DETAILED ACTION
Status of the Claims
Claims 323-348 are currently pending.
Claims 323-337 have been withdrawn as being drawn to non-elected subject matter (see below).
Claim 338 is currently amended.
Claim 348 is new.
Claims 338-348 are examined herein.
The following Office Action is in response to Applicant’s communication dated 04/09/2026. Rejection(s) and/or objection(s) not reiterated from previous office actions are hereby withdrawn. The following rejection(s) and/or objection(s) are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 04/09/2026 has been entered.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Restriction Requirement
Applicant’s election without traverse of Group II (claims 338-347) in the reply filed on 02/17/2025 is acknowledged.
Claims 323-337 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 02/17/2025.
Withdrawn Rejection(s) and/or Objection(s)
The objections to the specification and the drawings because of Figures 5 and 6 being mis-labeled are withdrawn in light of the amendment to the specification submitted by Applicant in the response of 12/31/2025.
Claim Rejections – 35 U.S.C. 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.
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.
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 factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Drmanac et al. and Staker
Claims 338-347 are rejected under 35 U.S.C. 103 as being unpatentable over Drmanac et al. (U.S. PGPub 2016/0017414, cited in IDS of 11/17/2023, of record) in view of Staker (U.S. PGPub 2011/0268347 A1).
Regarding claim 338, Drmanac discloses a method comprising:
providing a flow cell comprising a plurality of binding sites of at least 10,000 binding sites (e.g., high density as per ¶0034 and/or the Abstract) separated by disjunctions on a surface of the flow cell (e.g., flow cell as per ¶¶0086-0087);
delivering a plurality of nucleic acids to the plurality of binding sites on the surface of the flow cell (e.g., “Isolated concatemers are then disposed onto support surface to form a random array of single molecules” (internal references omitted) as per ¶0033, forming random arrays as per ¶0018, ¶0028, and/or Fig. 1);
obtaining a plurality of images of the flow cell (e.g., multiple section images acquired as per ¶0118);
aligning the disjunctions in a plurality of flow cell images to align the plurality of flow cell images (e.g., aligning images using empty regions as per ¶0118); and
sequencing the plurality of nucleic acids (e.g., “large scale sequence determination” as per ¶0097).
However, it is noted that while Drmanac discloses that the disjunctions between the concatemers are irregularly distributed (e.g., random arrays as per ¶0018, ¶0028, and/or Fig. 1), it is silent as to the disjunctions separating the binding sites are irregularly distributed, as set forth in claim 338.
Staker discloses a flow cell surface with functionalized DNA binding sites arranged in fields (e.g., as per ¶¶0032-0033, 0076, and/or 0122-0123), including fields having approximately 10,000 to 1,000,000 binding sites (e.g., as per ¶0040) for DNA concatemers to be delivered and sequenced (e.g., such as DNA nanoball concatemers as per ¶¶0038-0041, 0073, 0075, 0077, and/or 0121). Importantly, Staker discloses intentionally reserving predetermined sites which cannot be used as DNA binding sites for nanoballs, thus forming a two-dimensional “pseudo-random” pattern that reads on the limitation of irregularly spaced disjunctions of claim 338 (e.g., as per ¶¶0044-0046 and/or 0113-0117).
It would have been prima facie obvious to a person of ordinary skill in the art prior to the effective filing date of the application to form the flow cell with irregularly spaced DNA binding sites as per Staker in the flow cell as per Drmanac. One of ordinary skill in the art would have been motivated to do so since both references outline the same array-based DNA sequencing platform and the method of Drmanac provides a known method of making the clonally amplified concatemers that the disclosure of Staker images and aligns. In accordance with MPEP 2141 citing KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, 82 USPQ2d 1385,1395 (2007), "[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results”, and as per MPEP 2143(I)(A), the rationale to support a conclusion that the 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 yielded nothing more than predictable results to one of ordinary skill in the art. In the present case, all of the elements of the flow cell DNA sequencing platform were well known in the art, as per Drmanac and Staker, the mere combining of the individual elements in one embodiment in the manner of the claimed invention results in no change in the elements respective functions, and the combination yields nothing more than predictable results.
One of ordinary skill in the art would have had a reasonable expectation of success as of the application’s effective filing date in combining the teachings of the prior art references to arrive at the invention as presently claimed since Staker explicitly recites the assembly of DNA nanoball methods in flow cells of Drmanac as a “promising approach to whole genome studies” enabling “complete human genome sequencing for the detection of rare variants in large-scale genetic studies” (e.g., as per ¶¶0038-0039).
Regarding claim 339, Drmanac discloses the above, wherein the nucleic acids are concatemers that are rolling circle amplification (RCA) products (e.g., products of rolling circle replication as per ¶0033 and Fig. 1).
Regarding claim 340, Drmanac discloses the above, further comprising performing rolling circle amplification (RCA) in solution by extending an amplification primer or a splint primer with a plurality of templates to generate the concatemers, prior to depositing the concatemers on the binding sites (e.g., conjugates can be formed prior to disposal to the array as per ¶0041).
Regarding claim 341, Drmanac discloses the above, wherein the concatemer is bound to an intermediate nucleic acid, and wherein the intermediate nucleic acid is a DNA tile (e.g., a “macromolecular structure” such as concatemers made by rolling circle amplification as per ¶0040 and/or Fig. 1E).
Regarding claim 342, Drmanac discloses the above, comprising forming concatemers on the binding sites of the flow cell by rolling circle amplification (RCA) of a target nucleic acid from splint oligonucleotides (e.g., as per ¶0041 and/or Fig. 1I).
Regarding claim 343, Drmanac discloses the above, wherein the splint oligonucleotides are each presented by a DNA tile bound to a binding site of the plurality of binding sites (e.g., as per ¶0041 and/or Fig. 1G-1I).
Regarding claim 344, Drmanac discloses the above, wherein the DNA tile comprises a plurality of capture sequences each comprising a portion of a splint oligonucleotide (e.g., as per ¶0041 and/or Fig. 1G-1I).
Regarding claim 345, Drmanac discloses the above, comprising:
providing a plurality of asymmetric DNA tiles;
providing a plurality of concatemers;
binding individual concatemers to a first side of individual DNA tiles in solution;
and depositing the DNA tiles on the surface of the flow cell such that a second side of the individual DNA tiles binds to the binding sites of the surface while the first side of the individual DNA tiles remains bound to a concatemer (e.g., as per ¶0041 and/or Fig. 1G-1I).
Regarding claim 346, Drmanac discloses the above, wherein at least 50% of the binding sites comprise a single monoclonal nucleic acid cluster (e.g., substantially all as per the Abstract and/or ¶0008).
Regarding claim 347, Drmanac discloses the above, further comprising sequencing the concatemers (e.g., “large scale sequence determination” as per ¶0097).
Drmanac et al., Staker, and Gopinath et al.
Claims 338-348 are rejected under 35 U.S.C. 103 as being unpatentable over Drmanac et al. (U.S. PGPub 2016/0017414, cited in IDS of 11/17/2023, of record) in view of Staker (U.S. PGPub 2011/0268347 A1) further in view of Gopinath et al. (WO 2019/108954 A1).
Drmanac and Staker are relied on as above, however, the references are silent as to the limitation of the flow cell being generated using colloidal self-assembly, as set forth in claim 348.
Gopinath discloses methods of making high density DNA-binding site arrays using colloidal self-assembly (e.g., using close-packed nanosphere monolayers as per ¶¶0043-0046 and/or 0052-0054).
It would have been prima facie obvious to a person of ordinary skill in the art prior to the effective filing date of the application to form the flow cell with irregularly spaced DNA binding sites as per Gopinath in the flow cell as per Drmanac in view of Staker. One of ordinary skill in the art would have been motivated to do so since Gopinath explicitly presents their colloidal self-assembly methods as a highly scalable way of making high-density arrays (e.g., as per ¶¶0043-0046), which are of interest to Drmanac and Staker.
Note that the colloidal self-assembly method as disclosed by Gopinath does not explicitly state that it would result in irregularly spaced disjunctions, however, the method of Gopinath is substantially identical to that of the present invention, and therefore there would be reason to believe that the process of Gopinath would yield irregularly spaced disjunctions similar or the same as the present invention. It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter which there is reason to believe inherently includes functions that are newly cited or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to "prove that subject matter shown to be in the prior art does not possess characteristic relied on" (205 USPQ 594, second column, first full paragraph).
One of ordinary skill in the art would have had a reasonable expectation of success as of the application’s effective filing date in combining the teachings of the prior art references to arrive at the invention as presently claimed since Gopinath’s colloidal self-assembly process predictably produces a set array pattern, including disjunctions at domain boundaries that can be used for image alignment.
Conclusion
No claims are allowed.
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/JEREMY C FLINDERS/
Primary Examiner, Art Unit 1684
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