DETAILED ACTION
The Applicant’s filing, received 15 May 2023, has been fully considered. The following rejections and/or objections constitute the complete set presently being applied to the instant application.
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
The preliminary amendment received 21 September 2023 has been entered.
Claims 1-55 have been cancelled.
New claims 1-20 have been have been renumbered as claims 56-75, respectively, in accordance with 37 C.F.R. 1.126, as noted below in the Claim Objections section.
Claims 56-75 are pending.
Claims 56-75 are rejected.
Priority
This application is a CON of 16/479,864, filed 22 July 2019 (PAT 11,694,768)
which is a 371 of PCT/US18/15081, filed 24 January 2018
which claims benefit of 62/449,766, filed 24 January 2017.
Therefore, the effective filing date of the claimed invention is 24 January 2017.
Information Disclosure Statement
The information disclosure statements (IDS) received 03 October 2023, 11 September 2024, 01 September 2025, and 01 April 2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner.
Drawings
The drawings received 15 May 2023 are accepted in part, as noted below.
Sheets 1/6 (Fig. 1), 2/6 (Fig. 2), 3/6, (Fig. 3), 4/6 (Fig. 4), and 6/6 (Fig. 6) have been accepted. Sheet 5/6 (Figs. 5A-5D) has not been accepted.
The replacement drawing (Sheet 5/6 (Figs. 5A-5D)) received 30 September 2023 has been accepted.
Claim Objections
The numbering of claims is not in accordance with 37 CFR 1.126 which requires the original numbering of the claims to be preserved throughout the prosecution. When claims are canceled, the remaining claims must not be renumbered. When new claims are presented, they must be numbered consecutively beginning with the number next following the highest numbered claims previously presented (whether entered or not).
Misnumbered claim 1 has been renumbered claim 56;
Misnumbered claim 2 has been renumbered claim 57;
Misnumbered claim 3 has been renumbered claim 58;
Misnumbered claim 4 has been renumbered claim 59;
Misnumbered claim 5 has been renumbered claim 60;
Misnumbered claim 6 has been renumbered claim 61;
Misnumbered claim 7 has been renumbered claim 62;
Misnumbered claim 8 has been renumbered claim 63;
Misnumbered claim 9 has been renumbered claim 64;
Misnumbered claim 10 has been renumbered claim 65;
Misnumbered claim 11 has been renumbered claim 66;
Misnumbered claim 12 has been renumbered claim 67;
Misnumbered claim 13 has been renumbered claim 68;
Misnumbered claim 14 has been renumbered claim 69;
Misnumbered claim 15 has been renumbered claim 70;
Misnumbered claim 16 has been renumbered claim 71;
Misnumbered claim 17 has been renumbered claim 72;
Misnumbered claim 18 has been renumbered claim 73;
Misnumbered claim 19 has been renumbered claim 74; and
Misnumbered claim 20 has been renumbered claim 75.
Claim Rejections - 35 USC § 112
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 63-75 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.
Regarding claim 63, the recitation of “A system comprising: one or more data processors; and a non-transitory computer readable storage medium containing instructions which, when executed on the one or more data processors, cause the one or more data processors to perform: obtaining nucleic acid from a biological sample… sequencing the nucleic acid from the biological sample or derivatives thereof to obtain thousands to millions of sequence reads” is unclear and confusing because it is not clear if the “one or more data processors” are actually physically performing the steps of obtaining nucleic acid (i.e., molecules) from a biological sample and then actually performing the physical step of sequencing the nucleic acid molecules, or alternatively how the “one or more data processors” are receiving data of nucleic acid sequence reads. Thus, there are alternative interpretations and it is unclear which interpretation should be applied to the instant claims.
More clearly providing what the processor performs consistent with a processor function or additional elements of a system controlled by the processor would address the basis of the rejection.
Claims 64-69 are rejected for depending from claim 63 and for failing to remedy the aforementioned clarity issue of claim 63.
Regarding claim 66, the recitation of “wherein the one or more data processors is further configured to perform: capturing a set of fragments in the nucleic acid from the biological sample using a hybridization-based technique; ligating an adapter oligonucleotide to each fragment, wherein each adapter oligonucleotide comprises a unique barcode polynucleotide; and enriching the set of ligated fragments to obtain a library of nucleic acid, wherein the library of nucleic acid is the derivatives of the nucleic acid from the biological sample” is unclear and confusing because it is not clear if the “one or more data processors” are only receiving data of nucleic acid fragments, or alternatively, if the “one or more data processors” are actually performing the physical steps of capturing, ligating, and enriching nucleic acid fragments. Thus, there are alternative interpretations and it is unclear which interpretation should be applied to the instant claims.
More clearly providing what the processor performs consistent with a processor function or additional elements of a system controlled by the processor would address the basis of the rejection.
Claims 67-69 are rejected for depending from claim 66 and for failing to remedy the aforementioned clarity issue of claim 66.
Regarding claim 70, the recitation of “A non-transitory computer readable storage medium storing instructions that, when executed by one or more processors of a computing system, cause the computing system to perform: obtaining nucleic acid from a biological sample… sequencing the nucleic acid from the biological sample or derivatives thereof to obtain thousands to millions of sequence reads” is unclear and confusing because it is not clear if the “one or more data processors of a computing system” are only receiving data of nucleic acid sequence reads, or alternatively if the “one or more data processors of a computing system” are actually physically performing the steps of obtaining nucleic acid (i.e., molecules) from a biological sample and then actually performing the physical step of sequencing the nucleic acid molecules. Thus, there are alternative interpretations and it is unclear which interpretation should be applied to the instant claims.
More clearly providing what the computing system performs consistent with a processor function or additional elements of a system controlled by the processor would address the basis of the rejection.
Claims 71-75 are rejected for depending from claim 70 and for failing to remedy the aforementioned clarity issue of claim 70.
Regarding claim 72, the recitation of the “non-transitory computer readable storage medium of Claim 70, wherein the instructions are further configured to perform: capturing a set of fragments in the nucleic acid from the biological sample using a hybridization-based technique; ligating an adapter oligonucleotide to each fragment, wherein each adapter oligonucleotide comprises a unique barcode polynucleotide; and enriching the set of ligated fragments to obtain a library of nucleic acid, wherein the library of nucleic acid is the derivatives of the nucleic acid from the biological sample” is unclear and confusing because it is not clear if the instructions are causing the “one or more data processors of a computing system” to only receive data of nucleic acid fragments, or alternatively if the instructions are causing the “one or more data processors of a computing system” to actually perform the physical steps of capturing, ligating, and enriching nucleic acid fragments.
Claims 73-75 are rejected for depending from claim 72 and for failing to remedy the aforementioned clarity issue of claim 72.
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 56-75 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: Step 1 of the eligibility analysis asks: Is the claim to a process, machine, manufacture or composition of matter?
Claims 56-62 recite a computer-implemented method (i.e., a process); claims 63-69 recite a system comprising one or more data processors and a non-transitory computer readable storage medium (i.e., a machine or a manufacture); and claims 70-75 recite a non-transitory computer readable medium (i.e., a machine or a manufacture).
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 or described in the claim.
Independent claims 56, 63, and 70 recite the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
determining a presence or absence of a copy number variation based on an analysis of the thousands to millions of sequence reads, wherein the analysis comprises determining a plurality of sequence read quantifications corresponding to a plurality of segments (i.e., mental processes and mathematical concepts, e.g., comparing the read counts within sliding windows between the sample reads and a region of a reference genome, and then tallying the reads that are aligned at particular regions).
Dependent claims 60-62, 67-69, and 73-75 further recite the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas, as noted below.
Dependent claims 60, 67, and 73 further recite:
data-mining disease databases to determine a set of genomic regions (i.e., mental processes and mathematical concepts, e.g., using machine learning, statistics, and artificial intelligence to extract actionable insights that go beyond simple database queries);
aligning the thousands to millions of sequence reads to the set of genomic regions of a reference genome (i.e., mental processes, e.g., matching sequence reads to a reference sequence); and
retaining sequence reads aligned to a subset of the set of genomic regions by filtering out one or more portions of the set of genomic regions based on a predetermined criterion (i.e., mental processes, e.g., selecting a specific subset of data from a larger dataset by applying predefined rules or conditions).
Dependent claims 61, 68, and 74 further recite:
eliminating non-uniquely mapped sequence reads from the analysis (i.e., mental processes, e.g., selecting a specific subset of data from a larger dataset by applying predefined rules or conditions).
Dependent claims 62, 69, and 75 further recite:
determining the presence or absence of the copy number variation in a fetal fraction of the biological sample according to a set of consensus sequences generated from the sequence reads using the unique barcode polynucleotides (i.e., mental processes, e.g., evaluating the reads at each position of the alignment to find the most common bases (or bases) to determine a consensus sequence, and then comparing the read counts within sliding windows between the sample reads and a region of a reference genome, and then tallying the reads that are aligned at particular regions).
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 pen and paper (e.g., determining a presence or absence of a copy number variation based on an analysis of the thousands to millions of sequence reads), 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 (e.g., determining a plurality of sequence read quantifications corresponding to a plurality of segments which is simply counting the number of reads that map to a ‘segment’) are abstract ideas irrespective of whether or not the limitations are practical to perform in the human mind.
Therefore, claims 56-75 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)).
In this case, the claims provide additional elements to obtain ‘sequence reads’, but once the data is obtained nothing but analysis is performed using the data. There are no limitations recited by the claims to which the determination of copy number is applied in the present claims.
The judicial exceptions identified in Eligibility Step 2A Prong One are not integrated into a practical application because of the reasons noted below.
Dependent claims 60-62, 67-69, and 73-75 do not recite any elements in addition to the judicial exception, and thus are part of the judicial exception.
The additional elements in independent claim 56 include:
a computer;
and steps for obtaining nucleic acid from a biological sample that was obtained from a subject; and
sequencing the nucleic acid from the biological sample or derivatives thereof to obtain thousands to millions of sequence reads.
The additional elements in independent claim 63 include:
one or more data processors;
a non-transitory computer readable storage medium;
obtaining nucleic acid from a biological sample that was obtained from a subject; and
sequencing the nucleic acid from the biological sample or derivatives thereof to obtain thousands to millions of sequence reads.
The additional elements in independent claim 70 include:
a non-transitory computer readable storage medium;
one or more processors of a computing system;
obtaining nucleic acid from a biological sample that was obtained from a subject; and
sequencing the nucleic acid from the biological sample or derivatives thereof to obtain thousands to millions of sequence reads.
The additional elements in dependent claims 57, 64, and 71 include:
the biological sample is a liquid sample, and the nucleic acid is cell-free nucleic acid.
The additional elements in dependent claims 58 and 65 include:
the biological sample comprises a majority nucleic acid species and a minority nucleic acid species.
The additional elements in dependent claims 59, 66, and 72 include:
capturing a set of fragments in the nucleic acid from the biological sample using a hybridization-based technique;
ligating an adapter oligonucleotide to each fragment, wherein each adapter oligonucleotide comprises a unique barcode polynucleotide; and
enriching the set of ligated fragments to obtain a library of nucleic acid, wherein the library of nucleic acid is the derivatives of the nucleic acid from the biological sample.
The additional elements of a computer (claim 56); one or more data processors (claim 63); one or more processors of a computing system (claim 70); and a non-transitory computer readable storage medium (claims 63 and 70); invoke a computer and/or computer-related components merely as tools for use in the claimed process, such that they amount to no more than mere instructions to apply the exceptions using a generic computer (MPEP 2106.05(f)), and therefore are not an improvement to computer functionality itself, or an improvement to any other technology or technical field, and thus, do not integrate the judicial exceptions into a practical application (MPEP 2106.04(d)(1)).
The additional elements of obtaining nucleic acid from a biological sample that was obtained from a subject (claims 56, 63, and 70); the biological sample is a liquid sample, and the nucleic acid is cell-free nucleic acid (claims 57, 64, and 71); and the biological sample comprises a majority nucleic acid species and a minority nucleic acid species (claims 58 and 65); are merely part of the pre-solution activity of gathering data for use in the claimed process – a nominal or tangential addition to the claims that does not meaningfully limit the claims, and therefore does not add more than insignificant extra-solution activity to the judicial exceptions (MPEP 2106.05(g)).
The additional element of sequencing the nucleic acid from the biological sample or derivatives thereof to obtain thousands to millions of sequence reads (claims 56, 63, and 70); is merely part of the pre-solution activity of gathering data for use in the claimed process – a nominal or tangential addition to the claims that does not meaningfully limit the claims, and therefore does not add more than insignificant extra-solution activity to the judicial exceptions (MPEP 2106.05(g)).
The additional elements of capturing a set of fragments in the nucleic acid from the biological sample using a hybridization-based technique (claims 59, 66, and 72); ligating an adapter oligonucleotide to each fragment, wherein each adapter oligonucleotide comprises a unique barcode polynucleotide (claims 59, 66, and 72); and enriching the set of ligated fragments to obtain a library of nucleic acid, wherein the library of nucleic acid is the derivatives of the nucleic acid from the biological sample (claims 59, 66, and 72); are merely part of the pre-solution activity of gathering data for use in the claimed process – a nominal or tangential addition to the claims that does not meaningfully limit the claims, and therefore does not add more than insignificant extra-solution activity to the judicial exceptions (MPEP 2106.05(g)).
Thus, the additionally recited elements merely invoke a computer and/or computer related components as tools; and/or amount to insignificant extra-solution activity; and as such, when all limitations in claims 56-75 have been considered as a whole (i.e., the analysis takes into consideration all the claim limitations and how those limitations interact and impact each other when evaluating whether the exception is integrated into a practical application), the claims are deemed to not recite any additional elements that would integrate a judicial exception into a practical application, and therefore claims 56-75 are directed to an abstract idea (MPEP 2106.04(d)).
[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.
Dependent claims 60-62, 67-69, and 73-75 do not recite any elements in addition to the judicial exception(s).
The additional elements recited in independent claims 56, 63, and 70 and dependent claims 57-59, 64-66, 71, and 72 are identified above, and carried over from Step 2A Prong Two along with their conclusions for analysis at Step 2B. Any additional element or combination of elements that was considered to be insignificant extra-solution activity at Step 2A Prong Two was re-evaluated at Step 2B, because if such re-evaluation finds that the element is unconventional or otherwise more than what is well-understood, routine, conventional activity in the field, this finding may indicate that the additional element is no longer considered to be insignificant; and all additional elements and combination of elements were evaluated to determine whether any additional elements or combination of elements are other than what is well-understood, routine, conventional activity in the field, or simply append well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, per MPEP 2106.05(d).
The additional elements of a computer (claim 56); one or more data processors (claim 63); one or more processors of a computing system (claim 70); and a non-transitory computer readable storage medium (claims 63 and 70); are conventional computer components and/or functions (see MPEP at 2106.05(b) and 2106.05(d)(II) regarding conventionality of computer components and computer processes).
The additional elements of obtaining nucleic acid from a biological sample that was obtained from a subject (claims 56, 63, and 70); the biological sample is a liquid sample, and the nucleic acid is cell-free nucleic acid (claims 57, 64, and 71); and the biological sample comprises a majority nucleic acid species and a minority nucleic acid species (claims 58 and 65); are conventional. Evidence of conventionality is shown by:
Volik et al. (“Cell-free DNA (cfDNA): Clinical Significance and Utility in Cancer Shaped by Emerging Technologies.” Molecular Cancer Research, 2016, vol. 14(10), pp. 898-908).
Volik et al. reviews the clinical significance and utility of cell-free DNA (cfDNA) in cancer shaped by emerging technologies (Title; and Abstract); and in particular, reviews the collection and processing of blood for cfDNA (page 900, col. 2, paras. 2-3 through page 901, col. 1, para. 1); and further shows the chimeric nature of cfDNA, i.e., the presence of both normal and tumor DNA in blood plasma (page 899, col. 1, para. 1).
The additional element of sequencing the nucleic acid from the biological sample or derivatives thereof to obtain thousands to millions of sequence reads (claims 56, 63, and 70); is conventional. Evidence of conventionality is shown by:
Volik et al. (as cited above).
Volik et al. further reviews using massively parallel sequencing for analyzing cfDNA (page 903, col. 1, para. 2).
The additional elements of capturing a set of fragments in the nucleic acid from the biological sample using a hybridization-based technique (claims 59, 66, and 72); ligating an adapter oligonucleotide to each fragment, wherein each adapter oligonucleotide comprises a unique barcode polynucleotide (claims 59, 66, and 72); and enriching the set of ligated fragments to obtain a library of nucleic acid, wherein the library of nucleic acid is the derivatives of the nucleic acid from the biological sample (claims 59, 66, and 72); are conventional. Evidence of conventionality is shown by:
Volik et al. (as cited above).
Volik et al. further reviews methods for using next-generation sequencing (NGS) in cfDNA quantification, and shows that the methods can be broadly divided into two groups: 1) the first group relies on the amplification of the target regions using region-specific primers (often highly multiplexed), while the second group relies upon hybridization-based capture of target regions using complementary oligonucleotides with subsequent amplification of the captured DNA (library); and that both strategies are followed by highly redundant (“deep”) sequencing to allow the relative amount of mutant and wild-type DNA molecules at each locus to be accurately counted (page 903, col. 1, para. 2).
Therefore, when taken alone (i.e., individually), all additional elements in claims 56-75 do not amount to significantly more than the above-identified judicial exception(s). Even when evaluated as an ordered combination, the additional elements fail to transform the exception(s) into a patent-eligible application of that exception. Thus, claims 56-75 are deemed to not contribute an inventive concept, i.e., amount to significantly more than the judicial exception(s) (MPEP 2106.05(II)).
[Step 2B: NO]
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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 56-75 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Zhao et al. (“Methods and processes for non-invasive assessment of genetic variations.” US 2016/0224724, as cited in the Information Disclosure Statement received 03 October 2023).
Independent claims 56, 63, and 70, encompass method steps for determining a presence or absence of a copy number variation of a segment using data generated by sequencing a subject’s nucleic acid.
Dependent claims 57-62, 64-69, and 71-75 further define the physical processing of the biological sample (e.g., claims 57-59, 64-66, and 71-72) and further define the data analysis process (e.g., claims 60-62, 67-69, and 73-75).
Zhao et al. teaches methods, processes, and apparatuses for non-invasive assessment of genetic variation that make use of decision analyses that assess copy number relative to a reference genome segment.
Regarding independent claims 56, 63, and 70, Zhao et al. shows a system comprising one or more processors and memory (para. [0009]); acquisition of blood samples (para. [0060]); extraction of DNA (para. [0065]); nucleic acids are sequenced (para. [0140]); and determining a copy number variation (e.g., paras. [0145] and [0330]) which shows quantitating differences in expected read numbers in regions and correlating it to copy number variation.
Regarding dependent claims 57, 64, and 71, Zhao et al. shows that in some embodiments nucleic acid sequences are obtained from a sample obtained from a pregnant female (e.g., from the blood of a pregnant female) (para. [0050]).
Regarding dependent claims 58 and 65, Zhao et al. shows that a mixture of nucleic acids can comprise two or more nucleic acid fragment species having different nucleotide sequences, different fragment lengths, different origins (e.g., genomic origins, fetal vs. maternal origins, cell or tissue origins, sample origins, subject origins, and the like), or combinations thereof (para. [0052]).
Regarding dependent claims 59, 66, and 72, Zhao et al. shows a selective nucleic acid capture process is used to separate target and/or reference fragments away from the nucleic acid sample, and such methods typically involve hybridization of a capture oligonucleotide to a segment or all of the nucleotide sequence of a target or reference fragment (para. [0123]); nucleic acid library preparation comprises ligating an adapter oligonucleotide that may comprise an identifier (para. [0134]) wherein an identifier (e.g., a nucleic acid index or barcode) is a unique, known and/or identifiable sequence of nucleotides or nucleotide analogues (para. [0135]); and nucleic acid is enriched for certain target fragment species and/or reference fragment species (para. [0113]).
Regarding dependent claims 60, 67, and 73, Zhao et al. shows that sequence reads can be aligned with sequences in a reference genome, and further shows that sequence reads can be found and/or aligned with sequences in nucleic acid databases known in the art including, e.g., GenBank, dbEST, dbSTS, EMBL and DDBJ, and further shows that BLAST or a similar tool can be used to search the identified sequences against a sequence database, and then search hits can then be used to sort the identified sequences into appropriate portions (para. [0163]); and further shows that portions can be removed from consideration by a filtering process that removes certain portions and retains portions (e.g., a subset of portions) (para. [0242]).
Regarding dependent claims 61, 68, and 74, Zhao et al. shows that a read may uniquely or non-uniquely map to portions in a reference genome, and further shows that non-uniquely mapped reads can be eliminated from further analysis (e.g., quantification) (para. [0167]).
Regarding dependent claims 62, 69, and 75, Zhao et al. does not explicitly recite the term “consensus sequences” (i.e., one of skill in the art would understand a consensus sequence to be an idealized genetic sequence that represents the most common nucleotides or amino acids found at each position across multiple aligned, related sequences), however, Zhao et al. shows that mappability is assessed for a genomic region (e.g., portion, genomic portion) and that mappability is the ability to unambiguously align a nucleotide sequence read to a portion of a reference genome, typically up to a specified number of mismatches, including, for example, 0, 1, 2, or more mismatches, and that for a given genomic region, the expected mappability can be estimated using a sliding-window approach of a preset read length and averaging the resulting read-level mappability values, and genomic regions comprising stretches of unique nucleotide sequence sometimes have a high mappability value (para. [0170]).
Thus, Zhao et al. anticipates instant claims 56-75.
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 56-75 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,694,768 (Application No. 16/479,864). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-20 of the ‘768 patent anticipate instant claims 56-75.
Regarding independent claims 56, 63, and 70 of the instant application, independent claims 1, 8, and 15 of the ‘768 patent would be anticipatory of instant claims 56, 63, and 70 because the limitations at steps (d) and (e) recited by the ‘768 patent are species of the instant claim limitation reciting “determining a presence or absence of a copy number variation based on an analysis of the thousands to millions of sequence reads, wherein the analysis comprises determining a plurality of sequence read quantifications corresponding to a plurality of segments.”
Regarding dependent claims 57-62, 64-69, and 71-75 of the instant application, dependent claims 2-7, 9-14, and 16-20 of the ‘768 patent would be anticipatory of instant claims 57-62, 64-69, and 71-75 because the steps recited in the dependent claims of the ‘768 patent further define limitations that recite using predetermined sub-regions that are identified using one or more accuracy measures, and further define the types and locations of the copy number variation, and further define the cell-free DNA nucleic acid, which are all limitations that are species of the instant independent claims.
Conclusion
No claims are allowed.
This Office action is a Non-Final action. A shortened statutory period for reply to this action is set to expire THREE MONTHS from the mailing date of this application.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEVEN W. BAILEY whose telephone number is (571)272-8170. The examiner can normally be reached Mon - Fri. 1000 - 1800.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, KARLHEINZ SKOWRONEK can be reached at (571) 272-9047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/STEVEN W. BAILEY/Examiner, Art Unit 1687
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