DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of irradiating a plurality of regions on a substrate through a first photomask comprising openings that correspond to a subset of the plurality of regions; irradiating the plurality of regions through a second photomask comprising openings that correspond to a subset of the plurality of regions; the first photomask comprises openings that correspond to one or more of the rows and the second photomask comprises openings that correspond to one or more of the columns; the plurality of regions are arranged in a hexagonal array; the substrate is a wafer in the reply filed on 12/18/2025 is acknowledged.
Claim100-103 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/18/2025.
Priority
The instant application was filed 06/28/2023 Claims Priority from Provisional Application 63356926 , filed 06/29/2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/13/2023 and 3/25/2026 are being considered by the examiner.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, 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 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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 statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - Sequences appearing in the drawings (figure 11) are not identified by sequence identifiers in accordance with 37 CFR 1.831(c). Sequence identifiers for sequences (i.e., “SEQ ID NO:X” or the like) must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Amended 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 (i.e., “SEQ ID NO:X” or the like) 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.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 88-99, 104-107 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 88 recites, “(a) irradiating a plurality of regions on a substrate through a first photomask comprising openings that correspond to all or a subset of the plurality of regions, wherein first oligonucleotides of at least four nucleotides in length [[is]]are attached to oligonucleotide molecules in the plurality of regions to generate extended oligonucleotide molecules;.” The metes and bounds are unclear if the wherein clause provides for the intended outcome of the irradiating step (a) or require the 4 nucleotides are present on the substrate prior to step (a). Further it is unclear if “the plurality of regions” in the wherein clause is limiting all plurality of regions or the subset of plurality of regions of the step (a). Thus one of ordinary skill in the art is not adequately apprised to the limitations of the claims so as to avoid infringement.
Claim 88 provides a wherein clause after step (b) which recites, “ wherein [[a]] second oligonucleotides of at least four nucleotides in length [[is]]are attached to the extended oligonucleotide molecules in the plurality of regions to generate further extended oligonucleotide molecules.” It is unclear if “the plurality of regions” in the wherein clause is limiting all plurality of regions or the subset of plurality of regions of the step (b). Thus one of ordinary skill in the art is not adequately apprised to the limitations of the claims so as to avoid infringement.
Claim 94 recites, “universal oligonucleotide molecules.” The recitation of universal suggests there is less than universal. Thus the recitation is a relative term. Review of the specification does not provide a standard to differentiate universal from non-universal. Thus the metes and bounds are unclear.
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.
Claim(s) 88-96, 99, 104, 107 is/are rejected under 35 U.S.C. 103 as being unpatentable over Pirrung (US 20050118706).
With regards to claim 88, Pirrung, “[0009] The production of a substrate having a matrix of positionally defined regions with attached reagents exhibiting known recognition specificity can be used for the sequence analysis of a polymer. Although most directly applicable to sequencing, the present invention is also applicable to fingerprinting, mapping, and general screening of specific interactions. The VLSIPS.TM. Technology (Very Large Scale Immobilized Polymer Synthesis) substrates will be applied to evaluating other polymers, e.g., carbohydrates, polypeptides, hydrocarbon synthetic polymers, and the like. For these non-polynucleotides, the sequence specific reagents will usually be antibodies specific for a particular subunit sequence.” Pirrung teaches, “[0257] If, for example, it is desired to synthesize all 16 dinucleotides from four bases, a 1 cm square synthesis region is divided conceptually into 16 boxes, each 0.25 cm wide. Denote the four monomer units by A, B, C, and D. The first reactions are carried out in four vertical columns, each 0.25 cm wide. The first mask exposes the left-most column of boxes, where A is coupled. The second mask exposes the next column, where B is coupled; followed by a third mask, for the C column; and a final mask that exposes the right-most column, for D. The first, second, third, and fourth masks may be a single mask translated to different locations.” Pirrung teaches “[0259] The eight masks used to synthesize the dinucleotide are related to one another by translation or rotation. In fact, one mask can be used in all eight steps if it is suitably rotated and translated. For example, in the example above, a mask with a single transparent region could be sequentially used to expose each of the vertical columns, translated 90.degree., and then sequentially used to allow exposure of the horizontal rows.”
While, Pirrung teaches photolithography of nucleic acids to a solid support using masks which can be translated or rotated. Pirrung does not specifically attachment of 4 nucleotides to the substrate.
However Pirrung teaches, “ In some embodiments, the subunit sequence is a polynucleotide or a polypeptide, in others the preselected multi-subunit length is five subunits and the subunit sequence is a polynucleotide sequence. In other embodiments, the specific reagent is an oligonucleotide of at least about five nucleotides.”
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to attach 4 or more nucleotides to the substrate and iteratively adding 4 or more nucleotides at a time using a first, second and third photomask which correspond to subregions of the solid support. The artisan would be motivated as Pirrung specifically envisions the addition of 5 or more nucleotides at t time. The artisan would have a reasonable expectation of success as the artisan is merely following the teachings of the art.
With regards to claim 89, Pirrung teaches, “[0259] The eight masks used to synthesize the dinucleotide are related to one another by translation or rotation. In fact, one mask can be used in all eight steps if it is suitably rotated and translated. For example, in the example above, a mask with a single transparent region could be sequentially used to expose each of the vertical columns, translated 90.degree., and then sequentially used to allow exposure of the horizontal rows.” Pirrung thus teaches masks for rows and columns.
With regards to claim 90, Pirrung teaches rows and columns are parallel to each other (figures 4A-4E).
With regards to claim 91, Pirrung teaches the columns are rows are at 90 degrees from each other (figures 4A-4E).
With regards to claim 92, Pirrung teaches, “[0230] The substrate, the area of synthesis, and the area for synthesis of each individual polymer could be of any size or shape. For example, squares, ellipsoids, rectangles, triangles, circles, or portions thereof, along with irregular geometric shapes, may be utilized. “
With regards to claim 93, Pirrung teaches, “The mask is designed in such a way that the exposure sites can be selected, and thus specify the coordinates on the array where each nucleotide can be attached. The process can be repeated, a new mask is applied activating different sets of sites and coupling different bases, allowing different oligonucleotides to be constructed at each site. “ (0617)
With regards to claim 94, Pirrung teaches, “For example, in the example above, a mask with a single transparent region could be sequentially used to expose each of the vertical columns, translated 90.degree., and then sequentially used to allow exposure of the horizontal rows”. (0259)
With regards to claim 95, Pirrung teaches the columns do not overlap (figures 4A-4E).
With regards to claim 96, Pirrung teaches, “ illustrates a completed substrate.” Thus Pirrung teaches multiples cycles for completion of the substrates.
The specification teaches, “0213] The term “barcode,” comprises a label, or identifier, that conveys or is capable of conveying information (e.g., information about an analyte in a sample, a bead, and/or a capture probe). A barcode can be part of an analyte, or independent of an analyte. A barcode can be attached to an analyte. A particular barcode can be unique relative to other barcodes. Barcodes can have a variety of different formats. For example, barcodes can include polynucleotide barcodes, random nucleic acid and/or amino acid sequences, and synthetic nucleic acid and/or amino acid sequences. A barcode can be attached to an analyte or to another moiety or structure in a reversible or irreversible manner. A barcode can be added to, for example, a fragment of a deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) sample before or during sequencing of the sample. Barcodes can allow for identification and/or quantification of individual sequencing-reads (e.g., a barcode can be or can include a unique molecular identifier or “UMI”).” Thus the broadest reasonable interpretation of a barcode is a nucleotide sequence.
Thus the teachings or Pirrung with respect to claim 88 render claim 99 obvious.
The specification provides no limiting definition of lawn of universal oligonucleotides. Thus the broadest reasonable interpretation is 4 or more nucleotides attached to the substrate.
Thus the first 5 oligonucleotides attached to the substrate broadly encompass a lawn of universal oligonucleotide molecules.
With regards to claim 107, Pirrung teaches, “The substrate may be biological, nonbiological, organic, inorganic, or a combination of any of these, existing as particles, strands, precipitates, gels, sheets, tubing, spheres, containers, capillaries, pads, slices, films, plates, slides.” Pirrung does not teach a cell or tissue is present on the substrate.
Claim(s) 92, 97-98, 106 is/are rejected under 35 U.S.C. 103 as being unpatentable over Pirrung (US 20050118706) as applied to claims 88-96, 99, 104, 107 above, and further in view of Augusto ( US 20210189475 , published Jun 24, 2021).
The teachings of Pirrung are set forth above.
Pirrung does not specifically teach the use of splint oligonucleotides.
However, Augusto teaches, “[0263] A “splint oligonucleotide” is an oligonucleotide that, when hybridized to other polynucleotides, acts as a “splint” to position the polynucleotides next to one another so that they can be ligated together. In some embodiments, the splint oligonucleotide is DNA or RNA. The splint oligonucleotide can include a nucleotide sequence that is partially complimentary to nucleotide sequences from two or more different oligonucleotides. In some embodiments, the splint oligonucleotide assists in ligating a “donor” oligonucleotide and an “acceptor” oligonucleotide. In general, an RNA ligase, a DNA ligase, or another other variety of ligase is used to ligate two nucleotide sequences together [0264] In some embodiments, the splint oligonucleotide is between 10 and 50 oligonucleotides in length, e.g., between 10 and 45, 10 and 40, 10 and 35, 10 and 30, 10 and 25, or 10 and 20 oligonucleotides in length. In some embodiments, the splint oligonucleotide is between 15 and 50, 15 and 45, 15 and 40, 15 and 35, 15 and 30, 15 and 30, or 15 and 25 nucleotides in length.”
Thus it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to use splint oligonucleotides to extend the oligonucleotides of the photolithography array of Pirrung. The artisan would be motivated to use splint arrays to allow extension by hybridization. The artisan would have a reasonable expectation of success as the artisan is merely using splint oligonucleotides of Augusto in the method of Pirrung. (97-98)
With regards to claim106, Augusto teaches, “0795] (4) Feature Geometric Attributes Features on an array can have a variety of sizes. In some embodiments, a feature of an array can have an average diameter or maximum dimension between 500 nm m to 100 m. For example, between 500 nm to 2 μm, 1 μm to 3 μm, 1 μm to 5 μm, 1 μm to 10 μm, 1 μm to 20 μm, 1 μm to 30 μm, 1 μm to 40 μm, 1 μm to 50 μm, 1 μm to 60 μm, 1 μm to 70 μm, 1 μm to 80 μm, 1 μm to 90 μm, 90 μm to 100 μm, 80 μm to 100 μm, 70 μm to 100 μm, 60 μm to 100 μm, 50 μm to 100 μm, 40 μm to 100 μm, 30 μm to 100 μm, 20 μm to 100 μm, 10 μm to 100 μm, about 40 μm to about 70 μm, or about 50 μm to about 60 μm. In some embodiments, the feature has an average diameter or maximum dimension between 30 μm to 100 μm, 40 μm to 90 μm, 50 μm to 80 μm, 60 μm to 70 μm, or any range within the disclosed sub-ranges. In some embodiments, the feature has an average diameter or maximum dimension no larger than 95 μm, 90 μm, 85 μm, 80 μm, 75 μm, 70 μm, 65 μm, 60 μm, 55 μm, 50 μm, 45 μm, 40 μm, 35 μm, 30 μm, 25 μm, 20 μm, 15 μm, 14 μm, 13 μm, 12 μm, 11 μm, 10 μm, 9 μm, 8 μm, 7 μm, 6 μm, 5 μm, 4 μm, 3 μm, 2 μm, or 1 μm. In some embodiments, the feature has an average diameter or maximum dimension of approximately 65 μm. In some embodiments, the feature has an average diameter or maximum distance of approximately 55 μm”
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to provide an array with oligonucleotides in regions of 1micrometer to 5 micrometers in diameter. The artisan would be motivated to provide an array with oligonucleotides in regions of 1micrometer to 5 micrometers in diameter as Augusto specifically teaches it. The artisan would further be motivated as providing an array with oligonucleotides in regions of 1micrometer to 5 micrometers in diameter would allow for a large number of oligonucleotides or probes in a small space. The artisan would have a reasonable expectation of success as the art demonstrates regions of the claimed size were known.
With regards to claim 92, Augusto teaches, “an array in a specific pattern or design (e.g., hexagonal design) to aid in orientation of a biological sample on an array of features on the substrate.”0557
Claim(s) 105 is/are rejected under 35 U.S.C. 103 as being unpatentable over Pirrung (US 20050118706) as applied to claims 88-96, 99, 104, 107 above, and further in view of McGall (Proc. Natl. Acad. Sci. USA Vol. 93, pp. 13555–13560)
The teachings of Pirrung are set forth above.
Pirrung does not specifically teach the use of photoresist in photolithography.
However, McGall teaches, “In this report we demonstrate the first direct application of polymeric semiconductor photoresists to the synthesis of high density oligonucleotide arrays. Our approach was to use a patterned photoresist film as a physical barrier to ‘‘mask’’ selected regions of the substrate from exposure to standard chemical reagents used in oligonucleotide synthesis. Here we take advantage of the nonlinear behavior typical of semiconductor resists, such that the resist is completely removed in exposed regions and still represents an impervious layer in the unexposed regions, even with relatively low-contrast light images. With appropriate modification, this general approach should also be applicable to the construction of combinatorial arrays of peptides and other molecules.” (13555, 2nd column, 1st full paragraph).
Thus it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claims to use photoresist in the photolithography method of Pirrung. The artisan would be motivated as McGall teaches, “These results demonstrate that polymeric photoresists can be used to fabricate high-density oligonucleotide arrays with standard DMT-protected nucleoside phosphoramidites and conventional semiconductor microlithography tools. A bilayer resist process was utilized, in which an inert polymer layer protects the surface bound oligonucleotide precursors from the resist chemistry and processing. Fabrication of 8-m features was demonstrated and higher resolution is likely with further process optimization. Test arrays prepared by this method displayed hybridization characteristics equivalent to those fabricated by previously reported methods. The primary advantages of this approach are that it provides access to higher-resolution arrays, and a commensurate increase in the volume and complexity of sequence information that can be encoded in a given area. It appears likely that an order of magnitude improvement in resolution is attainable with the photoresist approach. Work is in progress to optimize photoresist-based processes for the fabrication of oligonucleotide arrays with features on the order of 1 µm.” The artisan would have a reasonable expectation of success as McGall demonstrates photoresist with photolithography was known.
Summary
No claims are allowed.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEVEN C POHNERT PhD whose telephone number is (571)272-3803. The examiner can normally be reached Monday- Friday about 6:00 AM-5:00 PM, every second Friday off.
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/Steven Pohnert/ Primary Examiner, Art Unit 1683
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