DTAILED 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 § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 7 is rejected under 35 USC § 101 because it is directed to non-statutory subject matter. The claim does not fall within at least one of the four categories of patent eligible subject matter because the broadest reasonable interpretation of the claim, when read in light of the instant specification, covers both non-transitory and transitory forms of signal transmission.
Claim 7 recites “a computer program product storing instructions.” The specification defines the computer program product broadly as “a computer program product for use with a computer system…comprise a series of computer readable instructions either fixed on a tangible medium, such as a nontransitory computer readable medium…also comprise a series of computer readable instructions transmittable to a computer system, via a modem or other interface device, either over a tangible medium… or intangibly using wireless techniques” (10:13-22). Thus, the specification expressly defines the claimed computer program product encompasses both tangible storge media and intangible/transitory signal-based embodiments. Transitory forms of signal transmission, such as propagation electrical or electromagnetic signals, are not a machine, manufacture, or composition of matter and therefore are not statutory subject matter under 35. U.S.C. 101. See In re Nuijten, 500 F.3d 1346, 84 USPQ2d 1495 (Fed. Cir. 2007); Mentor Graphics v. EVE-USA, Inc., 851 F.3d at 1294-95, 112 USPQ2d at 1134; MPEP 2106 – 2106.03.
The rejection of claim 7 under 35 U.S.C. 101 may be overcome by amending the claim such that the claim falls within at least one of the four statutory categories of patent eligible subject matter, for example, amending the claim to encompass only non-transitory computer-readable media.
Claim Rejections - 35 USC § 112
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 1-11 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.
Claims 6-8 each recites “using the average mass for the ion species determined from the mass to charge ratios measured in the second, charge-reduced state to determine an average charge for the ion species in the first state, prior to the charge reduction.” The specification explains that mass and charge information may be inferred from the produced m/z data using “MaxEnt or BayesSpray deconvolution,” and that the average mass determined from the second-state m/z measurements may then be used to determine what the average charge “would have been” for the ion species in the first state (19:23-24 and 5:14-17). However, this disclosure is insufficient to define the scope of the claim. Although the specification identifies deconvolution algorithms such as MaxEnt or BayesSpray for inferring mass and charge information from m/z data, the claim specifically requires using an average mass determined from the second, charge-reduced state to determine an average charge in the unreduced first state. The specification does not explain what first-state m/z value, charge-state envelope, peak group, intensity weighting, or ion population is used with the second-state deconvolved mass to calculate the claimed first-state “average charge.” Nor does merely naming MaxEnt or BayesSpray resolve the ambiguity, because those tools may infer mass/charge information from m/z data, but the claim does not specify which deconvolution output or correlation rule is used to convert the second-state mass determination into the first-state average charge.
Claim 1 recites the limitation ““wherein the step of obtaining an average ion mobility.” There is insufficient antecedent basis for this limitation in the claim since claim 6 (from which claim 1 dependent from) only recites “obtaining an ion mobility for the ion species.”
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 1-11 are rejected under 35 U.S.C. 103 as being unpatentable over US 2015/0219598 A1 [hereinafter Mordehai] in view of US 2012/0156707 A1[hereinafter Hartmer].
Regarding Claims 6-7:
Mordehai teaches:
a method for determining a collision cross section for an ion species (Abstract), the method comprising:
a computer program product storing instructions that when executed by a processor will cause the processor to perform a method for determining a collision cross section for an ion species (para. [0098]: “The executable instructions may be implemented as a computer program product having instructions stored therein which, when executed by a processing module of an electronic system...direct the electronic system to carry out the instructions”), the method comprising:
obtaining an ion mobility for the ion species, wherein the ion mobility has been determined using an ion mobility separation device for the ion species in a first state (paras. [0032, 0068]: IMS 108 includes a drift cell 142, and the method measures “a total drift time taken by the sample ion to travel from an entrance of an ion mobility spectrometry drift cell to an ion detector outside an exit of the drift cell”);
obtaining mass to charge ratios for the ion species, wherein the mass to charge ratios have been measured using a mass spectrometer (para. [0033]: “The MS 116 may generally include a mass analyzer 148 and an ion detector 150,” and the mass analyzer separates/sorts/filters analyte ions based on “their respective m/z ratios,” while the detector measures mass-discriminated ions);
using the average charge determined for the ion species, together with the average mass determined from the ion species, and the ion mobility determined for the ion species, to determine a collision cross section for the ion species (paras. [0008-0009]: CCS is determined by mobility K, charge ze, and ion mass mI under the Mason-Schamp equation).
Mordehai does not expressly teach that, prior to measuring the mass to charge ratios, ions in the first state have been subject to charge reduction to reduce the average charge of the ions and increase the mass to charge ratio spacings between different charge states for the ion species, such that the mass to charge ratios are measured for the ion species in a second, charge-reduced state; processing the mass to charge ratios measured for the ion species in the second, charge-reduced state to determine an average mass for the ion species; and using the average mass determined from the second, charge-reduced state to determine an average charge for the ion species in the first state, prior to charge reduction.
Hartmer teaches:
prior to measuring the mass to charge ratios, ions are subjected to charge reduction to reduce charge and shift/increase the m/z spacing between charge states (paras. [0020, 0024, 0027-0028]: “reducing the number Z of charges of the peptide ions by introducing reactant ions into the RF ion trap”; “acquiring a mass spectrum of the charge-reduced ions”; and the m/z values of charge-reduced ions are shifted out of the isolation mass window);
processing the mass to charge ratios measured for the ion species in the second, charge-reduced state to determine an average mass for the ion species (Claims 1 and 8; para. [0020]: “reduced ions with m/z-values outside this isolation mass window can now be measured as a well-resolved mass spectrum” and “[f]rom these mass spectra, it is possible to determine the masses m … of the digest peptide ions before their charge reduction”);
using the average mass determined from the mass to charge ratios measured in the second, charge-reduced state to determine an average charge for the ion species in the first state, prior to charge reduction (paras. [0020, 0044]: from the charge-reduced mass spectra, it is possible to determine both “the masses m” and “the charge states Z … of the digest peptide ions before their charge reduction”; Hartmer also explains that charge reduction shifts the same ions to higher m/z values by predictable charge-ratio factors, e.g., 4+ ions reduced to 3+, 2+, or 1+ shift by factors of 4/3, 2, or 4, respectively. Thus, Hartmer teaches determining the original/pre-reduction charge state from the charge-reduced mass spectra using the predictable mass-to-charge relationship).
As such, in the modified system, the CCS is determined using the average charge determined for the ion species in the first state, the average mass determined from the ion species in the second, charge-reduced state, and the ion mobility determined for the ion species in the first state, because Mordehai teaches CCS determination using ion mobility, charge, and mass under the Mason-Schamp equation, while Hartmer supplies the charge-reduction processing used to determine the ion mass and original charge state.
Mordehai teaches calculating CCS of a sample ion based on mobility, mass, and charge values, and explains that separating ions by mobility prior to transmission into the MS is “particularly useful in the analysis of complex chemical mixtures, including biopolymers such as polynucleotides, proteins, carbohydrates and the like” (para. [0004]). Hartmer teaches identifying digest peptides in complex protein mixtures by subjecting ions to a mass spectrometric analytical method with very low detection limits in an RF ion trap, where charge reduction shifts the ions outside the isolation mass window and the charge-reduced ions are then measured as a well-resolved mass spectrum with very high sensitivity, permitting determination of ion masses and pre-reduction charge states (paras. [0019-0020]). It would have been obvious to one of ordinary skill in the art, before the effective time of filing, to modify Mordehai’s post-IMS/pre-MS ion processing section to include Hartmer’s charge-reduction process before MS measurement, so that the multiply charged ions are shifted to higher m/z values outside the original isolation window and measured as a well-resolved, high-sensitivity spectrum from which the ion mass and original charge state can be determined. As such, the modified system would obtain more reliable mass and charge inputs for Mordehai’s CCS calculation.
Regarding Claim 8:
Mordehai teaches an ion mobility-mass spectrometer apparatus (Fig. 1A- IM-MS system 100) comprising:
an ion mobility separation device (Fig. 1A-IMS 108);
a mass spectrometer (Fig. 1A-MS116); and
the apparatus further comprising:
a controller (Fig. 1A- the computing device 118) that is configured to: determine an ion mobility for the ion species using the ion mobility separation device, wherein the ion mobility is determined for the ion species in the first state, without charge reduction; measure mass to charge ratios for the ion species using the mass spectrometer, the mass to charge ratio being measured for the ion species in the second, charge-reduced state (as discussed in claim 6);
However, Mordehai does not teach a charge reduction device positioned between the ion mobility separation device and the mass spectrometer, such that ions are passed though the ion mobility separation device in a first state, without charge reduction, whereas ions are passed to the mass spectrometer in a second, charge-reduced state, the controller further process the mass to charge ratios measured for the ion species in the second, charge-reduced state to determine an average mass for the ion species; use the average mass for the ion species determined from the mass to charge ratios measured in the second, charge-reduced state to determine an average charge for the ion species in the first state, prior to the charge reduction; and use the average charge determined for the ion species in the first state, together with the average mass determined from the ion species in the second, charge-reduced state and the ion mobility determined for the ion species in the first state, to determine a collision cross section for the ion species in the first state.
Hartmer teaches process the mass to charge ratios measured for the ion species in the second, charge-reduced state to determine an average mass for the ion species; use the average mass for the ion species determined from the mass to charge ratios measured in the second, charge-reduced state to determine an average charge for the ion species in the first state, prior to the charge reduction; and use the average charge determined for the ion species in the first state, together with the average mass determined from the ion species in the second, charge-reduced state and the ion mobility determined for the ion species in the first state, to determine a collision cross section for the ion species in the first state (as discussed in claim 6).
As such, the combined references teach a charge reduction device positioned between the ion mobility separation device and the mass spectrometer, such that ions are passed though the ion mobility separation device in a first state, without charge reduction, whereas ions are passed to the mass spectrometer in a second, charge-reduced state (Mordehai teaches an ion processing section 112 located between the exit of the IMS drift cell 142 and the entrance of the MS mass analyzer 148, and the ion processing section receives ions eluting from the drift cell and transfers them to the MS (para. [0034]). Hartmer teaches a charge-reduction process/device, i.e., an RF ion trap in which the number Z of charges of peptide ions is reduced by introducing reactant ions, followed by acquiring a mass spectrum of the charge-reduced ions (paras. [0024, 0027-0028]).
Regarding Claim 1:
Mordehai in view of Hartmer teaches the method of claim 6. Mordehai further teaches:
wherein the step of obtaining an average ion mobility for the ion species comprises determining an average ion mobility using an ion mobility separation device (para [0032]: IMS 108 includes drift cell 142, in which ions travel through a drift cell and become separated based on different CCSs/mobilities) and
wherein the step of obtaining mass to charge ratios for the ion species consists of measuring the mass to charge ratios using a mass spectrometer (para. [0033]: MS 116 includes mass analyzer 148 for separating/sorting/filtering analyte ions based on m/z ratios).
Regarding Claims 2 and 9:
Mordehai in view of Hartmer teaches the method of claim 1 and apparatus of claim 8, respectively. Mordehai further teaches wherein the ion mobility separation device comprises a linear drift tube ion mobility separation device (paras. [0002, 0052]: the IMS 108 can be “a gas-phase ion separation technique in which ions become separated in time as they travel through a drift cell (drift tube) of known length containing a buffer gas (drift gas)”).
Regarding Claims 3 and 10:
Mordehai in view of Hartmer teaches the method of claim 1 and apparatus of claim 8, respectively. Hartmer further teaches wherein the charge reduction process comprises electron transfer and/or electron capture (para. [0046]: charge reduction of positive digest peptide ions may be brought about by proton transfer reactions, “but also by electron transfer reactions with special radical anions of low electron affinity,” and if no special dissociation measures are taken, electron transfer “produces mainly charge-reduced ions without dissociation,” i.e., ETnoD).
Regarding Claims 4 and 11:
Mordehai in view of Hartmer teaches the method of claim 1 and apparatus of claim 8, respectively. Hartmer further teaches
wherein the ion species is generated from a sample by an ionisation source (paras. [0019, 0025]: peptides are ionized using an ionization method such as electrospray, which generates multiply charged ions), and
wherein the charge reduction process is set or selected based on the polarity of the ionisation source (para. [0020]: Hartmer teaches “negative reactant ions are used for the charge reduction of positively charged digest peptide ions, and positive reactant ions for the charge reduction of negative digest peptide ions.” Since the polarity of the digest peptide ions is produced by the ionization source/ionization mode, Hartmer renders obvious setting or selecting the charge reduction process based on the polarity of the ionisation source).
Regarding Claim 5:
Mordehai in view of Hartmer teaches the method of claim 2. The combined references further teach wherein the ions are passed in sequence from the ion mobility device to a charge reduction device and then onto the mass spectrometer, so that the measurements for determining ion mobility and mass to charge ratios are performed in single experimental cycle (Mordehai teaches passing ions in sequence from the ion mobility device toward the mass spectrometer in a single IM-MS workflow, and an ion processing section between the drift cell exit and the mass analyzer entrance that receives ions eluting from the drift cell and transfers them to the MS (paras. [0004, 0017, 0034]). Hartmer teaches performing charge reduction before acquiring the mass spectrum of the charge-reduced ions (paras. [0027-0028]). Thus, in the modified system, ions are passed in sequence from Mordehai’s IMS drift cell to a charge-reduction process/device in Mordehai’s post-IMS/pre-MS ion processing section, and then to the MS, so that ion mobility and m/z measurements are performed in one experimental IM-MS cycle).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JING WANG whose telephone number is (571)272-2504. The examiner can normally be reached M-F 7:30-17:00.
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/JING WANG/Examiner, Art Unit 2881
/DAVID E SMITH/Examiner, Art Unit 2881
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