DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Argument
The declaration (Kelleher Declaration 2) under 37 CFR 1.130(a) filed 12/11/2023 is sufficient to overcome the rejection of claims 1-7 and 10-19 based upon being anticipated under 35 USC 102(a)(1).
Status of Claims
Claims 1-2, 4-10, and 12-19 pending and examined on the merits.
Claims 3 and 11 cancelled.
Priority
The instant application filed on 10/19/2020 claims the benefit of priority to U.S. Patent Application No. 15/602,917 filed on 5/23/2017 (now allowed as U.S. Patent No. 10,808,256 on 10/20/2020), which claims the benefit of priority to U.S. Provisional Patent Application No. 62/340,116 filed on 5/23/2016. Thus, the effective filing date of the claims is 5/23/2016.
The applicant is reminded that amendments to the claims and specification must comply with 35 U.S.C. § 120 and 37 C.F.R. § 1.121 to maintain priority to an earlier-filed application. Claim amendments may impact the effective filing date if new subject matter is introduced that lacks support in the originally filed disclosure. If an amendment adds limitations that were not adequately described in the parent application, the claim may no longer be entitled to the priority date of the earlier filing.
Specification
The disclosure is objected to because of the following informalities:
Abstract, line 3, "the correlation off such metabolites" should read "the correlation of such metabolites".
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 1-2, 4-10, and 12-19 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea of a mental process, a mathematical concept, organizing human activity, or a law of nature or natural phenomenon without significantly more. In accordance with MPEP § 2106, claims found to recite statutory subject matter (Step 1: YES) are then analyzed to determine if the claims recite any concepts that equate to an abstract idea, law of nature or natural phenomenon (Step 2A, Prong 1). In the instant application, the claims recite the following limitations that equate to an abstract idea:
Claim 1: “screening metabolites produced by the host system to identify metabolite features produced by the test pBGC” provides an evaluation (screening requires an evaluation of [metabolite] features) that may be performed in the human mind and is therefore considered a mental process, which is an abstract idea.
“calculating a score for a metabolite feature based on a combination of (i) abundance of the metabolite feature in a sample from the host system and (ii) uniqueness of the feature compared to one or more control samples” provides a mathematical calculation (calculating score from abundance or uniqueness) that is considered a mathematical concept, which is an abstract idea. It also provides a comparison (comparing sample data to control data) that may be performed in the human mind and is therefore considered a mental process, which is an abstract idea.
“identifying: (i) the test pBGC as a biosynthetic gene cluster (BGC), and/or (ii) the metabolite feature as being produced by the test pBGC, if the score identifies the metabolite feature as being unique and abundant relative to other scored metabolite features” provides an evaluation (identifying gene clusters or metabolite features requires evaluation of data or scores) that may be performed in the human mind and is therefore considered a mental process, which is an abstract idea.
Claim 16: “identifying the particular metabolite” provides an evaluation (identifying a metabolite requires evaluation of data from techniques listed in claim 14) that may be performed in the human mind and is therefore considered a mental process, which is an abstract idea.
Claim 17: “dividing the abundance of the metabolite feature in the test sample by the average abundance of the metabolite feature in the one or more control samples” provides a mathematical calculation (dividing requires mathematical calculation) that is considered a mathematical concept, which is an abstract idea.
Claim 18: “multiplying the uniqueness of the metabolite feature among samples tested by the abundance of the metabolite feature in the test sample” provides a mathematical calculation (multiplying requires mathematical calculation) that is considered a mathematical concept, which is an abstract idea.
These recitations are similar to the concepts of collecting information, analyzing it, and displaying certain results of the collection and analysis in Electric Power Group, LLC, v. Alstom (830 F.3d 1350, 119 USPQ2d 1739 (Fed. Cir. 2016)), organizing and manipulating information through mathematical correlations in Digitech Image Techs., LLC v Electronics for Imaging, Inc. (758 F.3d 1344, 111 U.S.P.Q.2d 1717 (Fed. Cir. 2014)) and comparing information regarding a sample or test to a control or target data in Univ. of Utah Research Found. v. Ambry Genetics Corp. (774 F.3d 755, 113 U.S.P.Q.2d 1241 (Fed. Cir. 2014)) and Association for Molecular Pathology v. USPTO (689 F.3d 1303, 103 U.S.P.Q.2d 1681 (Fed. Cir. 2012)) that the courts have identified as concepts that can be practically performed in the human mind or are mathematical relationships. Therefore, these limitations fall under the “Mental process” and “Mathematical concepts” groupings of abstract ideas. As such, claims 1-2, 4-10, and 12-19 recite an abstract idea (Step 2A, Prong 1: YES).
Claims found to recite a judicial exception under Step 2A, Prong 1 are then further analyzed to determine if the claims as a whole integrate the recited judicial exception into a practical application or not (Step 2A, Prong 2). The judicial exceptions listed above are not integrated into a practical application because the claims do not recite an additional element or elements that reflects an improvement to technology. Specifically, the claims recite the following additional elements:
Claim 1: “expressing a test putative biosynthetic gene cluster (pBGC) in a host system” provides insignificant extra-solution activities (expressing genes in a host system is a pre-solution activity involving sample manipulation steps) that do not serve to integrate the judicial exceptions into a practical application.
“validating the identification made in step (d) by repeating steps (a) and (b) with a validation pBGC comprising a deletion within the test pBGC, wherein the validation confirms that the test pBGC is a BGC that produces the metabolite if the deletion reduces or eliminates production of the metabolite by the host system” provides insignificant extra-solution activities (validating an identification using a knock-out test is a post-solution activity involving sample manipulation steps) that do not serve to integrate the judicial exceptions into a practical application.
Claim 10: “subjecting the host system or test sample derived therefrom to the one or more bioanalytical techniques to identify bioanalytical features that correlate to metabolites produced by the host system expressing the test pBGC” provides insignificant extra-solution activities (running bioanalytical techniques is a pre-solution activity involving sample manipulation steps) that do not serve to integrate the judicial exceptions into a practical application.
Claim 15: “isolating the particular metabolite” provides insignificant extra-solution activities (isolating a metabolite is a pre-solution activity involving sample manipulation steps - per instant spec page 12) that do not serve to integrate the judicial exceptions into a practical application.
The steps for expressing genes, validating results via knock-outs, running bioanalytical techniques, and isolating metabolites are insignificant extra-solution activities that do not serve to integrate the recited judicial exceptions into a practical application because they are pre- and post-solution activities involving sample manipulation steps (see MPEP 2106.04(d)(2)). Therefore, claims 1-2, 4-10, and 12-19 are directed to an abstract idea (Step 2A, Prong 2: NO).
Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself (Step 2B). The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite additional elements that are insignificant extra-solution activities that do not serve to integrate the recited judicial exceptions into a practical application, or equate to mere instructions to apply the recited exception in a generic way or in a generic computing environment.
The limitations for expressing genes, validating results via knock-outs, running bioanalytical techniques, and isolating metabolites are insignificant extra-solution activities that do not serve to integrate the recited judicial exceptions into a practical application. Furthermore, no inventive concept is claimed by these limitations as they are well-understood, routine, and conventional.
The additional elements do not comprise an inventive concept when considered individually or as an ordered combination that transforms the claimed judicial exception into a patent-eligible application of the judicial exception. Therefore, the claims do not amount to significantly more than the judicial exception itself (Step 2B: No). As such, claims 1-2, 4-10, and 12-19 are not patent eligible.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-2, 4, 6, 8-9, 12-13, and 16-19 rejected under 35 U.S.C. 103 as being unpatentable over Shetty et al. (US-20150315599) in view of Vinaixa et al. (Vinaixa et al. "A guideline to univariate statistical analysis for LC/MS-based untargeted metabolomics-derived data." Metabolites 2.4 (2012): 775-795).
Regarding claim 1, Shetty teaches a method of screening for metabolites (Para.0110 " the present invention provides a method for identifying candidate proteins or enzymes of interest capable of performing a desired metabolic activity").
Shetty also teaches expressing a test putative biosynthetic gene cluster (pBGC) in a host system (Para.0086 "The term “expression vector” refers to a vector which is capable of expressing of a gene that has been cloned into it. Such expression can occur after transformation into a host cell, or in IVPS systems").
Shetty also teaches identifying: (i) the test pBGC as a biosynthetic gene cluster (BGC), and/or (ii) the metabolite feature as being produced by the test pBGC, if the score identifies the metabolite feature as being unique and abundant relative to other scored metabolite features (Para.0110 " the present invention provides a method for identifying candidate proteins or enzymes of interest capable of performing a desired metabolic activity").
Shetty does not explicitly teach: screening metabolites produced by the host system to identify metabolite features produced by the test pBGC; calculating a score for a metabolite feature based on a combination of (i) abundance of the metabolite feature in a sample from the host system and (ii) uniqueness of the feature compared to one or more control samples; nor validating the identification made in step (d) by repeating steps (a) and (b) with a validation pBGC comprising a deletion within the test pBGC, wherein the validation confirms that the test pBGC is a BGC that produces the metabolite if the deletion reduces or eliminates production of the metabolite by the host system.
However, Vinaixa teaches screening metabolites produced by the host system to identify metabolite features produced by the test pBGC (Page 14 paragraph 1 "it has been demonstrated that controlling the FDR at the screening stage of the research carries a benefit for the next research stages").
Vinaixa also teaches obtaining the uniqueness value of a mass-to-charge ratio as well as an intensity value indicative of abundance, the combination of which is an obvious design choice because there is no technical improvement shown (Page 2 paragraph 1 "Thousands of so called metabolite features (i.e., peaks corresponding to individual ions with a unique mass-to-charge ratio and a unique retention time or mzRT features from now on) can be routinely detected in biological samples. In addition, each mzRT feature in the dataset is associated with an intensity value (or area under the peak), which indicates its relative abundance in the sample").
Vinaixa also teaches validation studies and using knock-outs for comparison (page 15 paragraph 1 "In addition, we would like to comment that whenever a follow-up targeted validation study was going to be attempted, we would recommend considering those metabolites showing statistical significance after strict Bonferroni correction" and page 4 Table 1).
Therefore, it would have been obvious to one of ordinary skill in the art as of the effective filing date of the claimed invention to modify the methods of Shetty as taught by Vinaixa in order to apply the appropriate statistics to discover significantly altered features between samples (page 1 abstract "Statistical analysis, however, is needed in order to discover those features significantly altered between samples"). One skilled in the art would have a reasonable expectation of success because both methods utilize bioanalytical techniques for metabolite feature identification.
Regarding claim 2, Shetty in view of Vinaixa teach the methods of Claim 1 on which this claim depends/these claims depend, respectively. Vinaixa also teaches untargeted screening (Page 1 abstract "Characteristics and challenges of this analysis are discussed and illustrated using four different real LC/MS untargeted metabolomic datasets").
Regarding claim 4, Shetty in view of Vinaixa teach the methods of Claim 1 on which this claim depends/these claims depend, respectively. Shetty also teaches the test pBGC comprises a sequence derived from genomic DNA of a fungus of interest (Para.0107 "sources of encoding nucleic acids for enzymes for a biosynthetic pathway can include, for example, any species where the encoded gene product is capable of catalyzing the referenced reaction. Exemplary species for such sources include [] fungi").
Regarding claims 6 and 8, Shetty in view of Vinaixa teach the methods of Claim 1 on which this claim depends/these claims depend, respectively. Shetty also teaches the host system is a fungal cell or a fungal cell lysate (Para.0222 "Such types of models have been applied, for example, to analyze metabolic fluxes in organisms responsible for enhanced biological phosphorus removal in wastewater treatment reactors and in filamentous fungi producing polyketides", and a lysate is an obvious variant of a fungal host system, as analysis of metabolites would require lysis of the sample cells).
Regarding claim 9, Shetty in view of Vinaixa teach the methods of Claim 1 on which this claim depends/these claims depend, respectively. Shetty also teaches the host system is an in vitro expression system (Para.0035 "a method of introducing a conjugative plasmid into methylotrophic host cells is provided" and para.0083 "An mRNA lacking the Kozak consensus sequence may also be translated efficiently in an in vitro systems if it possesses a moderately long 5′-UTR that lacks stable secondary structure").
Regarding claims 12 and 13, Shetty in view of Vinaixa teach the methods of Claim 1 on which this claim depends/these claims depend, respectively. Vinaixa also suggests using control samples for examining variation, which includes comparing samples (Page 6 last paragraph "The ideal method to examine analytical variation is to analyze quality control (QC) samples, which will provide robust quality assurance of each detected mzRT feature").
Regarding claim 16, Shetty in view of Vinaixa teach the methods of Claim 1 on which this claim depends/these claims depend, respectively. Vinaixa also teaches identifying the particular metabolite (Page 1 Abstract "By comparing the retention time and MS/MS data of a model compound to that from the altered feature of interest in the research sample, metabolites can be then unequivocally identified").
Regarding claims 17 and 18, Shetty in view of Vinaixa teach the methods of Claim 1 on which this claim depends/these claims depend, respectively. Vinaixa also teaches simple data manipulation to compare and/or combine metabolite features, and dividing/multiplying abundance feature values is an obvious design choice because there is no technical improvement shown (Page 1 Abstract "By comparing the retention time and MS/MS data of a model compound to that from the altered feature of interest in the research sample, metabolites can be then unequivocally identified").
Regarding claim 19, Shetty in view of Vinaixa teach the methods of Claim 1 on which this claim depends/these claims depend, respectively. Vinaixa also teaches using control samples to examine analytical variation (Page 6 last paragraph "The ideal method to examine analytical variation is to analyze quality control (QC) samples").
Claims 5 and 7 rejected under 35 U.S.C. 103 as being unpatentable over Shetty et al. (US-20150315599) in view of Vinaixa et al. (Vinaixa et al. "A guideline to univariate statistical analysis for LC/MS-based untargeted metabolomics-derived data." Metabolites 2.4 (2012): 775-795) as applied to claims 1-2, 4, 6, 8-9, 12-13, and 16-19 above, and further in view of Bier et al. (WO-2016073559).
Shetty et al. in view of Vinaixa et al. are applied to claims 1-2, 4, 6, 8-9, 12-13, and 16-19.
Regarding claims 5 and 7, Shetty in view of Vinaixa teach the method of Claim 1 on which this claim depends/these claims depend.
Shetty nor Vinaixa explicitly teach the test pBGC has been inserted into a fungal artificial chromosome (FAC).
However, Bier teaches using an artificial chromosome in a model fungal organism, as well as the group of fungal cell organisms consisting of Ashbya gossypii, Aspergillus nidulans, Coprinus cinereus, Cryptococcus neoformans, Neurospora crassa, Saccharomyces cerevisiae, Schizophyllum commune, Schizosaccharomyces pombe, and Ustilago maydis (Para.0027 "In some embodiments of any one of the methods or constructs described herein, the gene encoding an endonuclease is located on a plasmid or artificial chromosome", and Para.0156 "Fungal model organisms include, but are not limited to, Ashbya gossypii; Aspergillus nidulans; Coprinus cinereus; Cryptococcus neoformans; Cunninghamella elegans; Neurospora crassa; Saccharomyces cerevisiae; Schizophyllum commune; Schizosaccharomyces pombe; Ustilago maydis; and any combination thereof").
Therefore, it would have been obvious to one of ordinary skill in the art as of the effective filing date of the claimed invention to modify the methods of Shetty and Vinaixa as taught by Bier in order to integrate multiple elements into a genome (para.0005 "MCR [mutagenic chain reaction] for autocatalytic genome editing is based on genomic integration of an MCR construct containing multiple elements"). One skilled in the art would have a reasonable expectation of success because both methods utilize transformed organisms for validation of results or production of molecules.
Claims 10 and 14-15 rejected under 35 U.S.C. 103 as being unpatentable over Shetty et al. (US-20150315599) in view of Vinaixa et al. (Vinaixa et al. "A guideline to univariate statistical analysis for LC/MS-based untargeted metabolomics-derived data." Metabolites 2.4 (2012): 775-795) as applied to claims 1-2, 4, 6, 8-9, 12-13, and 16-19 above, and further in view of Paillard et al. (WO-2016005527).
Shetty et al. in view of Vinaixa et al. are applied to claims 1-2, 4, 6, 8-9, 12-13, and 16-19.
Regarding claims 10 and 14-15, Shetty in view of Vinaixa teach the method of Claim 1 on which this claim depends/these claims depend.
Shetty nor Vinaixa explicitly teach: screening comprises subjecting the host system or test sample derived therefrom to the one or more bioanalytical techniques to identify bioanalytical features that correlate to metabolites produced by the host system expressing the test pBGC; the one or more bioanalytical techniques are selected from the group consisting of mass spectrometry (MS), tandem mass spectrometry (MS2), high performance liquid chromatography (HPLC), gas chromatography, ultra performance liquid chromatography (UPLC), supercritical fluid chromatography, nuclear magnetic resonance (NMR), liquid chromatography-mass spectrometry (LC-MS), gas chromatography-mass spectrometry (GC-MS), liquid chromatography-diode array detection (LC-DAD), capillary electrophoresis-mass spectrometry (CE-MS), and liquid chromatography-tandem mass spectrometry (LC-MS2); nor isolating the particular metabolite.
However, Paillard teaches bioanalytical techniques to identify bioanalytical features that correlate to metabolites produced by the host system expressing products, the one or more bioanalytical techniques are selected from the group consisting of mass spectrometry (MS), tandem mass spectrometry (MS2), high performance liquid chromatography (HPLC), gas chromatography, ultra performance liquid chromatography (UPLC), supercritical fluid chromatography, nuclear magnetic resonance (NMR), liquid chromatography-mass spectrometry (LC-MS), gas chromatography-mass spectrometry (GC-MS), liquid chromatography-diode array detection (LC-DAD), capillary electrophoresis-mass spectrometry (CE-MS), and liquid chromatography-tandem mass spectrometry (LC-MS2), and further comprising isolating the particular metabolite (Page 8 line 23 "As example, mention may be made of a validated LC-MS/MS (liquid chromatography-tandem mass spectrometry) bioanalytical method, preferably comprising preparing samples by solid phase extraction using ethyl acetate, drying, dissolving in a mixture of acetonitrile and ammonium acetate, performing a chromatographic separation in this liquid mobile phase and detecting by tandem mass spectrometry. Other bioanalytical methods can be based on techniques such as HPLC (high performance liquid chromatography), GC (gas chromatography), UPLC (ultra performance liquid chromatography), supercritical fluid chromatography, mass spectrometry, nuclear magnetic resonance, electrophoresis, ligand binding assays (dual polarisation interferometry, ELISA - enzyme-linked immunosorbent assay, MIA - magnetic immunoassay, RIA - radioimmunoassay), LC-MS (liquid chromatography-mass spectrometry), GC-MS (gas chromatography-mass spectrometry), LC- DAD (liquid chromatography-diode array detection), CE-MS (capillary electrophoresis-mass spectrometry). General reference is made to Venn, Principles and Practice of Bioanalysis (2.sup.n Edition, CRC Press, 2008)", as MS (and other techniques listed) isolate metabolites as described on page 13 of the instant specification).
Therefore, it would have been obvious to one of ordinary skill in the art as of the effective filing date of the claimed invention to modify the methods of Shetty and Vinaixa as taught by Paillard in order to quantify compounds in a sample (Page 8 line 24 "The quantification of befiradol in plasma samples can be realized with any convenient validated analytical method as determined by those skilled in the art). One skilled in the art would have a reasonable expectation of success because both methods are concerned with quantifying compounds using various techniques known in the art.
Citation of Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Galli-Taliadoros et al. "Gene knock-out technology: a methodological overview for the interested novice." Journal of immunological methods 181.1 (1995): 1-15
US-20040161828
US-20040241759
US-20050070005
US-20050118590
US-20110143394
US-20130137131
US-20130172215
US-20140295457
US-7393946
Conclusion
No claims are allowed.
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/R.A.P./Examiner, Art Unit 1686
/LARRY D RIGGS II/Supervisory Patent Examiner, Art Unit 1686