DETAILED ACTION
Applicant’s response, filed 02 Feb. 2026, has been fully considered. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 03 Feb. 2026 has been entered.
Status of Claims
Claims 10-11, 17-34, and 37-38 are cancelled.
Claims 1-9, 12-16, and 35-36 are pending.
Claims 1-9, 12-16, and 35-36 are rejected.
Claim Objections
The objection of claim 1 in the Office action mailed 19 Dec. 2025 has been withdrawn in view of the claim amendments received. 03 Feb. 2026.
Claim Interpretation
Claim 1 recites “transcription loci” in the customized reference genome. The limitation is interpreted to mean loci in the genome where transcription occurs (i.e. genes).
Claim 1 recites “mapping the proteins…to somatic and germline variants in the customized genome, thereby facilitating identification of possible therapeutic targets”. The courts have found that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)). See MPEP 2111.04. In the instant case, the phrase “thereby facilitating….” merely expressed the intended result of the process step of mapping the proteins, and therefore is not given patentable weight.
Claim 2 recites “virtual normal tissue sample”. The limitation is interpreted to mean a normal tissue sample acquired virtually (e.g. via a database) or a virtually generated (e.g. synthetic) normal tissue sample.
Claim Rejections - 35 USC § 112(b)
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.
Claims 1-9, 12-16, and 35-36 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention. Any newly recited portion is necessitated by claim amendment.
Claim 1, and claims dependent therefrom, are indefinite for recitation of “detecting peptide or protein sequences in a gene sequencing procedure from the one or more tissue samples and deriving therefrom nucleotide sequences, including RNA sequences, that correspond to the peptide or protein sequences detected”. It is unclear if the claims intend to require performing a sequencing procedure that directly detects protein sequences of a gene (e.g. mass spectrometry) or if the claims encompass performing an assay which detects RNA sequences (derived from tissue samples based on “derived therefrom”), such as mRNA which also corresponds to/detects an amino acid/protein sequence. That is, it is unclear if the claims require deriving RNA sequences from the tissue sample(s) (e.g. sequencing) or deriving RNA sequences from peptide/protein sequencing (analysis of mass spec data). It is noted that claim 5 recites “wherein the nucleotide sequences are provided from a whole genome sequencing (WGS) or whole exome sequencing (WES) procedure)”, which suggests claim 1 intends to encompass detecting DNA/RNA sequences, which are associated with a peptide sequence, by sequencing an exome. Furthermore, a review of the specification appears to support the interpretation that RNA sequences are derived directly from the one or more tissues, and the specification does not appear to provide support for directly determining a protein sequence and then converting the protein sequence to an RNA sequence for use in building the customized genome. Clarification is requested via claim amendment. For purpose of examination, the claims are interpreted to mean claim 1 encompasses using a gene sequencing procedure (e.g. WGS OR WES as recited in claim 5) to derive nucleotide sequences corresponding to peptide/protein sequences from tissue samples. It is noted that this rejection is previously cited.
Claim 4 recites “…wherein the alternative alleles in the germline variants comprise alternative alleles…”. There is insufficient antecedent basis for “the alternative alleles in the germline variants” because the claim does not previously recite alternative alleles in the germline variants. As a result, it is unclear what set of alternative alleles of the germline variants are being referenced (e.g. alternative alleles of the germline variants relative to alleles of a matched normal and/or relative to alleles of the virtual normal tissue sample, in addition to the alternative alleles relative to the reference genome? Or a set of alternative alleles relative to the reference genome?). To overcome the rejection, claim 4 should be amended to recite “wherein the germline variants comprise alternative alleles…”, as previously recited. This rejection is newly recited and necessitated by claim amendment.
Response to Arguments
Applicant's arguments filed 03 Feb. 2026 regarding 35 U.S.C. 112(b) have been fully considered but they are not persuasive.
Applicant remarks that claim 1 was amended to be consistent with the subject matter of dependent claim 5, and therefore the rejection should be withdrawn (Applicant’s remarks at pg. 6, para. 3).
This argument is not persuasive. Claim 5 recites that “the nucleotide sequences are provided from a whole genome sequencing (WGS) or whole exome sequencing (WES) procedure”, which would mean that the nucleotide sequence are detected from a gene sequencing procedure and are not derived from measured protein sequences, as suggested by claim 1. However, the amendment to claim 1 recites “detecting peptide or protein sequences in a gene sequencing procedure” and then also states “deriving therefrom nucleotide sequences”, suggesting that first, the protein/peptide (i.e. amino acid) sequence is physically detected and then, second, nucleotide sequences are inferred from the amino acid sequence. As a result, it is still unclear if the “gene sequencing procedure” is a sequencing procedure for nucleic acid, as suggested by claim 5, or if the “gene sequencing procedure” is a sequencing procedure for a protein of a gene (i.e. an amino acid sequence), as explained above.
If Applicant agrees with the interpretation provided in the above rejection, made in light of Applicant’s specification, claim 1 can be amended to recite “detecting nucleotide sequences, including RNA sequences that correspond to peptide or protein sequences, in a gene sequencing procedure from the one or more tissue samples”.
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 1-9, 12-16, and 35-36 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. Any newly recited portion is necessitated by claim amendment.
The Supreme Court has established a two-step framework for this analysis, wherein a claim does not satisfy § 101 if (1) it is “directed to” a patent-ineligible concept, i.e., a law of nature, natural phenomenon, or abstract idea, and (2), if so, the particular elements of the claim, considered “both individually and as an ordered combination,” do not add enough to “transform the nature of the claim into a patent-eligible application.” Elec. Power Grp., LLC v. Alstom S.A., 830 F.3d 1350, 1353 (Fed. Cir. 2016) (quoting Alice, 134 S. Ct. at 2355). Applicant is also directed to MPEP 2106.
Step 1: The instantly claimed invention (claim 1 being representative) is directed to a method. Therefore, the instantly claimed invention falls into one of the four statutory categories. [Step 1: YES]
Step 2A: First it is determined in Prong One whether a claim recites a judicial exception, and if so, then it is determined in in Prong Two if the recited judicial exception is integrated into a practical application of that exception.
Step 2A, Prong 1: Under the MPEP § 2106.04, the Step 2A (Prong 1) analysis requires determining whether a claim recites an abstract idea, law of nature, or natural phenomenon.
Claim 1 recites the following steps which fall under the mental processes, and/or certain groupings of abstract ideas:
identifying somatic and germline variants based on a reference genome and nucleotide sequences;
constructing a customized genome by modifying the reference genome based on the somatic and germline variants identified…wherein (a) the customized genome is constructed with a first group and a second group, the first group including (i) homozygous germline variants within the germline variants and (ii) consensus variants in a reference genome, and the second group including the somatic variants;
aligning RNA sequences to transcription loci in the customized genome;
assembling a detected transcriptome with transcripts derived from the aligned RNA sequences…wherein…(b) the detected transcriptome is assembled by merging partial detected transcriptomes formed, respectively, for [the] first and second groups in the customized genome;
associating the detected transcriptome with proteins in a protein database and including the associated proteins to form the sample-specific proteome;
mapping the proteins in the sample-specific proteome to somatic and germline variants in the customized genome, thereby facilitating identification of possible therapeutic targets.
The identified claim limitations falls into one of the groups of abstract ideas of mental processes for the following reasons. In this case, identifying somatic and germline variants based on a reference genome and nucleotide sequences encompasses performing data comparisons between sequences and a reference in any way to identify bases that do not match the reference, which is a mental process, similar to claims to "comparing BRCA sequences and determining the existence of alterations," where the claims cover any way of comparing BRCA sequences such that the comparison steps can practically be performed in the human mind, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 763, 113 USPQ2d 1241, 1246 (Fed. Cir. 2014). The step of constructing a customized genome can be practically performed in the mind aided with pen and paper by replacing particular positions of the reference genome with the identified variant sequences, including variants in the first and second recited groups as claimed, aided with pen and paper. The aligning RNA sequences to transcription loci in the customized genome also encompass performing data comparisons between references and a sequence, which is a mental process, similar to the claims in University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 763, 113 USPQ2d 1241, 1246 (Fed. Cir. 2014) as discussed above. Assembling a detected transcriptome using transcripts from the aligned RNA sequences can be practically performed in the mind by, for each partial transcriptome, determining which transcripts overlap based on their alignments, and connecting the transcripts in a partial assembly, and then merging the two partial assemblies together. Associating the detected transcriptomes with proteins can be practically performed in the mind by analyzing a database of proteins to identify a protein for each transcript, and then including the identified protein in a list of proteins defining a proteome. Last, mapping the proteins in the sample-specific proteome to somatic and germline variants in the customized genome amounts to data comparisons that can be practically performed in the mind, including identifying a protein of interest in the sample-specific proteome, reading the corresponding gene sequence corresponding to the protein in the customized genome, and identifying any somatic and germline variants in the corresponding gene. As presently recited, nothing in the claims precludes the steps from being practically carried out in the human mind aided with pen and paper. Therefore, these limitations recite a mental process. See MPEP 2106.04(a)(2) III.
Dependent claims 3-4, 6-8, 12-16, and 35-36 further recite an abstract idea and/or are part of the abstract idea of claims 1 and 17 above. Dependent claims 3-4 further limit the step of identifying variants to identify alternative alleles in a target sample relative to a normal sample and alleles found in the target or normal sample relative to a reference genome, and thus are part of the abstract idea. Dependent claim 6 recites the mental process of unmapping nucleotide sequences. Dependent claim 7 further limits the step of identifying variants to identify structural rearrangements. Dependent claim 8 further recites the mental process of assessing the identified germline variants. Dependent claims 12-13 further recite the mental process of detecting transcripts corresponding to structural rearrangements, including a gene fusion or tandem or exon duplications, in the customized genome in the aligned sequences, for example, by identifying aligned sequences with split alignments. Dependent claim 14 further recites the mental process of including the detected transcripts in the detected transcriptome. Dependent claims 15 further recites the mental process of extracting exons from transcripts in the assembled transcriptome and using the extracted exons to identify open read frames in the customized genome. Dependent claims 16 further recites the mental process of identifying proteins in the database corresponding to the identified open read frames. Dependent claims 35-36 further recite the mental process of when multiple variant loci are included in a peptide fragment of a length that spans 5 to 30 nucleotides, expanding the somatic and germline variants identified to include more than one possible nucleotide combination that spans one or more of the multiple loci. Therefore, claims 1-9, 12-16, and 35-36 recite an abstract idea. [Step 2A, Prong 1: YES]
Step 2A: Prong 2: Under the MPEP § 2106.04, the Step 2A, Prong 2 analysis requires identifying whether there are any additional elements recited in the claim beyond the judicial exception(s), and evaluating those additional elements to determine whether they integrate the exception into a practical application of the exception. This judicial exception is not integrated into a practical application for the following reasons.
Claims 3-4, 6-7, 12-16, and 35-36 do not recite any elements in addition to the abstract idea, and thus are part of the judicial exception.
The additional elements of independent claim 1 includes:
detecting peptide or protein sequences in a gene sequencing procedure from the one or more tissue samples and deriving therefrom nucleotide sequences, including RNA sequences, that correspond to the peptide or protein sequences detected (see interpretation under 112(b) above).
The additional elements of dependent claims 2 and 5 include:
wherein the one or more tissue samples comprise a tissue sample obtained from a diseased site (“target sample”) and a matched normal or virtual normal tissue sample; and
wherein the nucleotide sequences are provided from a whole genome sequencing (WGS) or whole exome sequencing (WES) procedure.
The additional elements of dependent claims 8-9 include:
using a deep-learning model, wherein the deep learning model is implemented on a convolution neural network.
The additional elements of claims 1-2 and 5 encompass performing whole genome sequencing or whole exome sequencing on a tissue sample from a diseased site to detect mRNA sequences of proteins. This additional element only serves to collect the necessary data for use by the abstract idea of predicting a proteome, and thus is not sufficient to integrate the recited judicial exception into a practical application. See MPEP 2106.05(g).
The additional element of claims 8-9 only serve to generally link the mental process of assessing a variant to the particular technological environment of neural networks, which does not integrate the recited judicial exception into a practical application. See MPEP 2016.05(h). Furthermore, the limitation amounts to mere instructions to apply the exception on a computer, which does not provide integration as set forth in MPEP 2106.05(f).
Therefore, the additionally recited elements amount to insignificant extra-solution activity, generally link the abstract idea to a particular technological environment, and amount to mere instructions to apply the exception, and, as such, the claims as a whole do no integrate the abstract idea into practical application. Thus, claims 1-9, 12-16, and 35-36 are directed to an abstract idea. [Step 2A, Prong 2: NO]
Step 2B: In the second step it is determined whether the claimed subject matter includes additional elements that amount to significantly more than the judicial exception. See MPEP § 2106.05.
The claims do not include any additional steps appended to the judicial exception that are sufficient to amount to significantly more than the judicial exception.
Claims 3-4, 6-7, 12-16, and 35-36 do not recite any elements in addition to the abstract idea, and thus are part of the judicial exception.
The additional elements of independent claim 1 includes:
detecting peptide or protein sequences in a gene sequencing procedure from the one or more tissue samples and deriving therefrom nucleotide sequences, including RNA sequences, that correspond to the peptide or protein sequences detected (see interpretation under 112(b) above).
The additional elements of dependent claims 2 and 5 include:
wherein the one or more tissue samples comprise a tissue sample obtained from a diseased site (“target sample”) and a matched normal or virtual normal tissue sample; and
wherein the nucleotide sequences are provided from a whole genome sequencing (WGS) or whole exome sequencing (WES) procedure.
The additional elements of dependent claims 8-9 include:
using a deep-learning model, wherein the deep learning model is implemented on a convolution neural network.
First, the additional elements of claims 1-2 and 5 of performing whole genome sequencing or whole exome sequencing on a tissue sample from a diseased site is well-understood, routine, and conventional. This position is supported by Applicant’s specification at para. [0032] which discloses that sequencing reads may be paired-end or single-end reads depending on the sequencing protocol as known to one of ordinary skill in the art. The courts have also recognized the following laboratory techniques as well-understood, routine, and conventional: amplifying and sequencing nucleic acid sequences, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014). It is noted that Applicant’s specification at para. [0003] and [0005] also demonstrates the conventionality of mass spectrometry for determining protein sequences. Last, Bao et al. (Review of Current Methods, Applications, and Data Management for the Bioinformatics Analysis of Whole Exome Sequencing, 2014, Cancer Informatics, 13s2, pg. 67-82; newly cited) reviews next-generation sequencing technologies (Abstract), and discloses common next-generation sequencing (NGS) applications include whole genome sequencing or whole exome sequencing (pg. 68, col. 1, para. 4 to col. 2, para. 1). Bao further discloses a plurality of available variant callers used for analyzing matched tumor-normal sequencing data (pg. 73, col. 2, para. 3), demonstrating the conventionality of sequencing a diseased site and matched normal pairs.
Regarding the additional element of claim 8-9 of applying the abstract idea using “a convolution neural network”, the courts have found the use of a computer or other machinery in its ordinary capacity for economic or other tasks (e.g., to receive, store, or transmit data) or simply adding a general purpose computer or computer components after the fact to an abstract idea (e.g., a fundamental economic practice or mathematical equation) does not provide significantly more. See Affinity Labs v. DirecTV, 838 F.3d 1253, 1262, 120 USPQ2d 1201, 1207 (Fed. Cir. 2016) (cellular telephone); TLI Communications LLC v. AV Auto, LLC, 823 F.3d 607, 613, 118 USPQ2d 1744, 1748 (Fed. Cir. 2016) (computer server and telephone unit). Furthermore, limitations that amount to merely indicating a field of use or technological environment in which to apply a judicial exception do not amount to significantly more than the exception itself, and cannot integrate a judicial exception into a practical application.
Therefore, taken alone, the additional elements do not amount to significantly more than the above-identified judicial exception(s). Even when viewed as a combination, the additional elements fail to transform the exception into a patent-eligible application of that exception. Thus, the claims as a whole do not amount to significantly more than the exception itself. [Step 2B: NO]
Therefore, the instantly rejected claims are not drawn to eligible subject matter as they are directed to an abstract idea without significantly more. For additional guidance, applicant is directed generally to applicant is directed generally to the MPEP § 2106.
Response to Arguments
Applicant's arguments filed 03 Feb. 2026 regarding 35 U.S.C. 101 have been fully considered but they are not persuasive.
Applicant remarks that claim 1 recites a non-abstract step of “detecting peptide or protein sequences”, which enables a detected transcriptome to be assembled, from which associated proteins are included in a sample-specific proteome, which allows the associated proteins to be mapped back to a customized genome, and therefore, claim 1 is directed to a significant improvement in the technical field of identifying therapeutic targets in prediction medicine (Applicant’s remarks at pg. 4 to pg. 8, para. 1).
This argument is not persuasive. This argument is not persuasive. It is important to note, the judicial exception alone cannot provide the improvement. The improvement can be provided by one or more additional elements or by the additional element(s) in combination with the recited judicial exception. Furthermore, it is important to keep in mind that an improvement in the abstract idea itself (e.g. a recited fundamental economic concept) is not an improvement in technology. See MPEP 2106.05(a).
Regarding Applicant’s argument that the detecting peptide/protein and nucleotide sequences helps identify transcribed genes in the customized genome and facilitate the identification fo therapeutic targets, any improvements in identifying transcribed genes and identifying a therapeutic target by analyzing sequence data amounts to an improved abstract idea, which is not an improvement to technology as set forth in MPEP 2106.05(a). Furthermore, any improvements in identifying a therapeutic target is not commensurate with the scope of the claims, because the claims do not positively recite any steps for identifying a therapeutic target. Instead, claim 1 recites “mapping the proteins…thereby facilitating identification of possible therapeutic targets…”, which merely expressed an intended result of the step of mapping proteins and does not have patentable weight as explained in claim interpretation above.
Applicant further remarks the non-abstract step of detecting sequences enables the forming of the sample-specific proteome, and thus is essential and necessary for identifying therapeutic targets in the technical field of precision medicine, and therefore, the claims amount to significantly more than the judicial exception (Applicant’s remarks at pg. 8, para. 2-3).
This argument is not persuasive. It is acknowledged that the step of detecting sequences enables the subsequent abstract idea of forming the sample-specific proteome. However, MPEP 2106.05(g) states when determining whether an additional element is insignificant extra-solution activity, examiners may consider the following: whether the limitation amounts to necessary data gathering and outputting, (i.e., all uses of the recited judicial exception require such data gathering or data output). See Mayo, 566 U.S. at 79, 101 USPQ2d at 1968; OIP Techs., Inc. v. Amazon.com, Inc., 788 F.3d 1359, 1363, 115 USPQ2d 1090, 1092-93 (Fed. Cir. 2015) (presenting offers and gathering statistics amounted to mere data gathering). This is considered in Step 2A Prong Two and Step 2B.
In the instant case, the additional elements of detecting sequences only serves to collect the necessary data for use by the abstract idea, which does not integrate the judicial exception into a practical application. Furthermore, as discussed in the above rejection under step 2B, detecting sequences as claimed is well-understood, routine, and conventional. Therefore, the step of detecting sequences amounts to a conventional step of gathering data for the abstract idea. As explained by the Supreme Court, the addition of insignificant extra-solution activity does not amount to an inventive concept, particularly when the activity is well-understood or conventional. Parker v. Flook, 437 U.S. 584, 588-89, 198 USPQ 193, 196 (1978).
Applicant remarks that claims 2-9, 12-16, and 35-36 are patent eligible for the same reasons discussed for claim 1 (Applicant’s remarks at pg. 8, para. 3).
This argument is not persuasive for the same reasons discussed above for claim 1.
Conclusion
No claims are allowed.
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/KAITLYN L MINCHELLA/Primary Examiner, Art Unit 1685