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 .
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-12, 15-16, and 19) in the reply filed on December 15, 2025 is acknowledged.
Claims 44-46 and 49-50 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on December 15, 2025.
Claims 1-12, 15-16, and 19 are under examination.
Information Disclosure Statement
The Information Disclosure Statements filed August 3, 2023 and November 27, 2023 have been considered.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," 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 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) 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") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) 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 of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
The Sequence Listing Incorporation by Reference paragraph lists the size of the ASCII text file as 5,002 bytes, whereas the ASCII text file itself lists the size as 5,954 bytes.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code at page 36, line 19; page 37, line 14; and page 38, line 19. 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 use of the terms MISEQ® at page 31, line 26; page 33, line 24; and Table 1, ISEQ® at page 32, line 17 and Table 1, NEXTSEQ® at page 33, line 25; page 34, lines 8 and 9 and Table 1, TAPESTATION® at page 33, lines 12 and 20, TWEEN® at page 33, line 17, and BIODEFENCE® at page 34, line 27, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claim 1 is objected to because of the following informalities:
At claim 1, line 3, “For” should be changed to “for.”
Appropriate correction is required.
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 9-11 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.
Claim 9 recites the limitation "the pooled sample" in line 40. There is insufficient antecedent basis for this limitation in the claim. It is not clear if the pooled sample of claim 9 is the same as the pooled sample of claim 1, since there are additional targets, adapters, and reaction mixtures.
Claims 10-11 depend from claim 9, and are therefore included in this rejection.
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 1-12, 15-16, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Apte et al. (U.S. Patent Application No. 2020/0123539, published April 23, 2020, and cited in the Information Disclosure Statement filed August 3, 2023) in view of Vermaas et al. (U.S. Patent Application Publication No. 2018/0305752, published October 25, 2018, and cited in the Information Disclosure Statement filed August 3, 2023).
Regarding claim 1, Apte teaches a method of detecting in vitro the presence or absence of a first target in a sample (abstract, Embodiments of a method 100 and/or system 200 or library preparation for next generation sequencing associated with microorganisms). Apte discloses preparing a set of unique molecular identifier (UMI)-based molecules associated with one or more targets, the first target being a single strand of nucleic acid (paragraph [0037). Apte discloses that targets can include single and double stranded DNA, the method comprising, for two or more samples the method can be implemented for one or more biological samples from a single user or for biological samples from a set of users (paragraph [0030]). Apte discloses admixing with each sample a first reaction mixture comprising a first adapter and a second adapter, the first adapter comprising from 5' to 3' a first primer binding region, a first sample identifying region (SIR), and a first target primer (paragraph [0018) and Figures 1 and 4). embodiments of a method for library preparation for sequencing associated with microorganisms can include preparing a set of unique molecular identifiers (UMI)-based molecules associated with one or more targets (paragraph [0044) and Figure 5). Apte discloses UMI-based molecules, such as UMI-based primers can include a configuration including 5'-external adapter-unique molecular identifier-linker-target DNA sequence-3’ (Figure 5, which shows amplification-generation primers as 5'-Adapter A1-target DNA sequence-forward-3' and (5'-adapter A2-target DNA sequence-forward-3'). Apte discloses that each first SIR comprising a sequence that identifies each sample (paragraph [0038]). Apte discloses that UMI-based molecules are preferably associated with a target-associated region including one or more sequence regions complementary to one or more sequence regions of the one or more nucleic acid targets, with the second adapter comprising from 5' to 3' a second primer binding region and a second target primer (paragraph [0018]). Apte disclose preparing a set of sequencing-based primers (paragraph [0044]). Apte discloses UMI-based molecules, which can be primers and can include a configuration including 5'-external adapter-unique molecular identifiers-linker-target DNA sequence-3’ (Figure 5, which shows amplification-generation primers as 5'-adapter A1-target DNA sequence-forward-3' and 5'-adapter A2-target DNA sequence-forward-3'). Apte discloses the admixing being under conditions when the first target is present in the sample (paragraph [0019]). Apte discloses generating a set of tagged target molecules based on a first amplification process, such as a polymerase chain reaction (PCR) process, with the set of UMI-based primers and at least one biological sample associated with the set of nucleic acid targets and generating a set of NGS-ready tagged target molecules based on a second amplification process (e.g., a second PCR process) with the tagged target molecules and the set of sequencing-based primers (paragraph [00201 and Figure 5). Apte discloses that one of the first adapter or the second adapter anneals to the first target, thereby obtaining a first target-bound adapter, which generates a set of tagged target molecules based on the set of UMI-based molecules and the one or more biological samples (paragraphs [0018] and [00201] and Figures 4-5). Apte discloses preparing a combined sequencing library, which can include generating a set of target-associated amplicons based on an amplification process (a first PCR process) with a set of amplicon-generation primers, such as the UMI-based primers and a set of targets from at least one biological sample associated with the microorganisms (paragraph [0018]). Apte discloses that the first target-bound adapter is elongated to obtain a first single-stranded product comprising the first target and the first primer binding region and first SIR or the second primer binding region (paragraph [0018] and Figure 4). Apte discloses generating a set of tagged target molecules based on the set of UMI-based molecules and one or more biological samples; the other of the first adapter or the second adapter anneals to the first single-stranded product and the other of the first target primer or the second target primer anneals to the first target, thereby obtaining a second target-bound adapter (paragraph [0018] and Figure 4). Apte discloses generating a set of tagged target molecules based on the set of UMI-based molecules and one or more biological samples and that the second target-bound adapter is elongated, to obtain a second single stranded product comprising the first primer binding region, the first SIR, the first target, and the second primer binding region (paragraph [0018) and Figure 4). Apte discloses generating a set of tagged target molecules based on the set of UMI-based molecules and one or more biological samples by pooling two or more of the first modified samples to obtain a pooled sample (paragraph [0090]). Apte discloses that generating the sequencing library can include using DNA templates including defined mixes of two bacterial DNA pools, which can be mixed in inverse proportions (Figure 6).
Apte further discloses annealing a first sequencing primer to the first primer binding region of the second primer binding region-bound second single-stranded product generating a set of sequencing-ready tagged target molecules based on the tagged target molecules and the set of sequencing-based primers (paragraph [0018]). Apte discloses sequencing-by-synthesis the first SIR and at least a first sequence within the first target, the first sequence within the first target being proximal to the first SIR, to obtain a plurality of first read signals comprising a plurality of first signals and a plurality of second signals, each of the first signals and each of the second signals having a location, the first signal comprising the signal from sequencing the first SIR, and the second signal comprising the signal from sequencing the at least the first sequence within the first target (paragraph [0010] and FIG. 6). Apte discloses a specific example of a comparison of assigned reads for 16S sequencing libraries assembled with classical sequencing primers or with UMI-based primers including 4N UMI regions (paragraph [0010] and Figure 6).
Regarding claim 3, Apte further comprises annealing the first primer binding region of the second primer binding region-bound single-stranded product to the first single-stranded nucleic acid and elongating the first single-stranded nucleic acid to obtain a first primer binding region-bound second single-stranded product comprising the second single-stranded product wherein the 5' end of the first primer binding region is bound to the substrate; annealing a second sequencing primer to the second primer binding region of the first primer binding region-bound second single-stranded product (Figure 5, sequencing-based primers). Apte discloses sequencing-by-synthesis at least a second sequence within the first target, the second sequence within the first target being proximal to the second primer binding region (paragraph [0010] and Figure 6). Apte discloses a specific example of a comparison of assigned reads for 16S sequencing libraries assembled with classical sequencing primers or with UMI-based primers including 4N UMI regions (Figure 6). Apte discloses that the sequencing-based primers Figure 5) would have provided a third signal to the clusters of the target nucleic acid (Figure 5).
Regarding claim 6, Apte discloses compiling the second sequence within the target and the first sequence within the target to generate the sequence of the first target when present in the sample (paragraph [0020]). Apte discloses generating a set of sequencing-ready target molecules based on the set of target-associated amplicons, the set of metagenome-associated fragments, and a set of sequencing-based primers (Figure 5, sequencing-ready target molecule).
Regarding claim 7, Apte discloses that targets include genes having mutation and can include biomarkers, genes, gene expression markers, sequence regions that identify a gene, chromosome, microorganism-related condition, conserved sequences and mutations (paragraph [0037]).
Regarding claim 12, Apte discloses that the first SIR comprises 15 or more nucleotides and that the UMI regions can include any suitable sequence length (e.g., at least 2 "N" bases; fewer than 21 "N" bases; any suitable number of "N" bases (paragraph [0039]).
Regarding claim 13, Apte discloses that the first SIR comprises 20 or more nucleotides and that the UMI regions can include any suitable sequence length (e.g., at least 2 "N" bases; fewer than 21 "N" bases; any suitable number of "N" bases (paragraph [0039]).
Regarding claim 14, Apte discloses that the target comprises DNA, which can be genomic DNA, chromosomal DNA, extrachromosomal DNA, mitochondrial DNA, plastid DNA, plasmid DNA, cosmid DNA, phagemid DNA, synthetic DNA, cDNA obtained from RNA, and single and double stranded DNA (paragraph [0037]).
Regarding claim 15, Apte discloses that the target can comprise RNA (paragraph [0037]). Apte discloses that the elongating steps comprise reverse transcription and that pre-processing can include, prior to fragmentation, transforming mRNA in total nucleic acids into cDNA by reverse transcriptase PCR (RT-PCR) (paragraph [0084]).
Regarding claim 16, Apte teaches a method of that the target DNA to be detected can be viral RNA (i.e., viruses with RNA based genomes) to detect the presence of and/or other characteristics of viruses (paragraph [0084]).
Apte does not specifically disclose flowing the pooled sample over a flow cell or bridge-amplifying the second single strand product. Apte does not specifically disclose generating a cluster-differentiated-by-SIR library or identifying the presence or absence of the first target in the sample. Apte does not specifically disclose that the presence of the first target in the sample can be identified by the presence of at least one cluster having third, second, and first signals, that the method can be used to identify a second target in the sample, using additional adapters and other sequences, or that the SIRs can be the same. Apte does not specifically disclose identifying the target by the presence of at least one cluster having the sequence of the first target and the first signal for the first SIR identifying said sample. Apte does not specifically disclose that the first target can be sudden acute respiratory syndrome associated coronavirus (SARS-CoV), SARS-CoV-2, or an influenza virus.
Vermaas discloses a method of preparing nucleic acid library for sequencing comprising providing a first library of polynucleotides have a first adapter-target-first adapter sequence comprising flowing the pooled sample over a flow cell comprising a substrate, a first single stranded nucleic acid, and a second single-stranded nucleic acid with the 5' end of each of the first single-stranded nucleic acid and the second single-stranded nucleic acid being bound to the substrate, the first single-stranded nucleic acid being capable of a first annealing to the first primer binding region, and the second single-stranded nucleic acid being capable of a second annealing to the second primer binding region, the flowing under conditions that permit at least one of the first annealing or the second annealing (claim 1 and paragraph [0167]). Vermaas discloses cluster amplification of a template polynucleotide by bridge-amplifying the second single-stranded product to obtain two or more clusters, each cluster comprising a second primer binding region-bound second single stranded product and having a location on the flow cell, the second primer binding region-bound second single-stranded product comprising the second single-stranded product with the 5' end of the second primer binding region is bound to the substrate and each second primer binding region-bound second single-stranded product in each cluster having the same SIR and being from the same sample (paragraph [0168] and Figure 4). Vermaas discloses that the first extension primer comprises a free 3' end, enabling nucleotides to be added to the 3' end using the template polynucleotide to produce a copy template strand attached to the solid surface in the presence of a polymerase (paragraph [0169] and Figure 4, second panel). Vermaas discloses that the second extension primer comprises a free 3' end so nucleotides may be added to the 3' end using the copy template polynucleotide as a template to produce an amplified template strand attached to the solid surface in the presence of a suitable polymerase (Figure 4, fourth panel). Vermaas discloses that additional rounds of amplification may be performed to produce a cluster of copy template strands and amplified template strands (Figure 4).
Regarding claim 2, Vermaas discloses that the first read signals further comprise a plurality of first background signals, each first background signal being from a location on the flow cell not having clusters and distinguishing each of the first background signals from the location of each first signal on the flow cell (paragraph [0134]). Vermaas discloses that this allows for identifying whether the second signal for one cluster is distinguishable from the first background signal (paragraph [0134]). Vermaas discloses that amplification sites in an array can be, but need not be, entirely clonal in particular embodiments or that an individual amplification site can be predominantly populated with amplicons from a first target nucleic acid and can also have a low level of contaminating amplicons from a second target nucleic acid (paragraph [0134]. Vermaas discloses that an array can have one or more amplification sites that have a low level of contaminating amplicons so long as the level of contamination does not have an unacceptable impact on a subsequent use of the array and that levels of contamination that can be acceptable at an individual amplification site for particular applications include, but are not limited to, at most 0.1%, 0.5%, 1%, 5%, 10% or 25% contaminating amplicon G (paragraph [0134]).
Regarding claim 4, Vermaas discloses that the second read signals further comprise a plurality of second background signals, each of the second background signals having a location on the flow cell not having clusters and distinguishing each of the second background signals from the location of each first signal on the flow cell, thereby identifying whether the third signal for one cluster is distinguishable from the second background signal (paragraph [0134]). Vermaas discloses that amplification sites in an array can be, but need not be, entirely clonal in particular embodiments and that, for some applications, an individual amplification site can be predominantly populated with amplicons from a first target nucleic acid and can also have a low level of contaminating amplicons from a second target nucleic acid (paragraph [0134]). Vermaas discloses that an array can have one or more amplification sites that have a low level of contaminating amplicons so long as the level of contamination does not have an unacceptable impact on a subsequent use of the array, which levels of contamination
that can be acceptable at an individual amplification site for particular applications include, but are not limited to, at most 0.1%, 0.5%, 1%, 5%, 10% or 25% contaminating amplicons (paragraph [0134]).
Regarding claims 9-10, Vermaas discloses multiplexing the method using a plurality of samples, which is interpreted as being able to detect and/or identify additional target sequences in the sample using additional adapters, primers, and SIRs having different or the same primer binding regions (paragraph [0041]).
Regarding claim 19, Vermaas discloses that the method can be used to identify targets in from 1000 to 5000 samples (paragraph [0041]). Because the method is used to detect and/or identify sequences in a plurality of samples, it is interpreted that the target is present in at least one sample (paragraph [0041]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have applied the known process of library preparation of Vermaas to the method of Apte because the combination of Vermaas and Apte will provide for distinguishing a target in a sample from other nucleotide sequences, as well as other potential contamination that may be present in a biological sample. One of ordinary skill in the art would have been motivated to do so in order to provide a highly reproducible and accurate in vitro method of determining the presence or absence of a specific target sequence in a biological sample, or a group of biological samples.
Given that two different adapters are present in the amplified target molecules, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have detected the first target by identifying the adapter A1 signal and the adapter A2 signal of Apte and to generate the cluster-differentiated-by-SIR library by identifying the location of each cluster on the flow cell by the location of each first signal on the flow cell according to Vermaas and to distinguishing within the plurality of second signals, each second signal by the location of each first signal on the flow cell, thereby distinguishing the second signal for one cluster from the second signals for all other clusters; and identifying the presence or absence of the first target in the sample, the presence of the first target in the sample being identified by the presence of at least one cluster having the second signal and the first signal for the first SIR identifying the sample. Thus, the combination of Apte and Vermaas is deemed to render claim 1 obvious.
Given that Apte teaches that amplicon-generation primers comprising adapter A1 and adapter A2 and the sequencing-based primers comprising adapter regions, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have identified a target nucleic acid by the signals from adapter A1, adapter A2 and sequencing index, as taught by Apte, and thus determine the presence of the first target in the sample is further identified by the presence of at least one cluster having the third signal, the second signal, and the first signal for the first SIR identifying said sample in the cluster differentiated-by-SIR library, and the absence of the first target in the sample is further identified by the absence of one cluster having the third signal, the second signal, and the first signal for the first SIR identifying said sample in the cluster-differentiated-by-SIR library according to the combination of Vermaas and Apte.
However, given that that Apte discloses adapters A1 and A2, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have applied the signals generated from adapter A1 and A2 to provide for the presence of the first target in the sample being identified by the presence of at least one cluster having the sequence of the first target and the first signal for the first SIR identifying said sample in the cluster-differentiated-by-SIR library, and the absence of the first target in the sample is identified by the absence of one cluster having the sequence of the first target and the first signal for the first SIR identifying said sample in the cluster-differentiated-by-SIR library according to the combination of Vermaas and Apte.
It would also have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the method disclosed and suggested by Apte and Vermaas could be expanded to include additional target sequences to be identified using additional adapters, primers, SIRs and UMI regions. One of ordinary skill in the art would have been motivated to do so in order to be able to determine the presence or absence of multiple target sequences in multiple samples using a variety of the same and/or different detection sequences because this provides for a method that can be implemented quickly, reproducibly, and accurately determine the presence or absence of multiple targets. This, in turn, provides for a method of determining the appropriate treatment (or no treatment) depending on the identification of the multiple target sequences in a multitude of samples.
It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention that the method disclosed and suggested by Apte and Vermaas could detect sudden acute respiratory syndrome associated coronavirus (SARS-CoV), SARS-CoV-2, or an influenza virus because, as disclosed by Apte, the method of detecting viral RNA would have been applied to the method of Apte and Vermaas to detect sudden acute respiratory syndrome associated coronavirus (SARS-CoV), SARS-CoV-2, or an influenza virus.
It would have been obvious to one with ordinary skill in the art before the effective filing date of the claimed invention to use the method disclosed and suggested by Apte and Vermaas to test a plurality of samples up to about 5,000 samples to determine the presence or absence of a single target sequence in the samples. One of ordinary skill in the art would have been motivated to do so in order to determine if a sample obtained from a particular subject has the sequence present or absent. Thus, one of ordinary skill in the art would have been able to determine a treatment, if any, would be useful in treating a subject.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Baer et al. (128(22) Blood 2027 (2016)) discloses the use of unique molecular identifiers (UMIs) to determine the presence of small TP53 mutated clones in leukemia (abstract). While Baer does disclose the use of UMIs, adapters, and the use of PCR to determine mutations, Baer does not disclose detecting a single strand nucleic acid target in a sample or a multitude of samples.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NANCY J LEITH whose telephone number is (313)446-4874. The examiner can normally be reached Monday - Thursday 8:00 AM - 6:30 PM.
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, NEIL HAMMELL can be reached at (571) 270-5919. 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.
NANCY J. LEITH
Primary Examiner
Art Unit 1636
/NANCY J LEITH/Primary Examiner, Art Unit 1636