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 15-26 are pending and examined herein.
Claims 3-5, 7-9, 13-14, 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
Information disclosure statements (IDS) were filed on 26 May 2023, 26 October 2023, 12 April 2024, 05 June 2024, 31 January 2025, and 05 August 2025. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the references are being considered by the examiner except where struck through, wherein references 432, 445, 448, and 472, which are not found in the IDS documented filed 26 May 2023.
Specification
The disclosure is objected to because of the following informalities: the last sentence on the paragraph ending on page 2 (line 9) concludes with an extra period and “like” on page 183 (line 6) has an unnecessary comma prior to the end parenthesis.
Appropriate correction is required.
Claim Objections
Claim 22 is objected to because of the following informality: “supernumery” is interpreted as a misspelling of “supernumerary”. Appropriate correction is required.
Claim Rejections - 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 17, 19, and 21-22 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 17 and 19 recite the term “about.” This is a relative term which renders the claim indefinite. The specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention, as the ranges given differ in up to two orders of magnitude (pg. 18, lines 9-12).
Claims 21 and 22 recite “the minimum threshold” and “the maximum threshold” respectively. These claims are dependent on claims 1 and 20, which do not recite a minimum threshold or a maximum threshold. Therefore, the terms “the minimum threshold” and “the maximum threshold” in claims 21 and 22 lack antecedent basis and are unclear. Amendment to change the claim dependency or other amendment may overcome this rejection.
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 15-26 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), a computer system (claim 25), and a non-transitory computer-readable medium (claim 26), 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.
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) and non-transitory computer readable media (claim 26).
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)).
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)). [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), and non-transitory computer readable media (claim 26).
Grati (Ultrasound in Obstetrics & Gynecology 48(4): 415-423, 2016; newly cited) 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.
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.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-2, 6, 10-12, 15-16, and 20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated Dyr (Plos One 14(8): 11 pgs., 2019; previously cited on the 05 August 2025 IDS form).
Claim 1 recites identifying, by a computing device, a genetic copy number variation region in a sample comprising circulating cell free nucleic acid from a pregnant female subject with multifetal gestation, wherein the genetic copy number variation region comprises a copy number variation and the circulating cell free nucleic acid comprises maternal nucleic acid and fetal nucleic acid.
Dyr teaches “cfDNA screening in multifetal pregnancies” (pg. 8, fourth paragraph) and detection of “fetal aneuploidy” (pg. 8, last paragraph), where aneuploidy is evidenced by copy number variation.
Claim 1 recites determining, by the computing device, a fraction of nucleic acid having the copy number variation in the circulating cell free nucleic acid; determining, by the computing device, a fraction of the fetal nucleic acid in the circulating cell free nucleic acid; and generating, by the computing device, a mosaicism ratio, wherein the mosaicism ratio is the fraction of nucleic acid having the copy number variation in the circulating cell free nucleic acid divided by the fraction of the fetal nucleic acid in the circulating cell free nucleic acid.
Dyr teaches “a mosaicism ratio is generated by dividing the fetal fraction estimated for only the aneuploid chromosome (or microdeletion event) by the fetal fraction estimated for all chromosomes in the sample” (pg. 8, fourth paragraph).
Claim 1 recites classifying, by the computing device, a presence or absence of a genetic mosaicism for the copy number variation region according to the mosaicism ratio based on the mosaicism ratio and a number of fetuses carried by the pregnant female subject.
Dyr teaches application of a mosaicism ratio in a multifetal pregnancy wherein a mosaicism ratio of approximately 0.5 suggests the presence of a single affected fetus (pg. 8, fifth paragraph).
Claim 2 recites the fraction of nucleic acid having the copy number variation in the circulating cell free nucleic acid is determined for the copy number variation region, and wherein the fraction of nucleic acid having the copy number variation in the circulating cell free nucleic acid is determined according to: (i) a sequencing-based fraction estimation, (ii) allelic ratios of polymorphic sequences, or (iii) a quantification of differentially methylated nucleic acid.
Dyr teaches genome-wide sequencing of cfDNA extracted from maternal plasma to detect chromosomal aneuploidy and in specified regions (pg. 3, first paragraph), where determining a fraction based on sequencing is considered to read on determining aneuploidy by sequencing.
Claim 6 recites the fraction of nucleic acid having the copy number variation in the circulating cell free nucleic acid is a fetal fraction determined for the copy number variation region, and wherein the fetal fraction of nucleic acid having the copy number variation in the circulating cell free nucleic acid is determined according to: (i) a sequencing-based fetal fraction estimation, (ii) allelic ratios of polymorphic sequences in the fetal nucleic acid and the maternal nucleic acid, or (iii) a quantification of differentially
methylated fetal and maternal nucleic acid.
Dyr teaches genome-wide sequencing of cfDNA extracted from maternal plasma to detect chromosomal aneuploidy and in specified regions (pg. 3, first paragraph), where determining a fraction based on sequencing is considered to read on determining aneuploidy by sequencing.
Claim 10 recites the fraction of the fetal nucleic acid in the circulating cell free nucleic acid is determined for a genomic region larger than the copy number variation region.
Dyr teaches determining a mosaicism ratio based on genome-wide sequencing (pg. 3, first paragraph), where the genome is larger than the specified chromosomal or subchromosomal regions of interest, and estimation for all chromosomes in a sample (pg. 8, fourth paragraph).
Claim 11 recites the fraction of the fetal nucleic acid in the circulating cell free nucleic acid is determined for a genomic region different than the copy number variation region.
Dyr teaches determining a mosaicism ratio based on genome-wide sequencing (pg. 3, first paragraph), where the genome is different than the specified chromosomal or subchromosomal regions of interest, and estimation for all chromosomes in a sample (pg. 8, fourth paragraph)..
Claim 12 recites the fraction of the fetal nucleic acid in the circulating cell free nucleic acid is determined according to: (i) a sequencing-based fetal fraction estimation, (ii) allelic ratios of polymorphic sequences in the fetal nucleic acid and the maternal nucleic acid, or (iii) a quantification of differentially methylated fetal and maternal nucleic acid.
Dyr teaches genome-wide sequencing of cfDNA extracted from maternal plasma to detect chromosomal aneuploidy and subsequent mapping (pg. 3, first paragraph), where determining a fraction based on sequencing is considered to read on determining aneuploidy by sequencing.
Claim 15 recites sequencing, by a massively parallel sequencer, nucleic acid from the sample that
generates reads; mapping, by the computing device, the reads to genomic portions of a reference genome;
counting, by the computing device, the reads mapped to the genomic portions, wherein the counting generates a quantification of the sequence reads mapped to the genomic portions of the reference genome;
wherein the mosaicism ratio is the fraction of nucleic acid having the copy number variation in the circulating cell free nucleic acid and divided by the fraction of the fetal nucleic acid in the circulating cell free nucleic acid are determined based on the quantification of the sequence reads.
Dyr teaches genome-wide sequencing (pg. 3, first paragraph), where massively parallel sequencing is considered to read on sequencing across the entire genome. Dyr teaches mapping fetal and maternal fragments to a genome (pg. 3, first paragraph). Dyr teaches counting unique reads indicating losses or gains in the genome profile (pg. 3, first paragraph), where quantification of reads is considered to read on counts. Dyr teaches using cfDNA and genome-wide sequencing to determine a mosaicism ratio (pg. 8, fourth paragraph) and at least fetal counts (pg. 7, last paragraph).
Claim 16 recites further comprising providing, by the computing system, no classification when the mosaicism ratio is less than a minimum threshold.
Dyr teaches a minimum threshold for fetal fraction in the case of multifetal pregnancy (pg. 3, second paragraph).
Claim 20 recites obtaining, by the computing system, positive screening results from a noninvasive prenatal testing (NIPT) for presence of one or more aneuploidies in a sample comprising circulating cell free nucleic acid from the pregnant female subject.
Dyr teaches a positive predictive value for aneuploidy based on cfDNA screening in multifetal pregnancy (pg. 8, fourth paragraph).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 25-26 are rejected under 35 U.S.C. 103 as being unpatentable over Dyr (Plos One 14(8): 11 pgs., 2019; previously cited on the 05 August 2025 IDS form), as applied to claims 1-2, 6, 10-12, 15-16, and 20 in the rejection under 35 USC 102(a)(1) above.
Claim 25 recites the steps of claim 1 performed on a computer system comprising one or more processors and memory coupled to said processor(s), wherein the memory is encoded with instructions to perform the steps.
Dyr does not explicitly teach a computer system. Computer-implemented functional claim limitations may also be broad because the term "computer" is commonly understood by one of ordinary skill in the art to describe a variety of devices with varying degrees of complexity and capabilities. Broadly claiming an automated means to replace a manual function to accomplish the same result does not distinguish over the prior art. That is, it would be obvious to automate the steps of claim 1 using a system as recited in claim 25. MPEP 2114(III) pertains.
Claim 26 recites a non-transitory computer readable medium storing instructions that, when executed by a computer, cause the computer to perform the steps recited in claim 1.
Dyr does not explicitly teach a computer-readable memory. Computer-implemented functional claim limitations may also be broad because the term "computer" is commonly understood by one of ordinary skill in the art to describe a variety of devices with varying degrees of complexity and capabilities. Broadly claiming an automated means to replace a manual function to accomplish the same result does not distinguish over the prior art. That is, it would be obvious to automate the steps of claim 1 using a computer-readable medium as recited in claim 25. MPEP 2114(IV) pertains.
Claims 17-19 and 21-24 are rejected under 35 U.S.C. 103 as being unpatentable over Dyr (Plos One 14(8): 11 pgs., 2019; previously cited on the 05 August 2025 IDS form), as applied to claims 1-2, 6, 10-12, 15-16, 20-23 and 25-26 above and further in view of McCullough (WO 2018170511 A1; previously cited on the 26 May 2023 IDS form).
Claim 17 recites the minimum threshold is about 0.1.
Dyr teaches adjustment of fetal fraction requirements for multiples in proportion to fetal number (pg. 3, second paragraph).
McCullough teaches a minimum threshold of about 0.2 (pg. 5, second paragraph), which makes obvious the instantly claimed range of about 0.1. It would have been prima facie obvious to one of ordinary skill in the art to select any portions of the disclosed ranges including the instantly claimed ranges from the ranges disclosed in the prior art references, particularly in view of the fact that: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set percentage ranges is the optimum combination of percentages" In re Peterson 65 USPQ2d 1379 (CAFC 2003). See also In re Malagari, 182 USPQ 549,533 (CCPA 1974) and MPEP 2144.05. Considering that Dyr motivates adjustment of fetal fraction requirements for multiples in proportion to fetal number (pg. 3, second paragraph), it would have been obvious to one of ordinary skill in the art to adjust the threshold taught by McCullough accordingly.
Claim 18 recites providing, by the computing system, no classification when the mosaicism ratio is greater than a maximum threshold.
McCullough teaches providing, by the computing system, no classification when the mosaicism ratio is greater than a maximum threshold (pg. 5, second paragraph).
Claim 19 recites the maximum threshold is about 1.7.
Dyr teaches adjustment of fetal fraction requirements for multiples in proportion to fetal number (pg. 3, second paragraph).
McCullough teaches the maximum threshold is about 1.3 (pg. 5, second paragraph), which makes obvious the instantly claimed range of about 1.7. It would have been prima facie obvious to one of ordinary skill in the art to select any portions of the disclosed ranges including the instantly claimed ranges from the ranges disclosed in the prior art references, particularly in view of the fact that: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set percentage ranges is the optimum combination of percentages" In re Peterson 65 USPQ2d 1379 (CAFC 2003). See also In re Malagari, 182 USPQ 549,533 (CCPA 1974) and MPEP 2144.05. Considering that Dyr motivates adjustment of fetal fraction requirements for multiples in proportion to fetal number (pg. 3, second paragraph), it would have been obvious to one of ordinary skill in the art to adjust the maximum threshold of 1.3 as taught by McCullough accordingly to arrive at around 1.7.
Claim 21 recites providing, by the computing system, an interpretation of the positive screening results from the NIPT as a negative result or the absence of the one or more aneuploidies when no classification is provided and the mosaicism ratio is less than the minimum threshold.
Dyr teaches adjustment of fetal fraction requirements for multiples in proportion to fetal number (pg. 3, second paragraph).
McCullough teaches providing, by the computing system, an interpretation of the positive screening results from the NIPT as a negative result or the absence of the one or more aneuploidies when no classification is provided and the mosaicism ratio is less than the minimum threshold (pg. 5, second paragraph).
Claim 22 recites providing, by the computing system, an interpretation of the positive screening results from the NIPT as supernumery or inconclusive when no classification is provided and the mosaicism ratio is greater than the maximum threshold.
Dyr teaches adjustment of fetal fraction requirements for multiples in proportion to fetal number (pg. 3, second paragraph).
McCullough teaches providing, by the computing system, an interpretation of the positive screening results from the NIPT as supernumery or inconclusive when no classification is provided and the mosaicism ratio is greater than the maximum threshold (pg. 5, second paragraph).
Claim 23 teaches providing, by the computing system, an interpretation of the positive screening results from the NIPT as positive with a comment concerning possibility of a mosaic presentation when the presence of the genetic mosaicism is classified for the copy number variation region.
Dyr teaches adjustment of fetal fraction requirements for multiples in proportion to fetal number (pg. 3, second paragraph).
McCullough teaches providing, by the computing system, an interpretation of the positive screening results from the NIPT as positive with a comment concerning possibility of a mosaic presentation when the presence of the genetic mosaicism is classified for the copy number variation region. (pg. 5, second paragraph).
Claim 24 recites providing, by the computing system, an interpretation of the positive screening results from the NIPT as positive when the absence of the genetic mosaicism is classified for the copy number variation region.
Dyr teaches adjustment of fetal fraction requirements for multiples in proportion to fetal number (pg. 3, second paragraph) and McCullough teaches providing, by the computing system, an interpretation of the positive screening results from the NIPT as positive when the absence of the genetic mosaicism is classified for the copy number variation region (pg. 5, lines 24-26).
Combining Dyr and McCullough
An invention would have been obvious to one of ordinary skill in the art if some motivation in the prior art would have led that person to modify prior art reference teachings to arrive at the claimed invention prior to the effective filing date of the invention. One would have been motivated to combine the work of McCullough, which is directed to assessment of genetic mosaicism, with that Dyr, because both are directed to genetic mosaicism in multiple pregnancies. Dyr teaches adjusting fetal fraction requirements (pg. 3, second paragraph) and McCullough teaches a benefit of the recited thresholds because interpretation of positive NIPT results is challenging due to differences in placenta and fetus (pg. 11, second paragraph) and modification of interpretation for multiple pregnancies (pg. 103, second paragraph). Dyr and McCullough are both directed to the shared field of endeavor of genetic mosaicism and thus their combination would be expected to succeed, and the invention is prima facie obvious.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-2, 6, 10-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, and 6-7 of U.S. Patent No. 12421550.
Claims 15-16, 20, and 25-26 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, and 6-7 of U.S. Patent No. 12421550 and further in view of Dyr.
Claims 17-19 and 21-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, and 6-7 of U.S. Patent No. 12421550 and further in view of Dyr and McCullough.
Regarding instant claim 1, reference claim 1 teaches the required limitations.
Regarding instant claim 2, reference claim 4 teaches the required limitations.
Regarding instant claim 6, reference claim 4 teaches the required limitations.
Regarding instant claim 10, reference claim 6 teaches the required limitations.
Regarding instant claim 11, reference claim 7 teaches the required limitations.
Regarding instant claim 12, reference claim 4 teaches the required limitations.
Regarding instant claim 15, Dyr teaches genome-wide sequencing (pg. 3, first paragraph), where massively parallel sequencing is considered to read on sequencing across the entire genome. Dyr teaches mapping fetal and maternal fragments to a genome (pg. 3, first paragraph). Dyr teaches counting unique reads indicating losses or gains in the genome profile (pg. 3, first paragraph), where quantification of reads is considered to read on counts. Dyr teaches using cfDNA and genome-wide sequencing to determine a mosaicism ratio (pg. 8, fourth paragraph) and at least fetal counts (pg. 7, last paragraph).
Regarding instant claim 16, Dyr teaches a minimum threshold for fetal fraction in the case of multifetal pregnancy (pg. 3, second paragraph).
Regarding instant claim 17, Dyr teaches adjustment of fetal fraction requirements for multiples in proportion to fetal number (pg. 3, second paragraph) and McCullough teaches a minimum threshold of about 0.2 (pg. 5, second paragraph), which makes obvious the instantly claimed range of about 0.1. It would have been prima facie obvious to one of ordinary skill in the art to select any portions of the disclosed ranges including the instantly claimed ranges from the ranges disclosed in the prior art references, particularly in view of the fact that: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set percentage ranges is the optimum combination of percentages" In re Peterson 65 USPQ2d 1379 (CAFC 2003). See also In re Malagari, 182 USPQ 549,533 (CCPA 1974) and MPEP 2144.05. Considering that Dyr motivates adjustment of fetal fraction requirements for multiples in proportion to fetal number (pg. 3, second paragraph), it would have been obvious to one of ordinary skill in the art to adjust the threshold taught by McCullough accordingly.
Regarding instant claim 18, McCullough teaches providing, by the computing system, no classification when the mosaicism ratio is greater than a maximum threshold (pg. 5, second paragraph).
Regarding instant claim 19, Dyr teaches adjustment of fetal fraction requirements for multiples in proportion to fetal number (pg. 3, second paragraph) and McCullough teaches the maximum threshold is about 1.3 (pg. 5, second paragraph), which makes obvious the instantly claimed range of about 1.7. It would have been prima facie obvious to one of ordinary skill in the art to select any portions of the disclosed ranges including the instantly claimed ranges from the ranges disclosed in the prior art references, particularly in view of the fact that: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set percentage ranges is the optimum combination of percentages" In re Peterson 65 USPQ2d 1379 (CAFC 2003). See also In re Malagari, 182 USPQ 549,533 (CCPA 1974) and MPEP 2144.05. Considering that Dyr motivates adjustment of fetal fraction requirements for multiples in proportion to fetal number (pg. 3, second paragraph), it would have been obvious to one of ordinary skill in the art to adjust the maximum threshold of 1.3 as taught by McCullough accordingly to arrive at around 1.7.
Regarding instant claim 20, Dyr teaches a positive predictive value for aneuploidy based on cfDNA screening in multifetal pregnancy (pg. 8, fourth paragraph).
Regarding instant claim 21, Dyr teaches adjustment of fetal fraction requirements for multiples in proportion to fetal number (pg. 3, second paragraph) and McCullough teaches providing, by the computing system, an interpretation of the positive screening results from the NIPT as a negative result or the absence of the one or more aneuploidies when no classification is provided and the mosaicism ratio is less than the minimum threshold (pg. 5, second paragraph).
Regarding instant claim 22, Dyr teaches adjustment of fetal fraction requirements for multiples in proportion to fetal number (pg. 3, second paragraph) and McCullough teaches providing, by the computing system, an interpretation of the positive screening results from the NIPT as supernumery or inconclusive when no classification is provided and the mosaicism ratio is greater than the maximum threshold (pg. 5, second paragraph).
Regarding instant claim 23, Dyr teaches adjustment of fetal fraction requirements for multiples in proportion to fetal number (pg. 3, second paragraph) and McCullough teaches providing, by the computing system, an interpretation of the positive screening results from the NIPT as positive when the absence of the genetic mosaicism is classified for the copy number variation region (pg. 5, second paragraph).
Regarding instant claim 24, Dyr teaches adjustment of fetal fraction requirements for multiples in proportion to fetal number (pg. 3, second paragraph) and McCullough teaches providing, by the computing system, an interpretation of the positive screening results from the NIPT as positive when the absence of the genetic mosaicism is classified for the copy number variation region (pg. 5, lines 24-26).
Regarding instant claim 25, Dyr teaches the method steps but does not explicitly teach a computer system. Computer-implemented functional claim limitations may also be broad because the term "computer" is commonly understood by one of ordinary skill in the art to describe a variety of devices with varying degrees of complexity and capabilities. Broadly claiming an automated means to replace a manual function to accomplish the same result does not distinguish over the prior art. That is, it would be obvious to automate the steps of claim 1 using a system as recited in claim 25. MPEP 2114(III) pertains.
Regarding instant claim 26, Dyr teaches the method steps but does not explicitly teach a computer-readable memory. Computer-implemented functional claim limitations may also be broad because the term "computer" is commonly understood by one of ordinary skill in the art to describe a variety of devices with varying degrees of complexity and capabilities. Broadly claiming an automated means to replace a manual function to accomplish the same result does not distinguish over the prior art. That is, it would be obvious to automate the steps of claim 1 using a system as recited in claim 25. MPEP 2114(III) pertains.
An invention would have been obvious to one of ordinary skill in the art if some motivation in the prior art would have led that person to modify prior art reference teachings to arrive at the claimed invention prior to the effective filing date of the invention. One would have been motivated to combine the work of the reference patent, McCullough, which is directed to assessment of genetic mosaicism, and Dyr, because each are directed to genetic mosaicism in multiple pregnancies. Dyr teaches adjusting fetal fraction requirements (pg. 3, second paragraph) and McCullough teaches a benefit of the recited thresholds because interpretation of positive NIPT results is challenging due to differences in placenta and fetus (pg. 11, second paragraph) and modification of interpretation for multiple pregnancies (pg. 103, second paragraph). Dyr and McCullough are both directed to the shared field of endeavor of genetic mosaicism and thus their combination would be expected to succeed, and the invention is prima facie obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1 and 25-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 16, and 31 of the reference application 19/161,983.
Claims 2, 6, 10-12, 15-16, 20, and 25-26 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 16, and 31 of the reference application and further in view of Dyr.
Claims 17-19 and 21-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 16, and 31 the reference application and further in view of Dyr and McCullough.
Regarding instant claim 1, reference claim 1 teaches the required limitations as mosaicism between individuals rather than mother and fetus.
Regarding instant claim 2, Dyr teaches genome-wide sequencing of cfDNA extracted from maternal plasma to detect chromosomal aneuploidy and in specified regions (pg. 3, first paragraph), where determining a fraction based on sequencing is considered to read on determining aneuploidy by sequencing.
Regarding instant claim 6, Dyr teaches genome-wide sequencing of cfDNA extracted from maternal plasma to detect chromosomal aneuploidy and in specified regions (pg. 3, first paragraph), where determining a fraction based on sequencing is considered to read on determining aneuploidy by sequencing.
Regarding instant claim 10, Dyr teaches determining a mosaicism ratio based on genome-wide sequencing (pg. 3, first paragraph), where the genome is larger than the specified chromosomal or subchromosomal regions of interest, and estimation for all chromosomes in a sample (pg. 8, fourth paragraph).
Regarding instant claim 11, Dyr teaches determining a mosaicism ratio based on genome-wide sequencing (pg. 3, first paragraph), where the genome is different than the specified chromosomal or subchromosomal regions of interest, and estimation for all chromosomes in a sample (pg. 8, fourth paragraph)..
Regarding instant claim 12, Dyr teaches genome-wide sequencing of cfDNA extracted from maternal plasma to detect chromosomal aneuploidy and subsequent mapping (pg. 3, first paragraph), where determining a fraction based on sequencing is considered to read on determining aneuploidy by sequencing.
Regarding instant claim 15, Dyr teaches genome-wide sequencing (pg. 3, first paragraph), where massively parallel sequencing is considered to read on sequencing across the entire genome. Dyr teaches mapping fetal and maternal fragments to a genome (pg. 3, first paragraph). Dyr teaches counting unique reads indicating losses or gains in the genome profile (pg. 3, first paragraph), where quantification of reads is considered to read on counts. Dyr teaches using cfDNA and genome-wide sequencing to determine a mosaicism ratio (pg. 8, fourth paragraph) and at least fetal counts (pg. 7, last paragraph).
Regarding instant claim 16, Dyr teaches a minimum threshold for fetal fraction in the case of multifetal pregnancy (pg. 3, second paragraph).
Regarding instant claim 17, Dyr teaches adjustment of fetal fraction requirements for multiples in proportion to fetal number (pg. 3, second paragraph) and McCullough teaches a minimum threshold of about 0.2 (pg. 5, second paragraph), which makes obvious the instantly claimed range of about 0.1. It would have been prima facie obvious to one of ordinary skill in the art to select any portions of the disclosed ranges including the instantly claimed ranges from the ranges disclosed in the prior art references, particularly in view of the fact that: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set percentage ranges is the optimum combination of percentages" In re Peterson 65 USPQ2d 1379 (CAFC 2003). See also In re Malagari, 182 USPQ 549,533 (CCPA 1974) and MPEP 2144.05. Considering that Dyr motivates adjustment of fetal fraction requirements for multiples in proportion to fetal number (pg. 3, second paragraph), it would have been obvious to one of ordinary skill in the art to adjust the threshold taught by McCullough accordingly.
Regarding instant claim 18, McCullough teaches providing, by the computing system, no classification when the mosaicism ratio is greater than a maximum threshold (pg. 5, second paragraph).
Regarding instant claim 19, McCullough teaches the maximum threshold is about 1.3 (pg. 5, second paragraph), which is within 10% of 0.1 as disclosed in the specification (pg. 18, lines 9-12).
Regarding instant claim 20, Dyr teaches a positive predictive value for aneuploidy based on cfDNA screening in multifetal pregnancy (pg. 8, fourth paragraph).
Regarding instant claim 21, Dyr teaches adjustment of fetal fraction requirements for multiples in proportion to fetal number (pg. 3, second paragraph) and McCullough teaches providing, by the computing system, an interpretation of the positive screening results from the NIPT as a negative result or the absence of the one or more aneuploidies when no classification is provided and the mosaicism ratio is less than the minimum threshold (pg. 5, second paragraph).
Regarding instant claim 22, Dyr teaches adjustment of fetal fraction requirements for multiples in proportion to fetal number (pg. 3, second paragraph) and McCullough teaches providing, by the computing system, an interpretation of the positive screening results from the NIPT as supernumery or inconclusive when no classification is provided and the mosaicism ratio is greater than the maximum threshold (pg. 5, second paragraph).
Regarding instant claim 23, Dyr teaches adjustment of fetal fraction requirements for multiples in proportion to fetal number (pg. 3, second paragraph) and McCullough teaches providing, by the computing system, an interpretation of the positive screening results from the NIPT as positive when the absence of the genetic mosaicism is classified for the copy number variation region (pg. 5, second paragraph).
Regarding instant claim 24, Dyr teaches adjustment of fetal fraction requirements for multiples in proportion to fetal number (pg. 3, second paragraph) and McCullough teaches providing, by the computing system, an interpretation of the positive screening results from the NIPT as positive when the absence of the genetic mosaicism is classified for the copy number variation region (pg. 5, lines 24-26).
Regarding instant claim 25, Dyr teaches the method steps but does not explicitly teach a computer system. Computer-implemented functional claim limitations may also be broad because the term "computer" is commonly understood by one of ordinary skill in the art to describe a variety of devices with varying degrees of complexity and capabilities. Broadly claiming an automated means to replace a manual function to accomplish the same result does not distinguish over the prior art. That is, it would be obvious to automate the steps of claim 1 using a system as recited in claim 25. MPEP 2114(III) pertains.
Regarding instant claim 26, Dyr teaches the method steps but does not explicitly teach a computer-readable memory. Computer-implemented functional claim limitations may also be broad because the term "computer" is commonly understood by one of ordinary skill in the art to describe a variety of devices with varying degrees of complexity and capabilities. Broadly claiming an automated means to replace a manual function to accomplish the same result does not distinguish over the prior art. That is, it would be obvious to automate the steps of claim 1 using a system as recited in claim 25. MPEP 2114(III) pertains.
An invention would have been obvious to one of ordinary skill in the art if some motivation in the prior art would have led that person to modify prior art reference teachings to arrive at the claimed invention prior to the effective filing date of the invention. One would have been motivated to combine the work of the reference application, McCullough, which is directed to assessment of genetic mosaicism, and Dyr, because each are directed to genetic mosaicism in multiple pregnancies. Dyr teaches adjusting fetal fraction requirements (pg. 3, second paragraph) and McCullough teaches a benefit of the recited thresholds because interpretation of positive NIPT results is challenging due to differences in placenta and fetus (pg. 11, second paragraph) and modification of interpretation for multiple pregnancies (pg. 103, second paragraph). Dyr and McCullough are both directed to the shared field of endeavor of genetic mosaicism and thus their combination would be expected to succeed, and the invention is prima facie obvious.
Conclusion
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/R.J.K./Examiner, Art Unit 1685
/JANNA NICOLE SCHULTZHAUS/Examiner, Art Unit 1685