DETAILED ACTION
Applicant’s response filed 05/13/2026 has been fully considered. Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied.
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 .
Election/Restrictions
Amended claims 17-21 and 27 are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons:
Independent claim 17 recites the application of a machine learning model to predict amino acid substrates for non-ribosomal peptide synthetase domains within the BGCs. None of independent claims 1, 17, or 20, as examined in the Non-Final Office action mailed 11/18/2025, disclose the use of a machine learning model to predict amino acid substrates, as the culmination of the previous examined claims results in the linkage of mass spec features with the BGCs responsible for metabolite synthesis (claim 1), a comparison of the degree of relatedness between pairs of BGCs (claim 17), or the generation of a network of mass spectrometric features based on a degree of relatedness (claim 20). Additionally, none of the dependent claims, as examined in the Non-Final Office action mailed 11/18/2025, recite the use of a machine learning model to predict amino acid substrates. Accordingly, independent claim 17, and its dependent claims 18 and 19 are directed to an invention that is independent and distinct from the invention originally claimed and analyzed in the Office Action mailed 11/18/2025.
Independent claim 20 recites the generation of consensus mass spectra by grouping based on precursors mass-to-charge ratio similarity and spectral similarity, and subsequent analysis of the consensus mass spectra by constructing a network of mass spectrometric features and applying a trained neural network to predict substructural features. None of independent claims 1, 17, or 20, as examined in the Non-Final Office action mailed 11/18/2025, disclose the generation or analysis of consensus mass spectra nor subsequent analysis of the consensus mass spectra using a trained neural network. Accordingly, independent claim 20, and its dependent claims 21 and 27 are directed to an invention that is independent and distinct from the invention originally claimed and analyzed in the Office Action mailed 11/18/2025.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 17-21 and 27 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Status of the Claims
Claims 1, 14-15, and 17-28 are pending in this action.
Claims 2-13 were canceled in the amendment filed 05/13/2026. Claim 16 was previously canceled.
Claims 17-21 and 27 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Claims 1, 14-15, 22-26 and 28 are examined herein.
Priority
The instant application is 371 of PCT/US2020/059502, filed 11/06/2020, which claims priority to U.S. Provisional Application number 62/932,128, filed 11/07/2019, as reflected in the filing receipt mailed 12/29/2022. The claim for domestic benefit for claims 1, 14-15, 22-26 and 28 is acknowledged. As such, the effective filing date of claims 1, 14-15, 22-26 and 28 is 11/07/2019.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
The domain substrate-binding residues in Fig. 13B are missing SEQ ID identifiers in accordance with 37 CFR 1.831(c). Applicant may remedy the deficiency by filing a replacement drawing for Figure 13B or by amending the short description of the drawings for Figure 13B to include the appropriate SEQ ID NO’s.
The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. Applicant may remedy the deficiency by including an Incorporation by Reference paragraph (See item 1(a) or 1(b) above).
Response to Arguments Regarding Sequence Requirements
Examiner notes that the requirement to include sequence disclosures as described on Pg. 2-5 of the Non-Final Rejection mailed 11/18/2025 and reiterated above were not addressed in the Response filed 05/13/2026. Accordingly, the specific deficiencies noted above are maintained.
Specification
Maintained Objections
The abstract of the disclosure is objected to because it is only one sentence and does not provide a complete description of the instant disclosure. The abstract should be within the range of 50 to 150 words in length and should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (Pg. 33, Line 17). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Response to Arguments under Specification
Applicant’s arguments filed 05/13/2026 have been fully considered but they are not persuasive.
1. Applicant argues that the Specification has been amended to address the objections raised by the examiner (Applicant’s Remarks, Pg. 7).
It is respectfully submitted that this is not persuasive for the following reasons:
Examiner notes that amendment filed 05/13/2026 does not include any amendments to the Abstract or Specification. Accordingly, the objections to the disclosure are maintained.
Claim Objections
Withdrawn Objections
The objections to claims 13 and 19 are withdrawn in view of Applicant’s amendments to the claims or cancelation of claims in the amendment filed 05/13/2026 (Applicant’s Remarks, Pg. 7).
Newly Recited Objections
Claim 22 is objected to because of the following informalities:
Claim 22 recites the phrase “wherein clustering the BGCs comprises DBSCAN clustering…”, which should be corrected to “wherein clustering the BGCs comprises Density-based spatial clustering of applications with noise (DBSCAN) clustering” to include the appropriate definition before the abbreviation.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
Withdrawn Rejections
The rejection of claims 1-15 and 17-21 under 35 U.S.C. 112(b) as being indefinite is withdrawn in view of Applicant’s amendments to the claims filed 05/13/2026 (Applicant’s Remarks, Pg. 7).
Newly Recited Rejections
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 14-15 and 28 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.
This rejection is newly recited and necessitated by claim amendment.
Claim 14 recites the limitation “comparing the pairwise distances of BGCs or GCFs within the BGC network with the pairwise distances of metabolite features or MFs within the metabolite feature network …”. There is insufficient antecedent basis for the BGC network and the metabolite feature network in the claim, as there is no prior mention of these phrases in claim 1, to which this claim depends. This rejection can be overcome by amendment of claim 14 to recite “comparing the pairwise distances of BGCs or GCFs within a BGC network with the pairwise distances of metabolite features or MFs within a metabolite feature network …”.
Claim 15 recites the limitation “comparing a frequency of BGCs or GCFs within the BGC network with a frequency of metabolite features or MFs within the metabolite feature network…”. There is insufficient antecedent basis for the BGC network and the metabolite feature network in the claim, as there is no prior mention of these phrases in claim 1, to which this claim depends. This rejection can be overcome by amendment of claim 14 to recite “comparing a frequency of BGCs or GCFs within a BGC network with a frequency of metabolite features or MFs within a metabolite feature network…”.
Claim 28 recites the limitation “wherein computing pairwise distance metrics comprises applying a Hungarian Matching algorithm to identify most likely pairs of homologous domains when duplicate core biosynthetic domains are present in the BGCs of a pair”. The metes and bounds of the claim are rendered indefinite due to the lack of clarity. It is unclear if the application of the Hungarian Matching algorithm is meant to be an additional pairwise distance metric, as step (b) of claim 1, to which claim 28 depends, recites the use of at least two distance metrics for pairs of identified BGCs. Alternatively, it is unclear if the Hungarian Matching algorithm is applied after the calculation of the pairwise distance metrics using at least two of the metrics recited in step (b), but before the clustering recited in step (c) of claim 1. Clarification through clearer claim language is respectfully requested.
Claim Rejections - 35 USC § 101
Maintained Rejections
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, 14-15, 22-26, and 28 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claims recite both (1) mathematical concepts (mathematical relationships, formulas or equations, or mathematical calculations) and (2) mental processes, i.e., concepts performed in the human mind (including observations, evaluations, judgements or opinions) (see MPEP § 2106.04(a)).
Any newly recited portion is necessitated by claim amendment.
Framework with which to evaluate Subject Matter Eligibility as outlined in MPEP § 2106:
Step 1: Are the claims directed to a process, machine, manufacture or composition of matter;
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of nature, a natural phenomenon, or an abstract idea;
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application (Prong Two); and
Step 2B: If the claims do not integrate the judicial exception, do the claims provide an inventive concept.
Framework as it pertains to the instant claims:
Step 1:
In the instant application, claims 1, 14-15, 22-26, and 28 are directed towards a method, which falls into one of the categories of statutory subject matter (Step 1: YES).
Step 2A, Prong One:
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 One). The following instant claims recite limitations that equate to one or more categories of judicial exceptions:
Claim 1 recites a mental process (i.e., an evaluation of fungal genomic sequences to determine biosynthetic gene clusters) in “identifying, biosynthetic gene clusters (BCGs) within genomic sequences from multiple strains of fungi”; a mathematical concept (i.e., calculating pairwise distance metrics) in “computing, pairwise distance metrics between pairs of identified BGCs, the pairwise distance metrics based on at least two of: (i) a sequence identity of a core biosynthetic domain between the BGCs of a pair, (ii) a Jaccard similarity of protein domains between the BGCs of a pair, and (iii) a longest common subsequence of protein domain strings between the BGCs of a pair”; a mental process (i.e., an evaluation of distance metrics to cluster into families) in “clustering the BGCs into gene cluster families (GCFs) based on the pairwise distance metrics”; a mathematical concept (i.e., calculating pairwise similarities) and a mental process (i.e., evaluating the similarities to group features) in “generating a network of mass spectrometric features from mass spectra of extracts from the multiple strains of fungi, wherein generating the network comprises computing pairwise similarities between mass spectra and grouping mass spectrometric features into molecular families (MFs) based on the pairwise similarities”; and a mathematical concept (i.e., computing a correlation matrix) and a mental process (i.e., an evaluation to determine correlations in the matrix) in “constructing, a correlation matrix comparing the frequences of GCFs with frequencies of mass spectrometric features or MFs across the multiple strains to identify correlations indicating that a GCF is associated with the production of a metabolite feature or MF”.
Claim 14 recites a mental process (i.e., a comparison of pairwise distances) in “wherein constructing the correlation matrix comprises comparing the pairwise distances of BCGs or GCFs within the BGC network with the pairwise distances of metabolite features or MFs within the metabolite feature network to identify correlations that indicate that a BCG or GCF is associated with a metabolite feature or MF”.
Claim 15 recites a mental process (i.e., a comparison of frequencies) in “wherein constructing the correlation matrix comprises comparing a frequency of BGCs or GCFs within the BCG network with a frequency of metabolite features or MFs within the metabolite feature network to identify correlations that indicate that a BCG or GCF is associated with a metabolite feature or MF”.
Claim 22 recites a mathematical concept (i.e., using DBSCAN clustering based on a weighted sum) in “wherein clustering the BGCs comprises DBSCAN clustering based on a weighted sum of the pairwise distance metrics”.
Claim 23 recites a mathematical concept (i.e., applying a random forest classifier) in “applying a random forest classifier to predict amino acid substrates for non-ribosomal peptide synthetase adenylation domains within the BGCs”.
Claim 25 recites a mathematical concept (i.e., performing a chi-squared test or a Bonferroni correction) in “wherein constructing the correlation matrix comprises performing a chi-squared test comparing frequencies of GCFs with frequencies of mass spectrometric features or MFs and applying a Bonferroni correction for multiple hypothesis testing”.
Claim 26 recites a mental process (i.e., an evaluation of the genomic sequences) in “wherein the genomic sequences are from 100 or more strains of fungi”.
Claim 28 recites a mathematical concept (i.e., applying a Hungarian Matching algorithm) in “wherein computing pairwise distance metrics comprises applying a Hungarian Matching algorithm to identify most likely pairs of homologous domains when duplicate core biosynthetic domains are present in the BGCs of a pair”.
These recitations are similar to the concepts of collecting information, 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)), 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)), and 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)) that the courts have identified as concepts that can be practically performed in the human mind or mathematical relationships.
The abstract ideas recited in the claims are evaluated under the broadest reasonable interpretation (BRI) of the claim limitations when read in light of and consistent with the specification, and are determined to be directed to mental processes that in the simplest embodiments are not too complex to practically perform in the human mind. Additionally, the recited limitations that are identified as judicial exceptions from the mathematical concepts grouping of abstract ideas are abstract ideas irrespective of whether or not the limitations are practical to perform in the human mind.
Specifically, claim 1 involves nothing more than identifying biosynthetic gene clusters (BGCs) in genomic sequences, computing pairwise distance metrics between pairs of BGCs, clustering the BGCs using the distance metrics, generating a network of mass spectrometric features by computing and comparing pairwise similarities, and constructing a correlation matrix to identify correlations to metabolite features. The steps reciting computing pairwise distance metrics between pairs of BGCs, generating a network by computing pairwise similarities, and constructing a correlation matrix are, under the BRI, performed using mathematical operations. The instant Specification (see Pg. 14, Line 30 – Pg 15, Line 5), as well as step (b) of claim 1, recites the use of a Hungarian matching algorithm to find maximum similarity, the determination of a Jaccard similarity, and the determination of the longest common subsequence. The instant Specification (see Pg. 33, Lines 2-6) also discloses that BGCs were grouped into families using the pairwise distance between BGCs and a clustering algorithm to yield GCFs. BGCs from antiSMASH were converted to arrays of protein domains then compared based on the fraction of shared domains and backbone protein domain sequence identity. The instant Specification (see Pg. 16, Lines 14-24) also discloses that the correlation matrix is constructed using statistical analysis, for example a chi-squared test comparing pairwise frequencies of gene cluster family subgraphs or using a Bonferroni correction to account for multiple hypothesis testing. Additionally, since there are no specifics in the methodology the steps reciting identifying biosynthetic gene clusters (BGCs) in genomic sequences, clustering the BGCs using the distance metrics, and generating a network of mass spectrometric features by comparing pairwise similarities, are something that, under the BRI, one could perform mentally, or using a computer as a tool. Therefore, the claimed steps are not further defined beyond something that reads on performing a calculation using a computer as a tool, and merely looking at data and making a determination. As such, said steps are directed to judicial exceptions. The instant claims must therefore be examined further to determine whether they integrate the abstract idea into a practical application (Step 2A, Prong One: YES).
Step 2A, Prong Two:
In determining whether a claim is directed to a judicial exception, further examination is performed that analyzes if the claim recites additional elements that when examined as a whole integrates the judicial exception(s) into a practical application (MPEP § 2106.04(d)). A claim that integrates a judicial exception into a practical application will apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception. The claimed additional elements are analyzed to determine if the abstract idea is integrated into a practical application (MPEP § 2106.04(d)(I)). If the claim contains no additional elements beyond the abstract idea, the claim fails to integrate the abstract idea into a practical application (MPEP § 2106.04(d)(III)). The following independent claims recite limitations that equate to additional elements:
Claim 1 recites “a computer-implemented method” and “one or more processors”.
Regarding the above cited limitations in claim 1 of (i) a computer-implemented method; and (ii) one or more processors. These limitations require only a generic computer component, which does not improve computer technology. Therefore, these limitations equate to mere instructions to implement an abstract idea on a generic computer, which the courts have established does not render an abstract idea eligible in Alice Corp. 573 U.S. at 223, 110 USPQ2d at 1983.
Additionally, none of the recited dependent claims recite additional elements which would integrate the judicial exception into a practical application. Specifically, claim 24 recites the application of a trained neural network to predict substructural features of metabolites, which equates to an extra-solution apply-it step (see MPEP § 2106.05(f)). As such, claims 1, 14-15, 22-26, and 28 are directed to an abstract idea (Step 2A, Prong Two: NO).
Step 2B:
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. The instant independent claim recites the same additional elements described in Step 2A, Prong Two above.
Regarding the above cited limitations in claim 1 of (i) a computer-implemented method; and (ii) one or more processors. These limitations equate to instructions to implement an abstract idea on a generic computing environment, which the courts have established does not provide an inventive concept (see MPEP § 2106.05(d) and MPEP § 2106.05(f)).
These 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 instant claims do not amount to significantly more than the judicial exception itself (Step 2B: NO). As such, claims 1, 14-15, 22-26, and 28 are not patent eligible.
Response to Arguments under 35 U.S.C. 101
Applicant’s arguments filed 05/13/2026 have been fully considered but they are not persuasive.
1. Applicant argues that under Step 2A, Prong One, the amended claims do not recite a mental process. The amended claims require computing pairwise distance metrics using defined mathematical operations (Jaccard similarity, longest common subsequence, core domain sequence identity) across all pairs of BGCs identified in genomic sequences from multiple strains of fungi. For a dataset of even modest size, the specification describes analysis of over 1,000 fungal genomes yielding over 36,000 BGCs. This entails computing distance metrics for hundreds of millions of BGC pairs. No human could practically perform this computation in the mind (Applicant’s Remarks, Pg. 8-9).
It is respectfully submitted that this is not persuasive for the following reasons:
The limitation in amended claim 1 of computing, by the one or more processors, pairwise distance metrics between pairs of identified BGCs, the pairwise distance metrics based on at least two of: (i) a sequence identity of a core biosynthetic domain between the BGCs of a pair, (ii) a Jaccard similarity of protein domains between the BGCs of a pair, and (iii) a longest common subsequence of protein domain strings between the BGCs of a pair recites a mathematical concept. Mathematical concepts are not required to be practically performed in the human mind, unlike the mental processes grouping of abstract ideas (see MPEP § 2106.04(a)). Additionally, nothing about the physical components of the computer nor the way the computer operates is changed by the limitations in claim 1. Therefore, the use of a computer to perform the limitations in claim 1 invokes a computer as a tool (see MPEP 2106.05(a)(I)). Therefore, amended claim 1 recites abstract ideas and this argument is not persuasive.
2. Applicant also argues that the claims also require constructing pairwise spectral similarity matrices, performing clustering operations, applying random forest classifiers, applying trained neural networks with 1,024-node hidden layers, and constructing chi-squared correlation matrices with Bonferroni corrections. These are not evaluations or observations; they are defined algorithmic operations that require computer implementation by their very nature (Applicant’s Remarks, Pg. 9).
It is respectfully submitted that this is not persuasive for the following reasons:
The limitations recited in amended claim 1 of constructing pairwise spectral similarity matrices and performing clustering operations recite mathematical concepts and mental processes, respectively (see Step 2A, Prong One above). The limitation reciting applying a random forest classifier in dependent claim 23 and constructing chi-squared correlation matrices with Bonferroni corrections in dependent claim 25 also recite mathematical concepts (see Step 2A, Prong One above). The limitation of applying a trained neural network in dependent claim 24 recites an extra-solution apply-it step because it recites the use of a trained neural network without providing any details about how to run the model, e.g., parameters, input/output, etc. (see Step 2A, Prong Two above and MPEP § 2106.05(f)). Examiner also notes that the limitations recited in the dependent claims are distinct from the eligibility of amended independent claim 1, since these dependent limitations are not required by claim 1. Accordingly, the constructing pairwise spectral similarity matrices and performing clustering operations in amended claim 1 recite judicial exceptions, using a computer as a tool, as described in argument (1) above. This argument is thus not persuasive.
3. Applicant also argues that the claims are analogous to those found eligible in Enfish, LLC v. Microsoft Corp., 822 F.3d 1327 (Fed. Cir. 2016), which were directed to a specific implementation of a solution to a problem in the software arts, and distinguishable from cases such as Electric Power Group, where the claims merely recited the collection and display of information without specifying how. Here, the amended claims specify precisely how the data is processed: through defined distance metrics, defined clustering algorithms, defined machine learning models, and defined statistical tests (Applicant’s Remarks, Pg. 9).
It is respectfully submitted that this is not persuasive for the following reasons:
Unlike the instant case, the claims in Enfish were not directed to an abstract idea, but rather an improvement to computer functionality. It was the Specification’s discussion of the prior art and how the invention improved the way the computer stores and retrieves data in memory in combination with the specific data structure recited in the claims that demonstrated eligibility (see MPEP § 2106.05(a)(I)). This is different from the instant case, which (a) recites abstract ideas (see Step 2A, Prong One and arguments (1)-(2) above) and (b) only requires generic computer components to carry out the claimed steps, as nothing about the physical components of the computer nor the way the computer operates is changed by the limitations in amended claim 1 (see MPEP § 2106.05(a)(I)).
As it pertains to the defined distance metrics in amended claim 1, step (b) recites mathematical concepts, analogous to Digitech Image Techs., LLC v Electronics for Imaging, Inc. (758 F.3d 1344, 111 U.S.P.Q.2d 1717 (Fed. Cir. 2014)) that the courts have identified as concepts that are mathematical relationships, rather than processes that can be practically performed in the human mind analogous to Electric Power Group, LLC, v. Alstom (830 F.3d 1350, 119 USPQ2d 1739 (Fed. Cir. 2016)). This argument is thus not persuasive.
4. Applicant argues that under Step 2A, Prong Two, the claims recite a specific technical solution to a specific technical problem. The problem is that the sheer scale of fungal genomic and metabolomic data, tens of thousands of BGCs across hundreds of genomes, and thousands of mass spectrometric features across hundreds of extracts, makes it impossible to link BGCs to their metabolite products through conventional one-off experimental approaches. The claims solve this problem by implementing a defined three-stage computational pipeline that (1) organizes BGCs into families using multi-metric distance computation and clustering, (2) organizes mass spectrometric data into networks using spectral similarity and neural network predictions, and (3) identifies statistically significant correlations between the two networks. This three-stage pipeline is not a conventional approach (Applicant’s Remarks, Pg. 9-10).
It is respectfully submitted that this is not persuasive for the following reasons:
MPEP 2106.04(d)(II) recites:
The analysis under Step 2A Prong Two is the same for all claims reciting a judicial exception, whether the exception is an abstract idea, a law of nature, or a natural phenomenon (including products of nature). Examiners evaluate integration into a practical application by: (1) identifying whether there are any additional elements recited in the claim beyond the judicial exception(s); and (2) evaluating those additional elements individually and in combination to determine whether they integrate the exception into a practical application, using one or more of the considerations introduced in subsection I supra, and discussed in more detail in MPEP §§ 2106.04(d)(1), 2106.04(d)(2), 2106.05(a) through (c) and 2106.05(e) through (h).
Furthermore, the limitations corresponding to (1)-(3) indicated by Applicant above, corresponding to steps (b)-(e) in amended claim 1 have been identified as a judicial exceptions in Step 2A, Prong One above. The integration of a judicial exception into a practical application can only be achieved by additional elements, not by limitations that recites a judicial exception. Thus, the recited limitations are not considered as an improvement in the method of linking BGCs to their metabolite products. This argument is thus not persuasive.
5. Applicant also argues that prior to the present invention, no method existed for performing this integrated analysis at the scale of hundreds of fungal genomes and metabolome datasets simultaneously. The pipeline produces a specific, useful result: a scored ranking of BGC-to-metabolite associations that allows for targeted discovery of natural products for pharmaceutical and agrochemical applications (Applicant’s Remarks, Pg. 10).
It is respectfully submitted that this is not persuasive for the following reasons:
MPEP 2106.05(a) recites:
After the examiner has consulted the specification and determined that the disclosed invention improves technology, the claim must be evaluated to ensure the claim itself reflects the disclosed improvement in technology. Intellectual Ventures I LLC v. Symantec Corp., 838 F.3d 1307, 1316, 120 USPQ2d 1353, 1359 (Fed. Cir. 2016) (patent owner argued that the claimed email filtering system improved technology by shrinking the protection gap and mooting the volume problem, but the court disagreed because the claims themselves did not have any limitations that addressed these issues). That is, the claim must include the components or steps of the invention that provide the improvement described in the specification. However, the claim itself does not need to explicitly recite the improvement described in the specification (e.g., thereby increasing the bandwidth of the channel"). The full scope of the claim under the BRI should be considered to determine if the claim reflects an improvement in technology (e.g., the improvement described in the specification). In making this determination, it is critical that examiners look at the claim "as a whole," in other words, the claim should be evaluated "as an ordered combination, without ignoring the requirements of the individual steps." When performing this evaluation, examiners should be "careful to avoid oversimplifying the claims" by looking at them generally and failing to account for the specific requirements of the claims. McRO, 837 F.3d at 1313, 120 USPQ2d at 1100.
The alleged improvements indicated by Applicant are not commensurate in scope with the claimed invention. Applicant appears to assert that the claimed features may provide a scored ranking of associations that allows for targeted discovery of natural products for pharmaceutical and agrochemical applications. However, amended claim 1 culminates in the identification of correlations between the GCF and a metabolite feature or MF, and does not provide any indication of a ranked score or subsequent use in pharmaceutical or agrochemical applications. Therefore, it appears the alleged improvements are not commensurate in scope with the claimed invention. This argument is thus not persuasive.
6. Applicant also argues that under Step 2B, the Office Action alleges that the additional elements as well-understood, routine, and conventional limitations, relying on Kelleher et al. and Doroghazi et al. to support this characterization. However, neither Kelleher nor Doroghazi teaches the specific combination of computational operations recited in the amended claims (Applicant’s Remarks, Pg. 10).
It is respectfully submitted that this is not persuasive for the following reasons:
As necessitated by claim amendment, the Office Action no longer relies on features from Kelleher et al. or Doroghazi et al. to teach well-understood routine and conventional limitations. As described in Step 2A, Prong Two and Step 2B above, the only additional elements are generic computer components. Under Step 2B, the courts have established that generic computer components do not provide an inventive concept (see MPEP § 2106.05(d) and MPEP § 2106.05(f)). This argument is thus not persuasive.
7. Applicant also argues that accordingly, the specific ordered combination of claim elements (i.e., multi-metric BGC distance computation, clustering, spectral network construction, machine learning predictions at both the genomic and metabolomic levels, and statistical correlation across the two networks) is not well-understood, routine, nor conventional in view of the prior art or the state of the field (Applicant’s Remarks, Pg. 10-11).
It is respectfully submitted that this is not persuasive for the following reasons:
MPEP § 2106.05(I) recites:
“Although the courts often evaluate considerations such as the conventionality of an additional element in the eligibility analysis, the search for an inventive concept should not be confused with a novelty or non-obviousness determination. See Mayo, 566 U.S. at 91, 101 USPQ2d at 1973 (rejecting "the Government’s invitation to substitute §§ 102, 103, and 112 inquiries for the better established inquiry under § 101 "). As made clear by the courts, the "‘novelty’ of any element or steps in a process, or even of the process itself, is of no relevance in determining whether the subject matter of a claim falls within the § 101 categories of possibly patentable subject matter." Intellectual Ventures I v. Symantec Corp., 838 F.3d 1307, 1315, 120 USPQ2d 1353, 1358 (Fed. Cir. 2016) (quoting Diamond v. Diehr, 450 U.S. at 188–89, 209 USPQ at 9). See also Synopsys, Inc. v. Mentor Graphics Corp., 839 F.3d 1138, 1151, 120 USPQ2d 1473, 1483 (Fed. Cir. 2016) ("a claim for a new abstract idea is still an abstract idea. The search for a § 101 inventive concept is thus distinct from demonstrating § 102 novelty."). In addition, the search for an inventive concept is different from an obviousness analysis under 35 U.S.C. 103. See, e.g., BASCOM Global Internet v. AT&T Mobility LLC, 827 F.3d 1341, 1350, 119 USPQ2d 1236, 1242 (Fed. Cir. 2016) ("The inventive concept inquiry requires more than recognizing that each claim element, by itself, was known in the art. . . . [A]n inventive concept can be found in the non-conventional and non-generic arrangement of known, conventional pieces."). Specifically, lack of novelty under 35 U.S.C. 102 or obviousness under 35 U.S.C. 103 of a claimed invention does not necessarily indicate that additional elements are well-understood, routine, conventional elements. Because they are separate and distinct requirements from eligibility, patentability of the claimed invention under 35 U.S.C. 102 and 103 with respect to the prior art is neither required for, nor a guarantee of, patent eligibility under 35 U.S.C. 101. The distinction between eligibility (under 35 U.S.C. 101) and patentability over the art (under 35 U.S.C. 102 and/or 103) is further discussed in MPEP § 2106.05(d).”
Additionally, whether or not the claimed elements appear to be free of the prior art is distinct from subject matter eligibility under 35 U.S.C. 101. As described in the rejection, and arguments above, only the additional elements can provide the technical improvements and amount to significantly more than the recited judicial exceptions. As described in arguments (4)-(6) above, the additional elements recite mere generic computer components and do not provide significantly more than the recited judicial exceptions. This argument is thus not persuasive and the rejection of claims 1, 14-15, 22-26, and 28 under 35 U.S.C. 101 is maintained.
Claim Rejections - 35 USC § 102
The rejection of claims 1-5 and 8-13 under 35 U.S.C. 102(a)(1) as being anticipated by Kelleher et al. is withdrawn in view of Applicant’s amendments to the claims filed 05/13/2026 and Applicant’s Remarks were found persuasive (Applicant’s Remarks, Pg. 11-12). Specifically, as amended, claim 1 recites a computational pipeline, not taught by the primarily experimental approach of Kelleher et al.
Claim Rejections - 35 USC § 103
Withdrawn Rejections
The rejection of claims 6-7 and 17-19 under 35 U.S.C. 103 as being unpatentable over Kelleher et al. in view of Doroghazi et al. is withdrawn in view of Applicant’s amendments to the claims filed 05/13/2026 and Applicant’s remarks were found persuasive (Applicant’s Remarks, Pg. 12-14). Specifically, Doroghazi also does not disclose the grouping of mass spectrometric feature into molecular families or subsequent construction of a correlation matrix as in steps (d) and (e) of amended claim 1.
The rejection of claims 14-15 under 35 U.S.C. 104 as being unpatentable over Kelleher et al. in view of Goering et al. is withdrawn in view of Applicant’s amendments to the claims filed 05/13/2026 and Applicant’s remarks were found persuasive (Applicant’s Remarks, Pg. 12-14). Specifically, Goering et al. also does not disclose the determination of pairwise distance metrics, the grouping of mass spectrometric feature into molecular families, or subsequent construction of a correlation matrix as in steps (b), (d), and (e) of amended claim 1.
The rejection of claims 20-21 under 35 U.S.C. 103 as being unpatentable over Kelleher et al. in view of Doroghazi et al. and Nguyen et al. is withdrawn in view of Applicant’s amendments to the claims filed 05/13/2026 and Applicant’s remarks were found persuasive (Applicant’s Remarks, Pg. 12-14). Specifically, Nguyen also does not teach the construction of a correlation matrix comparing GCFs with mass spectrometric features or MF to determine correlations as in step (e) of amended claim 1.
Conclusion
No claims allowed.
Claims 1, 14-15, 22-26, and 28 appear to be free from the prior art because the prior art does not fairly suggest or teach the construction of a correlation matrix comparing GCFs with mass spectrometric features or MFs. The closest prior art is Navarro-Muñoz et al. (A computational framework for systematic exploration of biosynthetic diversity from large-scale genomic data. bioRxiv 445270, 22 pages (2018); published 10/17/2018; newly recited). Navarro-Muñoz et al. discloses a computational workflow including tools to (a) calculate BGC sequence similarity networks to group gene clusters and (b) enable a phylogenomic approach to identify evolutionary relationships in GCFs. The computational pipeline was applied to correlate GCF output with metabolomic data for actinobacterial strains (Abstract). However, Navarro-Muñoz et al. does not teach the construction of a correlation matrix comparing frequencies of GCFs with frequencies of mass spectrometric features or MFs across multiple strains to identify correlations indicating that a GCF is associated with the production of a metabolite feature or MF, as disclosed in instant claim 1. Claims 14-15, 22-26, and 28 appear to be free from the prior art due to their dependency on claim 1.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/D.P.S./Examiner, Art Unit 1687
/Lori A. Clow/Primary Examiner, Art Unit 1687
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