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 .
Status of the Claims
Claims 1-2, 6, 10-12, and 15-16, 18, 21-23, 25-26, and 79-84 are pending and examined herein.
Claims 3-5, 7-9, 13-14, 17, 19-20, 24 and 27-78 are canceled.
Priority
As detailed on the 21 August 2024 filing receipt, the application claims priority as early as 31 October 2019 as found in provisional application 62/928,674. At this point in examination, all claims have been interpreted as being accorded this priority date as the effective filing date.
Information Disclosure Statement
An information disclosure statement (IDS) was filed on 04 May 2026. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the references are being considered by the examiner except where struck through. Additionally, in view of the remarks (pg. 16), all previously cited references have been considered.
Withdrawn Objections and/or Rejections
The objections to the specification are withdrawn in view of amendment correcting typographical errors.
The objection to the claims is withdrawn in view of correcting a typographical error.
The rejections of claims 17 and 19 under 35 USC 112(b) are withdrawn as the claims have been canceled.
The rejections of claims 21-22 under 35 USC 112(b) are withdrawn as the claims are amended such that the ambiguous “minimum” and “maximum” terms are removed.
The rejections under 35 USC 102, 103, and regarding non-statutory double patenting are overcome in view of amendment reciting specific ranges for interpreted the mosaicism ratio when there are a given number of fetuses in the person from whom the cf-DNA sample was collected, which differs from Dyr (Plos One 14(8): 11 pgs., 2019; previously cited on the 05 August 2025 IDS form) and McCullough (WO 2018170511 A1; previously cited on the 26 May 2023 IDS form).
Claim Interpretation
Claims 25-26 recite a system and computer-readable medium, respectively, and a claim element of triggering a high-throughput sequencer to sequence a sample. The sequencer is neither recited as part of the system in claim 25 nor operatively coupled to the computer-readable medium in claim 26. Both claims recite instructions for performing the sequencing but the sequencing performed by the sequencer is interpreted as outside the metes and bounds of the claims. Therefore, particularly in reference to interpretation regarding 35 USC 101, neither sequencing nor a sequencer is interpreted and thus recites merely transmitting data for the purposes of data gathering to perform the abstract steps. Furthermore, even if sequencing was required, this would also be a step directed to data gathering.
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 1-2, 6, 10-12, and 15-16, 18, 21-23, 25-26, and 79-84 are rejected under 35 USC § 101 because the claimed inventions are directed to an abstract idea without significantly more. "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 § I). Abstract ideas include mathematical concepts, and procedures for evaluating, analyzing or organizing information, which are a type of mental process (MPEP 2106.04(a)(2)). The claims as a whole, considering all claim elements both individually and in combination, do not amount to significantly more than the abstract idea of classifying the presence of absence of mosaicism.
MPEP 2106 organizes JE analysis into Steps 1, 2A (Prong One & Prong Two), and 2B as analyzed below.
Step 1: Are the claims directed to a process, machine, manufacture, or composition of matter (MPEP 2106.03)?
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of
nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))?
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
Step 1: Are the claims directed to a 101 process, machine, manufacture, or composition of matter (MPEP 2106.03)?
The claims are directed to a method (claims 1-2, 6, 10-12, 15-24, and 79-82), a computer system (claims 25 and 83), and a non-transitory computer-readable medium (claims 26 and 84), each of which falls within one of the categories of statutory subject matter. [Step 1: Yes]
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))?
With respect to Step 2A, Prong One, the claims recite judicial exceptions in the form of abstract ideas. MPEP § 2106.04(a)(2) further explains that abstract ideas are defined as:
• mathematical concepts (mathematical formulas or equations, mathematical relationships
and mathematical calculations) (MPEP 2106.04(a)(2)(I));
• certain methods of organizing human activity (fundamental economic principles or practices, managing personal behavior or relationships or interactions between people) (MPEP 2106.04(a)(2)(II)); and/or
• mental processes (concepts practically performed in the human mind, including observations, evaluations, judgments, and opinions) (MPEP 2106.04(a)(2)(III)).
Mathematical concepts recited in the independent claims include identifying genetic copy number variation, where determining variation is interpreted as counting reads mapping to regions of a reference; determining a fraction of nucleic acid having copy number variation, a fraction of fetal nucleic acid, and the ratio of those two fractions, where determining said fractions and ratios are verbal descriptions of mathematical concepts; and classifying the presence or absence of mosaicism, where the mosaicism is classified based on comparison to a threshold value and thus a numerical comparison.
Mental processes, defined as concepts practically performed in the human mind such as steps of observing, evaluating, or judging information, recited in the independent claims include identifying a copy number variation region, as the human mind can practically observe different patterns in data suggesting more or less reads in one region to another, and classifying the presence or absence of mosaicism, where it is data output judgement or evaluation to classifying a dataset as indicating the presence or absence of mosaicism and thus practically performed by the human mind. Counting the reads, determining a fetal fraction, and classification may also be construed as mental processes.
Claims 2, 6, and 12 recite additional information about the fraction(s) and origin of the data.
Claims 10-11 recite additional information about determining copy number variation.
Claim 12 recites counting reads mapped to the reference genome, which is a verbal description of mathematics.
Claim 15 recites mapping reads to portions of a reference genome, which is a mental process of data evaluation, while counting reads mapped to said portions is a mathematical concept. Furthermore, the fraction described in the ‘wherein’ clause is a mathematical concept based on quantification.
Claims 16 and 18 recite additional information about evaluating the data and thus a mental process as described above.
Claims 17 and 19 recite additional information about the numerical comparison and thus a mathematical concept. Comparing numbers may also be data evaluation and thus a mental process.
Claims 20-24 recite additional information about interpreting the data comparison result and thus are mental processes which are practically performed in the human mind.
Claims 79-81 and 83 recite additional information regarding interpreting the mosaicism ratio and thus directed to mental aspects of the invention.
Hence, the claims explicitly recite numerous elements that, individually and in combination,
constitute abstract ideas. The claims must therefore be examined further to determine whether they
integrate that abstract idea into a practical application (MPEP 2106.04(d)). [Step 2A: Yes]
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
The claims recite elements in addition to the abstract ideas: massively parallel sequencing (claim 15), mapping reads to a reference genome (claim 15), processors and memory (claims 25-26) which comprise a computer system (claim 26), non-transitory computer readable media (claim 26), and confirmatory tests which may comprise an amniocentesis test, a chorionic villus sampling test, a karyotyping test, or a microarray-based test (claim 82).
The sequencing and mapping steps are steps for obtaining the sequence data to perform the recited determination of fractions and classification based on the fractions. Therefore, these steps are considered insignificant extra solution activity and as such do not integrate the abstract ideas into a practical application (MPEP 2106.05(g)). Claims 25-26 recite data gathering from a sequencer outside the metes and bounds of the claim as discussed in the Claim Interpretation section above, and thus is insignificant extra-solution activity which fails to integrate the abstract idea into a practical application.
The claims comprising computer components do not describe any specific computational steps by which the computer performs or carries out the abstract idea, nor do they provide any details of how specific structures of the computer are used to implement these functions. The claims state nothing more than that a generic computer performs the functions that constitute the abstract idea. Hence, these are mere instructions to apply the abstract idea using a computer, and therefore the claim does not integrate that abstract idea into a practical application (see MPEP 2106.04(d) § I; and MPEP 2106.05(f)).
The claims recite confirmatory tests such as an amniocentesis test, a chorionic villus sampling test, a karyotyping test, or a microarray-based test. These tests are not interpreted as constituting an improvement because the test itself is not materially impacted by the results of the abnormality test and thus is broadly recited as applying it (MPEP 2106.05(f)) [Step 2A Prong Two: No]
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
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 of 101 analysis determines whether the claims contain additional elements that amount to an inventive concept, and an inventive concept cannot be furnished by an abstract idea itself (MPEP 2106.05).
The claims recite the following elements in addition to the abstract ideas: massively parallel sequencing (claim 15), mapping reads to a reference genome (claim 15), processors and memory (claims 25-26) which comprise a computer system (claim 26),non-transitory computer readable media (claim 26), and confirmatory tests which may comprise an amniocentesis test, a chorionic villus sampling test, a karyotyping test, or a microarray-based test (claim 82).
Grati (Ultrasound in Obstetrics & Gynecology 48(4): 415-423, 2016; previously cited on the 02 February 2026 PTO-892 form) teaches cell-free DNA testing for fetal mosaicism, including massively parallel shotgun sequencing (pg. 415, col. 1, last paragraph) to screen for copy number variation (pg. 418, col. 2, third paragraph), where copy number variation is determined by mapping. Grati also teaches verifying aneuploidy by amniocentesis (pg. 416, col. 1, second paragraph).
The claims recite a computer, interpreted as instructions to apply the abstract idea using a computer, where the computer does not impose meaningful limitations on the judicial exceptions, which can be performed without the use of a computer (MPEP 2106.04(d) § I; and MPEP 2106.05(f)). Storing data on a computer and performing repetitive calculations are conventional computer functions (Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015); OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93; Bancorp Services v. Sun Life, 687 F.3d 1266, 1278, 103 USPQ2d 1425, 1433 (Fed. Cir. 2012); MPEP 2106.05(d)(II)).
Therefore, the recited additional elements, alone or in combination with the judicial exceptions, do not appear to provide an inventive concept. [Step 2B: No]
Conclusion: Claims are Directed to Non-statutory Subject Matter
For these reasons, the claims, when the limitations are considered individually and as a whole,
are directed to an abstract idea and lack an inventive concept. Hence, the claimed invention does not
constitute significantly more than the abstract idea, so the claims are rejected under 35 USC § 101 as
being directed to non-statutory subject matter.
Response to the 04 May 2026 Applicant Remarks
Applicant remarks state, in reference to Step 2A Prong Two of 101 analysis, that the combination of cfDNA sequencing and the mosaicism ratio calculations provides a technical improvement in diagnosing chromosomal abnormalities (pg. 18, third paragraph; pg. 19, first paragraph). Applicant remarks continue to state there is a concrete classification rule which is not abstract and provides the improvement, thus overcoming the rejection (pg. 19, second paragraph).
This argument is not persuasive because the improvement is considered to be derived from the abstract mathematical steps and mental interpretation of the results of the mathematical calculations. The additional element of sequencing of cfDNA is within the state of the art for fetal abnormality testing, and the sequencing being performed on a person with multifetal pregnancy is not interpreted as changing the steps of the cfDNA sequencing. At Step 2A Prong Two, it is determined if the judicial exception is integrated into a practical application by an additional element (MPEP 2106.04(d)). Here, the additional element of cfDNA sequencing is considered data gathering to perform the genetic mosaicism ratio testing and thus insignificant extra-solution activity, which does not integrate the abstract idea into a practical application (MPEP 2106.05(g)).
Applicant remarks state, at Step 2B, that the ordered combination of sequencing circulating cell-free nucleic acid to generate an MR and applying the biologically driven 0.1 to 1.7 range for multifetal gestations was not part of the routine or conventional NIPT workflow at the time of filing (pg. 20, first paragraph), which is unconventional and provides a technical improvement (pg. 20, second paragraph).
This argument is unpersuasive because the elements in addition to the abstract ideas are considered to be conventional. At Step 2B, it is determined whether the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05). The recited sequencing of cfDNA is an element in addition to the abstract ideas whereas the generating of a mosaicism ratio and applying the recited range for diagnosis is not. Because this step is taught at least by Grati, and given an inventive concept cannot be furnished by an abstract idea itself, where the abstract idea is determining and interpreting the mosaicism ratio, the claims are not considered to recite an inventive concept which provides significantly more than the abstract ideas.
Therefore, the rejection under 35 USC 101 is maintained.
Conclusion
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 Robert J Kallal whose telephone number is (571)272-6252. The examiner can normally be reached Monday through Friday 8 AM - 4 PM EST.
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/R.J.K./Examiner, Art Unit 1685
/OLIVIA M. WISE/Supervisory Patent Examiner, Art Unit 1685
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