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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 43-56 in the reply filed on 02/12/2026 is acknowledged.
Claims 57-70 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 02/12/2026.
Claims Status
Claims 43-70 are pending.
Claims 57-70 are withdrawn from consideration.
Claims 43-56 are examined.
Priority
The instant application is a continuation of Application No. PCT/US2020/049557, filed 09/04/2020, which claims priority to provisional Application No. 63/005991, filed 04/06/2020, and provisional Application No. 62/896516, filed 09/05/2019. Therefore, the Effective Filing Date (EFD) assigned to each of the claims 43-56 is the provisional filing date of Application No. 62/896516, filed 09/05/2019.
Information Disclosure Statement
The Information Disclosure Statements filed 02/04/2025 is in compliance with the provisions of 37 CFR 1.97 and has therefore been considered. A signed copy of the IDS document is included with this Office Action.
Drawings
The drawings filed 03/02/2022 are accepted.
Specification
The disclosure is objected to because of the following informalities:
In paragraph [0107], line 2, “a brighfield or fluorescent image” should read “a brightfield or fluorescent image”
In paragraph [0144], line 9, “methods can effective discover” should read “methods can effectively discover”
Appropriate correction is required.
Claim Objections
Claim 44 is objected to because of the following informalities:
“discrepancy in distributing genetic variant alleles zygosities” should read “discrepancy in distributing genetic variant allele
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 53 and 54 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.
With respect to claim 53, the claim recites the limitation of “prioritizing a single nucleotide variant (SNV)…”. The claim is indefinite because it is unclear what the variant is prioritized for, as in which step in claim 43 it is prioritized for, or what it is being prioritized against. Thus, the limitations of this claim are not clear because it is not clear what the step entails.
With respect to claim 54, the claim recites the limitation of “automatically prioritizing compound heterozygous genotypes”. The claim is indefinite because it is unclear what the genotypes are prioritized for, as in which step in claim 43 it is prioritized for. Thus, the limitations of this claim are not clear because it is not clear what the step entails.
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 43-56 are rejected under 35 U.S.C. 101 because the claimed inventions are directed to an abstract idea of mental steps, mathematic concepts, or a natural law without significantly more.
The MPEP at MPEP 2106.03 sets forth steps for identifying eligible subject matter:
(1) Are the claims directed to a process, machine, manufacture or composition of
matter?
(2A)(1) Are the claims directed to a judicially recognized exception, i.e. a law of nature,
a natural phenomenon, or an abstract idea?
(2A)(2) If the claims are directed to a judicial exception under Prong One, then is the
judicial exception integrated into a practical application?
(2B) If the claims are directed to a judicial exception and do not integrate the judicial
exception, do the claims provide an inventive concept?
With respect to step (1): Yes, the claims are directed to methods.
With respect to step (2A)(1): The claims are directed to abstract ideas of mental processes, and laws of nature.
“Claims directed to nothing more than abstract ideas (such as a mathematical formula or equation), natural phenomena, and laws of nature are not eligible for patent protection” (MPEP 2106.04). Abstract ideas include mathematical concepts (mathematical formulas or equations, mathematical relationships and mathematical calculations), certain methods of organizing human activity, and mental processes (procedures for observing, evaluating, analyzing/judging and organizing information (MPEP 2106.04(a)(2)). Laws of nature or natural phenomena include naturally occurring principles/relations that are naturally occurring or that do not have markedly different characteristics compared to what occurs in nature (MPEP 2106(b)).
Mental processes recited in claim 43:
constructing a set of badges to span an exon, upstream region, a downstream region, a gene regulatory element, or any combination thereof of one or more genes or transcripts thereof
identifying one or more genetic variants having one or more attributes to a human subject and overlapping said set of badges, and using said one or more attributes to determine a ploidy of said one or more genetic variants in said set of badges
reporting a structural variant by using at least said ploidy determined in (b) to indicate a change in gene or regulatory element dosage caused by said structural variant that deviate from a normal human karyotype
Mental processes recited in claim 56:
providing one or more genetic variants attributable to a subject
identifying said one or more genetic variants overlapping one or more badges, wherein said one or more badges represents a portion of a human genome
determining a ploidy of said one or more genetic variants based at least in part on an analysis of sequencing read depth of said one or more genetic variants
reporting a structural variant by using at least said ploidy determined in (b) to indicate a change in gene or regulatory element dosage caused by said structural variant that deviates from a normal human karyotype
Dependent claims 44, and 46-55 recite additional steps that either are directed to abstract ideas or further limit the judicial exceptions in independent claim 43, and as such, are further directed to abstract ideas. Hence, the claims explicitly recite numerous elements that individually and in combination constitute abstract ideas. The relevant recitations are:
Claim 44: “wherein said ploidy is determined based at least in part on an analysis of (i) discrepancy in distributing genetic variant alleles zygosities from expectation for a genomic segment overlapped by said badges or (ii) a distribution of reads harboring alternative alleles for said one or more genetic variants overlapped by said badges”
Claim 46: “wherein said badges are configured to span (i) an exon region of a transcript of a human genome or (ii) each exon of said transcripts”
Claim 47: “wherein said badges further comprise (i) an upstream or a downstream buffer region associated with said exon region of said transcripts or (ii) a gene regulatory region”
Claim 48: “wherein said badges represent a DNA sequence coordinate of said exon region of said transcript”
Claim 49: “wherein said ploidy is determined based at least in part on (i) a frequency of its alleles in human populations of said one or more genetic variants or (ii) defining an expectation of zygosity of overlapping genetic variants from a subject by comparing to a frequency of its alleles in human populations of said one or more genetic variants”
Claim 50: “wherein said structural variant is associated with a disease phenotype or a gene associated with a disease phenotype”
Claim 51: “determining a score inferring severity of an impact of a structural variant on a structure of overlapping genes that can be associated with a disease phenotype”
Claim 52: “wherein said genetic variants or said genes or transcripts thereof have been ranked by VAAST, VVP, PHEVOR, pVAAST, SIFT, CAD, ANNOVAR, a burden-test, a sequence conservation scoring method, a machine learning method, or any combination thereof”
Claim 53: “prioritizing a single nucleotide variant (SNV), an insertion or deletion (INDEL), or said structural variant”
Claim 54: “automatically prioritizing compound heterozygous genotypes comprising a single nucleotide variant (SNV) or an insertion or deletion (INDEL) in trans to a larger structural variant”
Claim 55: “merging said badges if adjacent in genome coordinates, discrepant to expectation of said human normal karyotype, or are of similar inferred ploidy”
The abstract ideas in the claims are evaluated under Broadest Reasonable Interpretation (BRI) and determined herein to each cover mental processes and laws of nature because the claims recite no more than analyzing genomic data to annotate variants and functional effects of variants.
With respect to step (2A)(2): The claims must therefore be examined further to determine whether they integrate that abstract idea into a practical application (MPEP 2106.04(d)). The claimed additional elements are analyzed alone or in combination to determine if the judicial exception is integrated into a practical application (MPEP 2106.04(d).I.; MPEP 2106.05(a-h)). If the claim contains no additional elements beyond the judicial exception, the claim fails to integrate the abstract idea into a practical application (MPEP 2106.04(d).III).
Claim 43 recites the following additional element that is not abstract ideas:
computer-implemented
The claims are interpreted as being performed by a generic computer, as there are no recitations of specific structures which implement the steps. The courts have weighed in and consistently maintained that when, for example, a memory, display, processor, machine, etc. ... are recited so generically (i.e., no details are provided) that they represent no more than mere instructions to apply the judicial exception on a computer, and these limitations may be viewed as nothing more than generally linking the use of the judicial exception to the technological environment of a computer (see MPEP 2106.05(f)). Thus, applying the judicial exceptions to a generic computer is not sufficient to integrate the judicial exceptions into a practical application.
Dependent claim 45 recites a step limiting the manner in which the data is gathered, and is thus directed to a data gathering step, because it generates the data on which the judicial exceptions are performed. Data gathering does not impose any meaningful limitation on the abstract idea, or how the abstract idea is performed. Data gathering steps are not sufficient to integrate an abstract idea into a practical application (MPEP 2106.05(g)).
None of the dependent claims recite additional elements, alone or in combination, which would integrate a judicial exception into a practical application.
Lastly, the claims have been evaluated with respect to step (2B): Because the claims recite an abstract idea, and do not integrate that abstract idea into a practical application, the claims lack a specific inventive concept. Under said analysis, Applicant is reminded that the judicial exception alone cannot provide that inventive concept or practical application (MPEP 2106.05). Identifying whether the additional elements beyond the abstract idea amount to such an inventive concept requires considering the additional elements individually and in combination to determine if they provide significantly more than the judicial exception (MPEP 2106.05.A i-vi).
With respect to the instant claims, the additional elements described above do not rise to the level of significantly more than the judicial exception. As set forth in the MPEP at 2106.05(d).I, determinations of whether or not additional elements (or a combination of additional elements) may provide significantly more and/or an inventive concept rests in whether or not the additional elements (or combination of elements) represents well-understood, routine, conventional activity. Said assessment is made by a factual determination stemming from a conclusion that an element (or combination of elements) is widely prevalent or in common use in the relevant industry, which is determined by either a citation to an express statement in the specification or to a statement made by an applicant during prosecution that demonstrates a well-understood, routine or conventional nature of the additional element(s); a citation to one or more of the court decisions as discussed in MPEP 2106(d)(II) as noting the well-understood, routine, conventional nature of the additional element(s); a citation to a publication that demonstrates the well-understood, routine, conventional nature of the additional element(s); and/or a statement that the examiner is taking official notice with respect to the well-understood, routine, conventional nature of the additional element(s).
With respect to claim 43: The additional element of computer-implemented does not rise to the level of significantly more than the judicial exception. As exemplified in the MPEP at 2106.05(f) with reference to Alice Corp. 573 US at 223, 110 USPQ2d at 1983 “claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible”. Therefore, the device constitutes no more than a general link to a technological environment, which is insufficient to constitute an inventive concept that would render the claims significantly more than the abstract idea (see MPEP 2105(b)I-III). As such, it is recognized that these additional limitations are routine, well understood, and conventional in the art. These limitations do not improve the functioning of a computer, or comprise an improvement to any other technical field, they do not require or set forth a particular machine, they do not affect a transformation of matter, nor do they provide a non-conventional or unconventional step. As such, these limitations fail to rise to the level of significantly more.
With respect to claim 45: The additional element of whole-genome sequencing or whole-exome sequencing does not rise to the level of significantly more than the judicial exception. As recited in the Specification at paragraph [0002], “Next-generation sequencing of genomes and exomes is now being widely used for clinical diagnoses of Mendelian diseases, for idiopathic disease, and for fast diagnosis for newborns in NICUs”. As such, it is recognized that these additional limitations are routine, well understood, and conventional in the art. These limitations do not improve the functioning of a computer, or comprise an improvement to any other technical field, they do not require or set forth a particular machine, they do not affect a transformation of matter, nor do they provide a non-conventional or unconventional step. As such, these limitations fail to rise to the level of significantly more.
The claims have all been examined to identify the presence of one or more judicial exceptions. Each additional limitation in the claims has been addressed, alone and in combination, to determine whether the additional limitations integrate the judicial exception into a practical application. Each additional limitation in the claims has been addressed, alone and in combination, to determine whether those additional limitations provide an inventive concept which provides significantly more than those exceptions. Individually, the limitations of the claims and the claims as a whole have been found lacking.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 43-46, 48-52, 55, and 56 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Mankovich (US 20190362807, filed 09/28/2017).
Regarding claim 43, Mankovich teaches a method for inferring a structural variant, said method comprising:
constructing a set of badges to span an exon, an upstream region, a downstream region, a regulatory element, or any combination thereof of one or more genes or transcripts thereof: Mankovich teaches performing whole-exome sequencing and thus generating sequence data of only protein-encoding exons, the expressed genes of a patient (paragraph [0015]);
identifying one or more genetic variants having one or more attributes to a human subject and overlapping said set of badges, and using said one or more attributes to determine a ploidy of said one or more genetic variants in said set of badges: Mankovich teaches genetic variants with disease-correlation overlapping the exon genes and using the transcripts and copy number analysis to score the variant (paragraphs [0004]; [0017]; [0029]); and
reporting a structural variant by using at least said ploidy determined in (b) to indicate a change in gene or regulatory element dosage caused by said structural variant that deviates from a normal human karyotype: Mankovich teaches reporting the variant having a structural and functional effect and thus being a structural variant based on the identification in step b (paragraphs [0019]; [0021]; [0025])
Furthermore, Mankovich teaches the method being computer-implemented (paragraph [0022]).
Regarding claim 44, the claim is directed to said ploidy being determined based at least in part on an analysis of (i) discrepancy in distributing genetic variant alleles zygosities from expectation for a genomic segment overlapped by said badges or (ii) a distribution of reads harboring alternative alleles for said one or more genetic variants overlapped by said badges. Mankovich teaches the method of claim 43. Mankovich also teaches the ploidy being determined based on an analysis of the transcriptomics score, which is determined based on the distribution of reads coding for the variant of the position of the gene in the exon (paragraph [0029]).
Regarding claim 45, the claim is directed to said one or more genetic variants being from a whole-genome sequencing or whole-exome sequencing of a human subject. Mankovich teaches the method of claim 43. Mankovich also teaches the genetic variants being from whole-exome sequencing of a human subject (paragraphs [0015]; [0035]) and teaches also isolating and amplifying all DNA material with whole-genome sequencing (paragraph [0015]).
Regarding claim 46, the claim is directed to said badges being configured to span (i) an exon region of a transcript of a human genome or (ii) each exon of said transcripts. Mankovich teaches the method of claim 43. Mankovich also teaches the badges spanning each exon of a transcript (paragraph [0015]).
Regarding claim 48, the claim is directed to said badges representing a DNA sequence coordinate of said exon region of said transcript. Mankovich teaches the method of claim 43. Mankovich also teaches the badges comprising genes that are expressed and thus the badges represent DNA sequence coordinates of exon regions of a transcript (paragraph [0015]).
Regarding claim 49, the claim is directed to said ploidy being determined based at least in part on (i) a frequency of its alleles in human populations of said one or more genetic variants or (ii) defining an expectation of zygosity of overlapping genetic variants from a subject by comparing to a frequency of its alleles in human populations of said one or more genetic variants. Mankovich teaches the method of claim 43. Mankovich also teaches determining ploidy based on the transcriptomics score which is based on the frequency of the variant allele in comparison to reference populations as stored in databases (paragraphs [0027]; [0030]).
Regarding claim 50, the claim is directed to said structural variant being associated with a disease phenotype or a gene associated with a disease phenotype. Mankovich teaches the method of claim 43. Mankovich also teaches the structural variant being associated with a disease phenotype (paragraph [0025]).
Regarding claim 51, the claim is directed to determining a score inferring severity of an impact of a structural variant on a structure of overlapping genes that can be associated with a disease phenotype. Mankovich teaches the method of claim 43. Mankovich also teaches determining a score of the structural variants to determine its impact, based on the existence in other datasets, affect regulation of other genes and other functional, disease-related annotations (paragraphs [0021]; [0023]), and assigning a score based on the fraction of RNA transcripts of a gene to which the variant belongs (paragraphs [0029]; [0030]).
Regarding claim 52, the claim is directed to said genetic variants or said genes or transcripts thereof having been ranked by VAAST, VVP, PHEVOR, pVAAST, SIFT, CAD, ANNOVAR, a burden-test, a sequence conservation scoring method, a machine learning method, or any combination thereof. Mankovich teaches the method of claim 43. Mankovich also teaches ranking genetic variants by SIFT (paragraph [0025]).
Regarding claim 55, the claim is directed to merging said badges if adjacent in genome coordinates, discrepant to expectation of said human normal karyotype, or are of similar inferred ploidy. Mankovich teaches the method of 43. Mankovich also teaches merging the variants of the genes that differ from a reference sequence together in a Variant Call Format (paragraph [0002]).
Regarding claim 56, Mankovich teaches a method for inferring a structural variant, said method comprising:
providing one or more genetic variants attributable to a subject: Mankovich teaches determining a list of genetic variants of a current patient’s DNA sequence (paragraph [0006]);
identifying said one or more genetic variants overlapping one or more badges, wherein said one or more badges represents a portion of a human genome: Mankovich teaches identifying the genetic variants of the patient within reference database storing genetic variants of medical patients and determining if the occurrences meet a threshold level (paragraph [0006]);
determining a ploidy of said one or more genetic variants based at least in part on an analysis of sequencing read depth of said one or more genetic variants: Mankovich teaches assigning transcriptomic scores based on the measure of expression of the genetic variants in the transcript data and microarray data (paragraph [0006]), and variants are previously filtered for sequencing depth (paragraph [00035]); and
reporting a structural variant by using at least said ploidy determined in (b) to indicate a change in gene or regulatory element dosage caused by said structural variant that deviates from a normal human karyotype: Mankovich teaches reporting the variants based on disease correlation and transcriptomic scores (paragraph [0006]).
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 47, 53, and 54 are rejected under 35 U.S.C. 103 as being unpatentable over Mankovich, as applied to claims 43-46, 48-52, 55, and 56 in the 102 rejection above, in view of Yandell et al. (US 20160092631 A1, published 03/31/2016).
Regarding claim 47, the claim is directed to said badges further comprising (i) an upstream or a downstream buffer region associated with said exon region of said transcript or (ii) a gene regulatory region. Mankovich teaches the method of claim 43.
Mankovich does not teach the claim element of badges further comprising (i) an upstream or a downstream buffer region associated with said exon region of said transcript or (ii) a gene regulatory region.
However, Yandell et al. teaches a method and system for genome analysis to prioritize phenotype-causing genomic variants (Abstract). Yandell et al. teaches the genetic variants being within regions of regulatory sequences or regulatory sequence fragments (paragraph [0015]).
Regarding claim 53, the claim is directed to prioritizing a single nucleotide variant (SNV), an insertion or deletion (INDEL), or said structural variant. Mankovich teaches the method of claim 43.
Mankovich does not teach the claim elements of prioritizing a single nucleotide variant (SNV), an insertion or deletion (INDEL), or said structural variant.
However, Yandell et al. teaches prioritization being performed on single nucleotide variants (paragraph [0170]).
Regarding claim 54, the claim is directed to automatically prioritizing compound heterozygous genotypes comprising a single nucleotide variant (SNV) or an insertion or deletion (INDEL) in trans to a larger structural variant. Mankovich teaches the method of claim 43.
Mankovich does not teach the claim elements of automatically prioritizing compound heterozygous genotypes comprising a single nucleotide variant (SNV) or an insertion or deletion (INDEL) in trans to a larger structural variant.
However, Yandell et al. teaches a variant annotator that prioritizes compound heterozygous genotypes comprising the SNV or INDEL variant in trans to a larger structural variant in order to identify novel disease alleles in known disease genes and novel combinations of alleles, etc. (paragraph [0188]; [0205]; [0209])
Therefore, it would have been prima facie obvious to one of ordinary skill in the art to have incorporated the prioritization methods of variants of Yandell et al. to the method of Mankovich because both Mankovich and Yandell et al. are directed to variant prioritization analysis in regard to disease (see Abstract of both). Yandell et al. teaches following best variant calling practices as described by the Broad Institute (paragraph [0170]), and thus one of ordinary skill in the art would have a reasonable expectation of success of prioritizing the SNVs of the called variants by combining the prior art elements.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Emilie A Smith whose telephone number is (571)272-7543. The examiner can normally be reached 9am - 5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Larry D Riggs can be reached at (571)270-3062. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/E.A.S./Examiner, Art Unit 1686
/LARRY D RIGGS II/Supervisory Patent Examiner, Art Unit 1686