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 .
DETAILED ACTION
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office Action has been withdrawn pursuant to 37 CFR 1.114. Applicant’s submission filed on June 16, 2026 has been entered.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Status of Claims
Claims 15, 16, 18, 19, 21-25 and 27-35 are currently pending. Claims 15 and 18 have been amended by Applicants’ amendment filed 06-16-2026. Claim 36 has been canceled by Applicants’ amendment filed 06-16-2026. No claims have been added by Applicants’ amendment filed 06-16-2026.
Applicant's election without traverse of Group II, claims 15-20, directed to a method for sample identification; and the election of Species without traverse as follows:
Species (A): wherein identifying the same origin comprises identifying the presence or absence of the sample indexing sequence (claim 17); and
Species (D): wherein the cell membrane-permeable reagent is internalized into the one or more cells (claim 20), in the reply filed on August 26, 2021 was previously acknowledged.
Claims 1-14 and 21-25 (claims 1-14, now canceled) were previously withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claims 16, 19 and 27-35 were previously withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species, there being no allowable generic or linking claim.
The restriction requirement was deemed proper and was made FINAL.
The claims will be examined insofar as they read on the elected species.
Therefore, claims 16 and 18 are under consideration to which the following grounds of rejection are applicable.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on June 16, 2026 has been considered. An initialed copy of the IDS accompanies this Office Action.
Priority
The present application filed August 26, 2019 claims the benefit of US Provisional Patent Application 62/723,958, filed August 28, 2018.
Withdrawn Objections/Rejections
Applicants’ amendment and arguments filed June 16, 2026 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Any rejection and/or
objection not specifically addressed below are herein withdrawn.
Maintained Objections/Rejections
Claim Rejections - 35 USC § 112(b)
The rejection of claims 15 and 18 are maintained under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claim 15 is indefinite for the recitation of the term “associated with” such as recited in claim 15, lines 6, 7, 13, 33 and 35 because the term “associated with” is relative terms that renders the claim indefinite. The term “associated with” is not defined by the claim, and the Specification does not provide a standard for ascertaining a requisite amount or type of association as compared to some other value that qualifies as an association between a plurality of single cells and an indexing composition and/or a cell membrane-permeable reagent and a sample indexing oligonucleotide (e.g., encapsulated within, directly bound to, downstream of, at the 3’ end of, etc.), such that one of ordinary skill in the art would not be reasonably appraised of the scope of the invention and, thus, the metes and bounds of the claim cannot be determined.
Claim 15 is indefinite for the recitation of the term “adjacent to” such as recited in claim 15, line 29 because the term “adjacent to” is relative terms that renders the claim indefinite. The term “adjacent to” is not defined by the claim, and the Specification does not provide a standard for ascertaining a requisite location as compared to some other value that qualifies as the alignment sequence being adjacent to a poly(dA) region (e.g., hybridized to, downstream of, at the 3’ end of, between the sample index and the poly(dA) region, etc.), such that one of ordinary skill in the art would not be reasonably appraised of the scope of the invention and, thus, the metes and bounds of the claim cannot be determined.
Claims 15 and 18 are indefinite for the recitation of the term “based on sequence information corresponding to a sequence selected from…and a portion thereof” such as recited in claim 15, lines 41-42 because it is unclear where this sequencing information has come from given that instant claim 15 does not recite a step of “sequencing”, obtaining digitally stored information, etc. and, thus, the metes and bounds of the claim cannot be determined.
Claim 15 is indefinite for the recitation of the terms “identifying” and “identifying a presence or absence of sequence information corresponding to a sequence selected from…second sample indexing sequence, and a portion thereof” such as recited in claim 15, lines 47-54 because it is unclear how a cell and/or a cell origin are identified and/or where the “sequencing information” is acquired given that instant claim 15 does not recite a step of “sequencing” the first and/or second sample indexing sequences and, thus, the metes and bounds of the claim cannot be determined.
Claim 15 is indefinite for the recitation of the term “wherein the identifying comprises” such as recited in claim 15, lines 49-50 because claim 15 appears to recite multiple methods of ‘identifying’ such that it is unclear whether claim 15 requires three (3) separate methods to identify the origin of a cell including: (i) identifying a sample origin based on sequence information including selection from sample index sequences (lines 40-45); (ii) identifying whether the at least one single cell of the sorted sample originates from the first sample or the second sample (lines 46-48); and (iii) identifying comprises identifying the presence or absence of sequence information including sample index sequences (lines 49-54), such that it is unclear whether “identifying” comprises a single step; whether “identifying” requires three (3) separate steps; and/or whether “identifying” can be selected from one of the three (3) processes and, thus, the metes and bounds of the claim cannot be determined.
Claim 18 is indefinite for the recitation of the terms “identifying a presence or absence of sequence information…comprises” and “identifying the sample origin” such as recited in claim 18, lines 1-5 and 11-17 because claim 18 depends from instant claim 15, wherein claim 15 already recites what the step of “identifying” comprises, such that dependent claim 18 cannot recite that “identifying” comprises something different (e.g., identifying comprises replicating at least one of the first sample indexing oligonucleotide…) than previously recited in claim 15 and, thus, the metes and bounds of the claim cannot be determined. The Examiner suggests that Applicant amend claim 18 to recite, for example, “identifying further comprises…”.
Claim 18 is indefinite for the recitation of the term “at least one single cell” in claim 18, line 11. There is insufficient antecedent basis for the term “the at least one single cell” in the claim because claim 15, line 40 recites the term “at least one single cell of the sorted sample”, such that it is completely unclear which of the plurality of cells is being referred to in claim 18 and, thus, the metes and bounds of the claim cannot be determined.
Claim Rejections - 35 USC § 103
The rejection of claims 15 and 18 is maintained under 35 U.S.C. 103 as being unpatentable over Fan et al. (hereinafter “Fan”) (US Patent Application Publication 20160289669, published October 6, 2016; of record) in view of Mao et. al. (hereinafter “Mao”) (US Patent No. 9670363, issued June 6, 2017; of record) as evidenced by AAT Bioquest (AAT Bioquest, 2025, 1-10; of record); and Abcam (Abcam, 2014, 1-20; of record).
Regarding claims 15 (in part) and 18, Fan teaches the selection mechanism comprises use of dual-encoded beads wherein each individual bead is both optically-encoded and encoded by an attached oligonucleotide cellular label, and sequencing of the cellular labels attached to beads co-localized with cells of the identified subset of cells generates a list of sequence data to be included or excluded from further analysis (interpreted as indexing oligonucleotides, claim 15) (paragraph [0017]). Fan teaches sequence data analysis steps: (a) decoding or demultiplexing of sample barcode, cell barcode, molecular barcode, and target sequence data; (b) automated clustering of cellular labels to compensate for amplification or sequencing errors, wherein the sequence data is collected for a library of stochastically-labeled target oligonucleotide molecules; (c) alignment of sequence data with known reference sequences; (d) determining the number of reads per gene per cell, and the number of unique transcript molecules per gene per cell; (e) statistical analysis to predict confidence intervals for determinations of the number of transcript molecules per gene per cell; and (f) statistical analysis to cluster cells according to gene expression data or to identify subpopulations of rare cells (interpreting sample barcodes, cell barcodes, molecular barcodes and/or labels to including sample index compositions including indexing oligonucleotides; alignment sequences; and obtaining sequencing data, claims 15 and 18) (paragraph [0018]). Fan teaches that Figure 3A depicts single cells that are trapped in microwells along with beads comprising libraries of tethered stochastic labels (one cell and one bead per well); and that Figure 3B depicts principal component analysis of stochastic barcoding data for human peripheral blood mononuclear cells; and Figure 3C depicts principle component analysis of stochastic barcoding data for a rare cell population (interpreted as a first sample indexing composition and a second sample indexing composition, claim 15) (paragraph [0037]; and Figure 3A-C). Figures 3A and 3C are shown below:
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Fan teaches that a digital gene expression profile for each cell can be reconstructed when the barcoded transcripts are sequenced and assigned to the cell of origin (based on the cellular label identified) and counted (based on the number of unique molecular labels identified) (interpreted as determining cell/sample origin, claim 15) (paragraph [0159], lines 6-11). Fan teaches that the cells can be sorted prior to associating a cell with a bead including sorted by fluorescence-activated cell sorting (FACS), magnetic activated cell sorting, or more generally by flow cytometry (interpreted a sorting single cells including by flow cytometry, claim 15) (paragraph [0173]). Fan teaches loading cells, the concentration of the cell suspension (i.e. the number of cells per mL) is usually adjusted so that the probability of having more than one cell settle into a given microwell is very small; and typically, the concentration of the cell suspension will be adjusted so that the volume of cell suspension used to load, e.g. a microwell array, contains approximately one-tenth the number of cells as the number of wells in the microwell array (interpreted as single cells in a first sample; and single cells in a second sample, claim 15) (paragraph [0174]). Fan teaches that stochastic labels (also referred to as barcodes, tags, or indexes) used for single cell molecular barcoding studies comprise oligo-nucleotides, for example, oligo-deoxyribonucleotides (DNA), oligoribonucleotides (RNA), peptide nucleic acid (PNA) polymers, 2'-O-methyl-substituted RNA, locked nucleic acid (LNA) polymers, bridged nucleic acid (BNA) polymers, and the like (interpreted as sample/cell indexing or barcoding, claim 15) (paragraph [0176]). Fan teaches that stochastic labels can comprise a cellular label, such as a nucleic acid sequence that provides information for determining which target nucleic acid originated from which cell, wherein the cellular label is identical for all oligonucleotides attached to a given bead or solid support, but different for different beads or solid supports (interpreted as single cell indexing; for determining sample origin; and including a first index sequence and a second indexing sequence, claim 15) (paragraph [0182], lines 1-7). Fan teaches a subsection of the full array was cut and used, ranging from ~25,000 to 100,000 wells (Table 1), wherein Table 1 illustrates ~6250 K562 + Ramos cells loaded on an array; ~8000 Primary B + Ramos cells loaded; and an array comprising ~7680 anti-CD3/anti-CD28 negative control cells from Donor 1; ~4800 anti-CD3/anti-CD28 cells from Donor 2, etc. (interpreted as each plurality of single cells is at least 1000 single cells, claim 15) (paragraph [0481]; and Table 1). Fan teaches that the system software can provide integrated real-time image analysis and instrument control, so that cells may be optically monitored and classified according to a pre-determined set of characteristics, and subsequently included or excluded from the downstream sequence data analysis, wherein examples of cellular characteristics that can be optically monitored and used for classification purposes include, but are not limited to, cell size, cell shape, live cell/dead cell determination (e.g. using selectively absorbed chromophores such as Trypan blue, or fluorescent dyes such as calcein AM, ethidium homodimer-1, DiOCi3), DiOC5 (3), DiOCi3), DiSC3 (5), DiIC1(5), DiOC18(3), propidium iodide, SYBR14, SYTOX Green, etc.); cells exhibiting a specified range of intracellular pH (e.g. using intracellular pH-sensitive fluorescent probes such as 2',7'-Bis-(2-carboxyethy-1)-5-( and-6-)carboxy-fluorescein (BCECF), 2', 7'-bis-(2 carboxy-propyl)-5-( and-6-)-carboxy-fluorescein (BCPCF), etc.); cells exhibiting a specified range of membrane potential (e.g. using membrane potential sensitive fluorophores such as FluoVolt, di-3-ANEPPDHQ, Bis-(1, 3-Dibutylbarbituric Acid) Trimethine Oxonol (DiBACi3)), DiBACi5), DiSBACi(3), Merocyanine 540, JC-1, JC-9, Oxonol V, Oxonol VI, Tetramethylrhodamine methyl and ethyl esters, Rhodamine 123, Di-4-ANEPPS, Di-8-ANEPPS, Di-2-ANEPEQ, Di-3-ANEPPDHQ, Di-4-ANEPPDHQ, etc.), cells exhibiting a specified level of intracellular calcium (e.g. using Ca2+-sensitive fluorescent dyes such as fura-2, indo-1, fluo-3, fluo-4, Calcium Green-I, Quin 2, etc.); cells exhibiting one or more specified cell surface markers (e.g. using fluorescently-labeled antibodies directed towards the cell surface markers), cells expressing fluorescent proteins (e.g. GFP, bilirubin-inducible fluorescent protein, UnaG, dsRed, eqFP611, Dronpa, TagRFPs, KFP, EosFP, Dendra, IrisFP, etc.), and the like (interpreted as dye molecules and/or stains including calcein AM, claim 15) (paragraph [0438], lines 1-35), where it is known that when calcein AM permeates the cell membrane, it is converted to calcein, which fluoresces; however, calcein AM does not permeate the cell membrane of dead cells as evidenced by AAT Bioquest (pg. 2, last full paragraph; and pg. 3, Figure 1). Fan teaches that two or more dyes, fluorophores, or other optical probes having (e.g. non-overlapping excitation peaks, non-overlapping absorption non-overlapping spectral properties or emission peaks, etc.) can be selected so that cells can be simultaneously characterized with respect to two or more properties including real-time image processing and analysis is used to identify wells containing cells exhibiting one or more specified characteristics, followed by selection or exclusion of a subset of cells on the array from further analysis and/or real-time image processing and analysis is used to identify wells containing two or more cells, followed by the exclusion of the cells in those wells from further analysis, wherein as described above in more detail, examples of mechanisms that can be used to select or exclude a subset of cells from further analysis (interpreted as using calcein AM, a membrane-permeable reagent that becomes calcein; and an additional reagent for staining, claim 15) (paragraph [0438], lines 36-51). Fan teaches that a molecular label can comprise a nucleic acid sequence that provides information for identifying the specific type of target nucleic acid species hybridized to the oligonucleotide, wherein a molecular label can comprise a nucleic acid sequence that provides a counter for the specific occurrence of the target species hybridized to the oligonucleotide (interpreted as identifying the presence or absence of a sequence including a sample indexing sequence, claim 15) (paragraph [0188], lines 1-7). Fan teaches determining the number of different labeled nucleic acids can comprise determining the sequence of the labeled nucleic acid or any product thereof (e.g., labeled-amplicons, labeled-cDNA molecules), including conducting a sequencing reaction to determine the sequence of at least a portion of a sample label, a cellular label, a molecular label, at least a portion of the labeled target nucleic acid, a complement thereof, a reverse complement thereof, or any combination thereof (interpreted as identifying the sample origin or at least one single cell by identifying an indexing sequence, complement thereof or fragment thereof, claims 15 and 18) (paragraph [0230]). Fan teaches determining the sequence of the labeled nucleic acid or any product thereof comprises paired-end sequencing, nanopore sequencing, high-throughput sequencing, shotgun sequencing, dye-terminator sequencing, multiple-primer DNA sequencing, primer walking, Sanger dideoxy sequencing, Maxim-Gilbert sequencing, pyrosequencing, true single molecule sequencing, or any combination thereof, wherein high-throughput sequencing methods include platforms such as Roche 454, Illumina Solexa, ABI-SOLiD, ION Torrent, Complete Genomics, Pacific Bioscience, Helicos, or the Polonator platform (interpreted as determining a sequence; and replicating via NGS, claims 15 and 18) (paragraph [0232], lines 1-8; and [0233], lines 1-5). Fan teaches that individual cells or sub-populations of cells that exhibit a predefined set of characteristics, e.g. that express a particular cell surface receptor (marker) or set of cell surface receptors, can be identified through any of a variety of suitable techniques, e.g. through immunohistochemical staining of individual cells in a microwell array format using fluorescently-labeled antibodies directed towards the cell surface markers and fluorescence imaging techniques, or through the use of flow-cytometry and fluorescence-activated cell-sorting methods (interpreted as sorting single cells that comprise calcein and those that do not comprise anther stain, claim 15) (paragraph [0206], lines 28-38). Fan teaches that the instrument systems of the present disclosure can further comprise interfaces with PCR thermocyclers, sequencers, cell sorters, fluorescence activated cell sorter (FACS) instruments, or other types of lab automation equipment (interpreted as sorting single cells that comprise calcein and those that do not comprise anther stain, claim 15) (paragraph [0423]). Fan teaches an interface is provided for cell sorters or FACS instruments such that sorted cells are deposited directly into a microwell array or cartridge, wherein the interface for FACS instruments ca,, for example, include both hardware and software components, where the software provides the capability for simultaneous control of the FACS instrument and the single cell, stochastic labeling or molecular barcoding system, wherein the software can provide analysis capability for identifying correlations between the FACS data (e.g. the presence or absence of specified cell surface markers) and the copy numbers for one or more genes in a specified sub-population of cells, such that FACS machines can be used to sort single cells directly into the microwell array of the disclosure (paragraph [0425]). Fan teaches that the target molecules of interest are mRNA molecules expressed within a single cell, such that cDNA copies of all or a portion of the polyadenylated mRNA molecules in each cell are covalently archived on the surface of a corresponding bead (interpreted as the first sample indexing oligonucleotide comprises a polydA region; and oligo(dT) as an adjacent alignment sequence, claim 15) (paragraph [0159], lines 1-5). Fan teaches that Figure 1 shows an oligonucleotide attached to a bead, wherein the oligonucleotide comprises a cellular label and a molecular label (e.g., index sequences, claim 15); as well as, comprising a poly(A) region, and an adjacent oligo(dT) alignment sequence (Figure 1). Figure 1 (in part) is shown below:
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Fan also teaches that the beads were pooled and split into a set of 96 tubes for annealing to oligonucleotides bearing oligo(dA)17 on the 5' end, followed by a randomly synthesized 8 nucleotide sequence that serves as the molecular index, a third 8 nucleotide cell label, and a complementary sequence to the second linker, such that after enzymatic polymerization, the beads were pooled to derive the final library, wherein each resulting bead is coated with tens to hundreds of millions of oligo-dT oligonucleotides of the same clonally represented cell label (884,736 or 96x96x96 possible barcodes), and a molecular indexing diversity of 65,536 (48), such that the library size is increased exponentially by linearly increasing the diversity at each step of synthesis (interpreted as indexing oligonucleotides comprising a polydA region, and an alignment sequence, claim 15) (paragraph (0484]).
Fan does not specifically exemplify Draq7 (claim 15, in part).
Regarding claim 15 (in part), Mao teaches new substituted anthraquinone dyes that can be useful as cellular stains, wherein nuclear stains are useful for staining the nucleic of dead or fixed cells (Abstract, lines 1-4). Mao teaches that Draq5 and Draq7, two DNA-binding dyes developed by Biostatus (U.S. Pat. Nos. 7,605,280; 7,060, 427; and 6,468,753), are nuclear counterstains with far-red to near infrared fluorescence emission, which does not interfere with other detection channels in the visible spectral region useful for other probes; see also US Patent Application 2010/0062429; however, for fixed cells, the nuclear specificity of both Drq5 and Draq7 suffers, which poses problems for their application in immunofluorescence staining, where cell fixation and permeabilization is routine practice (col 2, lines 7-17). Mao teaches that counterstains for fixed and permeabilized cells are those anthraquinone dyes having the structures selected from Dye Nos. 6, 7, 9, 13, 15, 16 and 17. In various embodiments, the dyes are Dye Nos. 7, 13 and 15, where images of fixed and permeabilized cells stained with Dye Nos. 7, 13 and 15 and two commercial prior art nuclear counterstains Draq5 and Draq7 are shown in Figure 3, and Figure 4 shows that Dyn No. 7 can also be used to stain tissues with excellent nuclear specificity (interpreted as Draq7, claim 15) (col 29, lines 5-9 and 11-12). Mao teaches that the cell membrane impermeable anthraquinone dye is combined with another fluorescent probe selective for live cells, where such a staining method provides a way to detect the numbers of both live and dead cells in the same cell population, such that commercial fluorescent probes that are designed to detect live cells only are available, wherein calcein AM is a probe that enters live cells and becomes hydrolyzed intracellularly by endogenous esterases in live cells to produce a green fluorescent dye, while mitochondrial dyes that stain mitochondria in a membrane potential-dependent manner can be used to selectively stain live cells, which have healthy mitochondria, such that Dye No. 7 selectively staining dead cells in the presence of live cells is shown in Figure 5, where detection of emitted fluorescence signals can be made with a variety of instruments including, but not limited to, microscopes, flow cytometers, plate readers and any variations thereof (interpreted as combining calcein AM with Draq7, claim 15) (col 29, lines 21-38), wherein Draq7 is a cell impermeable fluorescent DNA dye that only stains the nuclei in dead and permeabilized cells, such that it does not enter intact, live cells as evidenced by Abcam (pg. 3, first and second full paragraphs).
It is prima facie obvious to combine prior art elements according to known methods to yield predictable results; the court held that, "…a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1395 (2007); Sakraida v. AG Pro, Inc., 425 U.S. 273, 282, 189 USPQ 449, 453 (1976); Anderson’s-Black Rock, Inc. v. Pavement Salvage Co., 396 U.S. 57, 62-63, 163 USPQ 673, 675 (1969); Great Atlantic & P. Tea Co. v. Supermarket Equipment Corp., 340 U.S. 147, 152, 87 USPQ 303, 306 (1950)”. Therefore, in view of the benefits of detecting live cells; as well as, fixed, dead and/or permeabilized cells in a sample as exemplified by Mao, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of using barcoded beads to individually index thousands of single cells arrayed within microwells of the device, such that cells comprising one or more predetermined characteristics such as live cells/dead cells can be detected and/or sorted using two or more fluorophores, chromophores, dyes, and/or stains including calcein AM and propidium iodide as disclosed by Fan, to include different combinations of dyes and stains such as calcein AM with anthraquinone dyes such as Draq7 as taught by Mao with a reasonable expectation of success in using a combination of indexed oligonucleotides, labels, and dyes/stains including calcein AM and Draq7 to increase molecular indexing diversity, and to determine at least one characteristic of the cell such as viability and/or the number of total, live cell counts; to selectively stain both live cells, dead cells, fixed cells and/or permeabilized cells within the arrays of single cells; in detecting the emitted fluorescence signals using flow cytometers for the automated, high-throughput selection and/or sorting of live cells from dead or permeabilized cells for further downstream processing such as amplification and sequencing; and/or in isolating specific subpopulations of single cells from heterogenous populations of single cells.
Thus, in view of the foregoing, the claimed invention, as a whole, would have been obvious to one of ordinary skill in the art at the time the invention was made. Therefore, the claims are properly rejected under 35 USC §103(a) as obvious over the art.
Response to Arguments
Applicant’s arguments filed June 16, 2026 have been fully considered but they are not persuasive. Applicants essentially assert that: (a) Fan does not teach a sample indexing oligonucleotide comprises a poly(dA) region and an adjacent alignment sequence having a G, C, T, U or combination thereof (Applicant Remarks, pg. 16, last partial paragraph through pg. 17, first partial paragraph); and (b) Mao does not remedy these issues (Applicant Remarks, pg. 17, first full paragraph).
Regarding (a) and (b), although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26USPQ2d 1057 (Fed. Cir. 1993). Additionally, MPEP § 2112.01(I) states that,
where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Moreover, it is noted that none of the references has to teach each and every claim limitation. If they did, this would have been anticipation and not an obviousness-type rejection. One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Applicant’s assertion that Fan does not teach the recited sample indexing oligonucleotides, is not found persuasive. The Examiner contends that the combined references of Fan and Mao teach all of the limitations of instant claim 15 including the recited sample indexing oligonucleotides. For example, Fan teaches the synthesis of a bead library, wherein beads are annealed to oligonucleotides bearing oligo(dA)17 on the 5' end, followed by a randomly synthesized 8 nucleotide sequence that serves as the molecular index, a third 8 nucleotide cell label, and a complementary sequence to the second linker (interpreted as indexing oligonucleotides comprising a poly(dA) region, and an alignment sequence, claim 15) (See; paragraph (0484]).
The combined references of Fan and Mao teach all of the limitations of the recited claims. Thus, the claims remain rejected.
Double Patenting
The provisional rejection of claims 15 and 18 is maintained, and claim 36 is newly provisionally rejected, on the ground of nonstatutory double patenting as being unpatentable over claims 20 and 22 of copending Application No. 16/540,971 in view of Fan et al. (US Patent Application No. 20160289669, published October 6, 2016) for the reasons of record.
The rejection of claims 15 and 18 is maintained, and claim 36 is newly rejected, on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent Nos. 10676779 and
claims 1-19 of US Patent Application No. 11834715 for the reasons of record.
Response to Arguments
Applicant’s arguments filed June 16, 2026 have been fully considered but they are not persuasive. Applicants essentially assert that: (a) Applicant requests the Examiner to hold the rejections in abeyance until the present application is otherwise in condition for allowance (Applicant Remarks, pg. 18, Double Patenting Rejections).
Regrading (a), Applicant did not specifically indicate how the claims of the copending applications recited supra are patentably distinct from the instant claims as required by 37 CFR 1.111(b). Thus, the claims remain rejected for the reasons already of record.
New Objections/Rejections
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 18 is rejected under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 18 recites (in part): “wherein identifying the presence or absence of sequence information corresponding to a sequence…indexing oligonucleotides in the obtained sequencing data” in lines 1-17, wherein claim 18 depends from instant claim 15, where claim 15 already recites what the step of “identifying” comprises, such that dependent claim 18 cannot recite that “identifying” comprises something different than previously recited in claim 15 (e.g., replicating sample indexing oligonucleotides, obtaining sequencing data, and identifying the sample origin). Thus, claim 18 is an improper dependent claim for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
Conclusion
Claims 15 and 18 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY M BUNKER whose telephone number is (313) 446-4833. The examiner can normally be reached on Monday-Friday (6am-2:30pm).
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, Heather Calamita can be reached on (571) 272-2876. The fax phone number for the organization where this application or proceeding is assigned is (571) 273-8300.
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/AMY M BUNKER/Primary Examiner, Art Unit 1684
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