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 .
Effective Filing Date
The present application, filed on May 26, 2022 claims the benefit of priority to U.S. Provisional Application No: 63/195,123, filed on May 31, 2021. Therefore, the effective filing date of the present application is determined to be May 31, 2021.
Claim Status/Action Summary
Claims 1-20 are pending in the present application.
Claims 1-20 are under examination.
Any objections and rejections not reiterated below are hereby withdrawn.
Claim Rejections - 35 USC § 102
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.
Claims 1, 4-9, 12-15, and 18-20 are/remain rejected under 35 U.S.C. 102(a)(1) as being anticipated by Fisher et al., WO 2020005503, published January 2, 2020.
This rejection has been updated as necessitated by the amendments to the claims.
Regarding claim 1, Fisher et al. teaches flow cells comprising a substrate, a plurality of reactive regions further comprising alternating first and second regions wherein the first and second regions are functionalized with different primer sets (Fisher et al., Figure 1A).
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Fisher et al. further teaches that the first and second regions directly abut each other (Fisher et al., Figure 1A) or are positioned on protrusions and adjacent depressions (Fisher et al., Figure 6A).
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Additionally, Fisher et al. teaches that each of the reactive regions including alternating first and second areas can be separated from each other by an “interstitial” (i.e. non-reactive) region to which primers are not attached (Fisher et al., Figure 24).
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Finally, Fisher et al. teach that while a single depression comprising the regions 14 and 16 are shown in figures 3A-6B, it is to be understood that a flow cell may include a plurality of depressions (Fisher et al., paragraph 0282) and that the layout of the depressions can include a hexagonal grid or an x-y format of depressions that are in rows and columns “for close packing and improved density” (Fisher et al., paragraph 0283) (i.e. a plurality of first areas and a plurality of second areas that are alternating)
Regarding claim 4, Fisher et al. teaches the non-reactive region is an exposed (i.e. uncoated) substrate region (26) (Fisher et al., Figure 6A and paragraph 0368).
Regarding claim 5, Fisher et al. teaches the primer sets are attached to the first and second areas through a polymer layer such as agarose, gelatin, or polyacrylamide polymers and copolymers (i.e. a polymeric hydrogel) (Fisher et al., paragraph 0219).
Regarding claim 6, Fisher et al. teaches that the first and second areas can be chemically different such that the first region has surface functional groups that can immobilize the first primer set, and the second region has different surface functional groups that can immobilize the second primer set (Fisher et al., paragraph 0220).
Regarding claim 7, Fisher et al. teaches first areas are positioned on protrusions and second areas are positioned on adjacent depressions separated by the sidewall of the depression (see Fisher et al., figure 6A above).
Regarding claim 8, Fisher et al. teaches a flow cell wherein the adjacent first and second areas are arranged into rows and columns (Fisher et al., paragraph 0283).
Regarding claim 9, Fisher et al. teaches the shape of the first and second areas can be a circle or a diamond (Fisher et al., paragraph 0283).
Regarding claim 12, Fisher et al. teaches the primer sets are attached to the first and second areas through a polymer layer such as agarose, gelatin, or polyacrylamide polymers and copolymers (i.e. a polymeric hydrogel) (Fisher et al., paragraph 0219).
Regarding claim 13, Fisher et al. teaches that the first and second areas can be chemically different such that the first region has surface functional groups that can immobilize the first primer set, and the second region has different surface functional groups that can immobilize the second primer set (Fisher et al., paragraph 0220).
Regarding claim 14, Fisher et al. teaches a flow cell with alternating regions of a first height and regions of a second height, wherein the two regions include primer sets that are different from each other (Fisher et al., Figure 6A and paragraph 0220).
Regarding claim 15, Fisher et al. teaches a flow cell comprising pillar-like features that were about 400 nm tall (i.e. at least 150 nm) (Fisher et al., paragraph 0583).
Regarding claim 18, Fisher et al. teaches that each of the reactive regions including alternating first and second areas can be separated from each other by an “interstitial” (i.e. non-reactive) region to which primers are not attached (Fisher et al., Figure 24) and the non-reactive region is an exposed (i.e. uncoated) substrate region (26) (Fisher et al., Figure 6A and paragraph 0368).
Regarding claim 19, Fisher et al. teaches the primer sets are attached to the first and second areas through a polymer layer such as agarose, gelatin, or polyacrylamide polymers and copolymers (i.e. a polymeric hydrogel) (Fisher et al., paragraph 0219).
Regarding claim 20, Fisher et al. teaches that the first and second areas can be chemically different such that the first region has surface functional groups that can immobilize the first primer set, and the second region has different surface functional groups that can immobilize the second primer set (Fisher et al., paragraph 0220).
Therefore, Fisher et al. teaches all of the recited features required by the claims.
Response to arguments
The response contrasts several figures from Fisher and the present application wherein the figures from the present application demonstrate an arrangement of first and second areas within each reactive region that directly abut one another (not separated by non-reactive or interstitial regions). The response asserts that the cited figures from Fisher illustrate one set of first and second areas are completely surrounded by the substrate or interstitial regions, and as such, the regions disclosed by Fisher are not arranged or combined in the same way as in the present claims.
This argument has been thoroughly reviewed and is not persuasive.
The teachings of Fisher et al. are not limited by the figures, and Fisher et al. expressly contemplates examples in which a plurality of arrayed first and second regions are directly adjacent to one another (Fisher et al., figure 24, and paragraphs 0572-0573) “each block [(58), comprising first and second areas 58A and 58B or 58C] includes a different block-specific functional group… block 58A serves as region 14 and block 58C serves as region 16. In another example, the regions 14, 16 may be blocks (e.g. 58A and 58B or 58B and 58C) that are directly adjacent to one another”. Therefore, the teachings of Fisher et al. are not limited to embodiments wherein each pair of first and second regions are completely surrounded by the substrate and encompass arrangements of including a plurality of depressions (i.e. reactive regions) (Fisher et al., paragraph 0282) and that the layout of the depressions can include a hexagonal grid or an x-y format of depressions that are in rows and columns “for close packing and improved density” (Fisher et al., paragraph 0283) (i.e. a plurality of first areas and a plurality of second areas that are alternating).
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.
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 3, 11, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Fisher et al., WO 2020005503, published January 2, 2020 in view of Yu et al., WO 2017/214561 A1, published December 14, 2017.
Regarding claim 3, Fisher et al. teaches flow cells comprising a substrate, a plurality of reactive regions further comprising alternating first and second regions wherein the first and second regions are functionalized with different primer sets (Fisher et al., Figure 1A).
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Fisher et al. further teaches that the first and second regions directly abut each other (Fisher et al., Figure 1A) or are positioned on protrusions and adjacent depressions (Fisher et al., Figure 6A).
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Finally, Fisher et al. teaches that each of the reactive regions including alternating first and second areas can be separated from each other by an “interstitial” (i.e. non-reactive) region to which primers are not attached (Fisher et al., Figure 24).
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Fisher et al. teaches that the first primer set includes an uncleavable first primer and a cleavable second primer, while the second primer set includes a cleavable first primer and an uncleavable second primer (Fisher et al., Figure 1, abstract). Fisher further teaches that the primer sets include P5 and P7 primers (Fisher et al., paragraph 0199-0200). In one example, Fisher teaches “the first primer set 12A includes P7, PSU and the second primer set 12A' includes PS, P7U. The primer sets 12A, 12A' have opposite linearization chemistries, which, after amplification, cluster generation, and linearization, enables forward template strands to be formed on one region 14 or 16 and reverse strands to be formed on the other region 16 or 14.” (Fisher et al., paragraph 0205).
Fisher et al. does not teach that one set of primers (i.e. 12A) can be 3’ blocked while the other set of primers (i.e. 12A’) is unblocked.
However, Yu et al. teaches 3’ blocked primers comprising a cleavable domain. Yu teaches the use of at least one such blocked primer in cluster-generation methods such as bridge amplification using blocked universal primers reduces nonspecific amplification products (Yu et al., paragraph 0005 and paragraph 00147).
Therefore, it would have been prima facie obvious prior to the effective filing date of the claimed invention for one of ordinary skill in the art to have modified one of the primer sets taught by Fisher et al. (i.e. 12A or 12A’) to further comprise 3’ blocking groups, as taught by Yu et al. The ordinary artisan would have been motivated to modify the primers taught by Fisher et al. with the 3’ blocking groups taught by Yu et al. because of the teaching of Yu et al. that 3’ blocking bridge amplification primers reduces nonspecific amplification. The ordinary artisan would have been reasonably confident that such a modification would have improved the specificity of the bridge amplification because Yu et al. teaches that said primers can be used in bridge amplification.
Regarding claim 11, Fisher et al. further teaches a flow cell wherein the adjacent first and second areas are arranged into rows and columns (Fisher et al., paragraph 0283).
Regarding claim 17, Fisher et al. further teaches a flow cell with alternating regions of a first height and regions of a second height, wherein the two regions include primer sets that are different from each other (Fisher et al., Figure 6A and paragraph 0220).
Response to arguments
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Claims 2, 10, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Fisher et al., WO 2020005503, published January 2, 2020 in view of Boutell et al., US 2009/0117621 A1, published May 7, 2009.
Regarding claim 2, Fisher et al. teaches flow cells comprising a substrate, a plurality of reactive regions further comprising alternating first and second regions wherein the first and second regions are functionalized with different primer sets (Fisher et al., Figure 1A) 12A, 12A’, 12B, 12B’, 12C, 12C’, and 12D, 12D’ (Fisher et al., paragraph 0193).
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Fisher et al. further teaches that the first and second regions directly abut each other (Fisher et al., Figure 1A) or are positioned on protrusions and adjacent depressions (Fisher et al., Figure 6A).
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Finally, Fisher et al. teaches that each of the reactive regions including alternating first and second areas can be separated from each other by an “interstitial” (i.e. non-reactive) region to which primers are not attached (Fisher et al., Figure 24).
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Fisher et al. teaches that the first primer set includes an uncleavable first primer and a cleavable second primer, while the second primer set includes a cleavable first primer and an uncleavable second primer (Fisher et al., Figure 1, abstract). Fisher further teaches that the primer sets include P5 and P7 primers (Fisher et al., paragraph 0199-0200). In one example, Fisher teaches “the first primer set 12A includes P7, P5U and the second primer set 12A' includes P5, P7U. The primer sets 12A, 12A' have opposite linearization chemistries, which, after amplification, cluster generation, and linearization, enables forward template strands to be formed on one region 14 or 16 and reverse strands to be formed on the other region 16 or 14.” (Fisher et al., paragraph 0205).
Fisher et al. does not teach that the second primer set includes any combination of “PA, PB, PC, and/or PD primers”. The “12A…12D” primer sets taught by Fisher et al., “are not shown for clarity” (Fisher et al., paragraph 0225).
However, Boutell et al. teaches several “universal” primer sets for cluster amplification and sequencing DNA (Boutell et al., paragraph 0008 and paragraph 0092 ;table 1) including primers “A” (SEQ ID NO:1), “B” (SEQ ID NO: 2), “C” (SEQ ID NO: 3), and “D” (SEQ ID NO: 4) that are identical to the claimed PA, PB, PC and PD primers (see alignments below).
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Therefore, it would have been prima facie obvious prior to the effective filing date of the claimed invention for one of ordinary skill in the art to have used the PA, PB, PC, and PD primers taught by Boutell et al. as the second primer sets 12A…12D in conjunction with P5/P7 first primer set as taught by Fisher et al. The ordinary artisan would have been motivated to select these primers as the second universal primer set for the flow cell taught by Fisher et al. because of the teaching of Boutell et al. that these primers constitute suitable universal primer pairs for cluster amplification and nucleic acid sequencing (Boutell et al., paragraph 0092-0100). The ordinary artisan would have been reasonably confident that the universal primers taught by Boutell et al. would have been suitable choices for the second primer set taught by Fisher et al. because Boutell et al. teaches using these primers in cluster generation for sequencing nucleic acids.
Regarding claim 10, Fisher et al. teaches a flow cell wherein the adjacent first and second areas are arranged into rows and columns (Fisher et al., paragraph 0283).
Regarding claim 16, Fisher et al. teaches a flow cell with alternating regions of a first height and regions of a second height, wherein the two regions include primer sets that are different from each other (Fisher et al., Figure 6A and paragraph 0220).
Response to arguments
In addition to the unpersuasive arguments regarding the teachings of Fisher (see response to arguments in the 102 section, the response argues that the combination of Fisher and Boutell does not teach or suggest using two completely different primer sets at different regions of the flow cell surface. This argument has been thoroughly reviewed and is not persuasive for the reasons which follow.
Fisher et al. expressly teach “Some of the flow cells include different primer sets attached to different regions of the flow cell substrate” (Fisher, paragraph 0138) and “The regions 14, 16 (see figures above) represent different areas on the substrate that have different primer sets 12A, 12A’, or 12B, 12B’, or 12C, 12C’, or 12D, 12D’ attached thereto.” (Fisher, paragraph 0211).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claim 4 of U.S. Patent No. 11,124,829 B2 issued September 21, 2021 (herein referred to as ‘829) in view of Fisher et al., WO2020005503.
This rejection has been updated as necessitated by the amendments to the claims.
Although the claims at issue are not identical, they are not patentably distinct from each other because ‘829 claims a flow cell comprising a substrate, a plurality of reactive regions (depressions) separated by interstitial regions (i.e. non-reactive regions; protrusions) wherein each of the depressions comprises a first and second region to which one of two primer sets is bound (‘829, claim 4). Claim 4 of ‘829 and amended claim 1 differ in the present claim recites that each of the reactive regions (i.e. depressions) comprises a plurality of first areas and a plurality of second areas that are alternating along the reactive region. The claims of ‘829 do not recite a plurality of alternating first and second areas within each reactive region. However, Fisher et al. teach that while a single depression comprising the regions 14 and 16 are shown in figures 3A-6B, it is to be understood that a flow cell may include a plurality of depressions (Fisher et al., paragraph 0282) and that the layout of the depressions can include a hexagonal grid or an x-y format of depressions that are in rows and columns “for close packing and improved density” (Fisher et al., paragraph 0283) (i.e. a plurality of first areas and a plurality of second areas that are alternating).
Therefore, it would have been prima facie obvious for one of ordinary skill in the art to have modified the invention of claim 4 (‘829) with the teachings of Fisher et al. to arrive at the invention of the present claim 1. The ordinary artisan would have been motivated to modify the invention of claim 4 with the teachings of Fisher et al. by the teaching of Fisher et al. that the layout of the depressions can include a hexagonal grid or an x-y format of depressions that are in rows and columns “for close packing and improved density” (Fisher et al., paragraph 0283).
Response to arguments
The response notes that “the PCT publication of U.S. Patent No. 11,124,829 is WO 2020/005503 (i.e., Fisher)” and asserts that the present claims are patentably distinct from the claims of the ‘829 patent for all the same reasons set forth (in the responses to the 102/103 rejections of record).
This argument has been thoroughly reviewed and is not persuasive. While the claims of ‘829 do not recite a plurality of first and second areas, the teachings of Fisher (published more than one year prior to the effective filing date of the claimed invention) are eligible as prior art under U.S.C. 102(a)(1). As described above, the recitation of “a plurality of first areas and a plurality of second areas” in the amended claim 1, while not anticipated by the claims of ‘829, would have been obvious over the claims of ‘829 in view of the disclosure of Fisher et al.
Conclusion
No claim is allowed
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/Z.M.T./Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682