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 .
Claim Status
Claims 1-20 are currently pending and are herein under examination.
Claims 1-20 are rejected.
Priority
The instant application claims domestic benefit to U.S. Provisional Application No. 63/310,876, filed 2/16/2022. The claim to domestic benefit is acknowledged. As such, the effective filing date for claims 1-20 is 2/16/2022.
Information Disclosure Statement
The IDS filed 06/01/2023 follow the provisions of 37 CFR 1.97 and have been considered in full. A signed copy of the list of references cited from these IDS is included with this Office Action.
Drawings
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they include the following reference character(s) not mentioned in the description: 396 in Fig. 7.
Corrected drawing sheets in compliance with 37 CFR 1.121(d), or amendment to the specification to add the reference character(s) in the description in compliance with 37 CFR 1.121(b) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Abstract
The abstract is objected to because it recites the following implied phrases “The presently described techniques provide” and “As discussed herein.”
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
Claim Rejections - 35 USC § 112
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.
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 19-20 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.
Claims dependent from a rejected claim are also rejected, unless otherwise noted.
Claim 19 recites “wherein the nucleic acid sequence data is derived from cfDNA” which renders the claim indefinite. It is unclear if the claim requires an active step of deriving/generating the nucleic acid data, or if it recites a product by process that merely defines how the nucleic acid data was previously derived before accessing/receiving it. This interpretation is reinforced by the fact that claim 14 accesses/receives the nucleic acids data rather than generating/deriving it. Clarify whether claim 19 requires an active step of deriving or recites a product by process.
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 1-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea and a natural phenomenon without significantly more.
Step 1:
Step 1 asks whether the claims recite statutory subject matter. In the instant application, claims 1-8 recite a method, claims 9-13 recite a system, and claims 14-20 recite a method. As such, these claims recite statutory subject matter (Step 1: YES).
Step 2A, Prong 1:
Claims that recite statutory subject matter are analyzed under Step 2A, Prong 1 to determine if they recite any concepts that equate to an abstract idea, law of nature or natural phenomena. The instant claims recite the following limitations that equate to one or more categories of judicial exception:
Claims 1 and 9 recite “generating, accessing, or receiving a nucleic acid sequence data set comprising a mixture of sequence data from two sources; filtering the nucleic acid sequence data set using a plurality of minimum fragment length thresholds to generate a respective filtered data set for each minimum fragment length threshold, wherein each respective filtered data set has a different proportion of contribution from a first source of the two sources; calculating a polygenic risk score for a polygenic trait of interest for each respective filtered data set to generate a plurality of polygenic risk scores; determining a relationship between the different proportions of contribution from the first source and the plurality of polygenic risk scores; based on the relationship, determining an unbiased polygenic risk score for a second source of the two sources corresponding to no contribution of sequence data by the first source; and outputting the unbiased polygenic risk score.”
Claims 2, 10 and 15 recite “wherein the nucleic acid sequence data set comprises a low- pass sequencing data set.”
Claims 3 and 11 recite “wherein the nucleic acid sequence data set comprises a non-invasive prenatal test (NIPT) sequence data set.”
Claims 4 and 17 recite “wherein the nucleic acid sequence data set comprises variants and imputed variants.”
Claims 5 and 12 recite “wherein the distribution of fragment lengths for each of the two sources differs.”
Claim 6 recites “wherein the relationship is a linear relationship.”
Claim 7 recites “wherein determining the relationship comprises performing a statistical fitting or analysis.”
Claims 8 and 13 recite “wherein determining the unbiased polygenic risk score comprises extrapolating a statistical fitting describing the relationship to a value that corresponds to no contribution of sequence data by the first source.”
Claim 14 recites “accessing or receiving a non-invasive prenatal test data set comprising nucleic acid sequence data from a mother and a fetus; filtering the nucleic acid sequence data using a plurality of minimum fragment length thresholds to generate a respective filtered data set for each minimum fragment length threshold, wherein each respective filtered data set has a different fetal fraction of contributed nucleic acid sequence data; calculating a polygenic risk score for a polygenic trait of interest for each respective filtered data set to generate a plurality of polygenic risk scores; performing a linear regression to determine a linear relationship between the different fetal fractions and the plurality of polygenic risk scores; extrapolating the linear relationship to an intercept corresponding to no contribution of sequence data by the fetus to determine a maternal polygenic risk score; and outputting the maternal polygenic risk score.”
Claim 16 recites “wherein the polygenic trait of interest comprises a disease or disorder.”
Claim 18 recites “wherein below a transition fragment length the proportion of fetal fragments exceed the proportion of maternal fragments.”
Claim 19 recites “wherein the nucleic acid sequence data is derived from cell-free DNA (cfDNA) fragments.”
Claim 20 recites “wherein the minimum fragment length thresholds filter out data from cfDNA fragments below the respective minimum fragment length thresholds.”
Limitations reciting a mental process.
Claims 1, 6-9 and 13-14 contain limitations recited at such a high level of generality that they equate to a mental process because they are similar to the concepts of collecting information, analyzing it, and displaying certain results of the collection and analysis in Electric Power Group, LLC, v. Alstom (830 F.3d 1350, 119 USPQ2d 1739 (Fed. Cir. 2016)), which the courts have identified as concepts that can be practically performed in the human mind. The paragraphs below discuss the broadest reasonable interpretation (BRI) of the limitations in these claims that recite a mental process.
Regarding claims 1, 9 and 14, collecting/accessing data is a mental process. Filtering nucleic acid data using different fragment length thresholds includes analyzing a set of sequence reads and determining which sequence reads are above or below a threshold; a human can organize and sort data. Calculating a plurality of PRS includes performing the calculations in specification para. [36] on pen and paper. Determining a relationship includes performing the calculations of a linear regression, as discussed in claims 6-7. Determining an unbiased/maternal polygenic risk score includes analyzing a linear regression between minimum fetal fractions and PRS to find a y-intercept that indicates no contribution from fetal fraction, as discussed in specification para. [83]. Outputting the unbiased/maternal PRS includes calculating and writing down the PRS, which equates to displaying the results of the data collection and analysis steps.
Claims 7 and 13-14 of extrapolating a relationship includes determining a y-intercept of a linear regression between fetal fractions and PRS, as discussed in specification para. [83].
Limitations reciting a mathematical concept.
Claims 1, 6-7, 9 and 14 recite limitations that equate to a mathematical concept because they are similar to the concepts of 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)), which the courts have identified as mathematical concepts. The paragraph below discusses the broadest reasonable interpretation (BRI) of the limitations in these claims that recite a mathematical concept.
Claims 1, 9 and 14 recite calculating PRS which equates to calculations using an equation, particularly the equation recited in specification para. [36]. Claims 1, 6-7, 9 and 14 recite determining a statistical relationship which may be a linear relationship, which includes calculating a linear regression.
Limitations reciting a natural phenomenon.
Claims 1, 9 and 14 recite limitations that are similar to the concept of a correlation between the presence of myeloperoxidase in a bodily sample (such as blood or plasma) and cardiovascular disease risk in Cleveland Clinic Foundation v. True Health Diagnostics, LLC, 859 F.3d 1352, 1361, 123 USPQ2d 1081, 1087 (Fed. Cir. 2017), which the courts have established as a natural phenomenon. Calculating a PRS from nucleic acid data recites a natural relationship between genetic data and genetic predisposition for disease.
Limitations included in the recited judicial exception.
Claims 2-5, 10-12, 15 and 17-20 are included in the judicial exception in claims 1, 9 and 14 of collecting/accessing nucleic acid data because it further limits the data that is collected/accessed. Claim 16 is included in the judicial exception of claim 14 of calculating PRS because it further limits the PRS.
As such, claims 1-20 recite an abstract idea and a natural phenomenon (Step 2A, Prong 1: YES).
Additional Elements:
Once limitations have been identified that recite a judicial exception, the claims are evaluated for additional elements. The additional elements are then analyzed under Step 2A, Prong 2 then Step 2B. The instant claims recite the following additional elements:
Claim 9 recites “A processor-based system, comprising: one or more memory structures configured to store data and processor-executable instructions; and one or more processors configured to execute the processor-executable instructions, wherein the processor-executable instructions, when executed, cause the one or more processors to performs actions comprising:”
Claims 10-13 recite “the processor-based system of claim 9.”
These above recited additional elements are analyzed below under both Step 2A, Prong 2 and Step 2B:
Step 2A, Prong 2:
Claims found to recite a judicial exception under Step 2A, Prong 1 are then further analyzed to determine if the claims as a whole integrate the recited judicial exception into a practical application or not (Step 2A, Prong 2). The judicial exception is not integrated into a practical application because the claims do not recite additional elements that reflect an improvement to a computer, technology, or technical field (MPEP § 2106.04(d)(1) and 2106.5(a)), require a particular treatment or prophylaxis for a disease or medical condition (MPEP § 2106.04(d)(2)), implement the recited judicial exception with a particular machine that is integral to the claim (MPEP § 2106.05(b)), effect a transformation or reduction of a particular article to a different state or thing (MPEP § 2106.05(c)), nor provide some other meaningful limitation (MPEP § 2106.05(e)). Rather, the claims include limitations that equate to an equivalent of the words “apply it” and/or to instructions to implement an abstract idea on a computer (MPEP § 2106.05(f)). The paragraphs below discuss the additional elements recited above in the instant claims.
Claims 1-8 and 14-20 do not recite any additional elements and thus are not being analyzed under Step 2A, Prong 2.
The processor based-system of claims 9-13 comprises processors and memories and thus equates to a generic computer, and there are no limitations requiring anything other than a generic computer. 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.
As such, claims 1-20 are directed to an abstract idea and a natural phenomenon (Step 2A, Prong 2: 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). These claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because these claims recite additional elements that equate to instructions to apply the recited exception in a generic way and/or in a generic computing environment (MPEP § 2106.05(f)) and to well-understood, routine and conventional (WURC) limitations (MPEP § 2106.05(d)). The paragraphs below discuss the additional elements recited above in the instant claims.
Claims 1-8 and 14-20 do not recite any additional elements and thus are not being analyzed under Step 2B.
The processor based-system of claims 9-13 comprises processors and memories and thus equates to a generic computer, and there are no limitations that requiring anything other than a generic computer. Therefore, 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 in Intellectual Ventures I LLC v. Capital One Bank (USA), 792 F.3d 1363, 1367, 115 USPQ2d 1636, 1639 (Fed. Cir. 2015).
Claims 9-13 recite storing instructions in memory, which the courts have established as a WURC function of a generic computer in Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015).
When these additional elements are considered individually and in combination, they do not provide an inventive concept because they equate to mere instructions to apply an abstract idea on a generic computer and to WURC functions/components of a generic computer. Therefore, these additional elements do not transform the claimed judicial exception into a patent-eligible application of the judicial exception and do not amount to significantly more than the judicial exception itself (Step 2B: No).
As such, claims 1-20 are not patent eligible.
Conclusion
No claims are allowed.
Claims 1-20 are free from the prior art because the prior art does not teach the following limitations: in claims 1 and 9 “calculating a polygenic risk score for a polygenic trait of interest for each respective filtered data set to generate a plurality of polygenic risk scores; determining a relationship between the different proportions of contribution from the first source and the plurality of polygenic risk scores; based on the relationship, determining an unbiased polygenic risk score for a second source of the two sources corresponding to no contribution of sequence data by the first source.” In claim 14 “calculating a polygenic risk score for a polygenic trait of interest for each respective filtered data set to generate a plurality of polygenic risk scores; performing a linear regression to determine a linear relationship between the different fetal fractions and the plurality of polygenic risk scores; extrapolating the linear relationship to an intercept corresponding to no contribution of sequence data by the fetus to determine a maternal polygenic risk score.”
The closest prior art includes Lo et al. (“Lo”; WO 2013/132305 A1), Budis et al. (“Budis”; EP 3,658,689 B1; application published 3 July 2020), Duenwald et al. (“Duenwald”; US Patent ref. 3 on IDS filed 06/01/2023; US 10,095,831 B2), Kumar et al. (“Kumar”; US 2023/0410942 A1; effective filing date 30 Oct 2020), and Leppert et al. (“Leppert”; JAMA psychiatry 76, no. 8 (2019): 834-842). The claim mapping below shows how the prior art maps onto the claims using claim 1 as a representative claim. The bold text below is the limitations of the instant claims used to map the prior art.
Claim 1:
accessing or receiving a nucleic acid sequence data set comprising a mixture of sequence data from two sources;
Lo calculates fractional concentration of DNA in a DNA mixture, containing fetal and maternal DNA or containing tumor and patient DNA, based on amounts of DNA fragments at multiple sizes (abstract).
filtering the nucleic acid sequence data set using a plurality of minimum fragment length thresholds to generate a respective filtered data set for each minimum fragment length threshold, wherein each respective filtered data set has a different proportion of contribution from a first source of the two sources;
Lo calculates size profiles of DNA fragments in a biological sample, indicating relative abundance of short and long DNA fragments. One size profile may be 140-146 bp and 163 to 169 bp while another size profile may be <150 bp and 163 to 169 bp [96-97]. These size profiles contain a ratio of the short fragments to the longer fragments. Each size profile is used to determine fetal fraction [101].
calculating a polygenic risk score for a polygenic trait of interest for each respective filtered data set to generate a plurality of polygenic risk scores; determining a relationship between the different proportions of contribution from the first source and the plurality of polygenic risk scores;
Duenwald uses cell-free DNA fragment sizes to determine copy number variations of fetuses using maternal samples comprising maternal and fetal cfDNA (abstract). Fetal fractions are used to evaluate CNVs (abstract).
Leppert associates maternal polygenic risk scores for neurodevelopmental disorders with early-life exposures previously linked to the disorders (abstract) (pg. 835, col. 2, last para.).
Kumar detects SNPs from cell-free fetal DNA [24]. The SNPs are used to calculate a polygenic risk score [32] [117].
based on the relationship, determining an unbiased polygenic risk score for a second source of the two sources corresponding to no contribution of sequence data by the first source; outputting the unbiased polygenic risk score.
Budis determines fetal aneuploidy and corresponding fetal fraction from maternal blood comprising a mixture of DNA fragments of fetal and maternal origin (abstract). The DNA mixture is filtered by calculating distributions of fragment lengths (abstract), and a fragment length distribution is calculated for when fetal fraction is at 0% [67].
However, these references do not render obvious calculating a PRS for each set of fragments defined by different minimum fragment length thresholds to then determine a relationship between each PRS and an associated proportion of contribution for each set of fragments. Nor do the references use the relationship to determine an unbiased/maternal PRS corresponding to a 0% contribution of a first source (in claims 1 and 9) and/or fetal source (claim 14).
Other prior art includes Li et al. (Genome research 31, no. 4 (2021): 529) discusses low-pass sequencing plus variant imputation decreases measurement error of polygenic risk scores (abstract) (instant claims 2, 4, 10, 15 and 17).
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Noah A. Auger whose telephone number is (703)756-4518. The examiner can normally be reached M-F 7:30-4:30 EST.
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/N.A.A./Examiner, Art Unit 1687
/KAITLYN L MINCHELLA/Primary Examiner, Art Unit 1685
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