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
Pursuant to a preliminary amendment, claims 1-7, 9-13, 15, 19-23, 25-28, 30, 33-35, 37, 39, 41, 43, 44, 46-48 and 51 are currently pending in the instant application.
Response to Election/Restriction
Applicant's initial election without traverse of Group I, claims 1-7, 9-13, 15, 19-23, 25 and 48, directed to an array, in the reply filed June 27, 2025 is acknowledged.
Supplemental Election-Restriction Requirement
Applicant's election with traverse of Group I, claims 1-7, 9-13 and 15, directed to an array; and the Supplemental election of Species (A) and (C) without traverse; and the Supplemental election of Species (B) with traverse as follows:
Species (A): wherein the array is a spatial array (claim 2);
Species (B): wherein the array is a spatial array (claim 10); and
Species (C): wherein the unique nucleic acid barcode sequence comprises at most 20 segments (claim 6);
Species (D): Applicant did not elect a species for (D), in the reply filed on November 7, 2025, is acknowledged.
Response to Traversals:
The traversal of is on the grounds that: (a) with respect to Groups I and II, Applicant submits that there would not be a serious search and/or examination burden in combining Groups I and II because independent claim 1 and independent claim 19 recite substantially similar limitations, allowing for identical fields of search to be used (Applicant Remarks, pgs. 3-4); and (b) regarding Species (B), at least claims 4, 5, 10, 11 and 15 should be searched together because any reasonable search for “a plurality of unique barcode sequences” would find references relating to instant claims 1 and 19 would find relevant references relating to these dependent claims (Applicant Remarks, pg. 5, first full paragraph).
Regarding (a), it is erroneous to suggest that the limitations recited in Groups I and II are ‘substantially similar’ and/or that they can be examined using identical fields of search. Group I is directed to an array, while Group II is directed to a composition, such that Group II encompasses any composition including an array. Additionally, there are substantial differences in the body of claims 1 and 19. For example:
Group I recites: an array comprising: a plurality of unique nucleic acid barcode sequences, wherein each unique nucleic acid barcode sequence defines a unique identifier associated with a specific location in the array.
Group II recites: a composition comprising: a plurality of target-specific probe molecules, wherein a target-specific probe molecule comprises a unique nucleic acid barcode sequence, wherein the unique nucleic acid barcode sequence defines a unique identifier associated with a specific location on the array.
Clearly, Group I and Group II represent patentably distinct inventions. There is a substantial difference between an array of barcode sequences, and any composition comprising a plurality of target-specific probes that comprise barcode sequences. Thus, there would be an serious search and/or examination burden on the Examiner. The requirement for restriction between the Groups is still deemed proper.
Regarding (b), claims 4, 10, 11-13 and 15 recite unique barcode sequences comprising different structural components, such that each unique barcode sequence as recited in the dependent claims comprises an entirely different structure a priori. Thus, each of the structurally different unique barcode sequences results in an array comprising very different structures (e.g., comprising barcodes attached to beads, individual nucleotides, a plurality of nucleotides, a GC content <10%, compatibility with a decoding dilution factor of at least 50%, etc.), which are likely designed for different purposes such as for use in error correction and/or for use in different assays. Moreover, the as-filed Specification teaches that the different unique barcodes represent completely different embodiments and/or barcodes having ”at least one additional characteristic” (See; paragraph [0011]). Contrary to Applicant’s assertion, searching for one different component would not necessarily produce results for arrays comprising all of the different unique barcode structures. Thus, there would be a serious search and/or examination burden on the Examiner. The requirement for restriction/election is still deemed proper.
Claims 19-23, 25-28, 30, 33-35, 37, 39, 41, 43, 44, 46-48 and 51 are 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. Applicant timely traversed the restriction (election) requirement in the reply filed on November 7, 2025.
Claims 3-7, 11-13 and 15 are 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 is still deemed proper and is therefore made FINAL.
Please Note: elected claim 6 depends from withdrawn claim 5, such that claim 6 will not be examined on the merits.
The claims will be examined insofar as they read on the elected species.
Therefore, claims 1, 2, 9 and 10 are under consideration to which the following grounds of rejection are applicable.
Priority
The present application filed September 15, 2021 claims the benefit of US Provisional Patent Applications: 63213447, filed June 22, 2021; 63079029, filed September 16, 202; 63079035, filed September 16, 2020; 63079004, filed September 16, 2020; 63079034, filed September 16, 2020; 63079007, filed September 16, 2020; and 63078999, filed September 16, 2020.
Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120 as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application 63213447, filed June 22, 2021, fails to provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for one or more claims of this application. The specific method steps recited in independent claim 1 does not have support for; “two spatial barcode segments separated by a non-barcode segment;” and “a total length of at least 10 nucleotides, a guanine-cytosine (GC) content of less than 50%, a maximum length for homopolymer subsequences within either spatial barcode segment of 7 nucleotides, and a dilution factor of at least 10% for at least one segment of the plurality of segments”. Therefore, the priority date for the presently claimed invention is September 15, 2021, the filing date of US Patent Application 17/476,395.
Applicants are invited to specifically indicate the location of the cited phrase pertinent to claims 1, 2, 9 and 10 of the instant application.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on November 24, 2021; June 27, 2025; and November 7, 2025 have been considered. Initialed copies of the IDSs accompany this Office Action.
Claim Objections/Rejections
Drawing Objection
(1) The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they include the following reference characters not mentioned in the description:
(a) Figure 2: illustrates bright and dark spots within the wells of the flow cell, which are not identified in the as-filed Specification, filed September 15, 2021.
(b) Figure 3: illustrates “red image” and “green image”, along with numbers and the letters A, C and T which are not identified in the as-filed Specification, filed September 15, 2021.
(c) Figure 10: illustrates density versus # of errors over 8bp barcode part, which is not identified in the as-filed Specification, filed September 15, 2021.
Corrected drawing sheets in compliance with 37 CFR 1.121(d), or amendment to the specification to add the reference character(s) in the description in compliance with 37 CFR 1.121(b) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
(2) The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they do not include the following reference signs mentioned in the description:
(a) The as-filed Specification teaches in Figure 1: Hamming distance HD, discrete barcode strings A1 x … x AL, designed barcode set X (paragraphs [0119], [0121] and [0167]). However, these are not illustrated in Figure 1 of the drawings filed 09/15/2021.
(b) The as-filed Specification teaches that Figure 3: illustrates that the stoichiometric ratios used are T : [0,1], C : [1:0]. A : [1:1], G : [0, 0]; and providing / Ai / x L probabilities as P0 (l = letter / fi = feature vector; fi, cycle i; cycle specific parameter qi and l Ԑ Ai (paragraphs [0142], [0149] and [0175]). However, these are not illustrated in Figure 3 of the drawings filed 09/15/2021.
(c) The as-filed Specification teaches that Figure 8: accuracy (in percent, %) (paragraph [0170]). However, these are not illustrated in Figure 8 of the drawings filed 03/17/2022.
(d) The as-filed Specification teaches that Figure 9: spheres of correction 11 having a radius of 1 (paragraph [0172]). However, these are not illustrated in Figure 9 of the drawings filed 03/17/2022.
(e) The as-filed Specification teaches that Figure 12: tuned state caller performance for decoding cycle 1 (paragraph [0185]). However, this is not illustrated in Figure 12 of the drawings filed 03/17/2022.
(f) The as-filed Specification teaches that Figure 13: PHRED quality score distribution and PHRED-like quality scores (paragraph [0063] and [0184]). However, these are not illustrated in Figure 13 of the drawings filed 03/17/2022.
(g) The as-filed Specification teaches that Figure 16: system 160000 (paragraph [0254]). However, this is not illustrated in Figure 16 of the drawings filed 09/15/2021.
(h) The as-filed Specification teaches that Figure 17: imaging module 1630 (paragraph [0212]). However, this is not illustrated in Figure 17 of the drawings filed 09/15/2021.
(i) The as-filed Specification teaches that Figure 18: imaging module 1630 (paragraph [0217]). However, this is not illustrated in Figure 18 of the drawings filed 09/15/2021.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 112(b)
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 1, 2, 9 and 10 are rejected 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 1 is indefinite for the recitation of the term “either spatial barcode segment” such as recited in claim 1, line 14. There is insufficient antecedent basis for the term “either spatial barcode segment” in the claim because claim 1, line 5 recites the term “two spatial barcode segments.”
Claim 2 is indefinite for the recitation of the term “different features” such as recited in claim 2, line 2. There is insufficient antecedent basis for the term “different features” in the claim because claim 1, lines 3-4 recites the term “a specific location.” Moreover, claim 2 depends from claim 1, wherein claim 1 does not recite that the array comprises “features” and/or “different features” and, thus, the metes and bounds of the claim cannot be determined.
Claim 9 is indefinite for the recitation of the term “the specified minimum pairwise edit distance comprises…Hamming distance of at least two times an error correction capability” in claim 9, lines 2-3 because claim 9 depends from claim 1, wherein claim 1 recites that that the “specified minimum pairwise edit distance” is 3 relative to other unique nucleic acid barcode sequences. Claim 1 does not recite a Hamming distance and, thus, the metes and bounds of the claim cannot be determined.
Claim 9 is indefinite for the recitation of the term “an error correction capability” such as recited in claim 9, line 3. There is insufficient antecedent basis for the term “the error correction capability.” Moreover, claim 9 depends from claim 1, wherein claim 1 does not recite any error correction capability including an error correction capability having a value and, thus, the metes and bounds of the claim cannot be determined.
Claim 10 is indefinite for the recitation of the term “less than about” such as recited in claim 10, line 3 because a broad range or limitation is together with a narrow range of limitation that falls within the broad range or limitation (in the same claim) is considered indefinite since the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). The limitation of “less than” refers to a GC content of less than 10%, and the limitation of “about” may start at a GC content of 10% or slightly greater than 10%. Therefore, the recitation of “less than about” is a recitation of two ranges making the claims indefinite.
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.
Claims 2 and 9 are 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 2 recites (in part): “and different unique nucleic acid barcode sequences are attached to different features of the spatial array” in lines 1-2 because claim 2 depends from instant claim 1, wherein claim 1 does not recite the presence of ‘features’ or ‘different features’ as part of the array and/or the plurality of unique nucleic acid barcode sequences. Thus, claim 2 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.
Claim 9 recites (in part): “wherein the specified minimum pairwise edit distance comprises a specified minimum pairwise Hamming distance of at least two times an error correction capability, and wherein the error correction capability has a value of at least one” because claims 9 depends from claim 1, wherein claim 1 recites that the “minimum pairwise edit distance” is 3; such that claim 1 does not recite a Hamming distance, any error correction capability, and/or any error correction capability having a value. Thus, claim 9 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.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 2, 9 and 10 are rejected under 35 U.S.C. 102(a1)/(a2) as being anticipated by Volkmuth et al. (hereinafter “Volkmuth”) (International Application 2015080266, published May 19, 2015) as evidenced by Hamady et al. (hereinafter “Hamady”) (Nature Methods, 2008, 5(3), 235-237).
Regarding claim 1, Volkmuth teaches methods for optimizing barcode design for multiplex DNA sequencing for use with particular sequencing technologies (Abstract). Volkmuth teaches using a plurality of barcodes to label a plurality of samples, wherein each barcode is used to label a distinct sample including identifying which heavy and light chain cDNA sequences came from a particular single B cell out of a collection of B cells, wherein DNA barcodes are sequences incorporated into DNA molecules and can be used to identify the sample from which the DNA was taken; and incorporating a distinct barcode for each of many samples allows for the pooling and parallel processing of the samples (interpreted as unique identifiers associated with a specific location, claim 1) (paragraphs [0033]; [0048], lines 1-5; and [0073]). Volkmuth teaches that the procedure can be generalized to accommodate the use of multiple barcodes, for example, a plate ID barcode and a well ID barcode separated by a universal primer sequence with a 3’ adaptor sequence (interpreting plate-ID and well-ID barcodes as an array of unique barcode sequences associated with a specific location on an array, claim 1) (paragraph [0100], lines 1-4). Volkmuth teaches that where multiple barcodes will be used, for example a plate and well barcode separated by intervening sequence segments, the procedure can include estimation of the misidentification error rate for the entire sequence construct including barcodes and the intervening sequences used to join them (interpreted as a plurality of segments comprising two spatial barcode segments separated by a non-barcode segment, claim 1) (paragraph [0125]). Volkmuth teaches a set of combined plate, universal primer and well sequences are created by concatenating together each combination of plate and well barcodes separated by the universal primer, with the adaptor at the 3' end, and with an intervening spacer between each of the plate, universal primer, well and adaptor sequences (interpreted as a plurality of segments comprising two spatial barcode segments separated by a non-barcode segment, claim 1) (paragraph [0100], lines 7-13). Volkmuth teaches that each barcode is from 5 to 40 nucleotides in length (interpreted as barcode segments having a length of at least 2 nucleotides; and encompassing a plurality of segments having a total length of at least 10 nucleotides, claim 1) (paragraph [0017]). Volkmuth teaches that when identifying which heavy and light chain cDNA sequences came from a particular single B cell out of a collection of, for example, 1760 B cells, with a sequencing platform having a 5% substitution error rate and a 15% insertion or deletion error rate, some sets of barcodes will have a minimum pairwise edit distance of 12, while a sequencing platform having a 1% substitution error rate and a 1% insertion or deletion error rate, some sets of barcodes will have a minimum pairwise edit distance of 5 (interpreted as encompassing a minimum pairwise edit distance of 3 relative to other unique nucleic acid barcode sequences, claim 1) (paragraphs [0074]; and [0075], lines 1-6). Volkmuth teaches that the barcodes are designed to ensure that the minimum pairwise edit distance between any two barcodes is greater than or equal to a certain threshold (interpreted as encompassing an edit distance of 3, claim 1) (paragraph [0081], lines 1-6). Volkmuth teaches that as an alternative to Hamming-distance based barcodes, others have selected sets of barcodes which satisfy a minimum pairwise edit distance (interpreted as encompassing a minimum pairwise edit distance of 3 relative to other unique nucleic acid barcode sequences, claim 1) (paragraph [0059], lines 14-16). Volkmuth teaches a GC content between 40% and 60% (interpreted as comprising a plurality of segments encompassing a GC content of less than 50%, claim 1) (paragraph [0085]). Volkmuth teaches that the method comprises filtering the first dataset to remove one or more barcodes whose sequences include a homopolymer run greater than or equal to 2 nucleotides in length (interpreted as a plurality of segments having maximum length for homopolymer subsequences of 7 nucleotides, claim 1) (paragraph [0017]).
Regarding claim 2, Volkmuth teaches that different sets of barcodes are tailored for specific sequencing platforms and the number of samples to be processed in parallel (interpreted as a spatial array and different unique barcodes sequences attached to different features of the spatial array, claim 2) (paragraph [0048], lines 10-12). Volkmuth teaches that every barcodes in a set is unique (interpreted as unique barcode sequences, claims 1 and 2) (paragraph [0064], line 1). Volkmuth teaches a set of combined plate, universal primer and well sequences are created by concatenating together each combination of plate and well barcodes separated by the universal primer, with the adaptor at the 3' end, and with an intervening spacer between each of the plate, universal primer, well and adaptor sequences (interpreting well barcodes and plate barcodes as encompassing being attached to different features of the spatial array, claim 2) (paragraph [0100], lines 7-13). Volkmuth teaches sets of barcodes useful for identifying which heavy and light chain cDNA sequences came from a particular single B cell out of a collection of B cells (interpreted as encompassing barcodes being attached to different features of the spatial array, claim 2) (paragraph [0073]). Volkmuth teaches that barcodes are incorporated via ligation and each barcode uniquely identifies a specific genomic region of each sample (interpreted as encompassing barcodes being attached to different features of the spatial array, claim 2) (paragraph [0157]).
Regarding claim 9, Volkmuth teaches that when identifying which heavy and light chain cDNA sequences came from a particular single B cell out of a collection of, for example, 1760 B cells, with a sequencing platforms, wherein some sets of barcodes will have a minimum pairwise edit distance of 12, while some sets of barcodes for other sequencing platforms will have a minimum pairwise edit distance of 5 (interpreted as encompassing a minimum pairwise Hamming distance of at least two times an error correction capability having a value of at least one, claim 9) (paragraphs [0074]; and [0075], lines 1-6). Volkmuth teaches that as an alternative to Hamming-distance based barcodes, others have selected sets of barcodes which satisfy a minimum pairwise edit distance (interpreted as encompassing a minimum pairwise Hamming distance of at least two times an error correction capability having a value of at least one, claim 9) (paragraph [0059], lines 14-16). Volkmuth teaches that one previously described approach for barcode design relies on generating oligonucleotides that are a certain Hamming distance (number of mismatches) apart, that follow an "error correcting" scheme such as a Hamming Code (see, e.g., Hamady et al., Nat. Method 5: 235-237 (interpreted as encompassing a minimum pairwise Hamming distance of at least two times an error correction capability having a value of at least one, claim 9) (paragraph [0076], lines 1-6), where it is known that the minimum Hamming distance between codewords needed to correct a single error is 3 as evidenced by Hamady (pg. 235, col 2; first full paragraph, lines 12-13). Volkmuth teaches that the present invention provides an approach to designing barcode tags that result in a higher success rate for correctly identifying the associated sample for a given sequencing platform (paragraph [0078]).
Regarding claim 10, Volkmuth teaches filtering the first dataset to remove one or more barcodes whose sequences have a G:C content above or below a predetermined threshold value; as well as, filtering the first dataset to remove one or more barcodes whose sequences include greater than three nucleotides in a row from the group consisting of G and C (interpreted combinations of barcodes 5 nucleotides in length as encompassing a GC content of less than 10%, claim 10) (paragraphs [0011]-[0012]; and [0016]). Volkmuth teaches that each barcode is from 5 to 40 nucleotides in length (interpreted combinations of barcodes 5 nucleotides in length and predetermined threshold values as encompassing a GC content of less than 10%, claim 10) (paragraphs [0017]).
Volkmuth meets all the limitations of the claims and, therefore, anticipates the claimed invention.
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 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 may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived 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, 2, 9 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Volkmuth et al. (hereinafter “Volkmuth”) (International Application 20150080266, published May 19, 2015) in view of Shum et. al. (hereinafter “Shum”) (US Patent Application Publication, 20190095578, published March 28, 2019) as evidenced by Hamady et al. (hereinafter “Hamady”) (Nature Methods, 2008, 5(3), 235-237).
The teachings of Volkmuth as applied to claims 1, 2, 9 and 10 are described supra.
Volkmuth does not specifically exemplify different features of the array (claim 2, in part).
Regarding claim 2 (in part), Shum teaches methods for determining occurrences of targets, comprising: (a) barcoding (e.g., stochastically barcoding) a plurality of targets using a plurality of barcodes (e.g., stochastic barcodes) to create a plurality of barcoded targets (e.g., stochastically barcoded targets), wherein each of the plurality of barcodes comprises a cell label and a molecular label, wherein molecular labels of at least two barcodes of the plurality of barcodes comprise different molecular label sequences, and wherein at least two barcodes of the plurality comprise cell labels with an identical cell label sequence; and (b) obtaining sequencing data of the barcoded targets (paragraph [0005], lines 1-13). Shum teaches that the term "adapter" can mean a sequence to facilitate amplification or sequencing of associated nucleic acids, wherein the associated nucleic acids can comprise target nucleic acids including one or more of spatial labels, target labels, sample labels, indexing label, or barcode sequences (e.g., molecular labels) (paragraph [0070], lines 1-7). Shum teaches a plurality of solid supports spaced in an array, wherein a solid support can be a bead; and that the term substrate can refer to an array, a cartridge, a chip, a device, and a slide (paragraphs [0082], lines 1-2 and 13-15; and [0083]). Shum teaches that Figure 1 shows that a barcode can comprise one or more labels including a universal label, a cell label, a barcode sequence (e.g., a molecular label), a sample label, a plate label, a spatial label, and/or a pre-spatial label (paragraph [0093], lines 1-5; and Figure 1). Shum teaches that the labels of the barcode (e.g., universal label, dimension label, spatial label, cell label, and barcode sequence) can be separated by 1, 2, 3, 4, 5…15, 16, 17, 18, 19, or 20 or more nucleotides, wherein a label can comprise a unique set of nucleic acid sub-sequences of defined length, e.g., seven nucleotides each (equivalent to the number of bits used in some Hamming error correction codes), which can be designed to provide error correction capability, wherein the set of error correction sub-sequences comprise seven nucleotide sequences can be designed such that any pairwise combination of sequences in the set exhibits a defined "genetic distance" (or number of mismatched bases), for example, a set of error correction sub-sequences can be designed to exhibit a genetic distance of three nucleotides; and the length of the nucleic acid sub-sequences used for creating error correction codes can vary including about 1, 2, 3, 4, 5…15, 20, 30, 31, 40, 50, or a number or a range between any two of these values, nucleotides in length, such that the nucleic acid sub-sequences of other lengths can be used for creating error correction codes (interpreting the genetic distance as a pairwise edit distance of 3; and error correction capabilities having a value of 1, claims 1 and 9) (paragraph [0094]). Shum teaches that a barcode can comprise one or more spatial labels comprising a nucleic acid sequence that provides information about the spatial orientation of a target molecule which is associated with the barcode, wherein the spatial label can be associated with a coordinate in a sample including a fixed coordinate, such as a coordinate fixed in reference to a substrate, in reference to a two or three-dimensional grid, and/or fixed in reference to a landmark (interpreting the coordinates as features, claim 2) (paragraph [0105], lines 1-10). Shum teaches that a spatial label can be associated with a physical partition such as a well, a container, or a droplet, such that multiple spatial labels can be used together to encode one or more positions in space (interpreting the physical partitions as features, claim 2) (paragraph [0105], lines 17-21). Shum teaches methods for estimating the number of distinct targets at distinct locations in a physical sample (e.g., tissue, organ, tumor, cell), which can comprise placing barcodes (e.g., stochastic barcodes) in close proximity with the sample, lysing the sample, associating distinct targets with the barcodes, amplifying the targets and/or digitally counting the targets method can further comprise analyzing and/or visualizing the information obtained from the spatial labels on the barcodes including visualizing the plurality of targets in the sample (interpreting distinct locations as features, claim 2) (paragraph [0154], lines 1-10).
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 barcoding distinct targets at distinct locations in a physical sample as exemplified by Shum, 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 for optimizing and producing barcodes designed for multiplex DNA sequencing, wherein the plurality of barcodes are used to label a plurality of samples as disclosed by Volkmuth to include the method of using an array of barcodes to estimate the number of distinct targets at distinct locations in a physical sample such as in a tissue, organ, tumor, or cell, as taught by Shum with a reasonable expectation of success in using barcoded beads to spatially label distinct targets within a physical sample; in associating distinct targets with unique barcodes such that the distinct targets within the sample can be digitally counted; and/or in analyzing and/or visualizing the information obtained from the spatial labels on the barcodes.
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.
Conclusion
Claims 1, 2, 9 and 10 are rejected.
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/AMY M BUNKER/Primary Examiner, Art Unit 1684