Xin WangDownload PDFPatent Trials and Appeals BoardFeb 12, 20212020001102 (P.T.A.B. Feb. 12, 2021) Copy Citation UNITED STATES PATENT AND TRADEMARK OFFICE UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O. Box 1450 Alexandria, Virginia 22313-1450 www.uspto.gov APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO. 13/822,922 03/13/2013 Xin Wang 37936-0002US1 8764 26211 7590 02/12/2021 FISH & RICHARDSON P.C. (NY) P.O. BOX 1022 MINNEAPOLIS, MN 55440-1022 EXAMINER DALBO, MICHAEL J ART UNIT PAPER NUMBER 2865 NOTIFICATION DATE DELIVERY MODE 02/12/2021 ELECTRONIC Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the following e-mail address(es): PATDOCTC@fr.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte XIN WANG Appeal 2020-001102 Application 13/822,922 Technology Center 2800 Before TERRY J. OWENS, N. WHITNEY WILSON, and JANE E. INGLESE, Administrative Patent Judges. OWENS, Administrative Patent Judge. DECISION ON APPEAL STATEMENT OF THE CASE Pursuant to 35 U.S.C. § 134(a), the Appellant1 appeals from the Examiner’s decision to reject claims 55, 56, and 59–86. We have jurisdiction under 35 U.S.C. § 6(b). We REVERSE. 1 We use the term “Appellant” to refer to “applicant” as defined in 37 C.F.R. § 1.42. The Appellant identifies the real party in interest as MassDefect Technologies, LLC (Appeal Br. 1). Appeal 2020-001102 Application 13/822,922 2 CLAIMED SUBJECT MATTER The claims are directed to background subtraction-mediated data- dependent acquisition. Claim 55, reproduced below, is illustrative of the claimed subject matter: 55. A method of analyzing mass spectrum of a sample containing at least one component of interest, comprising the steps of: obtaining a background data set from a background sample different from the sample containing at least one component of interest, the background sample being a biological sample and comprising a plurality of biological background components, and the sample containing at least one component of interest being a biological sample and further comprising the plurality of biological background components; after obtaining the background data set, performing a continuous chromatographic measurement of the sample containing at least one component of interest; acquiring an original mass spectrum of the sample containing at least one component of interest with a first mass spectrometric acquisition function at a first chromatographic time point by using a mass spectrometer, wherein the original mass spectrum comprises m/z and intensity information of ion signals detected at the first chromatographic time point; defining sections of data in the background data set at the first chromatographic time point specified in the acquiring step to form defined sections of the background data set, the defining comprises applying a chromatographic fluctuation time window and a mass precision window around ion signals in the background data set at the first chromatographic time point; conducting background subtraction for ions in the original mass spectrum using ion information in the defined sections of the background data set, resulting in a current background subtracted mass spectrum; and conducting an event of a data-dependent acquisition function of ion signals detected at a second subsequent Appeal 2020-001102 Application 13/822,922 3 chromatographic time point based on the current background- subtracted mass spectrum; wherein the background subtraction occurs in real time before conducting the event of the data-dependent acquisition function at the second subsequent chromatographic time point, the first and second chromatographic time points are two time points in the continuous chromatographic measurement, and the data-dependent acquisition function is a subsequent mass spectrometric measurement or diversion of the sample containing at least one component of interest. REFERENCES The prior art relied upon by the Examiner is: Name Reference Date McLafferty US 4,008,388 Feb. 15, 1977 Zhao US 2005/0048547 A1 Mar. 3, 2005 Overney US 2006/0243900 A1 Nov. 2, 2006 Senko US 2006/0284067 A1 Dec. 21, 2006 Le Blanc US 2006/0284069 A1 Dec. 21, 2006 Wang US 2013/0297226 A1 Nov. 7, 2013 Zhang 43 J. Mass. Spectrom. 1181–90 2008 REJECTIONS Claim(s) Rejected 35 U.S.C. § Reference(s)/Basis 55, 56, 60–63, 65, 67– 72, 74–85 103(a) Zhang, McLafferty, Le Blanc 59, 64 103(a) Zhang, McLafferty, Le Blanc, Wang 66 103(a) Zhang, McLafferty, Le Blanc, Zhao 73, 86 103(a) Zhang, McLafferty, Le Blanc, Senko Appeal 2020-001102 Application 13/822,922 4 OPINION We need address only the broadest independent claim, i.e., claim 55. That claim requires obtaining a background data set from a background sample comprising biological background components, then performing a continuous chromatographic measurement of a sample containing at least one component of interest and the background biological components, acquiring an original mass spectrum of the sample containing at least one component of interest with a first mass spectrometric acquisition function at a first chromatographic time point in the continuous chromatographic measurement, conducting in real time background subtraction for ions in the original mass spectrum, then conducting an event of a data-dependent acquisition function of ion signals detected at a second subsequent chromatographic time point in the continuous chromatographic measurement based on the current background-subtracted mass spectrum. Zhang discloses “a background subtraction algorithm using accurate mass data in control scans of a specified time window around an analyte scan to cope with possible LC [(liquid chromatography)] fluctuations between the control and analyte samples” (p. 1189). McLafferty discloses “an automated mass spectrometric system comprising (i) a mass spectrometer, including its electronics and vacuum system; (ii) a sample inlet device; and (iii) electronic analysis means for analyzing the mass spectra obtained from samples; and (iv) electronic control means for controlling the operation of the mass spectrometer and certain of its operating parameters” (col. 5, ll. 43–50). “The electronic analysis means provide the unique capability of searching for and identifying the presence of specific target compounds in a sample by Appeal 2020-001102 Application 13/822,922 5 analyzing the mass spectral data output by the spectrometer in real time, despite the presence of a great many confusing mass peaks attributable to residual background and sample impurities” (col. 6, ll. 31–37). LeBlanc discloses “automatic MS/MS acquisition using data- dependent acquisition techniques for identifying eluting compounds in a chromatography/mass spectrum system” (¶ 2). “Ions associated with fast- rising mass signals may be identified by, for example, subtracting one, or an average of, previously acquired mass spectrums from the current mass spectrum” (¶ 11). Le Blanc’s system “improves the efficiency in collection of useful information while minimizing the quantity of data collected” (¶ 70), thereby “minimizing the amount of information that has to be sifted through, and improving the real-time analysis capabilities for such data” (id.). Setting forth a prima facie case of obviousness requires establishing that the applied prior art would have provided one of ordinary skill in the art with an apparent reason to modify the prior art to arrive at the claimed invention. See KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007). The Examiner finds (Non-Final 5–6): Zhang does not expressly indicate that the chromatogram of the sample is a continuous chromatographic measurement of the sample; wherein the chromatogram of the sample is obtained after obtaining the background data set; and wherein the background subtraction occurs in real time and the first and second chromatographic time points are two time points in the continuous chromatographic measurement, i.e. the data-dependent acquisition function is trigged [sic] during the continuous chromatographic measurement. Appeal 2020-001102 Application 13/822,922 6 The Examiner finds that McLafferty discloses “the background subtraction occurs in real time (see column 4 lines 25-68 and column 11 lines 2-9 and column 6 lines 31-38: real time analysis, analysis includes background subtraction)” (Non-Final 6). Those portions of McLafferty disclose: This invention enables the identification of any one of a number of a preselected "target" compounds in unknown mixtures of compounds with little or no sample purification. Thus, for one thing, it enables the elimination of a gas chromatograph or, at the least, a substantial reduction in its complexity. As a result, this invention provides a system which is less complex and less expensive than the corresponding systems of the prior art. In addition to the elimination or simplification of the gas chromatograph, the present invention further reduces the cost and complexity of compound identification by eliminating bulk data storage means. This is the result of its incorporation of means capable of real time analysis [(col. 4, ll. 62–68)]. . . . The invented system, while not requiring purification of the sample by means such as a gas chromatograph, is nevertheless adapted to operate with a gas chromatograph; thereby, users of the present invention have a choice between a direct analysis mode and a gas chromatograph/mass spectrometer (GC/MS) analysis mode. In the latter mode any suitable adapter known in the art enables the continuous real time analysis of the effluent from the gas chromatograph [(col. 11, ll. 1–4)]. The Examiner does not establish that McLafferty’s disclosure of means capable of real time analysis when identifying a compound in an unknown mixture of compounds with little or no sample purification with a gas chromatograph or disclosure of using an adapter to enable real time analysis of gas chromatograph effluent would have provided one of ordinary Appeal 2020-001102 Application 13/822,922 7 skill in the art with an apparent reason to conduct real time background subtraction for ions in an original mass spectrum in Zhang in the above- stated sequence of steps required by the Appellant’s claim 55. The Examiner finds (Non-Final 7) that Le Blanc discloses “conducting an event of a data-dependent acquisition function of ion signals detected at a second subsequent chromatographic time point based on the current real time background subtracted mass spectrum (see paragraph 0002, 0011, 0041, 0034, 0045-0046, and 0070: uses an algorithm that triggers DDA based upon a real time dynamic background subtraction).” The Examiner does not establish that disclosure of an algorithm that triggers DDA based upon a real time dynamic background subtraction is a disclosure of conducting an event of a data-dependent acquisition function of ion signals detected at a second subsequent chromatographic time point based on the current real time background subtracted mass spectrum. The Examiner finds (Non-Final 7) that Le Blanc discloses wherein the first and second chromatographic time points are two time points in the continuous chromatographic measurement, i.e. wherein the data-dependent acquisition function is trigged [sic] during the continuous chromatographic measurement based on a background subtraction in real time (see Title and paragraphs 0026, 0031, 0041, 0043, 0045, 0046, 0063, and 0070: uses a dynamic background subtraction algorithm to allow for real-time automated adjustments of a MS to MS/MS data acquisition from a single LC/MS analysis). The Examiner does not establish that a disclosure of using a dynamic background subtraction algorithm to allow for real-time automated adjustments of an MS to MS/MS data acquisition from a single LC/MS analysis is a disclosure of first and second chromatographic time points that Appeal 2020-001102 Application 13/822,922 8 are two time points in a continuous chromatographic measurement wherein the data-dependent acquisition function is triggered during the continuous chromatographic measurement based on a background subtraction in real time. Thus, the Examiner has not set forth a factual basis that is sufficient to support a conclusion of obviousness of the Appellant’s claimed invention. See In re Warner, 379 F.2d 1011, 1017 (CCPA 1967) (“A rejection based on section 103 clearly must rest on a factual basis, and these facts must be interpreted without hindsight reconstruction of the invention from the prior art”). Accordingly, we reverse the rejections. CONCLUSION The Examiner’s decision to reject claims 55, 56, and 59–86 is REVERSED. Appeal 2020-001102 Application 13/822,922 9 DECISION SUMMARY Claim(s) Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 55, 56, 60– 63, 65, 67– 72, 74–85 103(a) Zhang, McLafferty, Le Blanc 55, 56, 60– 63, 65, 67– 72, 74–85 59, 64 103(a) Zhang, McLafferty, Le Blanc, Wang 59, 64 66 103(a) Zhang, McLafferty, Le Blanc, Zhao 66 73, 86 103(a) Zhang, McLafferty, Le Blanc, Senko 73, 86 Overall Outcome 55, 56, 59– 86 REVERSED Copy with citationCopy as parenthetical citation