DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Claim Status
Claims 1-20 are currently pending and examined on the merits.
Claims 1-20 are rejected.
Priority
The instant application is a CON of 16/215,254 filed on 12/10/2018 and claims benefit of 61/709,909 filed on 10/4/2012. At this point in examination, the effective filing date of claims 1-20 is 10/4/2012.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 2/8/2023, 3/28/2023, 11/8/2023, 1/18/2024, 4/4/2024, 4/26/2024, and 12/16/2025 are in compliance with the provisions of 37 CFR 1.97. A signed copy of the corresponding 1449 form has been included with this Office Action.
Specification
There are hyperlinks in the instant specification in pg. 110, para. 3, line 5, pg. 321, para. 2, line 5, and pg. 321, para. 3, line 1. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The specification, submitted 9/21/2022, require correction because several nucleotide and/or amino acid sequences in pg. 328-334, Table 6A, pg. 365-457, Table 9, pg. 462, and Table 13, pg. 470 do not meet the proper disclosure requirements, as detailed below.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.831-1.834 because it does not contain a “Sequence Listing XML” as a separate part of the disclosure. A “Sequence Listing XML” is required because sequence disclosures are located in the specification filed 9/21/2022 in pg. 328-334, Table 6A, pg. 365-457, Table 9, pg. 462, and Table 13, pg. 470.
Required response - Applicant must provide:
• A “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2.; together with
o A statement that indicates the basis for the amendment, with specific references to particular parts of the application as originally filed, as required by 37 CFR 1.835(a)(3);
o A statement that the “Sequence Listing XML” includes no new matter as required by 37 CFR 1.835(a)(4)
AND
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(a)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
o A statement that the substitute specification contains no new matter.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claims recite: (a) mathematical concepts, (e.g., mathematical relationships, formulas or equations, mathematical calculations); and (b) mental processes, i.e., concepts performed in the human mind, (e.g., observation, evaluation, judgement, opinion).
Subject matter eligibility evaluation in accordance with MPEP 2106:
Eligibility Step 1: Claims 1-20 are directed to a system (machine). Therefore, these claims are encompassed by the categories of statutory subject matter, and thus satisfy the subject matter eligibility requirements under Step 1.
[Step 1: YES]
Eligibility Step 2A: First, it is determined in Prong One whether a claim recites a judicial exception, and if so, then it is determined in Prong Two whether the recited judicial exception is integrated into a practical application of that exception.
Eligibility Step 2A, Prong One: In determining whether a claim is directed to a judicial exception, examination is performed that analyzes whether the claim recites a judicial exception, i.e., whether a law of nature, natural phenomenon, or abstract idea is set forth described in the claim.
Claims 1, 7, and 18 recite the following steps which fall within the mental processes and/or mathematical concepts groups of abstract ideas, as noted below.
Independent claim 1 further recites:
(a) from the counts in (1), generate an experimental Y chromosome representation (i.e., mental processes);
(b) determine a fraction of fetal nucleic acid in the test sample according to the experimental Y chromosome representation generated in (a), the median X chromosome representation for the set of pregnant females bearing a female fetus in (2), and the slope and the intercept in (3) (i.e., mental processes, mathematical concepts).
Dependent claim 7 further recites:
wherein the fraction of the fetal nucleic acid is determined according to equation (62):
f
=
2
I
+
S
x
-
y
S
(
x
)
(62)
wherein I is the intercept, S is the slope, (x) is the median X chromosome representation for the set of pregnant females bearing a female fetus and y is the experimental Y chromosome representation generated in (a) (i.e., mental processes, mathematical concepts).
Dependent claim 18 further recites:
wherein the instructions executable by the one or more processors are further configured to determine fetal sex (i.e., mental processes).
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. As noted in the foregoing section, the claims are determined to contain limitations that can practically be performed in the human mind with the aid of a pencil and paper, and therefore recite judicial exceptions from the mental process grouping of abstract ideas. 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. Dependent claims 2-6 and 8-17 recite information further limiting the judicial exceptions indicated above.
Therefore, claims 1, 7, and 18 recite an abstract idea.
[Step 2A, Prong One: YES]
Eligibility 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); MPEP 2106.05(a-h)). 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 judicial exceptions identified in Eligibility Step 2A, Prong One are not integrated into a practical application because of the reasons noted below.
Claim 19 recites a sequencing apparatus configured to generate the sequence reads from the circulating cell-free nucleic acid by a massively parallel sequencing process. The sequencing apparatus is capable of generating sequence reads for further analysis, which is considered a well-understood, routine, and conventional activity. Data gathering steps are extra-solution activity as they collect the data needed to carry out the JE. It does not impose any meaningful limitation on the JE or how the JE is performed (MPEP 2106.04/.05, citing Intellectual Ventures LLC v. Symantee Corp, McRO, TLI communications, OIP
Techs. Inc. v. Amason.com Inc., Electric Power Group LLC v. Alstrom S.A.). Therefore, the claimed additional element does not integrate the abstract ideas into a practical application.
Claim 20 recites wherein the sequencing apparatus is configured to generate the sequence reads from the circulating cell-free nucleic acid by a genome-wide massively parallel sequencing process. The sequencing apparatus is capable of generating sequence reads for further analysis, which is considered a well-understood, routine, and conventional activity. Data gathering steps are extra-solution activity as they collect the data needed to carry out the JE. It does not impose any meaningful limitation on the JE or how the JE is performed (MPEP 2106.04/.05, citing Intellectual Ventures LLC v. Symantee Corp, McRO, TLI communications, OIP
Techs. Inc. v. Amason.com Inc., Electric Power Group LLC v. Alstrom S.A.). Therefore, the claimed additional element does not integrate the abstract ideas into a practical application.
Claim 1 recites the additional non-abstract element (EIA) of a general-purpose computer system or parts thereof:
a system comprising one or more processors and a memory (claim 1).
The EIA do not provide any details of how specific structures of the computer elements are used to implement the JE. The claims require nothing more than a general-purpose computer to perform the functions that constitute the judicial exceptions. The computer elements of the claims do not provide improvements to the functioning of the computer itself (as in DDR Holdings, LLC v. Hotels.com LP); they do not provide improvements to any other technology or technical field (as in Diamond v. Diehr); nor do they utilize a particular machine (as in Eibel Process Co. v. Minn. & Ont. Paper Co.). Hence, these are mere instructions to apply the JE using a computer, and therefore the claim does not recite integrate that JE into a practical application.
Thus, the additionally recited elements merely invoke a computer as a tool, and/or amount to insignificant extra-solution data gathering activity, and as such, when all limitations in claims 1-20 have been considered as a whole, the claims are deemed to not recite any additional elements that would integrate a judicial exception into a practical application. Claims 1 and 19-20 contain additional elements that would not integrate a judicial exception into a practical application and are further probed for inventive concept in Step 2B.
[Step 2A, Prong Two: NO]
Eligibility Step 2B: Because the claims recite an abstract idea, and do not integrate that abstract idea into a practical application, the claims are probed for a specific inventive concept. The judicial exception alone cannot provide that inventive concept or practical application (MPEP 2106.05). Identifying whether the additional elements beyond the abstract idea amount to such an inventive concept requires considering the additional elements individually and in combination to determine if they amount to significantly more than the judicial exception (MPEP 2106.05A i-vi).
The claims do not include any additional elements that are sufficient to amount to significantly more than the judicial exception(s) because of the reasons noted below.
With respect to claim 1: The limitations identified above as non-abstract elements (EIA) related to general-purpose computer systems do not rise to the level of significantly more than the judicial exception. These elements do not improve the functioning of the computer itself, or comprise an improvement to any other technical field (Trading Technologies Int’l v. IBG, TLI Communications). They do not require or set forth a particular machine (Ultramercial v. Hulu, LLC., Alice Corp. Pty. Ltd v. CLS Bank Int’l), they do not affect a transformation of matter, nor do they provide an unconventional step. Simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception are insufficient to provide significantly more (as discussed in Alice Corp., CyberSource v. Retail Decisions, Parker v. Flook, Versata Development Group v. SAP America).
The additional element of a sequencing apparatus configured to generate the sequence reads from the circulating cell-free nucleic acid by a massively parallel sequencing process (claim 19) is conventional. Evidence for conventionality is shown by Lo et al. (Journal of Pathology, 2011, 225(3), 318-323). Lo et al. reviews “the recent advent of massively parallel sequencing has opened up the possibility of analysing plasma nucleic acids at a genome-wide level. Massively parallel DNA sequencing is a recently emerged technology in which single DNA molecules are spatially segregated and then either clonally amplified and sequenced (for the so-called ‘second-generation technology’) or directly sequenced without amplification (for the so-called ‘third-generation technology’). Depending on the platform, typically hundreds of thousands to millions or even billions of sequence reads can be obtained in a single run of the sequencer. Here we review the implications of massively parallel sequencing for developing novel diagnostic applications using circulating nucleic acids and for understanding its biology.” (pg. 318, col. 2, para. 1, lines 1-17). This describes platforms or sequencers capable of generating sequence reads from circulating nucleic acids through massively parallel sequencing, which makes it a conventional element in the art.
The additional element of wherein the sequencing apparatus is configured to generate the sequence reads from the circulating cell-free nucleic acid by a genome-wide massively parallel sequencing process (claim 20) is conventional. Evidence for conventionality is shown by Lo et al. (Journal of Pathology, 2011, 225(3), 318-323). Lo et al. reviews “the recent advent of massively parallel sequencing has opened up the possibility of analysing plasma nucleic acids at a genome-wide level. Massively parallel DNA sequencing is a recently emerged technology in which single DNA molecules are spatially segregated and then either clonally amplified and sequenced (for the so-called ‘second-generation technology’) or directly sequenced without amplification (for the so-called ‘third-generation technology’). Depending on the platform, typically hundreds of thousands to millions or even billions of sequence reads can be obtained in a single run of the sequencer. Here we review the implications of massively parallel sequencing for developing novel diagnostic applications using circulating nucleic acids and for understanding its biology.” (pg. 318, col. 2, para. 1, lines 1-17). This describes platforms or sequencers capable of generating sequence reads from circulating nucleic acids through massively parallel sequencing at a genome-wide level, which makes it a conventional element in the art.
[Step 2B: NO]
Therefore, claims 1-20 are patent ineligible under 35 U.S.C. § 101.
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 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 21, 25-26, 28-30, 32, 34-35, 38, 40-43, 47, and 49 of U.S. Patent No. 13/829,373. Although the claims at issue are not identical, they are not patentably distinct from each other because the instantly claimed invention is made obvious over the claims of U.S. Patent No. 13/829,373.
Regarding claim 1:
Regarding the recited system comprising one or more processors and a memory, claim 43 of ‘373 discloses “wherein: the computer comprises memory, and the experimental Y chromosome representation, the slope, the intercept, and/or the median X chromosome representation are stored in memory”.
Regarding the recited (1) counts of nucleic acid sequence reads mapped to genomic sections of a reference genome, which sequence reads are reads of circulating cell-free nucleic acid for a test sample from a pregnant female, claim 21, step (a) of ‘373 discloses “(a) sequencing a test sample, the test sample comprising circulating cell-free nucleic acid from a pregnant female, thereby generating nucleic acid sequence reads, wherein the sequencing is at about 1-fold genome coverage or less, and obtaining counts of the nucleic acid sequence reads mapped to genomic sections of a reference genome”.
Regarding the recited (2) a median X chromosome representation for a set of pregnant females bearing a female fetus, claim 21, step (c) of ‘373 discloses “a median X chromosome representation for a set of pregnant females bearing a female fetus”.
Regarding the recited (3) a slope and intercept from a linear regression of X chromosome representations and Y chromosome representations determined for a set of pregnant females bearing a male fetus, claim 21, step (c) of ‘373 discloses “a slope and intercept from a linear regression for X chromosome representations and Y chromosome representations determined for a set of pregnant females bearing a male fetus”.
Regarding the recited which memory comprises instructions executable by the one or more processors configured to: (a) from the counts in (1), generate an experimental Y chromosome representation, claim 21, step (b) of ‘373 discloses “(b) from the counts in (a), generating an experimental Y chromosome representation”. Claim 42 of ‘373 further discloses “wherein (b) and/or (c) are performed by a computer”.
Regarding the recited which memory comprises instructions executable by the one or more processors configured to: (b) determine a fraction of fetal nucleic acid in the test sample according to the experimental Y chromosome representation generated in (a), the median X chromosome representation for the set of pregnant females bearing a female fetus in (2), and the slope and the intercept in (3), claim 21, step (c) of ‘373 discloses “(c) determining the fraction of fetal nucleic acid in the test sample according to the experimental Y chromosome representation generated in (b), a median X chromosome representation for a set of pregnant females bearing a female fetus, and a slope and intercept from a linear regression for X chromosome representations and Y chromosome representations determined for a set of pregnant females bearing a male fetus”. Claim 42 of ‘373 further discloses “wherein (b) and/or (c) are performed by a computer”.
Regarding claim 2:
Regarding the recited wherein the median X chromosome representation for the set of pregnant females bearing a female fetus in (2) is the median of X chromosome representations, claim 21, step (c) of ‘373 discloses “the median X chromosome representation for the set of pregnant females bearing a female fetus is the median of X chromosome representations”.
Regarding claim 3:
Regarding the recited wherein at least one of the X chromosome representations is a ratio of (i) counts of sequence reads mapped to the genomic sections of the reference genome in the X chromosome, and (ii) counts of sequence reads mapped to genomic sections of the reference genome in a portion of the chromosomes or all of the chromosomes, claim 21, step (c) of ‘373 discloses “wherein each of the X chromosome representations is a ratio of (i) counts of sequence reads mapped to the genomic sections of the reference genome in the X chromosome, and (ii) counts of sequence reads mapped to genomic sections of the reference genome in a portion of the chromosomes or all of the chromosomes”.
Regarding claim 4:
Regarding the recited wherein at least one of the X chromosome representations for the set of pregnant females bearing a male fetus in (3) is a ratio of (i) counts of sequence reads mapped to the genomic sections of the reference genome in the X chromosome, and (ii) counts of sequence reads mapped to genomic sections of the reference genome in a portion of the chromosomes or all of the chromosomes, claim 21, step (c) of ‘373 discloses “each of the X chromosome representations for the set of pregnant females bearing a male fetus is a ratio of (i) counts of sequence reads mapped to the genomic sections of the reference genome in the X chromosome, and (ii) counts of sequence reads mapped to genomic sections of the reference genome in a portion of the chromosomes or all of the chromosomes”.
Regarding claim 5:
Regarding the recited wherein at least one of the Y chromosome representations for the set of pregnant females bearing a male fetus in (3) is a ratio of (i) counts of sequence reads mapped to the genomic sections of the reference genome in the Y chromosome, and (ii) counts of sequence reads mapped to genomic sections of the reference genome in a portion of the chromosomes or all of the chromosomes, claim 21, step (c) of ‘373 discloses “each of the Y chromosome representations for the set of pregnant females bearing a male fetus is a ratio of (i) counts of sequence reads mapped to the genomic sections of the reference genome in the Y chromosome, and (ii) counts of sequence reads mapped to genomic sections of the reference genome in a portion of the chromosomes or all of the chromosomes”.
Regarding claim 6:
Regarding the recited wherein the experimental Y chromosome representation in (a) is a ratio of (i) counts of sequence reads mapped to the genomic sections of the reference genome in the Y chromosome, and (ii) counts of sequence reads mapped to genomic sections of the reference genome in a portion of the chromosomes or all of the chromosomes for the test sample, claim 21, step (b) of ‘373 discloses “which experimental Y chromosome representation is a ratio of (i) counts of sequence reads mapped to the genomic sections of the reference genome in the Y chromosome, and (ii) counts of sequence reads mapped to genomic sections of the reference genome in a portion of the chromosomes or all of the chromosomes”.
Regarding claim 7:
Regarding the recited wherein the fraction of the fetal nucleic acid is determined according to equation (62):
f
=
2
I
+
S
x
-
y
S
(
x
)
(62)
wherein I is the intercept, S is the slope, (x) is the median X chromosome representation for the set of pregnant females bearing a female fetus and y is the experimental Y chromosome representation generated in (a), claim 25 of ‘373 discloses “wherein the fraction of the fetal nucleic acid is determined according to equation (62):
f
=
2
I
+
S
x
-
y
S
x
(62)
wherein I is the intercept, S is the slope, (x) is the median X chromosome representation for the set of pregnant females bearing a female fetus and y is the experimental Y chromosome representation generated in (b)”.
Regarding claim 8:
Regarding the recited wherein the linear regression in (3) is constrained by a point representing a median chromosome X representation and a median chromosome Y representation for pregnant females bearing a female fetus, claim 26 of ‘373 discloses “wherein the linear regression is constrained linear regression”. Claim 47 of ‘373 further discloses “wherein the regression is constrained by a point representing a median chromosome X representation and a median chromosome Y representation for pregnant females bearing a female fetus”.
Regarding claim 9:
Regarding the recited wherein the counts of sequence reads mapped to genomic sections of the reference genome in a portion of the chromosomes are the counts of sequence reads mapped to genomic sections of the reference genome in autosomes, claim 29 of ‘373 discloses “wherein the counts of sequence reads mapped to genomic sections of the reference genome in a portion of the chromosomes are the counts of sequence reads mapped to genomic sections of the reference genome in autosomes”.
Regarding claim 10:
Regarding the recited wherein the slope is determined according to X chromosome representations for a set of pregnant females bearing a male fetus, Y chromosome representations for the set of pregnant females bearing a male fetus, the median X chromosome representation for the set of pregnant females bearing a female fetus, and a median Y chromosome representation for a set of pregnant females bearing a female fetus, wherein: the median Y chromosome representation is the median of Y chromosome representations, and at least one of the Y chromosome representations is a ratio of (i) counts of sequence reads mapped to the genomic sections of the reference genome in the Y chromosome, and (ii) counts of sequence reads mapped to genomic sections of the reference genome in a portion of the chromosomes or all of the chromosomes, claim 30 of ‘373 discloses “wherein the slope is determined according to X chromosome representations for a set of pregnant females bearing a male fetus, Y chromosome representations for the set of pregnant females bearing a male fetus, the median X chromosome representation for a set of pregnant females bearing a female fetus, and a median Y chromosome representation for a set of pregnant females bearing a female fetus, wherein: the median Y chromosome representation is the median of Y chromosome representations, and each of the Y chromosome representations is a ratio of (i) counts of sequence reads mapped to the genomic sections of the reference genome in the Y chromosome, and (ii) counts of sequence reads mapped to genomic sections of the reference genome in a portion of the chromosomes or all of the chromosomes”.
Regarding claim 11:
Regarding the recited wherein the intercept is determined according to the slope, the median X chromosome representation for the set of pregnant females bearing a female fetus, and a median Y chromosome representation for a set of pregnant females bearing a female fetus, wherein: the median Y chromosome representation is the median of Y chromosome representations, and at least one of the Y chromosome representations is a ratio of (i) counts of sequence reads mapped to the genomic sections of the reference genome in the Y chromosome, and (ii) counts of sequence reads mapped to genomic sections of the reference genome in a portion of the chromosomes or all of the chromosomes, claim 32 of ‘373 discloses “wherein the intercept is determined according to the slope, the median X chromosome representation for a set of pregnant females bearing a female fetus, and a median Y chromosome representation for a set of pregnant females bearing a female fetus, wherein: the median Y chromosome representation is the median of Y chromosome representations, and each of the Y chromosome representations is a ratio of (i) counts of sequence reads mapped to the genomic sections of the reference genome in the Y chromosome, and (ii) counts of sequence reads mapped to genomic sections of the reference genome in a portion of the chromosomes or all of the chromosomes”.
Regarding claim 12:
Regarding the recited wherein each set of pregnant females in (2) and (3) is a set of about 500 or more females, claim 34 of ‘373 discloses “wherein each set of pregnant females in (c) is a set of about 500 or more females”.
Regarding claim 13:
Regarding the recited wherein the counts in (1) are normalized counts, claim 35 of ‘373 discloses “normalizing the counts in (a) according to guanine and cytosine (GC) content, thereby providing GC-normalized counts”.
Regarding claim 14:
Regarding the recited wherein the counts in (1) are guanine and cytosine (GC) normalized counts, claim 35 of ‘373 discloses “normalizing the counts in (a) according to guanine and cytosine (GC) content, thereby providing GC-normalized counts”.
Regarding claim 15:
Regarding the recited wherein the fetal fraction is provided with an accuracy of equal to or greater than 90% and/or a precision equal to or greater than 90%, claim 38 of ‘373 discloses “wherein the fetal fraction is provided with an accuracy of equal to or greater than 90% and/or a precision equal to or greater than 90%”.
Regarding claim 16:
Regarding the recited wherein the test sample is from a pregnant female bearing a male fetus, claim 28 of ‘373 discloses “wherein the test sample is from a pregnant female bearing a male fetus”.
Regarding claim 17:
Regarding the recited wherein the test sample is blood serum or blood plasma, claim 40 of ‘373 discloses “wherein the test sample is blood serum or blood plasma”.
Regarding claim 18:
Regarding the recited wherein the instructions executable by the one or more processors are further configured to determine fetal sex, claim 41 of ‘373 discloses “determining the gender of the fetus”. Claim 42 of ‘373 further discloses “wherein (b) and/or (c) are performed by a computer”.
Regarding claim 19:
Regarding the recited a sequencing apparatus configured to generate the sequence reads from the circulating cell-free nucleic acid by a massively parallel sequencing process, claim 49 of ‘373 discloses “wherein the sequencing comprises a genome-wide massively parallel sequencing process”.
Regarding claim 20:
Regarding the recited wherein the sequencing apparatus is configured to generate the sequence reads from the circulating cell-free nucleic acid by a genome-wide massively parallel sequencing process, claim 49 of ‘373 discloses “wherein the sequencing comprises a genome-wide massively parallel sequencing process”.
Therefore, the invention as recited in claims 1-20 is prima facie obvious over U.S. Patent No 13/829,373. One of ordinary skill in the art would have had a reasonable expectation of success given the lack of novelty. It would have been obvious to use a system for determining a fraction of fetal nucleic acid according to the limitations recited in claims 1-20 of the instant application based on claims 21, 25-26, 28-30, 32, 34-35, 38, 40-43, 47, and 49 of U.S. Patent No 13/829,373.
Conclusion
No claims are allowed.
It is noted that claims 1-20 are free from the prior art as the prior art does not teach nor fairly suggest (3) a slope and intercept from a linear regression of X chromosome representations and Y chromosome representations determined for a set of pregnant females bearing a male fetus and (b) determine a fraction of fetal nucleic acid in the test sample according to the experimental Y chromosome representation generated in (a), the median X chromosome representation for the set of pregnant females bearing a female fetus in (2), and the slope and the intercept in (3) in claim 1 for a system comprising instructions for determining fetal fraction. The closest prior art is Fan et al. (Proceedings of the National Academy of Sciences, 2008, 105(42), 16266-16271), as provided in the IDS filed 2/8/2023. Fan et al. discloses determination of fetal fractions of DNA in maternal samples of both male and female pregnancies (pg. 16268, col. 1-2, para. 2-4) and shows that the fetal fraction can be estimated from ratios of chromosome X and chromosome Y sequence tag densities (pg. 16271, col. 1-2, para. 3. However, Fan et al. is silent to the particular methods of determining a slope and intercept according to X chromosome and Y chromosome representations for both pregnant females bearing a male fetus and pregnant females bearing a female fetus, expressed in a linear regression as required by the instant claims.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jammy Luo whose telephone number is (571)272-2358. The examiner can normally be reached Monday - Friday, 9:00 AM - 5:00 PM EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Larry D Riggs can be reached at (571)270-3062. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/J.N.L./Examiner, Art Unit 1686
/LARRY D RIGGS II/Supervisory Patent Examiner, Art Unit 1686
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