DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined
under the first inventor to file provisions of the AIA .
Claim Objection
2. Claim 16 is objected to because of the following informalities:
In claim 16, the phrase “a processing coupled to the storage medium” is vague.
Appropriate correction is required.
Claim Rejections - 35 USC § 101
3. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 101 that form the basis for the rejections under this section made in this Office action:
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.
4. Claims 1-18 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Under the 2019 PEG (now been incorporated into MPEP 2106), the revised procedure for determining whether a claim is "directed to" a judicial exception requires a two-prong inquiry into whether the claim recites: (1) any judicial exceptions, including certain groupings of abstract ideas (i.e., mathematical concepts, certain methods of organizing human interactions such as a fundamental economic practice, or mental processes); and (2) additional elements that integrate the judicial exception into a practical application (see MPEP § 2106.05(a)-(c), (e)-(h)).
Only if a claim (1) recites a judicial exception and (2) does not integrate that exception into a practical application, do we then look to whether the claim: (3) adds a specific limitation beyond the judicial exception that is not "well-understood, routine, conventional" in the field (see MPEP § 2106.0S(d)); or (4) simply appends well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception.
Claims 1-18 are directed to an abstract idea of identifying molecular species in a mass spectrum.
Specifically, representative claim 16 recites:
A system for identifying one or more molecular species represented in mass spectrometry data, comprising:
a storage medium; and
a processing coupled to the storage medium, wherein the storage medium comprises processor-executable instructions for:
(S1) obtaining a set of candidate mass spectra for the mass spectrometry data, wherein each candidate mass spectrum corresponds to a respective candidate molecular species;
(S2) optimizing a set of mass spectra coefficients for the set of candidate mass spectra, based on the mass spectrometry data, wherein said optimizing comprises: varying the mass spectra coefficient values based on an objective function, wherein the objective function relates a linear combination of the candidate mass spectra, according to the mass spectra coefficients, to the mass spectrometry data, subject to a regularization term of the objective function constraining the number of non-zero mass spectra coefficient values; and
(S3) providing, for one or more of the candidate molecular species, a respective indication of a match in the mass spectrum, based at least in part on the optimized set of mass spectra coefficients.
The claim limitations in the abstract idea have been highlighted in bold above; the remaining limitations are “additional elements”.
The highlighted portion of the claim constitutes an abstract idea under the 2019 Revised Patent Subject Matter Eligibility Guidance and the additional elements are NOT sufficient to amount to significantly more than the judicial exceptions, as analyzed below:
Step
Analysis
1. Statutory Category ?
Yes.
System/Apparatus
2A - Prong 1: Judicial Exception Recited?
Yes.
See the bolded portion as listed above.
Under its broadest reasonable interpretation (BRI), the limitations (S2) recited in the bolded portion encompasses mathematical concepts and/or calculations, namely a series of calculations leading to one or more numerical results or answers, which also encompasses mental processes, i.e. data manipulation, evaluation and judgment, that can be performed in the human mind or by a human using a pen and paper.
Nothing in the bolded portion precludes this limitation from practically being performed in the mind and/or with the aid of pen/paper. Note, the courts consider a mental process (thinking) that "can be performed in the human mind, or by a human using a pen and paper" to be an abstract idea. See CyberSource Corp. v. Retail Decisions, Inc., 654 F.3d 1366, 1372, 99 USPQ2d 1690, 1695 (Fed. Cir. 2011). See also to MPEP 2106.04(a)(2).III
Therefore, the bolded portion of instant claim 16, reciting a series of mathematical concepts and mental process, amounts to an abstract idea falling within a combination of the “Mental Process” and “Mathematical Concepts” groupings of Abstract Ideas defined by the 2019 PEG.
2A - Prong 2: Integrated into a Practical Application?
No.
Representative claim 16 recites “a storage medium; and
a processor coupled to the storage medium, wherein the storage medium comprises processor-executable instructions” at a high level of generality. Under the BRI, the combination of the processor and the storage medium reads on a general-purpose computer performing a generic computer function of processing data. The generic processor limitation is no more than mere instructions to apply the abstract idea using the general-purpose computer. It is held that performing an abstract idea using a general-purpose computer system would not amount to significantly more than the abstract algorithm itself. See, for example, Whitserve LLC v. Dropbox, Inc. and MPEP 2106.05(f).
The limitation of “mass spectrometry data” is recited broadly. The claim does not require any particular devices or sensors to obtain the “mass spectrometry data”. It could just as easily relate to the acquisition of the “mass spectrometry data” from, e.g., look-up tables as opposed to the generation of actual measurement data in real-time. Thus claim 16 would monopolize the abstract idea across a wide range of applications
Under its BRI, the limitation (S1) encompasses a process of gathering the data/information necessary for performing the abstract idea. Thus, it does not impose any other meaningful limits on the claim. See MPEP 2106.05(g)(3): … that were described as mere data gathering in conjunction with a law of nature or abstract idea. See also Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; OIP Techs., Inc. v. Amazon.com, Inc., 788 F.3d 1359, 13863, 115 USPQ2d 1090, 1092-93 (Fed. Cir. 2015).
Under its BRI, the limitation (S3) encompasses a process of outputting the results of the abstract idea (such as printing or displaying the related information) which is treated as insignificant post-solution activity.
The claim as a whole does not meet any of the following criteria to integrate the abstract idea into a practical application:
An additional element reflects an improvement in the functioning of a computer, or an improvement to other technology or technical field;
an additional element that applies or uses a judicial exception to affect a particular treatment or prophylaxis for a disease or medical condition;
an additional element implements a judicial exception with, or uses a judicial exception in conjunction with, a particular machine or manufacture that is integral to the claim;
an additional element effects a transformation or reduction of a particular article to a different state or thing; and
an additional element applies or uses the judicial exception in some other meaningful way beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception.
Various considerations are used to determine whether the additional elements are sufficient to integrate the abstract idea into a practical application. However, in all of these respects, the claim fails to recite additional elements which might possibly integrate the claim into a particular practical application. At most, it only generally links the judicial exception to a particular technological environment or field of use. See MPEP 2106.04(d)(2).
2B: Claim provides an Inventive Concept?
No.
As analyzed in Step 2A - Prong 2, the claim does not recite any additional element that amounts to be “significantly more” to integrate the abstract idea into a practical application. Further, it is deemed that none of the recited additional limitations/elements reflect an inventive concept or a qualified improvement. See MPEP 2106.05.
The claim is therefore ineligible under 35 USC 101.
Claims 1 and 18 are treated as ineligible subject matter under 35 U.S.C. § 101 for the same reasons as for claim 16 set forth above.
The dependent claims 2-15 and 17 inherit attributes of the independent claim 1, but does not add anything which would render the claimed invention a patent eligible application of the abstract idea. The claim merely extends (or narrows) the abstract idea which does not amount for "significant more" because it merely adds details to the algorithm which forms the abstract idea as discussed above. In particular, limitations of the various physical parameters/variables recited in dependent claims 2-15 and 17, under the BRI, encompass merely data characterization which can be viewed as nothing more than an attempt to generally link the use of the judicial exception to the relevant technological environment or field of use.
5. Claim 18 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
Claim 18 drawn to a storage medium carrying processor executable instructions itself is directed non-statutory subject matter, since the BRI of machine readable media can encompass non-statutory transitory forms of signal transmission. The Federal Circuit court held that “a transitory, propagating signal does not fall within any statutory category [of 35 USC 101].” See MPEP 2106.03.
Claim Rejections - 35 USC § 102
6. 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; or
(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.
7. Claims 1-4, 6, 8-9, 12-14 and 16-18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Peckner et al. (Specter: linear deconvolution for targeted analysis of data-independent acquisition mass spectrometry proteomics, Nature Methods, 15(5): 371-378 (2018)).
Regarding claims 1, 16 and 18, Peckner discloses a system, a method, and computer program product, for identifying one or more molecular species represented in mass spectrometry data (Page 1, Abstract; Page 4, right column: “Specter identified both of the positional isomers … The peptide … is a constituent of the cytoskeletal cross-linking protein plectin … ”), comprising: a storage medium and a processor coupled to the storage medium, wherein the storage medium comprises processor-executable instructions (Page 2, left column: “Specter is built on the open-source distributed computing framework Apache Spark”; see also discussion of the “open-source software tool” on Pages 1, 12 and 14) for: obtaining a set of candidate mass spectra (L1, L2, …) for the mass spectrometry data (Page 9, left column, 1st paragraph: “ … The set of library members used to analyze S is determined by the following conditions (where L denotes a candidate library precursor): …”), wherein each candidate mass spectrum corresponds to a respective candidate molecular species (Page 9, right column, 2nd paragraph: “Indeed, the multiplication of a library spectrum L by a coefficient c is the mathematical analog of the physical fragmentation of c molecules of the precursor whose library spectrum is L”); optimizing a set of mass spectra coefficients (c1, c2, …) for the set of candidate mass spectra, based on the mass spectrometry data (Page 2, left column, last paragraph: “These algebraic coefficients are then analyzed further to determine the final identifications and quantifications of library members”; Page 9, left column: “Finding the optimal combination. …”; Page 9, right column, 2nd, 3rd and last paragraphs), wherein said optimizing comprises: varying the mass spectra coefficient values based on an objective function (Page 9, right column, 3rd paragraph: “We consider a library precursor to be identified by Specter if this elution profile contains a peak (local maximum) of at least five consecutive coefficients that are greater than 1 …. This is a physical constraint that recognizes that total ion intensities less than 1 cannot possibly correspond to meaningful signal”; see also discussion of the “Specter coefficient cj” on Page 9, right column, 2nd and last paragraphs), wherein the objective function relates a linear combination (“S = c1× L1+ c2 × L2 +…+ cm × Lm + N”) of the candidate mass spectra, according to the mass spectra coefficients, to the mass spectrometry data, subject to a regularization term (“the library spectra are normalized to have a total ion intensity of 1”) of the objective function constraining the number of non-zero mass spectra coefficient values (Page 9, right column, 2nd, 3rd and last paragraphs); and providing, for one or more of the candidate molecular species, a respective indication of a match in the mass spectrum, based at least in part on the optimized set of mass spectra coefficients (Page 2, left column, last paragraph: “These algebraic coefficients are then analyzed further to determine the final identifications and quantifications of library members”; Page 9, right column, last paragraph: “we used several chromatographic peak scores to rank the quality of our identifications … The four scores associated with the precursor were then …”).
Regarding claims 2-4 and 17, Peckner discloses: wherein the one or more molecular species are one or more precursor molecular species, the mass spectrometry data is a fragment mass spectrum derived from the one or more precursor molecular species (Page 1, right column, last paragraph), and each candidate mass spectrum is a candidate fragment mass spectrum corresponding to a respective candidate molecular species (Page 9, left column, 1st paragraph; Page 9, right column, 2nd paragraph); wherein the step of providing comprises identifying the one or more candidate molecular species as sample molecular species represented in a chimeric mass spectrum (Page 4, left column, 2nd paragraph: “We analyzed three families of synthetic peptides, each consisting of precursors whose spectra were highly similar and whose m/z (in charge state +2) fell into the same isolation windows for DIA (Fig. 4 and Supplementary Tables 1 and 2)”; Page 7, left column, 2nd paragraph) based on the optimized set of fragment mass spectra coefficients (Page 9, right column, 2nd, 3rd and last paragraphs); wherein the precursor molecular species represented in one or more candidate fragment mass spectra are peptides or peptide precursors (Page 1, right column, last paragraph).
Regarding claim 6, Peckner discloses: wherein the mass spectrometry data is an MS1 mass spectrum (Page 11, left column, 1st paragraph: “DDA and DIA data were acquired on the same instrument. For the MS1 scans the resolution was set at …”) and wherein one or more of the candidate mass spectra are selected as part of the set of candidate mass spectra based on an MS2 mass spectrum corresponding to the MS1 mass spectrum (Page 11, left column, 1st paragraph: “DDA and DIA data were acquired on the same instrument. For the MS1 scans the resolution was set … For DDA, MS2 scans on the top 12 peaks doubly charged and above were acquired at a resolution of
15,000 …”).
Regarding claim 8, Peckner discloses: wherein the respective indication comprises a quantity (e.g., a consecutive series of at least five candidates) of the corresponding candidate molecular species present in the mass spectrum (Page 9, right column, last paragraph).
Regarding claim 9, Peckner discloses: identifying the mass spectrometry data as a chimeric mass spectrum based on the optimized set of mass spectra coefficients based on the optimized set of fragment mass spectra coefficients (Page 4, left column, 2nd paragraph: “We analyzed three families of synthetic peptides, each consisting of precursors whose spectra were highly similar and whose m/z (in charge state +2) fell into the same isolation windows for DIA (Fig. 4 and Supplementary Tables 1 and 2)”; Page 7, left column, 2nd paragraph; see also Page 9, right column, 2nd, 3rd and last paragraphs).
Regarding claim 12, Peckner discloses: wherein the mass spectrometry data is part of a series of mass spectrometry data for a separation parameter wherein the regularization term comprises a constraint enforcing a relation between the mass spectra coefficient for a given candidate mass spectrum and a mass spectra coefficient of the same candidate mass spectrum determined for further mass spectrometry data of the series (Page 9, right column, 2nd paragraphs: “the library spectra are normalized to have a total ion intensity of 1 (Supplementary Note 3): when such a normalized spectrum L is multiplied by a coefficient c (meaning that the intensities of all of its peaks are multiplied by this constant), the total ion intensity of the resulting scaled spectrum c × L can be nothing other than c”; see also Page 9, right column, 3rd paragraph).
Regarding claim 13, Peckner discloses: wherein the regularization term comprises an L1 norm (e.g., at least five consecutive coefficients) of the mass spectra coefficient values, wherein optionally the regularization term comprises an L2 norm (coefficients must be greater than 1) of the mass spectra coefficient values (Page 9, right column, 3rd paragraph).
Regarding claim 14, Peckner discloses: wherein the optimizing step further comprises varying a parameter (e.g., the number of the “consecutive Coefficients” must be equal to or greater than five, “where coefficients are considered consecutive only if they are calculated relative to sequential MS2 spectra for which the precursor satisfies the conditions”) specifying a degree of regularization of the regularization term (Page 9, right column, 3rd and last paragraphs: by inherency, more number of “consecutive Coefficients” reflects higher degree of regularization of the regularization term).
Claim Rejections - 35 USC § 103
8. 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 of this title, 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.
9. Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Peckner et al. in view of GROTHE et al. (US 20140138537 A1).
Regarding claim 5, Peckner discloses: wherein the mass spectrometry data is an MS1 mass spectrum of the one or more molecular species (Page 4, right column: “The peptide … is a constituent of the cytoskeletal cross-linking protein plectin … ”; Page 11, left column, 1st paragraph: “DDA and DIA data were acquired on the same instrument. For the MS1 scans the resolution was set at 60,000 at 200 m/z and the automatic gain control (AGC) target was 3 × 106 with a maximum inject fill time of 20 ms”).
Peckner is silent on: each candidate mass spectrum comprises an isotope pattern corresponding to a respective candidate molecular species.
GROTHE discloses methods for generating a local mass spectral library for interpreting multiplexed mass spectra, comprising: accommodating the possibility that ions of multiple charge state and isotope composition may fall in a given mass rang (para. 0049).
Since Peckner teaches the general conditions of the mass spectrometry data and the spectral library and it is well-known that mass spectrometry analyzes the mass-to-charge ratio (m/z) of ions and molecular species present in mass spectra can be identified through their isotope patterns, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the Peckner spectral library as taught by GROTHE and apply the Peckner’s “Specter” to a specific set of candidate mass spectra containing an isotope profile of at least one ion of interest (wherein each candidate mass spectrum comprises an isotope pattern corresponding to a respective candidate molecular species) to arrive the claimed invention. The skilled person would conceive and apply such modification, as intended use of known inventions, without needing inventive skill but depending on practical considerations and according to the dictates of the circumstances. It has been held that a recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. In a claim drawn to a process of making, the intended use must result in a manipulative difference as compared to the prior art. See In re Casey, 152 USPQ 235 (CCPA 1967) and In re Otto, 136 USPQ 458, 459 (CCPA 1963).
10. Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Peckner et al. in view of Wang et al. (US 20060255258 A1).
Regarding claim 15, Peckner does not mention explicitly: wherein the objective function provides a measure of difference between the linear combination of the candidate mass spectra and the mass spectrometry data, optionally wherein the step of varying is carried out to obtain an extremum value of the objective function.
Wang discloses a computer-implemented system and method for identifying one or more molecular species represented in mass spectrometry data (para. 0016, 0048, 0060: “performing chromatographic peak detection using known peak shape functions with regression analysis; reporting regression coefficients from the regression analysis as one of peak area and peak location”) by optimizing a set of mass spectra coefficients for a linear combination (para. 0119: “r=Kc+e”) of a set of candidate mass spectra (para. 0121: “The components arranged in the columns of matrix K will be referred to as peak components, which may optionally include any baseline of known functionality …”) based on measured mass spectrometry data (para. 0119-0122), wherein said optimizing comprises: varying the mass spectra coefficient values (inherent to the least squares fitting process discussed in para. 0198, 0126 and 0132) based on an objective function (e.g., the residual sum of squares RSS, which is calculated as the sum of the squared residuals across all data points, wherein the RSS is minimized by finding the optimal coefficients that minimize the objective function, ensuring an efficient fit to the data), wherein the objective function relates a linear combination (para. 0119: “r=Kc+e”) of the candidate mass spectra, according to the mass spectra coefficients, to the mass spectrometry data, and wherein the objective function provides a measure of difference between the linear combination of the candidate mass spectra and the mass spectrometry data, optionally wherein the step of varying is carried out to obtain an extremum value (i.e., a minimum of the RSS) of the objective function (para. 0126, 0132).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate Wang’s teaching of linear regression fitting technique into Peckner to provide an alternative mechanism for identifying one or more molecular species represented in mass spectrometry data. The skilled person would conceive and apply such modification, as intended use of known inventions, without needing inventive skill but depending on practical considerations and according to the dictates of the circumstances. Further, one of ordinary skill in the art would have recognized that the results of such a combination were predictable for performing chromatographic peak detection since the use of that known technique provides the rationale to arrive at a conclusion of obviousness.
Examiner’s Note
11. While there are related references that discuss identifying molecular species in a mass spectrum, the prior art of record does not specifically provide teachings for the claimed limitations including: wherein for a given candidate mass spectrum: a spectrum similarity score is calculated between the given candidate mass spectrum and a further mass spectrum, wherein the further mass spectrum is generated by subtracting each of the other candidate mass spectra from the mass spectrometry data according to the optimized set of mass spectra coefficients (as recited in claim 7); wherein the step of providing further comprises generating reporter ion intensities for one or more of candidate mass spectra and generating corrected reporter ion intensities for at least one of the precursor molecular species based on a difference between a reporter ion intensity for the precursor molecular species generated from the mass spectrometry data and the reporter ion intensities for the one or more candidate mass spectra scaled by the corresponding optimized mass spectra coefficients (as recited in claim 10), obtaining a respective set of reporter ion intensities for each item of mass spectrometry data, each reporter ion intensity of the set corresponding to a respective isobarically labelled sample of the mixed sample, and calculating, for at least one of the peptide precursors, a fraction of the abundance of the peptide in the mixed sample corresponding to one of the samples, based on the sets of reporter ion intensities and the sets of optimized mass spectra coefficients (as recited in claim 11). It is these limitations, as they are claimed in the combination in independent claim 1, that would make the claims 7, 10 and 11 distinguish over the prior art of record.
Contact Information
12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to XIUQIN SUN whose telephone number is (571)272-2280. The examiner can normally be reached 9:30am-6:00pm.
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/X.S/Examiner, Art Unit 2857
/SHELBY A TURNER/Supervisory Patent Examiner, Art Unit 2857
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