the ion. Collisional dissociation is a technique used to induce fragmentation of selected ions. Ogra teaches using Deuterium gas as an effective gas for dissociating polyatomic interferences and removing bromine interferences during Se determination and speciation (Ogra; Abstract). As shown in Fig. 4 of Ogra, some of the ion readings do not change between the non-reaction mode and the deuterium reaction mode. From this we can surmise these ions are not dissociating in the deuterium. However, since the ions are in the gas, they must interact kinetically. If ions are in the gas interacting kinetically, but not dissociating, then the gas is acting as a damping gas. Therefore, Ogra teaches the use of deuterium gas to induce collisional damping of ion.
As explained by Ogra, “Se speciation techniques are essential to reveal the biological effects of Se on the human body” (Ogra; para. [0002]). Further, Ogra finds “the D2 reaction mode provides more accurate results for Se detection in extracellular fluids” (Ogra; conclusion). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device described in Sano to include the teachings of Ogra by using the ion trap of Sano with deuterium as a reaction gas for selenium detection. Doing so is motivated by the need to further understand the physiological and toxicological effects of Se.
Regarding claim 2, Sano teaches the analytical instrument of claim 1, wherein the analytical instrument comprises a mass spectrometer (As shown in FIG. 22a, in this embodiment, an ion trap mass spectroscopy unit is provided as the mass spectroscopy unit (col. 21, lines 43-45)).
Regarding claim 3, Sano teaches the analytical instrument of claim 1, wherein the ion trap is a quadrupole ion trap (Thus, in the ion trap, there is mainly generated a high-frequency quadrupole electric field (col. 21, lines 51-52)).
Regarding claim 5, Sano teaches the analytical instrument of claim 1, wherein the analytical instrument comprises a chromatography system in combination with a mass spectrometer (FIG. 2. In the mass spectroscopy system 19, a sample as the object of analysis is preprocessed in a preprocessing system 11, such as a liquid chromatography. For example, if the sample is a protein, the protein is broken up by a digestive enzyme into the size of polypeptides, and then separated and fractionated by gas chromatography (GC) or liquid chromatography (LC) in a preprocessing system 11. (col. 8, lines 3-9)).
Regarding claim 10, Sano teaches the ion trap is a mass analyzer (As shown in FIG. 22a, in this embodiment, an ion trap mass spectroscopy unit is provided as the mass spectroscopy unit (col. 21, lines 43-45)).
Sano fails to teach a method of using a gas in an analytical instrument, the method comprising: using a deuterium gas in an ion trap, wherein the deuterium gas is used to induce collisional damping of ions in the ion trap.
However, Ogra teaches teach a method of using a gas in an analytical instrument, the method comprising: using a deuterium gas in an ion trap (In this study, the utility of deuterium (D2) in place of H2 as a reaction gas was clarified (para. [0004])) (table 1 as annotated above).
The reaction cell in Ogra is an octopole reaction cell which is a type of ion trap. Therefore, the reaction cell contains an ion trap in which deuterium is used as a primary gas.
Further, Ogra teaches wherein the deuterium gas is used to induce collisional damping of ions in the ion trap.
Ogra teaches the use of deuterium for collisional damping. Collisional damping refers to collisions resulting in less kinetic energy of the ion. Collisional dissociation is a technique used to induce fragmentation of selected ions. Ogra teaches using Deuterium gas as an effective gas for dissociating polyatomic interferences and removing bromine interferences during Se determination and speciation (Ogra; Abstract). As shown in Fig. 4 of Ogra, some of the ion readings do not change between the non-reaction mode and the deuterium reaction mode. From this we can surmise these ions are not dissociating in the deuterium. However, since the ions are in the gas, they must interact kinetically. If ions are in the gas interacting kinetically, but not dissociating, then the gas is acting as a damping gas. Therefore, Ogra teaches the use of deuterium gas to induce collisional damping of ion.
As explained by Ogra, “Se speciation techniques are essential to reveal the biological effects of Se on the human body” (Ogra; para. [0002]). Further, Ogra finds “the D2 reaction mode provides more accurate results for Se detection in extracellular fluids” (Ogra; conclusion). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device described in Sano to include the teachings of Ogra by using the ion trap of Sano with deuterium as a reaction gas for selenium detection, such that the deuterium gas is used to induce collisional damping of ions in the ion trap. Doing so is motivated by the need to further understand the physiological and toxicological effects of Se.
Regarding claim 11, Sano teaches the method of claim 10, further comprising using the ion trap in a mass spectrometer (The mass spectrometer is a quadrupole ion trap time-of-flight mass spectrometer (col. 12, lines 39-40)) in combination with a chromatography system (FIG. 2. In the mass spectroscopy system 19, a sample as the object of analysis is preprocessed in a preprocessing system 11, such as a liquid chromatography. For example, if the sample is a protein, the protein is broken up by a digestive enzyme into the size of polypeptides, and then separated and fractionated by gas chromatography (GC) or liquid chromatography (LC) in a preprocessing system 11. (col. 8, lines 3-9)).
Regarding claim 12, Sano teaches the method of claim 11, wherein the chromatography system is a gas chromatography system (FIG. 2. In the mass spectroscopy system 19, a sample as the object of analysis is preprocessed in a preprocessing system 11, such as a liquid chromatography. For example, if the sample is a protein, the protein is broken up by a digestive enzyme into the size of polypeptides, and then separated and fractionated by gas chromatography (GC) or liquid chromatography (LC) in a preprocessing system 11. (col. 8, lines 3-9)).
Regarding claim 13, Sano teaches the method of claim 11, wherein the chromatography system is a liquid chromatography system (FIG. 2. In the mass spectroscopy system 19, a sample as the object of analysis is preprocessed in a preprocessing system 11, such as a liquid chromatography. For example, if the sample is a protein, the protein is broken up by a digestive enzyme into the size of polypeptides, and then separated and fractionated by gas chromatography (GC) or liquid chromatography (LC) in a preprocessing system 11. (col. 8, lines 3-9)).
Regarding claim 16, Sano teaches the method of claim 10, wherein the ion trap is a quadrupole ion trap (The mass spectrometer is a quadrupole ion trap time-of-flight mass spectrometer (col. 12, lines 39-40)).
Regarding claim 17, Sano teaches a method of mass spectrometry, the method comprising: generating first ions (After the separation and fractionation of the sample, the sample is ionized in an ionization unit 12); wherein the ion trap is a mass analyzer (As shown in FIG. 22a, in this embodiment, an ion trap mass spectroscopy unit is provided as the mass spectroscopy unit (col. 21, lines 43-45)).
Sano fails to teach processing the first ions in an ion trap filled with a deuterium gas, the processing comprises confining the first ions in the ion trap while collisionally damping the first ions with the deuterium gas; and analysing the first ions or second ions derived from the first ions or both.
However, Ogra teaches processing the first ions in an ion trap filled with a deuterium gas (Ogra; Table 1 above), the processing comprises confining the first ions in the ion trap while collisionally damping the first ions with the deuterium gas (D2 reaction mode (Section 3.1, para. [0001]));
Ogra teaches an octopole collision cell filled with deuterium gas, wherein an octopole is a type of ion trap.
Further, Ogra teaches the use of deuterium for collisional damping ions. Collisional damping refers to collisions resulting in less kinetic energy of the ion. Collisional dissociation is a technique used to induce fragmentation of selected ions. Ogra teaches using Deuterium gas as an effective gas for dissociating polyatomic interferences and removing bromine interferences during Se determination and speciation (Ogra; Abstract). This is conducted in an ion trap filled with deuterium gas. As shown in Fig. 4 of Ogra, some of the ion readings do not change between the non-reaction mode and the deuterium reaction mode. From this we can surmise these ions are not dissociating in the deuterium. However, since the ions are confined in the ion trap in the gas, they must interact kinetically. If ions are in the gas interacting kinetically, but not dissociating, then the gas is acting as a damping gas. Therefore, Ogra teaches the use of deuterium gas to induce collisional damping of ions confined in the ion trap.
Finally, Ogra teaches analysing the first ions (Hence, the effects of D2 not only on the determination but also on the speciation of Se in ICP-MS were evaluated (Introduction; para. [0004])) or second ions derived from the first ions or both.
As explained by Ogra, “Se speciation techniques are essential to reveal the biological effects of Se on the human body” (Ogra; para. [0002]). Further, Ogra finds “the D2 reaction mode provides more accurate results for Se detection in extracellular fluids” (Ogra; conclusion). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device described in Sano to include the teachings of Ogra by using the ion trap of Sano with deuterium as a reaction gas for selenium detection. Doing so is motivated by the need to further understand the physiological and toxicological effects of Se.
Regarding claim 18, Sano fails to teach the method of claim 17, wherein processing the first ions comprises collisionally cooling the first ions (D2 reaction mode (Section 3.1, para. [0001])).
However, Ogra teaches wherein processing the first ions comprises collisionally cooling the first ions.
Ogra teaches the use of deuterium for collisional cooling. Collisional cooling refers to collisions resulting in less kinetic energy of the ion. Collisional dissociation is a technique used to induce fragmentation of selected ions. Ogra teaches using Deuterium gas as an effective gas for dissociating polyatomic interferences and removing bromine interferences during Se determination and speciation (Ogra; Abstract). As shown in Fig. 4 of Ogra, some of the ion readings do not change between the non-reaction mode and the deuterium reaction mode. From this we can surmise these ions are not dissociating in the deuterium. However, since the ions are in the gas, they must interact kinetically. If ions are in the gas interacting kinetically, but not dissociating, then the gas is acting as a cooling gas. Therefore, Ogra teaches the use of deuterium gas to induce collisional cooling of the ions.
Regarding claim 19, Sano fails to teach the method of claim 17, wherein processing the first ions comprises fragmenting the first ions by colliding them with the deuterium gas to produce fragment ions, and the analysing comprises analysing the fragment ions.
However, Ogra teaches the method of claim 17, wherein processing the first ions comprises fragmenting the first ions by colliding them with the deuterium gas to produce fragment ions, and the analysing comprises analysing the fragment ions (Thus, D2 was effective in dissociating polyatomic interferences and removing Br interferences during Se determination and speciation (abstract)) (In the D2 reaction mode, the interference was well dissociated at m/z 82, and the formation of 81Br2D+ was newly observed at m/z 83. 82Se1H+ and 82Se2D+ were detected at m/z 83 and 84, respectively (para. [0012])).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device described in Sano to include the teachings of Orga such that the first ions are fragmented by colliding them with deuterium gas and analysing the fragment ions. Doing so overcomes the problems posed by the polyatomic interferences for Se detection and lends to understanding the physiological and toxicological effects of Se.
Regarding claim 20, Sano fails to teach the method of claim 17, wherein processing the first ions comprises reacting the first ions with the deuterium gas to produce secondary ions, and the analysing comprises analysing the secondary ions.
However, Ogra teaches the method of claim 17, wherein processing the first ions comprises reacting the first ions with the deuterium gas (In this study, deuterium (D2) was evaluated for possible use as a reaction gas) to produce secondary ions, and the analysing comprises analysing the secondary ions ((Thus, D2 was effective in dissociating polyatomic interferences and removing Br interferences during Se determination and speciation (abstract)) (In the D2 reaction mode, the interference was well dissociated at m/z 82, and the formation of 81Br2D+ was newly observed at m/z 83. 82Se1H+ and 82Se2D+ were detected at m/z 83 and 84, respectively (para. [0012])).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device described in Sano to include the teachings of Ogra by reacting the first ions with the deuterium gas to produce secondary ions, analysing the secondary ions. Doing so overcomes the problems posed by the polyatomic interferences for Se detection and lends to understanding the physiological and toxicological effects of Se.
Regarding claim 24, Sano fails to teach the analytical instrument of claim 1, wherein the deuterium gas is a background or buffer gas.
However, Ogra teaches wherein the deuterium gas is a background or buffer gas (Table 1 above).
The specifications explain “[i]on traps utilize a background or buffer gas to induce collisional damping and thus increase mass resolution and sensitivity” (para. [0006]). Ogra teaches the use of deuterium for collisional damping. Collisional damping refers to collisions resulting in less kinetic energy of the ion. Collisional dissociation is a technique used to induce fragmentation of selected ions. Ogra teaches using Deuterium gas as an effective gas for dissociating polyatomic interferences and removing bromine interferences during Se determination and speciation. As shown in Fig. 4 of Ogra, some of the ion readings do not change between the non-reaction mode and the deuterium reaction mode. From this we can surmise these ions are not dissociating in the deuterium. However, since the ions are in the gas, they must interact kinetically. If ions are in the gas interacting kinetically, but not dissociating, then the gas is acting as a damping gas. Therefore, Ogra teaches the use of deuterium gas as a background or buffer gas.
Regarding claim 25, Sano fails to teach the method of claim 10, wherein the deuterium gas is used as a background or buffer gas.
However, Ogra teaches wherein the deuterium gas is used as a background or buffer gas (Table 1 above).
The specifications explain “[i]on traps utilize a background or buffer gas to induce collisional damping and thus increase mass resolution and sensitivity” (para. [0006]). Ogra teaches the use of deuterium for collisional damping. Collisional damping refers to collisions resulting in less kinetic energy of the ion. Collisional dissociation is a technique used to induce fragmentation of selected ions. Ogra teaches using Deuterium gas as an effective gas for dissociating polyatomic interferences and removing bromine interferences during Se determination and speciation. As shown in Fig. 4 of Ogra, some of the ion readings do not change between the non-reaction mode and the deuterium reaction mode. From this we can surmise these ions are not dissociating in the deuterium. However, since the ions are in the gas, they must interact kinetically. If ions are in the gas interacting kinetically, but not dissociating, then the gas is acting as a damping gas. Therefore, Ogra teaches the use of deuterium gas as a background or buffer gas.
Claims 6-7 and 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Sano in view of Ogra, and in further view of Hatanaka.
Regarding claim 6, Sano does not teach wherein the gas is provided by a cylinder of deuterium gas.
However, Hatanaka teaches wherein the gas is provided by a cylinder of deuterium gas (gas cylinder 14).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device described in Sano such that the deuterium gas is stored in a cylindrical container in order to achieve the predictable result of safely storing the deuterium gas at high pressures.
Regarding claim 7, Sano does not explicitly teach wherein the gas is provided by a deuterium generator.
However, Hatanaka teaches wherein the gas is provided by a deuterium generator (Further, as a method for supplying deuterium, it is possible not only to easily control the amount of deuterium atoms generated by passing through a diffusion and permeation process in the Pd film, but also to reduce the mixing of impurity gas (para. [0020])).
It would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device described in Sano to include a deuterium generator, taught by Hatanaka, to provide deuterium to the ion trap.
Regarding claim 14, Sano fails to teach the method of claim 12, further comprising providing the deuterium gas via a deuterium gas generator system or via a compressed cylinder of deuterium gas.
However, Hatanaka teaches further comprising providing the deuterium gas via a deuterium gas generator system or via a compressed cylinder of deuterium gas (deuterium gas cylinder 14).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device described in Sano such that the deuterium gas is stored in a cylindrical container in order to achieve the predictable result of safely storing the deuterium gas at high pressures.
Regarding claim 15, Sano fails to teach the method of claim 13, further comprising providing the deuterium gas via a deuterium gas generator system or via a compressed cylinder of deuterium gas.
However, Hatanaka teaches, further comprising providing the deuterium gas via a deuterium gas generator system or via a compressed cylinder of deuterium gas (deuterium gas cylinder 14).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the device described in Ogra such that the deuterium gas is stored in a cylindrical container in order to achieve the predictable result of safely storing the deuterium gas at high pressures.
Claims 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over Sano in view of Ogra, and in further view of Enke.
Regarding claim 8, Sano does not explicitly teach the analytical instrument of claim 1, wherein the gas is provided at a pressure of at least 0.1 mTorr.
However, Enke teaches wherein the gas is provided at a pressure of at least 0.1 mTorr (A collision gas, which may be argon, is introduced into the quadrupole-type device at pressures up to 2.times.10.sup.-3 torr, or even higher (col. 6, lines 2-4)) (.002 Torr= 2 mTorr).
Optimizing the pressure of a collision gas in mass spectrometry is well within the bounds of normal experimentation. See MPEP 2144.05 II (A). “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to dis-cover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Furthermore, “[a] particular parameter must first be recognized as a result-effective variable, i.e., a variable which achieves a recognized result, before the determination of the optimum or workable ranges of said variable might be characterized as routine experimentation.” In re Antonie, 559 F.2d 618, 195 USPQ 6 (CCPA 1977). In the case at hand, Enke teaches that “The collection efficiency in the quadrupole CID region has been found experimentally to be virtually 100%. There is no detectable loss of ions due to scattering, neutralization, or similar mechanisms at pressures up to 2.times.10.sup.-4 torr (col. 12, lines 5-9)” . As such, Enke identifies gas pressure as a variable which achieves a recognized result, i.e., [minimizing the loss of ions due to scattering, neutralization, or similar mechanisms]. Accordingly, it would have been obvious to one of ordinary skill in the art before the effective time of filing to optimize gas pressure in Sano, in view of Ogra, such that the gas, taught by Ogra to be Deuterium, is provided at atleast 0.1 mTorr, as taught by Enke, since it is not inventive to dis-cover the optimum or workable ranges by routine experimentation.
Regarding claim 9, Sano fails to teach the analytical instrument of claim 8, wherein the gas is provided at a pressure of about 1 mTorr to about 10 mTorr.
However, Enke teaches wherein the gas is provided at a pressure of about 1 mTorr to about 10 mTorr (A collision gas, which may be argon, is introduced into the quadrupole-type device at pressures up to 2.times.10.sup.-3 torr, or even higher(col. 6, lines 2-4)) (.002 Torr= 2 mTorr).
Conclusion
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/MICA JILLIAN EINHORN/ Examiner, Art Unit 2881
/ROBERT H KIM/Supervisory Patent Examiner, Art Unit 2881
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