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 .
Elections/Restrictions
Applicant’s election with traverse of Group II, claims 175-178, in the reply filed on July 9, 2026 is acknowledged. Applicant traverses the restriction between Groups II and III on the grounds that claim 175 itself recites spatial reconstruction and correlation, that the claims of Groups II and III contain overlapping method steps and split-pool indexing operations, and that previously cited reference, Cao (Restriction Requirement: 1/9/2026), does not teach spatially resolve gene-expression information. These arguments have been fully considered, but are not persuasive.
Under 37 CFR 1.475(a) and PCT Rule 13.2, the presence of overlapping subject matter or common method steps does not, by itself, establish unity of invention. The claimed inventions must share one or more of the same or corresponding special technical features, meaning features that define a contribution that each claimed invention, considered as a whole, makes over the prior art. The Examiner does acknowledge that claim 175 of Group II recites correlating spatial and cellular barcode sequence with a subsample positioned in a particular microwell and that the subsample corresponds to a spatial position of a cell relative to other cells in the sample. However, this does not establish that Groups II and III share the same special technical feature. In Group II, the recited correlation is employed as part of a method for quantifying gene expression at the single-cell level by associating sequencing information with a particular subsample, cell, and microwell. And further, by contrast, Group III is directed to generating high-resolution spatial positioning of nucleic acid expression and requires the further reconstruction and correlation of expression information with distinct spatial locations within the original tissue sample, including correlating spatially barcoded domains with tissue positions or images and mapping expression data back to these locations. Thus, although the methods may produce some overlapping positional information, Group II does not require the particular high-resolution tissue-position reconstruction and mapping operations defining the contribution of Group III.
Further, the Applicant argues that Groups II and III share steps (a) through (h), provide spatial information concerning subsamples, and use split-pool indexing. The existence of common steps does not establish unity where those steps do not themselves define a contribution over the prior art. As previously shown in the previous restriction (1/9/2026), Cao teaches barcode-bearing primers, split-pool indexing, pooling and redistribution, and additional indexing, amplification, sequencing, and associating reads with cellular or well-specific barcodes. These common features therefore are not a shared special technical feature. As of note, Cao does not need to teach the full spatial-reconstruction method of Group III. Its relevance is that the features common to Groups II and III were known. Cao’s lack of tissue-position mapping instead conforms that high-resolution spatial reconstruction is an additional contribution specific to Group III.
More so, the Applicant’s reliance on overlapping classifications or fields of search is not persuasive. Under 37 CFR 1.475, the issue is whether the groups share the same or corresponding special technical feature contributing over the prior art, not whether they contain overlapping steps or could be searched together. In the same regard, the arguments concerning Group I are also unpersuasive. Group I is distinguished by its system architecture, including the array or microwell structure, primer arrangement, well geometry, and cell-loading parameters. Groups II and III do not require those structural limitations, while Group I does not require the quantification or spatial-mapping operations of the method groups. The shared barcode and indexing features do not establish unity because they do not define a contribution over Cao (see Restriction requirement, 1/9/2026).
Accordingly, Groups I-III do not share the same or corresponding special technical feature defining a contribution that each invention, considered as a whole, makes over the prior art. The requirement for restriction set forth in the Office action mailed 1/9/2026 is therefore maintained. Claims 169-174 and 179-187 are withdrawn from further consideration as being directed to nonelected inventions, there being no allowable genetic or linking claim. Thus, claims 175-178 are under examination (7/9/2026).
Claim Status
Claims 169-187 are pending (7/9/2026). Claims 175 and 179 have been amended (7/9/2026). No new matter was added. Applicant previously selected Group II with traverse, as addressed above, in response to the Restriction Requirement (1/9/2026), thus, claims 175-178 are under examination (7/9/2026).
Priority
Claims 175-178 receive a priority date of 2/20/2020, the effective filing date of US Provisional Patent 62979235.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure
statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information
submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be
incorporated into the specification but must be submitted in a separate paper." Therefore, unless
the references have been cited by the examiner on form PTO-892, they have not been
considered.
Information disclosure statements (IDS) were submitted on 5/21/2024, and 1/26/2026 (2) are being considered by the examiner.
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 - This application fails to comply with the requirements of 37 CFR 1.821 - 1.825 because it does not contain a "Sequence Listing" as a separate part of the disclosure or a CRF of the “Sequence Listing.”.
Required response - Applicant must provide:
A "Sequence Listing" part of the disclosure; together with
An amendment specifically directing its entry into the application in accordance with 37 CFR 1.825(a)(2);
A statement that the "Sequence Listing" includes no new matter as required by 37 CFR 1.821(a)(4); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(a)(3).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also 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.
If the "Sequence Listing" part of the disclosure is submitted according to item 1) c) or d) above, applicant must also provide:
A CRF in accordance with 37 CFR 1.821(e)(1) or 1.821(e)(2) as required by 1.825(a)(5); and
A statement according to item 2) a) or b) above.
Drawings
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 – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers (Figure 7F) in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, 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.
Specification
The disclosure is objected to because of the following informalities (see MPEP § 608.01):
The use of the terms “SCIENION” (p. 61 and used throughout the Specification), “Norland” (p. 66), “Agilent” (p. 66 and used throughout the Specification), “Sylgard” (p. 67), “Illumina” (p. 78 and used throughout the Specification), “Jackson Laboratories” (p. 79), “Thermo Scientifics” (p. 80), “Fisher Scientific” (p. 81), “Beckman” (p. 82), “Invitrogen” (p. 82), which are trade names or marks used in commerce, have been noted in this application. The terms 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.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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 175-178 are rejected under 35 U.S.C. 103 as being unpatentable over So et al. (USPGPub 2018/0245142 A1, published: 8/30/2018) and Dura et al. (“scFTD-seq: freeze-thaw lysis based, portable approach toward highly distributed single-cell 3′mRNA profiling”, Nucleic Acids Research, published 2019).
Regarding claim 175, So teaches methods and compositions for spatial detection and analysis of nucleic acids in a tissue ample, where the methods can enable the characterization of transcriptomes and/or genomic variations in tissues while preserving spatial information about the tissue (Abstract). Further, So teaches that the present disclosure is further based on the realization that spatial addressing of nucleic acids from a tissue sample can involve two-dimensional spatial addressing, e.g., to correlate the position of a nucleic acid on a two-dimensional capture array with the position of the nucleic acid in a two-dimensional tissue section, where spatial addressing can be performed also in additional dimensions (Paragraph 94, lines 1-5). So teaches that for example, spatial address sequences can be added to nucleic acids to describe the relative spatial position of a nucleic acid in a third or fourth dimension, e.g., by describing the position of a tissue section in a tissue biopsy, or the position of a tissue biopsy in a subject's organ and temporal address sequences could be added to nucleic acids from a tissue sample to denote a timepoint in a time course experiment, e.g., inquiring into changes of gene-expression in a cell in response to a physical or chemical stimulus, such as a drug treatment during a clinical trial (Paragraph 94, lines 5-10).
So also teaches that covalent attachment can be used, but all that is required is that the nucleic acids remain stationary or attached to a support under conditions in which it is intended to use the support, for example, in applications requiring nucleic acid amplification and/or sequencing, where oligonucleotides to be used as capture primers or amplification primers can be immobilized such that a 3′-end is available for enzymatic extension and at least a portion of the sequence is capable of hybridizing to a complementary sequence immobilization can occur via hybridization to a surface attached oligonucleotide (Paragraph 109, lines 1-10). Further, So teaches a pair of gene-specific capture oligonucleotides that flank a region of interest are hybridized in situ to genomic DNA, where for example, a first capture oligonucleotide that hybridizes 5′ to a region of interest can comprise a gene-specific sequence and a universal capture sequence where a second capture oligonucleotide that hybridizes 3′ to the region of interest can comprise a second gene-specific sequence and an SBS primer sequence (Paragraph 181, lines 1-5).
Also, So teaches that the method further comprises any one or more of the following steps: (b) contacting the capture array with a tissue sample such that the position of a capture site on the array can be correlated with a position in the tissue sample; (c) allowing nucleic acids of the tissue sample to hybridize to the capture region of the second capture probe; (d) extending the capture region of the second capture probe to form an immobilized first complementary strand of the nucleic acid hybridized to the gene-specific sequence; (e) ligating the immobilized first complementary strand to the spatial address sequence of a first capture probe to immobilize the first complementary strand at both ends; (f) synthesizing a second complementary strand using a primer complementary to the first primer binding sequence of the first capture probe; (f) releasing the second complementary strand from the surface of the capture array; (g) analyzing the sequence of the released second complementary strand, and (h) correlating the sequence of the released second complementary stand to the position of the nucleic acid in the tissue sample (Paragraph 278, lines 1-15).
Additionally teaches FIG. 9, which illustrates an embodiment of the steps of a method 800 of FIG. 8 where namely, a tissue section (not shown) comprises a target genomic DNA molecule 910 and target DNA molecule 910 can include a mutation 915, where at step 810, a first gene-specific capture oligonucleotide 920 and a second gene-specific capture oligonucleotide 925 that flank a region of interest are hybridized in situ to DNA molecule 910 and capture oligonucleotide 920 comprises a gene-specific region 930 and a universal capture region 935 or capture oligonucleotide 920 can also comprise a UMI region (not shown) (Paragraph 185, lines1-5).
So also teaches that as used herein, the term “nucleic acid” is intended to be consistent with its use in the art and includes naturally occurring nucleic acids or functional analogs thereof and particularly useful functional analogs are capable of hybridizing to a nucleic acid in a sequence specific fashion or capable of being used as a template for replication of a particular nucleotide sequence where naturally occurring nucleic acids generally have a backbone containing phosphodiester bonds or an analog structure can have an alternate backbone linkage including any of a variety of those known in the art. Naturally occurring nucleic acids generally have a deoxyribose sugar (e.g. found in deoxyribonucleic acid (DNA)) or a ribose sugar (e.g. found in ribonucleic acid (RNA)) (Paragraph 114, lines 1-5). So teaches that a nucleic acid can contain any of a variety of analogs of these sugar moieties that are known in the art. A nucleic acid can include native or non-native bases. In this regard, a native deoxyribonucleic acid can have one or more bases selected from the group consisting of adenine, thymine, cytosine or guanine and a ribonucleic acid can have one or more bases selected from the group consisting of uracil, adenine, cytosine or guanine (Paragraph 114, lines 1-10). More so, So teaches capture region 135 can be, for example, a universal (general) capture region. In some embodiments, capture region 135 comprises a poly-T oligonucleotide that can be used to capture total mRNA in a tissue sample as described in more detail with reference to FIG. 3. In some embodiments, capture region 135 is a universal capture region that can be used to capture cDNA synthesized by in situ reverse transcription of RNA as describe in more detail with reference to FIG. 6. In some embodiments, capture region 135 is a universal capture region that can be used to capture genomic DNA amplicons as described in more detail with reference to FIG. 9 and FIG. 10 (Paragraph 143, lines 1-5). Further, So teaches that in some embodiments, capture region 135 is a gene-specific or target-specific capture region that can be used to capture a specific nucleic acid in a tissue sample. Each capture probe 115 on capture array 100 can comprise one or more unique gene-specific capture region 135 (Paragraph 144, lines 1-5).
Regarding claim 176, So teaches that in one example, a spatially addressed capture probe comprises a random primer sequence that is used for in situ synthesis of cDNA from total RNA in a tissue sample (Paragraph 348, lines 1-5). Further, So teaches that for example, a reverse-transcription master mix solution is flowed between the coverslip and glass slide into the semi-permeabilized tissue section where the coverslip acts as a barrier to prevent evaporation during the reaction and because of the internal biotin label in the spatially addressed capture probes used in the reverse transcription reaction, first strand cDNA is biotinylated (Paragraph 353, lines 1-5).
Regarding claim 177, So teaches that the methods described herein can be used in conjunction with a variety of nucleic acid sequencing techniques and particularly applicable techniques are those wherein nucleic acids are attached at fixed locations in an array such that their relative positions do not change and wherein the array is repeatedly imaged where embodiments in which images are obtained in different color channels, for example, coinciding with different labels used to distinguish one nucleotide base type from another are particularly applicable and in some embodiments, the process to determine the nucleotide sequence of a target nucleic acid can be an automated process, but preferred embodiments include sequencing-by-synthesis (“SBS”) techniques (Paragraph 610, lines 1-5).
So does not teach or suggest lysing the cells following sorting the cells into the microwell arrays, as set forth in dependent claim 178.
Regarding claim 178, Dura teaches that cellular barcoding of 3′ mRNAs enabled massively parallel profiling of single-cell gene expression and has been implemented in droplet and microwell based platforms, where the latter further adds the value for compatibility with low input samples, optical imaging, scalability, and portability (Abstract). Dura teaches however, cell lysis in microwells remains challenging despite the recently developed sophisticated solutions and here, they present scFTD-seq, a microchip platform for performing single-cell freeze-thaw lysis directly toward 3′mRNA sequencing that offers format flexibility with a simplified, widely adoptable workflow that reduces the number of preparation steps and hands-on time, with the quality of data and cost per sample matching that of the state-of-the-art scRNA-seq platforms (Abstract). Additionally, Dura teaches that cFTD-seq utilizes microwell arrays as the platform for co-isolating single cells and uniquely barcoded mRNA capture beads (SupplementaryFigureS1A) prior to freeze-thaw cell
Lysis where the design of the microwell arrays are similar to the ones described before, and arrays are made from polydimethylsiloxane (PDMS) (Results, Paragraph 1). Dura also teaches that afterwards, the downstream processes including cell lysis, mRNA capture, bead retrieval, reserve transcription, amplification, and library preparation, are performed similar to that described for open-surface format (Figure 1D, E) (Results: Paragraph 5).
It would have been obvious to one of ordinary skill in the art, prior to the effective filing date of the claimed invention, to modify the method of So to include isolating or sorting cells into microwell arrays and lysing the cells into microwell arrays and lysing the cells after such isolation, including by the freeze-thaw lysis taught by Dura. So and Dura are both directed to array-based analysis of cellular nucleic acids using nucleic-acid capture followed by reverse transcription, amplification, library preparation, and sequencing. So teaches spatially addressed capture probes that permit captured nucleic acid sequences to be correlated with the corresponding position in a tissue sample. Dura teaches co-isolating individual cells and barcoded mRNA-capture elements within microwells before performing freeze-thaw lysis, followed by mRNA capture, reverse transcription, amplification, and library preparation.
One of ordinary skill would have been motivated to incorporate Dura’s post-isolation lysis technique into So’s spatially addressed capture workflow to release intracellular nucleic acids directly after the cells had been confined to their respective array locations. Performing lysis after isolation would reduce sample transfers and handling, prevent nucleic acids released from different cells or subsamples from becoming intermixed, and thereby maintain the association between the released nucleic acids and the corresponding spatially addressed array location. The modification would also provide the advantages expressly identified by Dura, including compatibility with low-input samples and optical imaging, scalability, portability, a simplified workflow, fewer processing steps, and reduced hands-on time.
The proposed combination would merely use Dura’s known microwell isolation and freeze-thaw lysis technique for its established purpose in So’s known spatial capture method. So’s capture probes would continue to perform their disclosed functions of capturing nucleic acids and providing spatial-position information, while Dura’s freeze-thaw treatment would continue to perform its disclosed function of releasing intracellular mRNA from isolated cells. Dura further demonstrates that microwell-based freeze-thaw lysis is compatible with the same general downstream operations employed by So, including nucleic acid capture, reverse transcription, amplification, and library preparation. Accordingly, one of ordinary skill would have had a reasonable expectation of success that Dura’s lysis procedure could be incorporated into So’s workflow successfully and without changing the respective principles of operation of either reference.
Therefore, the predictable result of the combination would have been So’s spatially resolved nucleic acid analysis performed using cells that are isolated in microwell arrays and lysed following such isolation. The combination does not require replacing So’s spatially addressed, surface-attached capture probes with Dura’s capture beads; Dura is relied upon for the known arrangement and timing of cell isolation and subsequent lysis. So’s teachings regard random primer capture and reverse transcription and regarding nucleic acid sequencing, including sequencing by synthesis, would remain applicable to the combined method and additional limitations of the dependent claims.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELIZABETH ROSE LAFAVE whose telephone number is (703)756-4747. The examiner can normally be reached Compressed Bi-Week: M-F 7:30-4:30.
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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/ELIZABETH ROSE LAFAVE/ Examiner, Art Unit 1684
/HEATHER CALAMITA/ Supervisory Patent Examiner, Art Unit 1684