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 Objections
Claim 3 is objected to because of the following informalities:
In claim 3, line 4, change “spectrometer,.” to -spectrometer.-.
Appropriate correction is required.
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.
Claims 1-21 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (abstract idea) without significantly more.
Under Step 1 of the 2019 Revised Patent Subject Matter Eligibility Guidance, the claims are directed to a process (claim 1, a method), which are statutory category.
However, evaluating claim 1, under Step 2A, Prong One, the claim is directed to the judicial exception of an abstract idea using the grouping of a mathematical relationship/mental process. The limitations include:
b. selecting a relevant retention time window for presence of possible compounds of interest; c. using positively identified analytes from a sample run to convert retention time into retention index d. determining a retention index range for said relevant retention time window; e. using the acquired spectral data in said relevant retention time window to perform a spectral library search to identify possible compounds; f. selecting a subset of possible compounds based on at least one of their retention index values and spectral library search scores; g. performing a regression analysis, between the spectral data within said retention time window and the library spectrum of at least one of a subset of possible compounds; and h. reporting the regression coefficients as representative of the concentrations or chromatograms of said possible compounds.
These steps amount to data acquisition and mathematical analysis of information, which constitutes a judicial exception (e.g., mathematical concepts and data analysis) consistent with Electric Power Group, LLC v. Alstom S.A. 830 F.3d 1359 (Fed. Cir. 2016).
The claim does not integrate the abstract idea into practical application. Although the claim references “mass spectral detection system” and separation over time, these elements are used merely as generic data sources, and the claim does not recite any other physical components. The claim does not control or modify instrument operation, or address a technological problem in mass spectrometry or chromatography. Instead, the focus of the claim remains on post-acquisition data processing and analysis.
Therefore, the claims are directed to an abstract idea.
At Step 2B, consideration is given to additional elements that may make the abstract idea significantly more. Under Step 2B, there are no additional elements that make the claim significantly more than the abstract idea.
The additional elements of “acquiring mass spectral data for a sample” is considered insignificant extra-solution activity of collecting data that is not sufficient to integrate the claim into a particular practical application. The act of data gathering is considered insufficient to elevate the claim to a practical application.
The limitations have been considered individually and as a whole and do not amount to significantly more than the abstract idea itself.
Dependent claims 2-21 do not add anything which would render the claimed invention a patent eligible application of the abstract idea. The claim merely extends (or narrow) the abstract idea which do not amount for "significant more" because it merely adds details to the algorithm which forms the abstract idea as discussed above.
Regarding claim 2, the additional element “where the technique for separation is one of gas chromatography (GC), liquid chromatography (LC), supercritical fluid chromatography, ion chromatography (IC), capillary electrophoresis (CE), gel electrophoresis, ion mobility, and pyrolysis” recites separation techniques that represent generic classes of separation methods and do not impose meaningful limits on the claim. The claim does not recite a specific machine configuration or require that the abstract data analysis be performed by or transform a particular machine. Accordingly, the claim does not make the abstract idea significantly more.
Regarding claim 3, the additional element “where the mass spectral detection system is one of a sector mass spectrometer, quadrupole mass spectrometer, ion trap mass spectrometer, Time-of-Flight (TOF) mass spectrometer, Orbitrap mass spectrometer, Fourier-transform ion cyclotron resonance (FT ICR) mass spectrometer” recites broad classes mass spectrometer that cover the entire family of instruments, each of which includes many different implementations and has different architectures and operate. The claim does not integrate the abstract idea into a practical application and does not add elements that amount to significantly more that the judicial exception.
Regarding claim 21, the element of “a computer readable medium having computer readable program” is recited at a high level of generality and are recited as performing generic computer functions routinely used in computer applications. Generic computer components recited as performing generic computer functions that are well-understood, routine and conventional activities amount to no more than implementing the abstract idea with a computerized system (Alice Corp. Pty. Ltd. v. CLS Bank Int’l 573 U.S. __, 134 S. Ct. 2347, 110 U.S.P.Q.2d 1976 (2014)).
Claim 21 is rejected under 35 U.S.C. 101 because the claimed invention is
directed to non-statutory subject matter.
Claim 21 presents "a computer readable medium". The broadest reasonable interpretation of a claim drawn to a computer readable medium typically covers forms of non-transitory tangible media and transitory propagating signals per se in view of the ordinary and customary meaning of computer readable media, particularly when the specification is silent See MPEP 2111.01.
As currently claimed, the language a computer readable medium does not specify if the computer readable medium is "transitory" or "non-transitory" and therefore claim 21 is considered to be non-statutory under 35 U.S.C. 101 (See In re Nuijten, 500 F.3d 1346, 1356-57 (Fed. Cir. 2007) (transitory embodiments are not directed to statutory subject matter) and Interim Examination Instructions for Evaluating Subject Matter Eligibility Under 35 U.S.C. § 101, Aug. 24, 2009; p. 2).
In order to overcome this rejection, the following language is suggested:
“21. (Currently amended) A non-transitory computer readable medium having computer-executable components …”
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.
Claims 1-5, 7, 11, 12 and 17-21 are rejected under 35 U.S.C. 103 as being
unpatentable over Wang et al. (Pub. No. US 2006/0255258 (hereinafter Wang) in view of Spartz et al. (Pub. No. US 2019/0017873) (hereinafter Spartz).
As per claims 1, 4 and 20, Wang teaches a. acquiring mass spectral data for a sample (see ¶ [0037], i.e., “Liquid chromatography interfaced with (tandem) mass spectrometry (LC/MS or LC/MS/MS) has been widely utilized for obtaining structural information of molecules such as the sequence of proteins and metabolic pathways of pharmaceuticals”); b. selecting a relevant retention time window for presence of possible compounds of interest (see ¶¶ [0037], i.e., “multiple mass spectral scans from a time dependent measurement such as GC/MS or LC/MS experiments need to be combined to create a chromatogram, one typically has to open a large mass window to integrate the ion intensities and plot them as a function of time to generate a chromatogram called extracted ion chromatogram (XIC)” and [0135], i.e., summing or averaging mass spectral scans within a selected retention time range and generating chromatographic representations from such data).
Wang further teaches g. performing a regression analysis, between the spectral data within said retention time window and the library spectrum of at least one of a subset of possible compounds (see ¶¶ [0065]-[0067], [0119]-[0127] and [0132], i.e., performing regression analysis between measured spectral data and known spectral response components ([0122]-[0123], “the peak component in matrix K … the known mass spectral peak shape function”), solving for regression coefficients, and reporting the regression coefficient as representative of concentrations and/or chromatograms of compounds of interest, including plotting regression coefficients versus retention time to generate extracted ion chromatogram).
Wang fails to explicitly teach c. using positively identified analytes from a sample run to convert retention time into retention index d. determining a retention index range for said relevant retention time window; e. using the acquired spectral data in said relevant retention time window to perform a spectral library search to identify possible compounds; f. selecting a subset of possible compounds based on at least one of their retention index values and spectral library search scores; and h. reporting the regression coefficients as representative of the concentrations or chromatograms of said possible compounds.
However, Spartz teaches determining retention index values using hydrocarbon reference standards or utilized from current mass spectral library data (corresponding to step c.) (see ¶¶ [0144] and [0174]), Spartz further teaches determining and using a “retention index window” and analyzing compounds based on when they are expected to elute during chromatography. Specifically, Spartz states that “an initial prediction could be performed to determine which compounds within a retention index window might actually be present” (see ¶ [0144]). Spartz further states “as the chromatography gets to a certain retention index, the compounds that could elute near that time will be added to the prescreening and/or analysis algorithm” (see ¶ [0176]). Additionally, teaches choosing a subset (selecting compounds) “based on elution time or retention time index” and considering “only compounds that are likely to elute for the elution time of the sample spectrum being analyzed” (corresponding to step d.) (see ¶ [0221]). Spartz further teaches accessing stored library spectra associated with retention index information (corresponding to step f.) (see ¶¶ [0113], [0217]-[0219] and [0221]). Spartz further teaches performing regression analysis between the measured spectral data and selected library spectra for compounds within the retention index window, including multiple linear regression and least-squares analysis (see ¶¶ [0146] , [0167] and [0219]). Spartz further teaches reporting regression results as concentrations and chromatographic representations, including compound specific chromatograms and bar-graph plots at respective indices (see ¶¶ [0057], [0148] and [0224]-[0225] and Figures 12A and 12B).
It would have been obvious to one having ordinary skill in the art before the effective filling date of the claimed invention to incorporate the retention index, spectral library searching, and subset selection techniques taught by Spartz into the regression-based chromatographic and mass spectral data analysis of Wang because doing so would reduce interference from unrelated compounds, thereby enhancing the accuracy and robustness of mass spectral compound identification and quantification.
As per claim 2, Wang further teaches that the technique for separation is one of gas chromatography (GC), liquid chromatography (LC), supercritical fluid chromatography, ion chromatography (IC), capillary electrophoresis (CE), gel electrophoresis, ion mobility, and pyrolysis (see ¶ [0016]).
As per claim 3, Wang further teaches that the mass spectral detection system is one of a sector mass spectrometer, quadrupole mass spectrometer, ion trap mass spectrometer, Time-of-Flight (TOF) mass spectrometer, Orbitrap mass spectrometer, Fourier-transform ion cyclotron resonance (FT ICR) mass spectrometer (see ¶ [0016]).
As per claim 5, the combination of Wang and Spartz teach the system as stated above. Spartz further teaches that the retention index values have been previously obtained from measured retention times through the use of calibration standards referenced to n-alkane for gas chromatography (¶ [0188], e.g., “obtain the calibration library, each material is measured on a GC with potential columns and stationary phases and compared to standards to determine its retention index. Alternatively, the retention index for each material could be acquired from the literature or mass spectral libraries”, the examiner notes that “compared to standards to determine its retention index” means comparison to n-alkane standards).
As per claim 7, the combination of Wang and Spartz teach the system as stated above. Spartz further teaches that the regression model is a multiple linear regression model (see ¶¶ [0146]), with optional background components included (see ¶ [0146], i.e., “Very high concentration components, internal standards or solvents can be present in a select set or in all regressions”).
As per claim 11, the combination of Wang and Spartz teach the system as stated above. Wang further teaches reporting regression statistics, including one of regression residual, error bars and t-statistics, for each possible compound (see ¶ [0066], i.e., “plotting the weighted regression coefficient against the retention time to generate an extracted ion chromatogram” and ¶ [0127], i.e., “it is advantageous to use weighted regression in the above model where the weight at each mass sampling point would be inversely proportional to the signal variance at this mass spectral sampling point”).
As per claim 12, the combination of Wang and Spartz teach the system as stated above. Wang further teaches regression model that generates fitting residuals, mass error, and statistically weighted solutions (see ¶¶ [0066]-[0067], [0120] and [0132]). Wang does not explicitly teach iterative refinement of the regression models by adding or removing candidate compounds. It would have been obvious to one having ordinary skill in the art before the effective filling date of the claimed invention to iteratively refine such a regression model based on these statistical outputs by mathematically modifying the set of spectral components represented in the regression matrix, for example by adding or removing component vectors corresponding to candidate compounds, as this constitutes a routine and predictable mathematical manipulation used to improve model fit and quantitative accuracy. Furthermore, Spartz teaches prescreening and removal of candidate compounds based on elution behavior (see ¶¶ [0221]-[0223]), providing additional motivation to iteratively adjust the candidate compound set within the regression model in view of the statistical results.
As per claims 17 and 18, the combination of Wang and Spartz teach the system as stated above. Wang further teaches that the regression analysis includes one of spectral baseline or background as additional spectral components to be considered (see ¶¶ [0065] and [0026]).
As per claim 19, the combination of Wang and Spartz teach the system as stated above. Spartz further teaches that one of the spectral baseline or background is the actual measured spectral data from one of blank or control sample from one of the same or nearby retention time windows (see ¶ [0102], i.e., acquiring background spectra prior to analyte elution and dynamically generating background spectra from previous measured spectra close in time to the current spectra).
As per claim 21, the combination of Wang and Spartz teach the system as stated above. Wang further teaches a computer associated with a mass spectral detection system including a mass spectrometer, a computer readable medium having computer readable program instructions readable by the computer (see Abstract and ¶¶ [0007]-[0009]).
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Wang in view
of Spartz and further in view Treado et al. (Pub. No. US 2009/0012723) (hereinafter Treado).
As per claim 8, the combination of Wang and Spartz teach the system as stated above except that the spectral search involves the projection of a library spectrum onto the subspace spanned by the spectral data within the retention time window range.
Treado teaches performing spectral library search by applying principal component analysis (PCA) to measure spectral data to form a reduced dimensional data space and projecting each reference (library) spectrum as a vector into that reduced dimensional subspace for comparison, including calculating similarity metrics based on the projection (see ¶ [0047], “each sublibrary reference data set is projected as a vector in the reduced m-dimensional data space”). It would have been obvious to one having ordinary skill in the art before the effective filling date of the claimed invention to incorporate the subspace projection based spectral library searching technique of Treado into the combination of Wang and Spartz’s teaching because projecting library spectra into the same reduced dimensional subspace spanned by measured spectral data is known and effective way to compare reference spectra with measured spectra in multivariate analysis, thereby improving robustness, discrimination, and computational efficiency of compound identification when applied to spectral data limited to a relevant chromatographic retention time window.
Claims 13 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over
Wang in view of Spartz and further in view Maggard (Patent No. US 5,243,546).
As per claims 13 and 14, the combination of Wang and Spartz teach the system as stated above except that the regression statistics are used to determine the number of possible compounds included in the regression model.
Maggard teaches that in PCA pr PLS-based multivariate calibration, only a statistically determined number of components are included in the regression model, where the optimal model dimension h is selected based on the rank of the spectral data matrix and variance contribution of extracted components, with residuals defining model adequacy, and where loading vectors are extracted iteratively until the desired model is obtained (see col. 3, line 48 through col. 5,line 11, discussion of equations 8) and (9)). It would have been obvious to one having ordinary skill in the art before the effective filling date of the claimed invention to incorporate Maggard’s teaching into the combination of Wang and Spartz’s teaching because the appropriate number of compounds in a multivariate regression model would be determined, thereby enabling a predictable and refinement of the compound set in the regression for improved quantitative accuracy of compounds in the system.
Examiner’s Notes
Claims 6, 9, 10, 15 and 16 distinguish over the prior art of record.
Regarding claim 6, none of the prior art of record teaches of fairly suggests a
method for the analysis of compounds of interest through separation over time when using a mass spectral detection system, including the steps of: selecting a subset of possible compounds based on at least one of their retention index values and spectral library search scores, where the retention index values are obtained from a retention index calibration curve built from the same data acquisition using co-existing compounds with known retention index values after positive identification through a spectral library search, in combination with the rest of the claim limitations as claimed and defined by the applicant.
Regarding claim 9, none of the prior art of record teaches of fairly suggests a
method for the analysis of compounds of interest through separation over time when using a mass spectral detection system, including the steps of: selecting a subset of possible compounds based on at least one of their retention index values and spectral library search scores, where the subset is selected based on reverse spectral library search quality above a given quality threshold, in combination with the rest of the claim limitations as claimed and defined by the applicant.
Regarding claim 10, none of the prior art of record teaches of fairly suggests a
method for the analysis of compounds of interest through separation over time when using a mass spectral detection system, including the steps of: selecting a subset of possible compounds based on at least one of their retention index values and spectral library search scores, where the subset is selected based on one of the difference between and combination of a forward and a reverse spectral search, in combination with the rest of the claim limitations as claimed and defined by the applicant.
Regarding claim 15, none of the prior art of record teaches of fairly suggests a
method for the analysis of compounds of interest through separation over time when using a mass spectral detection system, including the steps of: reporting the regression coefficients as representative of the concentrations or chromatograms of said possible compounds, wherein a possible compound having reported concentrations or chromatograms indicating lower than a given positive or negative threshold is removed from the regression, in combination with the rest of the claim limitations as claimed and defined by the applicant.
Regarding claim 16, none of the prior art of record teaches of fairly suggests a
method for the analysis of compounds of interest through separation over time when using a mass spectral detection system, including the steps of: reporting the regression coefficients as representative of the concentrations or chromatograms of said possible compounds, where regression coefficients representative of the compound concentrations or chromatograms after area integration are used for one of semi-quantitation based on relative ratioing and full quantitation based on standard curves, in combination with the rest of the claim limitations as claimed and defined by the applicant.
Prior art
The prior art made record and not relied upon is considered pertinent to applicant’s
disclosure:
Wyatt et al. [‘694] discloses an analysis system includes a separation system that provides compounds to a sample cell of a spectrometric system. The system analyzes spectral information from the spectrometric system by optimizing retention windows for the compounds and identifies quantities of the compounds by comparing spectral information within and outside the respective retention windows.
Sadowski et al. [‘751] discloses methods and systems for identifying unknown compounds by gas chromatography-mass spectrometry by use of retention index as a second dimension for identification.
Contact information
Any inquiry concerning this communication or earlier communications from the
examiner should be directed to MOHAMED CHARIOUI whose telephone number is (571)272-2213. The examiner can normally be reached Monday through Friday, from 9 am to 6 pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew Schechter can be reached on (571) 272-2302. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Mohamed Charioui
/MOHAMED CHARIOUI/Primary Examiner, Art Unit 2857