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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/16/2023 is being considered by the examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 100 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 100 recites the limitation "the sub-regions irradiated in step (a)". There is insufficient antecedent basis for this limitation in the claim. Claim 96 in which 100 depends on, does not mention irradiation taking place in step (a).
Claim Rejections - 35 USC § 103
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.
Claim(s) 96-102 and 104-119 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mcdermott et. al (WO 2022147134 A1, Filed 12/29/21) IDS REF. in view of Burgess et. al. (WO 2021167807 A1, Published 8/26/21) IDS REF.
The applied reference has a common assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Mcdermott teaches a method for generating a molecular array by irradiation of a substrate through a first photomask comprising an opening corresponding to a region of a plurality of regions on the substrate, wherein a first oligonucleotide of at least four nucleotides in length is attaches to oligonucleotide molecules in the region to generate extended oligonucleotide molecules. Multiple cycles of the irradiation and oligonucleotide attachment can be performed, one cycle for each set of subregions, by translating the second photomask across the substrate until all sub-regions of all regions have received the second oligonucleotide, thereby providing on the substrate an array comprising oligonucleotide molecules ([0148], instant claims 96, 100, 101, 109, and 110). The sub-regions of the reference, equates to the second plurality of spatially separated regions of instant claims 109 and 110. Instant claim 96 requires delivering a solution that comprises a ligase as defined by paragraph [0021] of the specifications. Examiner is interpreting the composition containing ligase of the reference ([0059]), as the solution of instant claim 96.
Mcdermott teaches that photo-cleavable moieties of oligonucleotide molecules in the first region are cleaved to render oligonucleotide molecules in the first region available for hybridization and/or ligation, whereas oligonucleotide molecules in the second region are protected by photo-cleavable moieties of oligonucleotide molecules in the second region from hybridization and/or ligation ([0055], instant claim 97).
Mcdermott teaches the polynucleotide comprising the first barcode may comprise a photocleavable moiety that blocks hybridization and/or ligation, as shown in Figure 3 ([0096], instant claim 98).
Mcdermott teaches an embodiment where the surface of the substrate is coated with a photoresist ([0147], instant claim 99).
Mcdermott teaches the printing of the first solution onto the substrate ([0079], instant claim 102).
Mcdermott teaches instant claim 104, wherein the first oligonucleotide comprises a first barcode sequence, and the first barcode sequence for a given spatially separated region is different in sequence from the first barcode sequence for another spatially separated region ([0020]).
Mcdermott teaches claim 105, wherein the first oligonucleotide comprises a sequence that hybridizes to a first splint which in turn hybridizes to the oligonucleotide molecules, wherein the first oligonucleotide is ligated to the oligonucleotide molecules using the first splint as a template to generate the extended oligonucleotide molecules ([0058]).
Mcdermott teaches barcode sequences for different cycles (e.g., each cycle for a different region of the substrate) in the same round can comprise the same or different sequences, and preferably the barcode sequences for different cycles are different ([0052], instant claim 106).
Mcdermott teaches that hybridization can be blocked using a synthetic nucleotide with a photo-cleavable protecting group on a nucleobase and/or a photo-cleavable hairpin that dissociates upon cleavage ([0077], instant claim 107).
Mcdermott teaches cycles of two rounds can be combined into one cycle and the regions in these cycles receive the same oligonucleotide, and in Round 3 the regions after Cycle (N - 1) may be grouped into two sets where each set may receive a different oligonucleotide ([0053], instant claim 108).
Mcdermott teaches the method comprising M rounds, wherein M is an integer of 2 or greater, and each of the M rounds comprises one or more cycles for attaching oligonucleotides to polynucleotide molecules in one or more regions of the substrate (e.g., for one or more features on the array). The method of Mcdermott further comprises irradiating the substrate through a second photomask comprising multiple openings corresponding to a set of sub-regions each of which is in one of the regions, wherein a second oligonucleotide of at least four nucleotides in length is attached to the extended oligonucleotide molecules in the set of subregions to generate further extended oligonucleotide molecules. Multiple cycles of the irradiation and oligonucleotide attachment can be performed, one cycle for each set of subregions, by translating the second photomask across the substrate until all sub-regions of all regions have received the second oligonucleotide. A third round is performed in the same manner, wherein the substrate is irradiated through a third photomask comprising multiple openings corresponding to a set of sub- sub-regions each of which is in one of the sub-regions, wherein a third oligonucleotide of at least four nucleotides in length is attached to the further extended oligonucleotide molecules in the set of sub- sub-regions to generate even further extended oligonucleotide molecules ([0053], [0148], instant claims 111 and 118).
Mcdermott teaches the first polynucleotide is barcoded with the first barcode and the second polynucleotide is barcoded with the second barcode ([0014], instant claim 113).
Mcdermott teaches in Figure 11 for each well, uncaging of 100 x 5-micron segments leading to the addition of 20 different barcode sequences during the first round and a second round similarly ([0244], instant claim 114).
Mcdermott teaches repeating rounds to achieve barcode diversity, for example, by attaching a round 2 barcode (which may be the same or different for molecules in any two given features) to each growing oligonucleotide in the features, teaching on the limitation of claim 115 ([0080]). The art further teaches that multiple cycles of the irradiation and oligonucleotide attachment can be performed, one cycle for each set of subregions, by translating the second photomask across the substrate until all sub-regions of all regions have received the second oligonucleotide, thereby providing on the substrate an array comprising oligonucleotide molecules. The specifications of the instant application do not define “spatially separated” as possessing a defined boundary or wall. Therefore, subregions within the plurality of round 2 regions are interpreted by the examiner as being spatially separated ([0148], instant claims 116 and 117).
Mcdermott teaches an embodiment where a substrate structure is flat, the substrate structure can be any appropriate type of support having a flat surface (e.g., a chip, wafer, die, or a slide such as a microscope slide). Mcdermott further teaches that in some embodiments, oligonucleotides may be immobilized by spotting (e.g., DNA printing), indicating array generation in the absence of a cell or tissue sample on a substrate ([0079], [0146], instant claim 119).
Mcdermott fails to teach rotating the substrate and performing the Round 2 wherein the spatially separated regions intersect with the Round 1 spatially separated regions (limitations of instant claim 111) and a Round 3 spatially separated region overlaps with a Round 1 spatially separated region and/or a Round 2 spatially separated region (limitation of instant claim 118).
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Burgess teaches in FIG. 7 above, a magnified view of a portion of individual light -emitting areas (“pixels”) 150, each of which defines the surface of a distinct micro-LED light source within the array. Discrete pixels are surrounded and separated by a contiguous non-light-emitting surface area 180. The pixels of the reference could be grouped within the substrate to form regions that undergo the rounds of the claimed method in the instant application. The specifications of the instant application do not define a pattern in which the regions must intersect or a direction the substrate must be rotated. Examiner is interpreting the position of the pixels 150 in FIG. 7 as capable of being grouped in multiple regions that overlap and intersect at various points to be considered in multiple rounds simultaneously, teaching the limitations of instant claims 111 and 118. The contiguous non-light-emitting surface area 180 separates the pixel regions at 90-degree angles, teaching claim 112.
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to have modified the teachings of Mcdermott to incorporate the teachings of Burgess to generate an array with a plurality of spatially separated and uniformly arranged regions for processing large numbers of genes, proteins, or other biologically active molecules simultaneously. This high-throughput capability allows for rapid identification and assessment of genetic expression levels across an entire genome.
Claim(s) 103 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mcdermott et. al (WO 2022147134 A1, Filed 12/29/21) IDS REF. and Burgess et. al. (WO 2021167807 A1, Published 8/26/21) IDS REF. as applied to claims 96-102 and 104-119 above, and further in view of Onsemi (Onsemi, Semiconductor Components Industries, 2022).
The teachings of Mcdermott and Burgess are discussed above. Mcdermott and Burgess fail to teach a plurality of regions spatially separated on the substrate by regions having a width of about 1 mm or greater and a length of about 3 mm or greater. However, Onsemi teaches Silicon Photomultipliers (SiPM) formed of hundreds of thousands of microcells. Each microcell is an avalanche photodiode arranged in a close-packed array. Table 2 displays the SiPM sensor general parameters with an active area of 3 x 3 mm² on the microcells within the array, encompassing the spatial dimensions of claim 103 (pgs.5-6, instant claim 103).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to take the teachings of Mcdermott and Burgess to incorporate the teaching of Onsemi to generate a molecular array with spatially separated regions that possess the claimed dimensions, to maintain uniformity in hybridization conditions and prevent mixing of multiple samples on a substrate.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Avanda Harvey-Butler whose telephone number is (571)272-6511. The examiner can normally be reached M-F, 9-5 ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne Gussow can be reached at (571) 272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/A.H.B./Examiner, Art Unit 1683 /ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683