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 filed on 06/30/2026 have been fully considered but they are not persuasive.
The indefiniteness rejections of record are withdrawn in light of applicant’s amendments.
The U.S.C. 103 rejections to independent claims 1 and 19 and their dependent claims of record are withdrawn in light of applicant’s amendments.
Regarding 103 rejection for amended independent claim 10:
Applicant argues that amended claim 10 are patentable because Remes, Hauschild, and Moor do not teach or suggest the newly added limitations (which are incorporated from previously presented claims 13 and 14). This argument is not persuasive.
Amended claim 10 does not recite any special criterion for selecting the “additional range of m/z values,” nor does it require that the additional range be selected due to m/z-dependent ion transfer efficiency, variable ion cloud sizes, or C-trap operation. Rather, amended claim 10 broadly requires only that the same type of analysis already recited for one m/z range also be performed for an additional m/z range, and that the resulting second-ion-population totals be combined into an overall total. As explained in the Non-Final Office Action, because the claims do not require any special selection criterion for either range, there would have been no meaningful difference between performing the known claim-10 analysis for the first range and performing those same steps for the additional range. It therefore would have been obvious to repeat the same total-ion-count/peak-ion-count analysis for another selected range of the same mass spectrum. Further, once the total ion count of the second ion population is determined for the first range and the additional range, it would have been obvious to determine an overall total ion count across both ranges by combining those range-specific totals, since the overall total is simply the aggregate of partial totals for different regions of the same second-ion-population spectrum.
Accordingly, Applicant’s amendment to claim10 does not overcome the rejection.
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 10-11 and 15-18 are rejected under 35 U.S.C. 103 as being unpatentable over US 2015/0364303 A1 [hereinafter Remes] in view of US 2014/0061460A1 [hereinafter Hauschild] and US 2013/0035867 A1 [hereinafter Moor].
Regarding Claim 10:
Remes teaches a system (a MS system includes hybrid MS analyzers) comprising:
an electron multiplier-based mass analyzer configured to perform a mass analysis on a first ion population produced from a sample (para. [0027]: “a first group of ions generated by ion source 110... and mass analyzed in quadrupole ion trap mass analyzer 150”);
a controller (Fig.1 -instrument controller) configured to
determine, based on the mass analysis performed by the electron multiplier-based mass analyzer, a mass spectrum comprising one or more peaks representing intensity as a function of mass-to-charge ratio (m/z) of the first ion population across a range of m/z values (Claim 1 and paras. [0027-0028]: “mass analyzing the first ion group to generate a mass spectrum”; the first ion group is mass analyzed to generate a mass spectrum, and that selected-ion abundances are read from peaks in that spectrum), and
determine, based on the mass spectrum, a peak ion count associated with a peak located at a particular m/z value within the range of m/z values (para. [0028]: “the abundances are determined for a set of selected ion species...in the mass spectrum produced in step 210... the abundance for a particular ion species is determinable from the height or integrated area of its peak in the mass spectrum”); and
an image current-based mass analyzer configured to perform, subsequent to the mass analysis performed by the electron multiplier-based mass analyzer, a mass analysis on a second ion population produced from the sample (para. [0042]: “a second group of ions is accumulated to the target ion population value determined in step 240, and the accumulated second ion group is mass analyzed in FT analyzer 140”);
However, Remes does not specifically note that determine, based on the mass spectrum, a total ion count of the first ion population across the range of m/z values; determine, based on the mass analysis performed by the image current-based mass analyzer on the second ion population, an additional mass spectrum comprising one or more peaks representing intensity as a function of m/z of the second ion population across the range of m/z values, determine, based on the additional mass spectrum, an additional peak ion count associated with a peak located at the particular m/z value within the range of m/z values, and determine, based on the total ion count of the first ion population, the peak ion count, and the additional peak ion count, a total ion count of the second ion population. In addition, Remes does not teach wherein the mass spectrum further comprises one or more additional peaks representing intensity as a function of mass-to-charge ratio (m/z) of the first ion population across an additional range of m/z values, and wherein the process further comprises: determining, based on the mass spectrum, an additional total ion count of the first ion population across the additional range of m/z values and an additional peak ion count associated with an additional peak located at a particular m/z value within the additional range of m/z values; and determining, based on the additional total ion count and the additional peak ion count, an additional total ion count of the second ion population across the additional range of m/z values; and determining, based on the total ion count of the second ion population and the additional total ion count of the second ion population, an overall total ion count of the second ion population across both the range of m/z values and the additional range of m/z values.
Hauschild teaches:
determine, based on the mass spectrum, a total ion count of the first ion population across the range of m/z values (para. [0035]: “The previous detected signal is preferably used to determine a total ion content (or ion number) of the ions in the previous batch in the analyser”);
determine, based on the mass analysis performed by the image current-based mass analyzer on the second ion population, an additional mass spectrum comprising one or more peaks representing intensity as a function of m/z of the second ion population across the range of m/z values (para. [0028]: “From the detected signal using image current detection in the mass analyser, a mass spectrum may thereby be obtained, typically using Fourier transformation”),
As such, Remes in view of Hauschild teaches:
determine, based on the additional mass spectrum, an additional peak ion count associated with a peak located at the particular m/z value within the range of m/z values. Since Remes teaches the routine use of peak height / area to obtain abundance from a spectrum, while Hauschild teaches that image-current detection produces a mass spectrum; together they suggest that once the image-current analyzer has produced the second spectrum, the abundance of a particular peak at the chosen m/z can be determined in the same routine way as for the first spectrum.
In addition, Hauschild teaches a ratio-based scaling of total ion content for the image current based analyzer between reference and target conditions (see Hauschild para. [0041]). However, Hauschild does not teach determine, based on the total ion count of the first ion population, the peak ion count, and the additional peak ion count, a total ion count of the second ion population.
Moor explains that TIC-based normalization is a standard normalization approach and teaches that peak heights from different mass spectra are projected onto a common intensity scale and compared across spectra (see Moor paras. [0007 and 0114]). As such, Hauschild in view of Moor teaches the determination step for the total ion count of the second ion group. In the modified system, the total ion count of the first ion population provides the refence total ion baseline, while the peak ion count from the first mass spectrum and the additional peak ion count from the second mass spectrum provide the cross spectrum peak quantities used in the normalization relationship taught by Moor, which is then used within Hauschild’s scaling framework to determine the total ion count of the second ion population injected into the image current based mass analyzer, as recited in claim 10.
In addition, the combined references teach wherein the mass spectrum further comprises one or more additional peaks representing intensity as a function of mass-to-charge ratio (m/z) of the first ion population across an additional range of m/z values, and wherein the process further comprises: determining, based on the mass spectrum, an additional total ion count of the first ion population across the additional range of m/z values and an additional peak ion count associated with an additional peak located at a particular m/z value within the additional range of m/z values; and determining, based on the additional total ion count and the additional peak ion count, an additional total ion count of the second ion population across the additional range of m/z values; and determining, based on the total ion count of the second ion population and the additional total ion count of the second ion population, an overall total ion count of the second ion population across both the range of m/z values and the additional range of m/z values. The determination steps of additional total ion count of the first ion population and the additional total ion count of the second ion population merely repeats the previous steps for an additional range for m/z values of the same mass spectrum. Because the claims do not require any special selection criterion for either range, there would have been no meaningful difference between performing the determination steps for the first range and performing those same steps for the additional range. Further, since once the total ion count for the second population is determined for the first ion range and the additional ion range, it would have been obvious to determine an overall total ion count across both ranges by combining those range specific totals.
Regarding Claim 11:
The combined references teach the system of claim10. Hauschild further teaches wherein the controller is further configured to set, based on the total ion count of the second ion population, a calibration parameter for the image current-based mass analyzer (paras. [0022-0023, 0040-0041]: “The image current detector needs to be calibrated in order to measure absolute numbers of ions in a pre-scan”; determine “a total ion content (or ion number) of the ions in the previous batch in the analyser” from the detected signal, and the algorithm for the image current based analyzer includes “a calibration coefficient C” and that adjustment of the algorithm parameter(s) “comprises a calibration for the previous detected signal obtained using image current detection”).
Regarding Claim 15:
The combined references teach the system of claim 10. Remes further teaches:
directing an ion source to inject the first ion population into the electron multiplier-based mass analyzer as part of a pre-scan operation (para. [0027]: In “step 210, first group of ions generated by ion source 110 and delivered by ion optics 120 of mass spectrometer 100…and mass analyzed in quadrupole ion trap mass analyzer 150… the mass analysis scan (prescan) may be performed in ion trap mass analyzer”); and
directing the ion source to inject the second ion population into the image current-based mass analyzer as part of a mass spectrometry acquisition operation performed subsequent to the pre-scan operation (para. [0042]: “Next, in step 250 a second group of ions is accumulated to the target ion population value determined in step 240, and the accumulated second ion group is mass analyzed in FT analyzer”).
Regarding Claim 16:
The combined references teach the system of claim 10. Remes further teaches wherein the electron multiplier-based mass analyzer is implemented by a linear ion trap or a time-of-flight mass analyzer (para. [0027]: teaches a quadrupole ion trap mass analyzer for the first analysis).
Regarding Claim 17:
The combined references teach the system of claim 10. Remes further teaches wherein the image current-based mass analyzer is implemented by an orbital electrostatic trap mass analyzer or a Fourier transform ion cyclotron resonance mass analyzer (para. [0022]: “FT analyzer 140… is commercially available... include ion cyclotron resonance (ICR) mass analyzers”).
Regarding Claim 18:
The combined references teach the system of claim 10. Remes further teaches wherein the sample is produced using a liquid chromatography procedure (para. [0021]: “Ion source 110 may take the form of any suitable source known in the art for ionizing a sample material (e.g., the eluate from a liquid chromatography column)”).
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over US Remes in view of Hauschild and Moor, and further in view of US 2023/0046906 A1 [hereinafter Jarrold].
Regarding Claim 12:
Hauschild teaches for “mass spectrometry employing image current detection of ions… mass analysers having a trapping volume therein in which the ions may be trapped and preferably oscillate with a frequency which depends on their mass-to- charge and which can be detected using image current detection” (see Hauschild para. [0025]). However, Hauschild does not teach wherein the calibration parameter is configured to set a mapping between frequency of oscillation of the second ion population within the image current-based mass analyzer to the m/z values.
Jarrold teaches wherein the calibration parameter is configured to set a mapping between frequency of oscillation of the second ion population within the image current-based mass analyzer to the m/z values (para. [0050]: “the mass-to-charge ratio (m/z) of the ion was calculated from the fundamental oscillation frequency (f0) of the signal using a calibration constant (C)”).
Therefore, it would have been obvious for an ordinary skilled person in the art, before the effective time of filing, to incorporate the calibrating approach of Jarrold into Hauschild’s image current based analyzer so that the calibration parameter sets the mapping between oscillation frequency and m/z value, thereby improving the accuracy and definition of the mass-scale conversion already performed in Hauschild.
Allowable Subject Matter
Claims 1-2, 5-9, and 19-20 are allowed.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JING WANG whose telephone number is (571)272-2504. The examiner can normally be reached M-F 7:30-17:00.
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. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JING WANG/Examiner, Art Unit 2881
/DAVID E SMITH/Examiner, Art Unit 2881
Prosecution Insights