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 .
Information Disclosure Statement
The information disclosure statements (IDS) were submitted on 03/26/2025, 09/13/2024, 03/26/2024. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claims 16 and 34 are objected to because of the following informalities:
Claim 16 details “where c is an experimental factor, where c is an experimental factor”. Claim 16 should not repeat itself and should only state that “c is an experimental factor” one time instead of back to back.
Claim 34 details the limitation “wherein the set of instructions comprises determining the MSP by calculating a ratio of the intensity of the main intensity peak over an intensity peak of other ions”. As Claim 34 is dependent on Claim 18, this is the first reference to “MSP”, so the correct antecedent basis should be “a” rather than “the”. Furthermore, for clarity of record, Examiner suggests detailing what the acronym MSP stands.
Appropriate correction is required.
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 1-2, 4-6, 11, 13, 16, 18-19, 21-23, 28, 33-34, 38, and 42 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 1 and 18 detail the limitations:
deriving a measured isotope profile based on the collected mass spectrometry data, the measured isotope profile including intensity measurements for a main peak and for one or more isotope peaks, the main peak and the one or more isotope peaks corresponding to the given compound;
determining a predicted isotope profile, the predicted isotope profile comprising intensity predictions for a main peak and for one or more isotope peaks corresponding to the given compound;
determining a first quality score for the mass analysis data, the first quality score being based on a relationship between an intensity of the main peak and intensities of the one or more isotope peaks;
determining a second quality score for the mass analysis data, the second quality score being based on a signal-to-noise ratio of the mass analysis data;
determining an overall quality score as a combination of the first quality score and the second quality score; and
assessing a quality of a compound library based on the determined overall quality score.
Limitation (c) relates to limitation (a), limitation (e) relates to limitation (c) and (d), and limitation (f) relates to limitation (e). That is, limitation (b) of the predicted isotope profile is not relied upon in any of the preceding or subsequent limitations, and thus it is not clear why a determination of the predicted isotope profile is performed since it is not utilized in the determination of the quality scores, and thus not used to assess the quality of the compound library.
As dependent Claims 3 and 20 detail that the first quality score is detailed by an equation with the predicted intensity signal utilized in the determination of the first quality score, Examiner interprets the claim limitation of (c) as “determining a first quality score for the mass analysis data, the first quality score being based on a relationship between an intensity of the main peak, intensities of the one or more isotope peaks, and the predicted isotope profile”.
Claims 2, 4-6, 11, 13, 16 are rejected due to dependence on Claim 1
Claims 19, 21-23, 28, 33-34, 38, and 42 are rejected due to dependence on Claim 18.
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 1-6, 11, 13, 16, 18-23, 28, 33-34, 38, and 42 are rejected under 35 U.S.C. 101. The claimed invention is directed to the abstract concept of performing abstract steps without significantly more. The claim(s) recite(s) the following abstract concepts in BOLD of
1. (Original) A method of assessing a quality of mass analysis data generated by a mass analysis device, the method comprising:
collecting mass spectrometry data for a given compound from operation of the mass analysis device;
deriving a measured isotope profile based on the collected mass spectrometry data, the measured isotope profile including intensity measurements for a main peak and for one or more isotope peaks, the main peak and the one or more isotope peaks corresponding to the given compound;
determining a predicted isotope profile, the predicted isotope profile comprising intensity predictions for a main peak and for one or more isotope peaks corresponding to the given compound;
determining a first quality score for the mass analysis data, the first quality score being based on a relationship between an intensity of the main peak and intensities of the one or more isotope peaks;
determining a second quality score for the mass analysis data, the second quality score being based on a signal-to-noise ratio of the mass analysis data;
determining an overall quality score as a combination of the first quality score and the second quality score; and
assessing a quality of a compound library based on the determined overall quality score.
18. A sample analyzing system comprising:
a sample receiver;
a mass analysis device fluidically coupled to the sample receiver;
a processor operatively coupled to the sample receiver and to the mass analysis device; and
a memory coupled to the processor, the memory storing instructions that, when executed by the processor, perform a set of operations comprising:
collecting, via the mass analysis device, mass spectrometry data for a given compound;
deriving, via the processor, a measured isotope profile based on the collected mass spectrometry data, the measured isotope profile comprising intensity measurements for a main peak and for one or more isotope peaks, the main peak and the one or more isotope peaks corresponding to the given compound;
determining, via the processor, a predicted isotope profile, the predicted isotope profile comprising intensity predictions for a main peak and for one or more isotope peaks corresponding to the given compound;
determining, via the processor, a first quality score for the mass analysis data, the first quality score being based on a relationship between an intensity of the main peak and intensities of the one or more isotope peaks;
determining, via the processor, a second quality score for the mass analysis data, the second quality score being based on a signal-to-noise ratio of the mass analysis data;
determining, via the processor, an overall quality score as a combination of the first quality score and the second quality score; and
assessing, via the processor, a quality of a compound library based on the determined overall quality score.
Under step 1 of the eligibility analysis, we determine whether the claims are to a statutory category by considering whether the claimed subject matter falls within the four statutory categories of patentable subject matter identified by 35 U.S.C. 101: process, machine, manufacture, or composition of matter. The above claims are considered to be in a statutory category.
Under Step 2A, Prong One, we consider whether the claim recites a judicial exception (abstract idea). In the above claim, the highlighted portion constitutes an abstract idea because, under a broadest reasonable interpretation, it recites limitation the fall into/recite abstract idea exceptions. Specifically, under the 2019 Revised Patent Subject Matter Eligibility Guidance, it falls into the grouping of subject matter that, when recited as such in a claim limitation, covers performing mathematics or mental steps.
Next, under Step 2A, Prong Two, we consider whether the claim that recites a judicial exception is integrated into a practical application. In this step, we evaluate whether the claim recites additional elements that integrate the exception into a practical application of that exception.
This judicial exception is not integrated into a practical application because there is no improvement to another technology or technical field; improvements to the functioning of the computer itself; a particular machine; effecting a transformation or reduction of a particular article to a different state or thing. Examiner notes that since the claimed methods and system are not tied to a particular machine or apparatus, they do not represent an improvement to another technology or technical field. Similarly there are no other meaningful limitations linking the use to a particular technological environment. Finally, there is nothing in the claims that indicates an improvement to the functioning of the computer itself or transform a particular article to a new state.
Finally, under Step 2B, we consider whether the additional elements are sufficient to amount to significantly more than the abstract idea. Claims 1 and 18 do not include additional elements that are sufficient to amount to significantly more than the judicial exception because collecting mass spectrometry data for a given compound from operation of the mass analysis device is considered necessary data gathering. As recited in MPEP section 2106.05(g), necessary data gathering (i.e. collecting mass spectroscopy data) is considered extra solution activity in light of Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; OIP Techs., Inc. v. Amazon.com, Inc., 788 F.3d 1359, 1363, 115 USPQ2d 1090, 1092-93 (Fed. Cir. 2015). The additional limitation of Claim 18 of the processor and memory are interpreted under broadest reasonable interpretation to be a generic computer elements. Generic computer elements are not considered significantly more than the abstract idea and do not integrate the abstract idea into a practical application. As recited in the MPEP, 2106.05(b), merely adding a generic computer, generic computer components, or a programmed computer to perform generic computer functions does not automatically overcome an eligibility rejection. Alice Corp. Pty. Ltd. v. CLS Bank Int'l, 134 S. Ct. 2347, 2359-60, 110 USPQ2d 1976, 1984 (2014). See also OIP Techs. v. Amazon.com, 788 F.3d 1359, 1364, 115 USPQ2d 1090, 1093-94. The additional limitation of Claim 18 of the sample receiver and mass analysis device fluidically coupled to the sample receiver are well understood, routine, and conventional in the art, as evidenced by Datwani (US20190157061) in Figure 1 and Hattingh (US20140283627) in [0007].
Claims 2-6, 11, 13, 16, 19-23, 28, 33-34, and 42 further limit the abstract ideas without integrating the abstract concept into a practical application or including additional limitations that can be considered significantly more than the abstract idea.
The additional limitation of Claim 38 of the non-contact sample ejector with the sample receiver with the mass analysis device are well understood, routine, and conventional in the art, as evidenced by Datwani (US20190157061) in Figure 1 and Hattingh (US20140283627) in [0007].
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 5, 18, and 22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bas (Jansen Bas C. ET AL; “MassyTools: A high-Throughput Targeted Data Processing Tool for Relative Quantitation and Quality Control developed for glycomic and glycoproteomic MALDI-MS”, Journal of Proteome Research, Vol 14, No 12, December 4th 2015; Pages 5088-5098).
In regards to claim 1, Bas teaches “collecting mass spectrometry data for a given compound from operation of the mass analysis device (“One of the most rapid approaches to analyze glycans is matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry (MS)” – Introduction, page 5088; “Derivatized glycan and native glycopeptide samples were analyzed using the reflectron positive ion mode of an Ultraflextreme MALDI-TOF-MS (Bruker Daltonics), equipped with a Smartbeam-II laser and operated by flexControl 3.4, build 135. Prior to measurement, the instrument was calibrated with a peptide calibration standard (Bruker Daltonics). Analyte acceleration was performed at 25 kV with 140 ns delayed extraction. For glycan samples, 20 000 spectra were accumulated within a window from m/z 1000 to 5000. Glycopeptide samples were analyzed within a window from m/z 1000 to 4000, accumulating 5000 spectra. Spectra were acquired using a random walk pattern at a laser repetition rate of 2000 Hz. In order to perform MassyTools processing, the obtained spectra were exported into a simple text-based format. The format consisted of an m/z and intensity value per line separated by a tab, from now on referred to as an (x,y) file.” – Page 5090);
deriving a measured isotope profile based on the collected mass spectrometry data, the measured isotope profile including intensity measurements for a main peak and for one or more isotope peaks, the main peak and the one or more isotope peaks corresponding to the given compound (“In order to perform MassyTools processing, the obtained spectra were exported into a simple text-based format. The format consisted of an m/z and intensity value per line separated by a tab, from now on referred to as an (x,y) file” – Data Acquisition on Page 5090; “The isotopic distribution is calculated for all supplied compositions, making use of the isotopic abundance ratios in the building blocks section of the program.39 Briefly, the isotopic pattern is calculated per chemical element using a binomial distribution. Subsequently, all elemental isotopic distributions are combined into a single molecular isotopic distribution. Lastly, isotopic species with the same nominal mass but different mass defects, resolved only at very high mass resolutions, are summed within a user-specified distance (ε), with the default being m/z 0.1. The isotopic pattern calculation has been made available as a separate python package in the GitHub repository of MassyTools (https://github.com/ Tarskin/MassyTools). For extraction, all isotopic peaks contributing at least 1% to the overall isotopic distribution of an analyte are extracted.” – Isotopic Distribution Calculation on Page 5090);
determining a predicted isotope profile, the predicted isotope profile comprising intensity predictions for a main peak and for one or more isotope peaks corresponding to the given compound (“comparing the measured isotopic pattern with the theoretical isotopic pattern and relating the result to the noise, as reported previously (Supporting Information, Figure S1).40 Briefly, the difference between the measured (Si(obs)) pattern and theoretical (Si(est)) pattern is calculated per isotope (i), squared, and divided by the noise (N) squared. The square root of the sum of all isotope QC values yields the analyte QC value (eq 2). This QC value can be used to identify overlapping analytes and peak saturation, since either of the described problems can cause the observed isotopic pattern to deviate from the calculated one.” – Isotopic Quality Control Page 5091; Figure 6 shows the theoretical isotopic pattern);
determining a first quality score for the mass analysis data, the first quality score being based on a relationship between an intensity of the main peak and intensities of the one or more isotope peaks (“comparing the measured isotopic pattern with the theoretical isotopic pattern and relating the result to the noise, as reported previously (Supporting Information, Figure S1).40 Briefly, the difference between the measured (Si(obs)) pattern and theoretical (Si(est)) pattern is calculated per isotope (i), squared, and divided by the noise (N) squared. The square root of the sum of all isotope QC values yields the analyte QC value (eq 2). This QC value can be used to identify overlapping analytes and peak saturation, since either of the described problems can cause the observed isotopic pattern to deviate from the calculated one.” – Isotopic Quality Control Page 5091);
determining a second quality score for the mass analysis data, the second quality score being based on a signal-to-noise ratio of the mass analysis data (“Curation of analytes based on their relative abundance, as shown previously (Relative Quantitation section), may result in the loss of relevant features. Therefore, we evaluated the performance of the analyte quality criteria by curating the list of 108 analytes that were previously observed in the TPNG data.37 We used the difference between the theoretical isotopic pattern and measured isotopic pattern (QC value) and the maximum S/N ratio of an analyte as curation parameters. We removed all analytes that had a maximum S/N below 9 and a QC value below 1.0 × 10−5.” – Analyte Curation Page 5096);
determining an overall quality score as a combination of the first quality score and the second quality score (“We used the difference between the theoretical isotopic pattern and measured isotopic pattern (QC value) and the maximum S/N ratio of an analyte as curation parameters. We removed all analytes that had a maximum S/N below 9 and a QC value below 1.0 × 10−5. The resulting list of 40 analytes was used for integration and yielded an RSD of 6.0% for the main peak..” – Analyte Curation, Page 5096); and
assessing a quality of a compound library based on the determined overall quality score (The resulting list of 40 analytes was used for integration and yielded an RSD of 6.0% for the main peak - Analyte Curation, Page 5096; “Here, we have presented an easy-to-use high-throughput data processing tool for the analysis of MALDI-MS glycosylation data. MassyTools was applied to a biopharmaceutical sample and a complex (TPNG) sample to compare its performance with existing and commonly used data processing tools. The results show that MassyTools calibration performs better than flexAnalysis calibration. Furthermore, quantitation using MassyTools is better than quantitation using flexAnalysis for analytes below 0.1% relative abundance, as demonstrated by lower RSD values. Importantly, MassyTools was significantly faster in all aspects of the analysis (calibration and quantitation). MassyTools allows a user unskilled in scripting to repeatedly integrate and analyze a set of analytes from MS glycosylation data. The program outputs quality control criteria to judge the validity of single analytes, as well as whole spectra. These are invaluable tools in the analysis of large clinical cohorts and biopharmaceuticals data sets, and we envision that MassyTools will enable researchers to focus on the interpretation of data rather than the technical aspects of data processing.” – Concluding Remarks Page 5096).”
In regards to Claim 5 and 22, Bas teaches the claimed limitation as detailed above. Bas further teaches “wherein determining the overall quality score comprises calculating one of a linear relationship between the first quality score and the second quality score and a non-linear relationship between the first quality score and the second quality score (“We used the difference between the theoretical isotopic pattern and measured isotopic pattern (QC value) [i.e. linear relationship] and the maximum S/N ratio of an analyte as curation parameters [i.e. nonlinear relationship]. We removed all analytes that had a maximum S/N below 9 and a QC value below 1.0 × 10−5. The resulting list of 40 analytes was used for integration and yielded an RSD of 6.0% for the main peak..” – Analyte Curation, Page 5096).”
In regards to Claim 18, Bas teaches “a sample receiver; a mass analysis device fluidically coupled to the sample receiver (“One of the most rapid approaches to analyze glycans is matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry (MS). MALDI-MS shows intrinsic robustness, accuracy, speed, and high versatility, allowing the detection of free glycans as well as glycoconjugates such as glycopeptides.12,13 MALDI-MS also exhibits high-throughput potential and the option to combine it with robotized sample preparation techniques.14 Currently, © 2015 American Chemical Society high-throughput MALDI-MS is regularly used in clinical microbiology and clinical metabolomic, proteomic, and glycomic analyses,4,15−19 as well as for quality control of biopharmaceuticals (e.g., the monitoring of fragment crystallizable (Fc)-linked N-glycosylation of monoclonal antibodies).4,15−20 Moreover, several recent reports have demonstrated that this technology allows quantitative measurements to be obtained when appropriate sample preparation methods and internal standards are applied” – Introduction, Page 5088);
a processor operatively coupled to the sample receiver and to the mass analysis device; and a memory coupled to the processor, the memory storing instructions that, when executed by the processor (“Geany 0.21 was used as an integrated development environ ment (IDE) for developing MassyTools. MassyTools was written in the Python 2.7 programming language.33 MassyTools uses the nonstandard Python libraries NumPy,34 SciPy,35 matplotlib,36 and TkInter. These packages are all included in the Anaconda distribution of python. Benchmarks were performed on an Intel i3-3220 CPU desktop computer with 16 GB of RAM running 64-bit Windows 7 SP1.” – Software and Hardware, Page 5089), perform a set of operations comprising:
collecting, via the mass analysis device, mass spectrometry data for a given compound (“One of the most rapid approaches to analyze glycans is matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry (MS)” – Introduction, page 5088; “Derivatized glycan and native glycopeptide samples were analyzed using the reflectron positive ion mode of an Ultraflextreme MALDI-TOF-MS (Bruker Daltonics), equipped with a Smartbeam-II laser and operated by flexControl 3.4, build 135. Prior to measurement, the instrument was calibrated with a peptide calibration standard (Bruker Daltonics). Analyte acceleration was performed at 25 kV with 140 ns delayed extraction. For glycan samples, 20 000 spectra were accumulated within a window from m/z 1000 to 5000. Glycopeptide samples were analyzed within a window from m/z 1000 to 4000, accumulating 5000 spectra. Spectra were acquired using a random walk pattern at a laser repetition rate of 2000 Hz. In order to perform MassyTools processing, the obtained spectra were exported into a simple text-based format. The format consisted of an m/z and intensity value per line separated by a tab, from now on referred to as an (x,y) file.” – Page 5090);
deriving, via the processor, a measured isotope profile based on the collected mass spectrometry data, the measured isotope profile comprising intensity measurements for a main peak and for one or more isotope peaks, the main peak and the one or more isotope peaks corresponding to the given compound (“In order to perform MassyTools processing, the obtained spectra were exported into a simple text-based format. The format consisted of an m/z and intensity value per line separated by a tab, from now on referred to as an (x,y) file” – Data Acquisition on Page 5090; “The isotopic distribution is calculated for all supplied compositions, making use of the isotopic abundance ratios in the building blocks section of the program.39 Briefly, the isotopic pattern is calculated per chemical element using a binomial distribution. Subsequently, all elemental isotopic distributions are combined into a single molecular isotopic distribution. Lastly, isotopic species with the same nominal mass but different mass defects, resolved only at very high mass resolutions, are summed within a user-specified distance (ε), with the default being m/z 0.1. The isotopic pattern calculation has been made available as a separate python package in the GitHub repository of MassyTools (https://github.com/ Tarskin/MassyTools). For extraction, all isotopic peaks contributing at least 1% to the overall isotopic distribution of an analyte are extracted.” – Isotopic Distribution Calculation on Page 5090);
determining, via the processor, a predicted isotope profile, the predicted isotope profile comprising intensity predictions for a main peak and for one or more isotope peaks corresponding to the given compound (“comparing the measured isotopic pattern with the theoretical isotopic pattern and relating the result to the noise, as reported previously (Supporting Information, Figure S1).40 Briefly, the difference between the measured (Si(obs)) pattern and theoretical (Si(est)) pattern is calculated per isotope (i), squared, and divided by the noise (N) squared. The square root of the sum of all isotope QC values yields the analyte QC value (eq 2). This QC value can be used to identify overlapping analytes and peak saturation, since either of the described problems can cause the observed isotopic pattern to deviate from the calculated one.” – Isotopic Quality Control Page 5091; Figure 6 shows the theoretical isotopic pattern);
determining, via the processor, a first quality score for the mass analysis data, the first quality score being based on a relationship between an intensity of the main peak and intensities of the one or more isotope peaks (“comparing the measured isotopic pattern with the theoretical isotopic pattern and relating the result to the noise, as reported previously (Supporting Information, Figure S1).40 Briefly, the difference between the measured (Si(obs)) pattern and theoretical (Si(est)) pattern is calculated per isotope (i), squared, and divided by the noise (N) squared. The square root of the sum of all isotope QC values yields the analyte QC value (eq 2). This QC value can be used to identify overlapping analytes and peak saturation, since either of the described problems can cause the observed isotopic pattern to deviate from the calculated one.” – Isotopic Quality Control Page 5091);
determining, via the processor, a second quality score for the mass analysis data, the second quality score being based on a signal-to-noise ratio of the mass analysis data (“Curation of analytes based on their relative abundance, as shown previously (Relative Quantitation section), may result in the loss of relevant features. Therefore, we evaluated the performance of the analyte quality criteria by curating the list of 108 analytes that were previously observed in the TPNG data.37 We used the difference between the theoretical isotopic pattern and measured isotopic pattern (QC value) and the maximum S/N ratio of an analyte as curation parameters. We removed all analytes that had a maximum S/N below 9 and a QC value below 1.0 × 10−5.” – Analyte Curation Page 5096);
determining, via the processor, an overall quality score as a combination of the first quality score and the second quality score (“We used the difference between the theoretical isotopic pattern and measured isotopic pattern (QC value) and the maximum S/N ratio of an analyte as curation parameters. We removed all analytes that had a maximum S/N below 9 and a QC value below 1.0 × 10−5. The resulting list of 40 analytes was used for integration and yielded an RSD of 6.0% for the main peak..” – Analyte Curation, Page 5096); and
assessing, via the processor, a quality of a compound library based on the determined overall quality score (The resulting list of 40 analytes was used for integration and yielded an RSD of 6.0% for the main peak - Analyte Curation, Page 5096; “Here, we have presented an easy-to-use high-throughput data processing tool for the analysis of MALDI-MS glycosylation data. MassyTools was applied to a biopharmaceutical sample and a complex (TPNG) sample to compare its performance with existing and commonly used data processing tools. The results show that MassyTools calibration performs better than flexAnalysis calibration. Furthermore, quantitation using MassyTools is better than quantitation using flexAnalysis for analytes below 0.1% relative abundance, as demonstrated by lower RSD values. Importantly, MassyTools was significantly faster in all aspects of the analysis (calibration and quantitation). MassyTools allows a user unskilled in scripting to repeatedly integrate and analyze a set of analytes from MS glycosylation data. The program outputs quality control criteria to judge the validity of single analytes, as well as whole spectra. These are invaluable tools in the analysis of large clinical cohorts and biopharmaceuticals data sets, and we envision that MassyTools will enable researchers to focus on the interpretation of data rather than the technical aspects of data processing.” – Concluding Remarks Page 5096).
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 2 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Bas in view of Monnig (US5352891).
In regards to Claims 2 and 19, Bas teaches the claimed limitation as detailed above. Bas is silent with regards to the language of “wherein determining the first quality score comprises calculating a ratio of the intensity of the main peak to the intensities of the one or more isotope peaks”
Monnig teaches “wherein determining the first quality score comprises calculating a ratio of the intensity of the main peak to the intensities of the one or more isotope peaks (“In other embodiments the predetermined threshold has a characteristic maximum value for each spectrum at which a quality factor, QF, is maximized. The predetermined threshold is set at the maximum value to maximize the quality factor. The quality factor is defined as the ratio of the intensity peaks of the subpopulations at a true molecular mass divided by intensity peaks at mass values other than the true molecular mass and integer multiples” – Column 3, Lines 55-65)”
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Bas to incorporate the teaching of Monnig to utilize the ratio of peak intensities as a quality factor. By utilizing the ratio of the peak intensities as a quality factor, this is an improvement that yields predictable results in the evaluation of the quality of the mass spectroscopy measurements.
Claim 38 is rejected under 35 U.S.C. 103 as being unpatentable over Bas in view of Datwani (US20190157061).
In regards to Claim 38, Bas discloses the claimed invention as detailed above. Bas is silent with regards to the language of “a non-contact sample ejector;
wherein the set of operations further comprises collecting the mass spectrometry data by receiving an ejected sample at the sample receiver; and
wherein receiving the ejected sample comprises introducing, with the non-contact sample ejector, the sample from a well plate into the sample receiver.”
Datwani teaches “a non-contact sample ejector (“acoustically coupling an acoustic droplet ejector that generates acoustic radiation to a reservoir containing the fluid sample having a fluid surface” - [0016]);
wherein the set of operations further comprises collecting the mass spectrometry data by receiving an ejected sample at the sample receiver (“2.5 nL droplets were acoustically ejected over a 1 second period at a repetition rate of 10 Hz from the source well into the open port of the flow probe. The impact of flow pattern at the sampling tip on MS peak shape was measured by slowly varying the active flow control solvent flow rate starting with a balanced configuration (as illustrated in FIG. 2 and more particularly described in Rapid Comm. Mass Spectrometry, 2015, 29, 1749-1756, the contents of which are incorporated by reference) and gradually increasing the solvent flow rate to form a pendent drop (as also illustrated in FIG. 2). As can be seen in the real-time mass spectrum obtained, in FIG. 3, the peaks are initially tall and sharp. When the solvent flow rate was increased, and the balanced configuration transitioned to the large pendent drop configuration, the MS peaks became shorter and wider, as can be seen throughout the 17 min-39 min time period. Decreasing the solvent flow rate thereafter returned the flow configuration to the balanced state, and the peaks obtained were once again tall and sharp, as can be seen in the 41 min-45 min time period. Analyte elution profile and measured ion signal peak shape thus vary with the flow configuration at the open port, with the large pendent droplet flow pattern leading to greater dilution of the droplet and broader, lower intensity peaks, with a balanced flow configuration giving rise to tall, sharp peaks” – [0152]); and
wherein receiving the ejected sample comprises introducing, with the non-contact sample ejector, the sample from a well plate into the sample receiver (“activating the acoustic ejector to generate acoustic radiation toward the reservoir and into the fluid sample in a manner effective to eject a droplet of the fluid sample from the fluid surface into a sampling tip of a continuous flow sampling probe, where the ejected droplet combines with a circulating solvent within the flow probe to form an analyte-solvent dilution, said sampling probe spaced apart from the fluid surface to provide a gap between the fluid surface and the sampling tip” – [0017]; “transporting the received fluid sample droplet in the form of the analyte-solvent dilution through a sample transport capillary within the sampling probe to a sample outlet, where the analyte-solvent dilution is directed away from the sampling probe to an analytical instrument” – [0018])
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Bas to incorporate the teaching of Datwani to utilize an acoustic ejector with the mass spectrometry system. By utilizing an acoustic ejector this is an improvement that yields predictable results in the operation of the mass spectroscopy system.
Examiner’s Note
Claims 3-4, 6, 11, 13, 16, 20-21, 23, 28, 33-34, 42 are not rejected under a prior art rejection.
In regards to Claims 3 and 20, Bas is silent with regards to the language of “wherein determining the first quality score comprises calculating:
P1=1/(100*ARD);
where:
ARD is an average ratio differential and is equal to (ΣRDi)/i for each isotope i of the one or more isotopes; and
RDi=ABS((ImM+i/ImM)-(IpM+i/IpM))/(IpM+i/IpM);
where:
ABS is indicative of the absolute value;
Im M+i is a measured intensity signal for the isotope peak corresponding to isotope i;
Im M is a measured intensity signal for the main peak of the given compound;
Ip M+i is a predicted intensity signal for the isotope peak corresponding to isotope i; and
Ip M is a predicted intensity signal for the main peak of the given compound.”
Claim 11 is dependent on Claim 3. Claim 28 is dependent on Claim 20.
In regards to claim 4 and 21, Bas is silent with regards to the language of “wherein determining the second quality score comprises calculating:
P2=log10(S/N)/10;
where P2 is the second quality score; and
S/N is a signal-to-noise ratio for the collected mass analysis data.”
In regards to Claim 6 and 23, Bas is silent with regards to the language of “wherein determining the overall quality score comprises calculating:
P=aP1+bP2; where P is the overall quality score; P1 is the first quality score;
P2 is the second quality score; a and b are experimental parameters; and a+b=2.”
In regards to Claim 13, Tolmachev (US20090048797) teaches “determining a mass accuracy of the mass analysis device (mass accuracy – Abstract)
Bas in view of Tolmachev is silent with regards to the language of “wherein when the mass accuracy is above a predetermined threshold, the overall quality score is set to zero.”
In regards to Claim 16 and 33, Kurata (US20090095896) teaches “determining a mass spectral purity (MSP) of the mass analysis data (calculating the mass spectral purity – [0192]).”
Bas in view of Kurata is silent with regards to the language of “calculating the overall quality score comprises calculating P=a P1+b P2+c MSP, where c is an experimental factor, where c is an experimental factor.”
In regards to Claim 34, Bas is silent with regards to the language of “wherein the set of instructions comprises determining the MSP by calculating a ratio of the intensity of the main intensity peak over an intensity peak of other ions.”
In regards to Claim 42, Bas is silent with regards to the language of “wherein the set of operations comprises determining the overall quality score by calculating:
P=αP12+βP22+γP1+δP2+ε;
where
P is the overall quality score;
P1 is the first quality score;
P2 is the second quality score; and
α, β, γ, δ and ε are experimental parameters.”
Conclusion
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/YOSSEF KORANG-BEHESHTI/Primary Examiner, Art Unit 2857
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