DETAILED ACTION
Applicant’s response filed 9/10/2025 has been fully considered. The following rejections and/or objections are either reiterated or newly applied.
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 1-10 and 12-21 are pending and under consideration in this action. Claim 11 is canceled.
Priority
The instant application is 371 of PCT/KR2020/002359, filed 02/19/2020, which claims priority to Republic of Korea Application Number 10-2019-0019315, filed 02/19/2019, as reflected in the filing receipt mailed on 02/03/2022. The claims to the benefit of priority are acknowledged and the effective filing date of claims 1-21 is 02/19/2019.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 9/10/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS has been considered by the examiner.
Claim Objections
Withdrawn Objections
The objections to claims 1, 5-6, and 8 have been withdrawn in view of Applicant’s amendments to the claims filed 9/10/2025. The objection to claim 11 is withdrawn because Applicant has canceled the claim.
Newly Recited Objections
Claims 1, 18, and 20 are objected to because of the following informalities. Appropriate correction is required.
Claims 1, 18, and 20 recite “I-score” in steps (f-iii), (iii), and (f-iii), respectively, which should be changed to “I score” for consistency.
Claim 18 recites the phrase “using the obtained chromosome length in step (f-ii)”, which should be corrected to “using the obtained chromosome length in step (ii)” for clarity.
Claim Rejections - 35 USC § 112(b)
The rejection of claims 1-21 as being indefinite for failing to particularly point out and distinctly claim the subject matter of the invention is withdrawn in view of Applicant’s amendments to claims 1, 3, 7, 18, and 20 filed 9/10/2025.
Withdrawn Rejections
35 U.S.C. 103
The rejection of claims 1, 4-5, 10, 14-15, and 17-21 as being unpatentable over Chan et al. (Noninvasive detection of cancer-associated genome-wide hypomethylation and copy number aberrations by plasma DNA bisulfite sequencing. Proc. Natl. Acad. Sci. U.S.A 110 (47), 18761-18768 (2013)) in view of Park et al. (Biomarker analysis in circulating cell-free DNA in patients treated with sorafenib for advanced hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4600) is withdrawn in view of the declaration filed under 37 CFR § 1.130(a) of inventors Baek-Yeol Ryoo, Sook Ryun Park, Eun Hae Cho, Junnam Lee, Sun-Young Kong, and Min Kyeong Kim establishing that the cited Park reference is disqualified as prior art.
The rejection of claims 2-3, 6, 11, and 12 as being unpatentable over Chan et al. in view of Park et al. and Cho et al. (WIPO Application, WO 2019/139363 A1) is withdrawn for the same reason as described above for claims 1, 4-5, 10, 14-15, and 17-21.
The rejection of claims 7 and 9 as being unpatentable over Chan et al. in view of Park et al. and Xu et al. (Non-invasive analysis of genomic copy number variation in patients with hepatocellular carcinoma by Next Generation DNA Sequencing. J. Cancer. 6 (3), 247-253 (2015)) is withdrawn for the same reason as described above for claims 1, 4-5, 10, 14-15, and 17-21.
The rejection of claim 8 as being unpatentable over Chan et al. in view of Park et al. and Chen et al. (Noninvasive prenatal diagnosis of fetal trisomy 18 and trisomy 13 by maternal plasma DNA sequencing. PloS One. 6 (7), e21791 (2011)) is withdrawn for the same reason as described above for claims 1, 4-5, 10, 14-15, and 17-21.
Claim Rejections - 35 USC § 101
Withdrawn Rejections
The rejection of claims 20-21 under 35 USC 101 as being directed towards non-statutory subject matter as “signals per-se” is withdrawn in view of Applicant’s claim amendments filed 9/10/2025.
Maintained Rejections
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-10 and 12-21 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claims recite both (1) mathematical concepts (mathematical relationships, formulas or equations, or mathematical calculations) and (2) mental processes, i.e., concepts performed in the human mind (including observations, evaluations, judgements or opinions) (see MPEP § 2106.04(a)).
Any newly recited portions herein are necessitated by claim amendment.
Step 1:
In the instant application, claims 1-10 and 12-17 are directed toward a method, claims 18-19 are directed towards a machine, and claims 20-21 are directed towards a manufacture, which falls within one of the categories of statutory subject matter (Step 1: YES).
Step 2A, Prong One:
In accordance with MPEP § 2106, claims found to recite statutory subject matter (Step 1: YES) are then analyzed to determine if the claims recite any concepts that equate to an abstract idea, law of nature or natural phenomenon (Step 2A, Prong One). The following instant claims recite limitations that equate to one or more categories of judicial exceptions:
Claims 1 and 20 recite a mental process (i.e., a judgement in determining quality) and a mathematical concept (i.e., values equal to or higher than a cut-off value) in step c) of “detecting a quality of the aligned reads and selecting only reads having a quality equal to or higher than a cut-off value”; a mathematical concept (i.e., binning data and normalizing values) in step d) of “segmenting the reference genome into predetermined bins, and detecting and normalizing amounts of the selected reads in the respective bins”; a mathematical calculation in step e) of “calculating a mean and a standard deviation of normalized reads matched to each bin of the reference group and then calculating a Z score from normalized values in step d)”; a mathematical concept (i.e., binning data and calculating an I score) in step f) of “segmenting chromosome using the Z score and calculating an I score”; a mental process (i.e., an evaluation of prognosis) and a mathematical concept (i.e., determining if values are higher than a cut-off value) in step g) of “determining that a prognosis of liver cancer is bad when the resulting I score is higher than a cut-off value”; mathematical concepts (i.e., binning data and calculating an I-score) in step (f-i) of “segmenting a chromosome region using circular binary segmentation (CBS) based on a Z score in each bin”, and in step (f-iii) of “calculating an I-score using the obtained chromosome length in step (f-ii) and Z score of the area in step (f-ii)”; and a mental process (i.e., an evaluation of whether a value is greater than or equal to a cut-off value) in step (f-ii) of “obtaining a chromosome length (size) of an area where a mean absolute value of a Z score of the segmented region is greater than or equal to a cut-off value”.
Claim 5 recites a mental process (i.e., a judgement in selecting a specific region or sequence) in “specifying a region of each aligned nucleic acid sequence” and “selecting a sequence satisfying a cut-off value of a mapping quality score and a cut-off value of a GC (guanine and cytosine) ratio within the region”.
Claim 6 recites a mental process (i.e., an evaluation of whether a value falls within a range) in “wherein the cut-off value of the mapping quality score is 15 to 70 and the cut-off value of the GC (guanine and cytosine) ratio is 30 to 60%”.
Claim 7 recites a mental process (i.e., a judgement to exclude data) in “excluding data of a centromere or a telomere of the chromosome”.
Claim 8 recites a mathematical concept (i.e., binning, calculating a number in a bin, performing regression analysis, and normalizing) in steps (d-i) of “segmenting the reference genome into predetermined bins”, step (d-ii) of “calculating a number of reads aligned in each bin and an amount of GC (guanine and cytosine) of the reads”, step (d-iii) of “performing a regression analysis based on the number of reads and the amount of GC (guanine and cytosine) to calculate a regression coefficient”, and step (d-iv) of “normalizing the number of reads using the regression coefficient”.
Claim 9 recites a mental process (i.e., a judgment in selecting bin size) in “the predetermined bin in step (d-i) is 100 kb to 2,000 kb in length”.
Claim 10 recites a mathematical calculation in “the calculation is caried out using Formula 1 below”.
Claim 12 recites a mental process (i.e., an evaluation of whether a value falls within a range) in “the cut-off value of the mean absolute value of the Z score is 1 to 2”.
Claim 13 recites a mental process (i.e., an evaluation of whether a value is above a cut-off value) in “the cut-off value of the I score is 1637”.
Claim 14 recites a mental process (i.e., an evaluation of whether a value is higher than the cut-off) in “determining a case where the concentration of the cell-free DNA is higher than a cut-off value to be a bad prognosis”.
Claim 15 recites a mental process (i.e., an evaluation of whether a value is above a cut-off value) in “the cut-off value of the isolated cell-free DNA concentration is 0.71 ng/μl”.
Claim 16 recites a mental process (i.e., an evaluation of the group that a value falls into) in “classifying a case where the I score is 1638 to 3012 as a moderate risk group, classifying a case where the I score is 3013 to 13672 as a high risk group, and classifying a case where the I score is 13673 to 28520 as an ultra-high risk group”.
Claim 17 recites a mental process (i.e., an evaluation of the prognosis) in “determining a prognosis of liver cancer”.
Claim 18 recites a mental process (i.e., an evaluation of quality) and a mathematical concept (i.e., values higher than a cut-off value) in “a quality controller for selecting only reads having a quality equal to or higher than a cut-off value from the aligned reads”, and mental process (i.e., an evaluation of whether a value is above a cut-off value and an evaluation of the prognosis) and a mathematical concept (i.e., calculating a Z score and an I score) in “a determiner for calculating a Z score through comparison of selected reads with a reference group sample, calculating an I score based on the Z score and determining the prognosis of liver cancer is bad when the I score is higher than a cut-off value”; mathematical concepts (i.e., binning data and calculating an I-score) in step (i) of “segmenting a chromosome region using circular binary segmentation (CBS) based on a Z score in each bin” and in step (iii) of “calculating an I-score using the obtained chromosome length in step (ii) and Z score of the area in step (ii)”; and a mental process (i.e., an evaluation of whether a value is greater than or equal to a cut-off value) in step (ii) of “obtaining a chromosome length (size) of an area where a mean absolute value of a Z score of the segmented region is greater than or equal to a cut-off value”.
Claims 19 and 21 recite a mental process (i.e., an evaluation of prognosis based on a value above a cut-off) in “determining that the prognosis is bad when the concentration of the cell-free DNA is higher than a cut-off value”.
These recitations are similar to the concepts of collecting information, and displaying certain results of the collection and analysis is Electric Power Group, LLC, v. Alstom (830 F.3d 1350, 119 USPQ2d 1739 (Fed. Cir. 2016)), comparing information regarding a sample or test to a control or target data in Univ. of Utah Research Found. v. Ambry Genetics Corp. (774 F.3d 755, 113 U.S.P.Q.2d 1241 (Fed. Cir. 2014)) and Association for Molecular Pathology v. USPTO (689 F.3d 1303, 103 U.S.P.Q.2d 1681 (Fed. Cir. 2012)), and organizing and manipulating information through mathematical correlations in Digitech Image Techs., LLC v Electronics for Imaging, Inc. (758 F.3d 1344, 111 U.S.P.Q.2d 1717 (Fed. Cir. 2014)) that the courts have identified as concepts that can be practically performed in the human mind or mathematical relationships.
The abstract ideas recited in the claims are evaluated under the broadest reasonable interpretation (BRI) of the claim limitations when read in light of and consistent with the specification, and are determined to be directed to mental processes that in the simplest embodiments are not too complex to practically perform in the human mind. Additionally, the recited limitations that are identified as judicial exceptions from the mathematical concepts grouping of abstract ideas are abstract ideas irrespective of whether or not the limitations are practical to perform in the human mind. The instant claims must therefore be examined further to determine whether they integrate the abstract idea into a practical application (Step 2A, Prong One: YES).
Step 2A, Prong Two:
In determining whether a claim is directed to a judicial exception, further examination is performed that analyzes if the claim recites additional elements that when examined as a whole integrates the judicial exception(s) into a practical application (MPEP § 2106.04(d)). A claim that integrates a judicial exception into a practical application will apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception. The claimed additional elements are analyzed to determine if the abstract idea is integrated into a practical application (MPEP § 2106.04(d)(I)). If the claim contains no additional elements beyond the abstract idea, the claim fails to integrate the abstract idea into a practical application (MPEP § 2106.04(d)(III)). The following claims recite limitations that equate to additional elements:
Claim 1 recites “obtaining at least 1 million reads (sequence information) of cell-free DNA isolated from a biological sample” and “aligning the reads to a reference genome database of a reference group”.
Claim 2 further recites “removing proteins, fats, and other residues from the isolated cell-free DNA using a salting-out method, a column chromatography method, or a bead method to obtain purified nucleic acids”, “producing a single-end-sequencing or pair-end-sequencing library from the purified nucleic acids”, “applying the produced library to a next-generation sequencer”, and “obtaining reads of the nucleic acids from the next-generation sequencer”.
Claim 3 further recites “randomly fragmenting the nucleic acids purified in the step (a-i) by an enzymatic digestion, or pulverization method to produce the single-end sequencing or pair-end sequencing library”.
Claim 4 further recites “obtaining the isolated cell-free DNA through full-length genome sequencing with a depth of 1 million to 100 million reads”.
Claims 14, 19, and 21 further recite “measuring a concentration of the isolated cell-free DNA”.
Claim 18 recites “decoding at least 1 million reads (sequence information) of cell-free DNA isolated from a biological sample” and “aligning the decoded reads to a reference genome database of a reference group”.
Claim 20 recites “an instruction configured to be executed by a processor”, “obtaining at least 1 million reads (sequence information) of cell-free DNA isolated from a biological sample”, and “aligning the reads to a reference genome database of a reference group”.
Regarding the above cited limitations in claim 20 of (i) an instruction configured to be executed by a processor. These limitations require only a generic computer component, which does not improve computer technology. Therefore, these limitations equate to mere instructions to implement an abstract idea on a generic computer, which the courts have established does not render an abstract idea eligible in Alice Corp. 573 U.S. at 223, 110 USPQ2d at 1983.
Regarding the above cited limitations in claims 1-4, 14, and 18-21 of (ii) obtaining/decoding [at least 1 million] reads (sequence information) of cell-free DNA isolated from a biological sample, (iii) aligning the [decoded] reads to a reference genome database of a reference group, (iv) removing proteins, fats, and other residues from the isolated cell-free DNA using a salting-out method, a column chromatography method, or a bead method to obtain purified nucleic acids, (v) producing a single-end-sequencing or pair-end-sequencing library from the purified nucleic acids, (vi) applying the produced library to a next-generation sequencer, (vii) obtaining reads of the nucleic acids from the next-generation sequencer, (viii) randomly fragmenting the nucleic acids purified in the step (a-i) by an enzymatic digestion, or pulverization method to produce the single-end sequencing or pair-end sequencing library, (ix) obtaining the isolated cell-free DNA through full-length genome sequencing with a depth of 1 million to 100 million reads, and (x) measuring a concentration of the isolated cell-free DNA. These limitations equate to insignificant, extra-solution activity of mere data gathering because these limitations gather data before or after the recited judicial exceptions of determining that a prognosis of liver cancer is bad when the resulting I score is higher than a cut-off value (see MPEP § 2106.04(d)). As such, claims 1-10 and 12-21 are directed to an abstract idea (Step 2A, Prong Two: NO).
Step 2B:
Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself (Step 2B). The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite additional elements that equate to well-understood, routine and conventional (WURC) limitations (MPEP § 2106.05(d)). The instant claims recite the same additional elements as described in Step 2A: Prong Two above.
Regarding the above cited limitation in claim 20 of (i) an instruction configured to be executed by a processor. This limitation equates to instructions to implement an abstract idea on a generic computing environment, which the courts have established does not provide an inventive concept (see MPEP § 2106.05(d) and MPEP § 2106.05(f)).
Regarding the above cited limitations in claims 1-2, 4, 14, and 18-21 of (ii) obtaining/decoding [at least 1 million] reads (sequence information) of cell-free DNA isolated from a biological sample, (iii) aligning the [decoded] reads to a reference genome database of a reference group, (vi) applying the produced library to a next-generation sequencer, (vii) obtaining reads of the nucleic acids from the next-generation sequencer, (ix) obtaining the isolated cell-free DNA through full-length genome sequencing with a depth of 1 million to 100 million reads, and (x) measuring a concentration of the isolated cell-free DNA. These limitations equate to laboratory techniques that are WURC limitations in the life science arts (see MPEP § 2106.05(d)). Detecting DNA or enzymes in a sample is a WURC limitation in Sequenom, 788 F.3d at 1377-78, 115 USPQ2d at 1157, and Cleveland Clinic Foundation 859 F.3d at 1362, 123 USPQ2d at 1088 (Fed. Cir. 2017). Analyzing DNA to provide sequence information or detect allelic variants is a WURC limitation in Genetic Techs. Ltd., 818 F.3d at 1377; 118 USPQ2d at 1546. Amplifying and sequencing nucleic acid sequences is a WURC limitation in University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 764, 113 USPQ2d 1241, 1247 (Fed. Cir. 2014).
Regarding the above cited limitations in claims 2 and 3 of (iv) removing proteins, fats, and other residues from the isolated cell-free DNA using a salting-out method, a column chromatography method, or a bead method to obtain purified nucleic acids, (v) producing a single-end-sequencing or pair-end-sequencing library from the purified nucleic acids, and (viii) randomly fragmenting the nucleic acids purified in the step (a-i) by an enzymatic digestion, or pulverization method to produce the single-end sequencing or pair-end sequencing library. These limitations when viewed individually and in combination, are WURC limitations as taught by Chan et al. (Noninvasive detection of cancer-associated genome-wide hypomethylation and copy number aberrations by plasma DNA bisulfite sequencing. Proc. Natl. Acad. Sci. U.S.A 110 (47), 18761-18768). Chan et al. discloses that the PCR products were purified using AMPure XP magnetic beads (limitation (iv)) (Pg. 18768, Col. 1, Para. 2). Chan et al. also discloses that DNA libraries were prepared using the Paired-End Sequencing Sample Preparation Kit (Illumina) with methylated adapters according to the manufacturer’s instructions (limitation (v)) (Pg. 18768, Col. 1, Para. 1). Chan et al further discloses that DNA extracted from tumor tissues and buffy coat, DNA was fragmented to about 200 bp in length using the Covaris S220 System (limitation (viii)) (Pg. 18767, Col. 2, Para. 7 – Pg. 18768, Col. 1, Para. 1).
These additional elements do not comprise an inventive concept when considered individually or as an ordered combination that transforms the claimed judicial exception into a patent-eligible application of the judicial exception. Therefore, the instant claims do not amount to significantly more than the judicial exception itself (Step 2B: NO). As such, claims 1-10 and 12-21 are not patent eligible.
Response to Arguments under 35 U.S.C. 101
Applicant’s arguments filed 9/10/2025 have been fully considered but they are not persuasive.
Applicant argues that the abstract of the present application addresses the practical application achieved by the claimed invention (Pg. 12, Para. 4 of Applicant’s Remarks). Applicant’s arguments are not persuasive for the following reasons:
MPEP 2106.05(a) recites:
"After the examiner has consulted the specification and determined that the disclosed invention improves technology, the claim must be evaluated to ensure the claim itself reflects the disclosed improvement in technology. Intellectual Ventures I LLC v. Symantec Corp., 838 F.3d 1307, 1316, 120 USPQ2d 1353, 1359 (Fed. Cir. 2016) (patent owner argued that the claimed email filtering system improved technology by shrinking the protection gap and mooting the volume problem, but the court disagreed because the claims themselves did not have any limitations that addressed these issues). That is, the claim must include the components or steps of the invention that provide the improvement described in the specification. However, the claim itself does not need to explicitly recite the improvement described in the specification (e.g., "thereby increasing the bandwidth of the channel"). The full scope of the claim under the BRI should be considered to determine if the claim reflects an improvement in technology (e.g., the improvement described in the specification). In making this determination, it is critical that examiners look at the claim "as a whole," in other words, the claim should be evaluated "as an ordered combination, without ignoring the requirements of the individual steps." When performing this evaluation, examiners should be "careful to avoid oversimplifying the claims" by looking at them generally and failing to account for the specific requirements of the claims. McRO, 837 F.3d at 1313, 120 USPQ2d at 1100."
The alleged improvement is not commensurate in scope with the claimed invention. Applicant appears to assert that the claim uses next generation sequencing so as to increase the accuracy of prognosis prediction of a liver cancer patient and also increase the accuracy of prognosis prediction based on a very low concentration cell-free DNA, of which detection has been difficult, thereby increasing the commercial utilization thereof (see Abstract). However, the claim does not provide any indication of an increase in accuracy for prognosis prediction, based on a low concentration of cell-free DNA and/or next generation sequencing. The claimed invention merely determines the prognosis in step (g). Therefore, it appears that the alleged improvements are not commensurate in scope with the claimed invention. This argument is thus not persuasive.
Applicant argues that amended claim 1 requires at least 1 million reads as an informatics basis for the specified methodology, thereby establishing the segmenting, binning, detecting, and normalizing of subsequent step d) as an operation that cannot be practically performed in the human mind and therefore is not characterizable as a mental process, that does not set forth any mathematical relationships, calculations, formulas, or equations and correspondingly cannot be denominated as a mathematical concept, and that is substantively significant in the claimed methodology so that it cannot be dismissed as insignificant extra-solution activity, and thus is an additional element that integrates any judicial exceptions in the claim into a practical application of prognosis of liver cancer based on cell-free DNA (Pg. 12, Para. 5 – Pg. 13, Para. 1 of Applicant’s Remarks). Applicant’s arguments are not persuasive for the following reasons:
As described in Step 2A, Prong One above, step d) of “segmenting the reference genome into predetermined bins, and detecting and normalizing amounts of the selected reads in the respective bins” has been identified as a mathematical concept, not as a mental process, or as insignificant extra-solution activity. The broadest reasonable interpretation (BRI) of this limitation is binning data, and subsequent normalization of the values in each of the respective bins, both of which are mathematical concepts. Since the mathematical concepts grouping of abstract ideas are not required to be performed entirely in the human mind, or using a pen and paper, as required in mental processes group of abstract ideas, the requirement of at least 1 million reads in step a) does not change the identification of step d) as a mathematical concept (see MPEP 2106.04(a)(2)(I) and MPEP 2016.04(a)(2)(III)).
MPEP 2106.04(d)(II) recites:
The analysis under Step 2A Prong Two is the same for all claims reciting a judicial exception, whether the exception is an abstract idea, a law of nature, or a natural phenomenon (including products of nature). Examiners evaluate integration into a practical application by: (1) identifying whether there are any additional elements recited in the claim beyond the judicial exception(s); and (2) evaluating those additional elements individually and in combination to determine whether they integrate the exception into a practical application, using one or more of the considerations introduced in subsection I supra, and discussed in more detail in MPEP 2106.04(d)(l), 2106.04(d)(2), 2106.05(a) through (c) and 2106.05(e) through (h).
Additionally, the integration of a judicial exception into a practical application can only be achieved by additional elements, not by a limitation that recites a judicial exception. Since step d) has been identified as reciting a judicial exception (mathematical concept), this limitation cannot integrate the judicial exceptions into a practical application of improving the prognosis of liver cancer based on cell-free DNA.
Applicant argues that similar “additional element” character is present in the segmenting and binning operations of step (f-i) in claim 1, in step (i) in claim 18, and in step (f-i) in claim 20, as likewise is effective to integrate any judicial exceptions in those respective claims into a practical application of prognosis of liver cancer based on cell-free DNA (Pg. 13, Para. 2 of Applicant’s Remarks). Applicant’s arguments are not persuasive for the following reasons:
The limitations of segmenting and binning operations in step (f-i) of claim 1, in step (i) in claim 18, and in step (f-i) in claim 20 have been identified as reciting a judicial exception (mathematical concept), as described above in Step 2A, Prong One. As disclosed in MPEP 2106.04(d)(II) directly above, the integration of a judicial exception into a practical application can only be achieved by additional elements, not by a limitation that recites a judicial exception. Thus, the recited limitations cannot integrate the judicial exceptions into a practical application for predicting prognosis of liver cancer based on cell-free DNA. This argument is thus not persuasive.
Conclusion
No claims allowed.
Claims 1-10 and 12-21 are free from the prior art because the prior art does not fairly suggest or teach the calculation of an I score and subsequent use in the determination of a poor liver cancer prognosis. The closest prior art is Chan et al. (Noninvasive detection of cancer-associated genome-wide hypomethylation and copy number aberrations by plasma DNA bisulfite sequencing. Proc. Natl. Acad. Sci. U.S.A 110 (47), 18761-18768 (2013); previously cited). Chan et al. discloses a method of detecting genome-wide hypomethylation in plasma using shotgun massively parallel bisulfite sequencing, which could be used as a marker for hepatocellular carcinoma. The method includes obtaining and aligning reads, and subsequent calculation of a Z score. However, Chan et al. does not teach the calculation of an I score using the Z score, and its subsequent use in the determination of a poor liver cancer prognosis, as disclosed in instant claims 1, 18 and 20. Claims 2-10, 12-17, 19, and 21 are free from the prior art due to their dependency on claims 1, 18, and 20.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/D.P.S./Examiner, Art Unit 1687
/Karlheinz R. Skowronek/Supervisory Patent Examiner, Art Unit 1687
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