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 .
Applicant’s Response
Applicant’s response, filed 06/12/2026, 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 Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn.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. They constitute the complete set presently being applied to the instant application.
Claims Status
Claims 71-76 are new.
Claims 46, 48, and 55 are canceled.
Claims 43-45, 47, 49-54, and 56-76 are pending.
Claims 57-70 are withdrawn from consideration.
Claims 43-45, 47, 49-54, 56, and 71-76 are examined.
Withdrawn Objections/Rejections
The objection to the Specification is withdrawn in view of the amendments submitted
The objection to claim 44 is withdrawn in view of the amendments submitted
The rejection of claims 53 and 54 under 35 USC 112(b) is withdrawn
The rejection of claims 43-46, 48-52, 55, and 56 under 35 USC 102(a)(2) over Mankovich is withdrawn in view of the amendments submitted
The rejection of claims 47, 53, and 54 under 35 USC 103 over Mankovich in view of Yandell et al. is withdrawn in view of the amendments submitted
Information Disclosure Statement
The Information Disclosure Statement filed 06/12/2026 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.
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 71 and 75 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 is a new rejection as necessitated by claim amendments.
With respect to claim 71, the claim recites the limitation of “said upstream region or said downstream region may comprise”. The claim is indefinite because the use of the phrase “may comprise” makes it unclear if the upstream region or downstream region comprising less than 3000 bases is an actual limitation of the claim or not.
With respect to claim 75, the claim recites the limitation of “modifying said determined pathogenicity of said structural variant based on said direction of said anomalous ploidy”. The claim is indefinite because there is no antecedent basis for “said direction” in claim 43, from which claim 75 depends, and thus it is not clear based on what the pathogenicity is modified.
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 43-45, 47, 49-54, 56, and 71-76 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. Any newly recited portion is necessitated by claim amendments.
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:
processing said sequence reads to determine a genomic location corresponding to at least a portion of said set of RNA transcripts
constructing a set of badges representing one or more sequence coordinates of said genomic location determined in (c), wherein said set of badges spans an exon, upstream region, and a downstream region of said at least said portion of said set of RNA transcripts
identifying one or more genetic variants having one or more attributes of said subject and overlapping said set of badges
determining a ploidy of said one or more genetic variants in said set of badges, based at least in part on said one or more attributes
determining a ploidy of one or more badges adjacent to a badge of said set of badges, wherein said ploidy is indicative of a zygosity of said one or more genetic variants
grouping said one or more badges having said same ploidy, thereby generating one or more groups of badges, wherein said ploidy is an anomalous ploidy
detecting (1) a structural variant based at least in part on a size of at least a portion of said one or more groups of badges having said same anomalous ploidy, and (2) a pathogenicity of said structural variant, based at least in part on a copy number amplification or copy number deletion of said anomalous ploidy
Mental processes recited in claim 56:
processing said sequence reads to determine a genomic location corresponding to at least a portion of said set of RNA transcripts
determining one or more genetic variants of said sequence reads that are attributable to said subject
identifying a subset of said one or more genetic variants having a genomic segment overlapping one or more badges, wherein said one or more badges represents one or more sequence coordinates of a portion of a human genome
determining a sequencing read depth of said subset of said one or more genetic variants
determining a ploidy of said subset of said one or more genetic variants based at least in part on said determined sequencing read depth of said subset of said one or more genetic variants, wherein said ploidy is indicative of a zygosity of said subset of said one or more genetic variants
determining one or more groups of said subset of said one or more genetic variants having the same ploidy, wherein said ploidy is an anomalous ploidy
detecting (1) a structural variant based at least in part on a size of at least a portion of said one or more groups of said subset of said one or more genetic variants having said same anomalous ploidy, and (2) a pathogenicity of said structural variant, based at least in part on a copy number amplification or copy number deletion of said anomalous ploidy
reporting the structural variant by using at least said pathogenicity detected in (i)
Dependent claims 44, 47, 49-54, and 71-76 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 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 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 71: “wherein said upstream region or said downstream region may comprise less than 3000 bases”
Claim 72: “wherein said pathogenicity of said structural variant is determined with a sensitivity of 97%”
Claim 73: “wherein said pathogenicity of said structural variant is determined with a positive predictive value of 94%”
Claim 74: “wherein said pathogenicity of said structural variant is determined with a positive predictive value of 98%”
Claim 75: “modifying said determined pathogenicity of said structural variant based on said directed of said anomalous ploidy”
Claim 76: “wherein determining the pathogenicity of said structural variant comprises determining that said structural variant is pathogenic, likely pathogenic, benign, likely benign, or a variant of uncertain significance”
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).
Claims 43 and 56 recite the following additional element that is not abstract ideas:
one or more computer processors
subjecting a set of deoxyribonucleic acid (DNA) molecules obtained or derived from a subject to whole genome sequencing, thereby generating sequence reads
retrieving a set of ribonucleic acid (RNA) transcripts obtained or derived from a reference population of subjects
The steps of subject a set of DNA molecules to whole genome sequencing to generate reads and retrieving RNA transcripts are directed to data gathering steps because they generate 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)). The claims are interpreted as being performed by a generic computer due to limitations reciting performing steps by one or more computer processors. 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.
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 claims 43 and 56: The additional elements of one or more computer processors, subjecting a set of DNA molecules obtained or derived from a subject to whole genome sequencing, and retrieving a set of RNA transcripts obtained or derived from a reference population of subjects do not rise to the level of significantly more than the judicial exception. With respect to the processors, 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). With respect to whole genome sequencing and RNA transcripts, Piskol et al. (“Reliable Identification of Genomic Variants from RNA-Seq Data, The American Journal of Human Genetics, published 2013) discloses that whole-genome sequencing or whole-exome sequencing having been a common practice in many large-scale projects, and that RNA sequencing is arguably a more popular application (page 641, column 1, paragraph 1). Furthermore, the step of retrieving a set of RNA transcripts, under Broadest Reasonable Interpretation, can be interpreted as merely a step of retrieving data. As exemplified in the MPEP at 2106.05(d).II with respect to Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015) and OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93, storing and retrieving information in memory is well-understood, routine, and conventional. 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 stated above, Piskol et al. discloses that whole-genome sequencing or whole-exome sequencing having been a common practice in many large-scale projects, and that RNA sequencing is arguably a more popular application (page 641, column 1, paragraph 1). 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.
Response to Arguments
Applicant states that “claim 43 is not directed to an abstract idea, for at least the reasons that this claim recites additional elements that are not abstract ideas. […] each and every element of claim 43 recites at least one of these additional elements that are not abstract ideas. These elements necessitate (1) subject DNA to whole-genome sequencing, (2) computer-implemented database retrieval, (3) computer-implemented processing of sequence reads, (4) computer-implemented constructing of badges, (5) computer-implemented identifying of genetic variants, (6) computer-implemented determining of ploidy of genetic variants, (7) computer-implemented determining of a ploidy of badges, (8) computer-implemented grouping of badges, and (9) computer-implemented detecting of a structural variant and a pathogenicity. Further Applicant submits that, under the Step 2A, Prong One analysis of the USPTO’s 2019 Revised Patent Subject Matter Eligibility Guidance […], claim 43 is not directed to an abstract idea, law of nature or natural phenomenon (judicial exception), for at least the reason that this claim recites specific elements that are not practical to be performed in the mind and not merely natural phenomenon, at least because these elements necessitate (1) subjecting DNA molecules obtained or derived from a subject to whole genome sequencing, and (2) performing a database retrieval of a set of RNA transcripts. Consequently, with respect to the Step 2A, Prong One analysis, the instant claims do not recite a mental process or natural phenomenon.”
It is respectfully submitted that this is not persuasive. It is acknowledged that the steps of whole genome sequencing and retrieving RNA transcripts are not abstract ideas and that they are interpreted as additional elements. The steps gather the data on which the judicial exceptions are performed and are thus data gathering steps. 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)). Furthermore, the additional elements of performing the method using one or more computer processors does not prevent the claims from being abstract. See MPEP 2106.04(d)(2).III.C. 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, the claims recite mental processes that are performed on gathered data and are applied using a generic computer. Thus, the rejection under 35 USC 101 is maintained.
Furthermore, Applicant states that “claim 43 is patent-eligible, at least because this claim provides a specific inventive concept. With respect to the Step 2B analysis, claim 43 recites additional elements that, when considered as an ordered combination, are not routinely performed by those of skill in the art. For example, none of the cited art, when considered individually or in combination, discloses at least the combination of: ‘(a) subjecting a set of deoxyribonucleic (DNA) molecules obtained or derived from a subject to whole genome sequencing, thereby generating sequence reads’; ‘(b) retrieving, by one or more computer processors, a set of ribonucleic acid (RNA) transcripts obtained or derived from a reference population of subjects’; ‘(c) processing, by said one or more computer processors, said sequence reads to determine a genomic location corresponding to at least a portion of said set of RNA transcripts’; ‘(d) constructing, by said one or more computer processors, a set of badges representing one or more sequence coordinates of said genomic location determined in (c), wherein said set of badges spans an exon, an upstream region, and a downstream region of said at least said portion of said set of RNA transcripts’; ‘(e) identifying, by said one or more computer processors, one or more genetic variants having one or more attributes of said subject and overlapping said set of badges’; ‘(f) determining, by said one or more computer processors, a ploidy of said one or more genetic variants in said set of badges, based at least in part on said one or more attributes’; ‘(g) determining, by said one or more computer processors a ploidy of one or more badges adjacent to a badge of said set of badges, wherein said ploidy is indicative of a zygosity of said one or more genetic variants’, ‘(h) grouping, by said one or more computer processors, said one or more badges having said same ploidy, thereby generating one or more groups of badges, wherein said ploidy is an anomalous ploidy’ ‘(i) detecting, by said one or more computer processors, (1) a structural variant based at least in part on a size of at least a portion of said one or more groups of badges having said same anomalous ploidy, and (2) a pathogenicity of said structural variant, based at least in part on a copy number amplification or copy number deletion of said anomalous ploidy’. Claim 43 recites an ordered combination of at least nine additional elements (a), (b), (c), (d), (e), (f), (g), (h), and (i) that was routine nor conventional as of the earliest benefit date of the invention. Therefore, even if the instant claims were found to recite a judicial exception (which Applicant does not concede), the claims are patent-eligible since they recite additional elements beyond the alleged judicial exception that provide an inventive concept, thereby amounting to significantly more than the alleged judicial exception. Applicant submits that claim 56 is patent-eligible, at least because claim 56 recites similar limitations as claim 43.”
It is respectfully submitted that this is not persuasive. It is the additional elements that are examined to determine if there is an inventive concept (MPEP 2106.05.A i-vi). The additional elements in claims 43 and 56 comprise one or more computer processors, subjecting a set of DNA molecules obtained or derived from a subject to whole genome sequencing, and retrieving a set of RNA transcripts obtained or derived from a reference population of subjects. With respect to the processors, 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).Furthermore, Piskol et al. discloses that whole-genome sequencing or whole-exome sequencing having been a common practice in many large-scale projects, and that RNA sequencing is arguably a more popular application (page 641, column 1, paragraph 1). Additionally, as stated by the applicant the step of retrieving transcripts is a step of retrieving RNA data from a database. As exemplified in the MPEP at 2106.05(d).II with respect to Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015) and OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93, storing and retrieving information in memory is well-understood, routine, and conventional. As such, it is recognized that these additional limitations are routine, well understood, and conventional in the art. Therefore, the rejection under 35 USC 101 is maintained.
Conclusion
No claims are allowed.
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.
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
/OLIVIA M. WISE/Supervisory Patent Examiner, Art Unit 1685
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