Ilumina, Inc.

Patent Trials and Appeals Board

Jan 10, 2022

2020005167 (P.T.A.B. Jan. 10, 2022)

UNITED STATES PATENT AND TRADEMARK OFFICE UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O. Box 1450 Alexandria, Virginia 22313-1450 www.uspto.gov APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO. 15/471,730 03/28/2017 M. Shane Bowen IP-1334-US 1075 29389 7590 01/10/2022 Illumina, Inc 5200 Illumina Way San Diego, CA 92122 EXAMINER BUNKER, AMY M ART UNIT PAPER NUMBER 1639 NOTIFICATION DATE DELIVERY MODE 01/10/2022 ELECTRONIC Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the following e-mail address(es): Illuminadocket@illumina.foundationip.com hfoster@illumina.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte M. SHANE BOWEN, MICHAEL GRAIGE, STANLEY S. HONG, JOHN A. MOON, and MEREK SIU Appeal 2020-005167 Application 15/471,730 Technology Center 1600 Before JEFFREY N. FREDMAN, TAWEN CHANG, and MICHAEL A. VALEK, Administrative Patent Judges. CHANG, Administrative Patent Judge. Appeal 2020-005167 Application 15/471,730 2 DECISION ON APPEAL Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the Examiner’s decision to reject claims 1, 3, 7, 9, 11-13, 21, and 22.2 We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. STATEMENT OF THE CASE “Various protocols in biological or chemical research involve performing a large number of controlled reactions on solid support surfaces or within predefined reaction chambers.” Spec. 1:11-13. “In some conventional fluorescent-detection protocols, an optical system is used to direct an excitation light onto fluorescently-labeled analytes and to also detect the fluorescent signals that may emit from the analytes.” Id. at 1:23- 25. According to the Specification, “[t]he resolution of standard imaging techniques is constrained by the number of pixels available in the detection device, among other things,” and “these optical systems can be relatively expensive and require a relatively large bench-top footprint when detecting surfaces having large collection of analytes.” Id. at 1:25-29. Further according to the Specification, “[l]imits in resolution increase cost and 1 We use the word “Appellant” to refer to “applicant” as defined in 37 C.F.R. § 1.42. Appellant identifies the real party in interest as Illumina, Inc. Appeal Br. 2. The Appeal Brief and the Reply Brief are not paginated; we refer to page numbers of the Appeal Brief and Reply Brief in this decision as if the briefs were consecutively numbered starting with the first page. 2 Claims 2, 4-6, 8, 10, 14, 15, and 17-20 has been cancelled, and claim 16 has been withdrawn. Appeal Br. 21-22 (Claims App.). Appeal 2020-005167 Application 15/471,730 3 decrease accuracy in these analyses,” and, “[t]hus, there exists a need for higher resolution apparatus and methods.” Id. at 2:1-3. CLAIMED SUBJECT MATTER The claims are directed to an array. Claim 1 is illustrative: 1. An array, comprising: a solid support having an exterior surface comprising a first set of wells interleaved with a second set of wells, the first set of wells each having a first bottom at a first elevation, z1, from a base of the solid support, the second set of wells each having a second bottom at a second elevation, z2, from the base of the solid support; wherein a height difference between the first bottom of each of the first set of wells at the first elevation, z1, and the second bottom of each of the second set of wells at the second elevation, z2, along the z axis is greater than 0.5 μm and less than 25 μm, wherein a first analyte of interest of a first well of the first set of wells is optically distinguishable when an optical detector is focused for a first focal plane for the first set of wells and a second analyte of interest of a second well of the second set of wells is not optically distinguishable when the optical detector is focused for the first focal plane for the first set of wells; wherein the first set of wells have a first pitch of at most 0.5 μm; wherein the second set of wells have a second pitch of at most 0.5 μm; and wherein a pitch between each of the first set of wells and each adjacent well of the second set of wells is less than 0.4 μm. Appeal Br. 21 (Claims App.). Appeal 2020-005167 Application 15/471,730 4 REJECTIONS A. Claims 1, 3, 7, 9, 11-13, 21, and 22 are rejected under 35 U.S.C. § 102(a1)/(a2) as being anticipated by Barnard.3 Ans. 4. B. Claims 1, 3, 9, 11-13, 21, and 22 are rejected under 35 U.S.C. § 102(a1)/(a2) as being anticipated by Law.4 Ans. 6. C. Claims 1, 3, 7, 9, 11-13, 21, and 22 are rejected under 35 U.S.C. § 102(a1)/(a2) as being anticipated by Chou.5 Ans. 8. D. Claims 1, 3, 7, 9, 11-13, 21, and 22 are rejected under 35 U.S.C. § 103 as being unpatentable over Barnard. Ans. 9. E. Claims 1, 3, 7, 9, 11-13, 21, and 22 are rejected under 35 U.S.C. § 103 as being unpatentable over Law and Barnard. Ans. 12. OPINION A. Claim Construction We begin our analysis with claim construction. “It is axiomatic that, in proceedings before the PTO, claims in an application are to be given their broadest reasonable interpretation consistent with the specification and that claim language should be read in light of the specification as it would be interpreted by one of ordinary skill in the art.” In re Sneed, 710 F.2d 1544, 1548 (Fed. Cir. 1983) (citation omitted). i. Wells “The Examiner interpret[s] the terms ‘a first set of wells’ and ‘a second set of wells’ to refer to wells of any form including, for example, 3 Barnard et al., US 2014/0243224 A1, published Aug. 28, 2014. 4 Law et al., US 2013/0065794 A1, published Mar. 14, 2013. 5 Chou et al., WO 2013/154770, published Oct. 17, 2013. Appeal 2020-005167 Application 15/471,730 5 holes, pits, matrices, grooves, ridges, spots and/or depressions in any surface including, for example, chromatography plate, membrane, optical film, microwell plate, polymer surface, a set of test tubes, a set of flasks on a benchtop, a microfluidic chip, multiwall culturing plate, a concrete or asphalt road, etc.” Ans. 3. Appellant contends that, “in the context of the Specification, the appropriate broadest reasonable interpretation of the term ‘wells’ is ‘wells of any form including, for example, holes and/or depressions in any surface.’” Reply Br. 2. We agree with Appellant that the Examiner’s construction of wells, which appears to include raised structures (e.g., ridges) that do not contain a concave feature, is unreasonably broad. See, e.g., Ans. 8 (interpreting “a plurality of pillars” as “a first set of wells”), 19 (interpreting a “peak” as z1, i.e., the elevation of the bottom of a first set of wells from a base of the solid support). The Examiner asserts that the Specification does not define the terms “a first set of wells” and “a second set of wells” and that, “[a]s to the ordinary or customary meaning of the term, . . . a ‘well’ is defined in part as a source from which something may be drawn as needed.” Ans. 22-23. Id. at 23. The Examiner asserts that the Specification teaches that “substrates can include glass, quartz, plastic such as polystyrene, acrylic copolymer, silicon, nylon, latex, dextran and gel matrix,” and that she interprets this list of substrates as “materials having pores, wherein the pores within the materials as wells and sets of wells.” Id. The Examiner further asserts that the Specification teaches that “analytes can be attached via intermediate structures including beads, wherein beads, gels or a polymer mesh can be Appeal 2020-005167 Application 15/471,730 6 present in a well, on a post or at other surface contours set forth therein,” and that, “[t]hus, the wells and contours of the instant structure are inherently present on, and/or can be modified to, comprise the ‘sets of wells’ of the instant invention.” Id. We are not persuaded. “Although the PTO must give claims their broadest reasonable interpretation, this interpretation must be consistent with the one that those skilled in the art would reach.” In re Cortright, 165 F.3d 1353, 1358 (Fed. Cir. 1999). Plain and ordinary meanings of “well” include a “space having a . . . shape suggesting a well for water” and “an open space extending vertically through floors of a structure.”6 Although the Examiner is correct that another meaning of “well” is “a source from which something may be drawn as needed,” we conclude that this definition is unreasonably broad when read in light of the Specification. For example, wells are separately enumerated from other structures, e.g., depressions, pits, channels, projections, posts, pillars, ridges, raised regions, and pegs in the Specification, suggesting that the term describes more than simply any type of source from which something may be drawn. Spec. 5:20-21, 7:23-25, 8:26-29, 15:23-24. Similarly, “[p]rior art references may be ‘indicative of what all those skilled in the art generally believe a certain term means . . . [and] can often help to demonstrate how a disputed term is used by those skilled in the art.’” In re Cortright, 165 F.3d at 1358. In this case, Barnard, a cited prior art reference in an analogous art, defines “well” as 6 “well.” MERRIAM-WEBSTER, https://www.merriam-webster.com/ dictionary/well (last visited Dec. 17, 2021). Appeal 2020-005167 Application 15/471,730 7 a discrete concave feature in a solid support having a surface opening that is completely surrounded by interstitial region(s) of the surface. Wells can have any of a variety of shapes at their opening in a surface . . . . The cross section of a well taken orthogonally with the surface can be curved, square, polygonal, hyperbolic, conical, angular, etc. Barnard ¶ 46. This definition is consistent with the plain and ordinary meaning of well as a “space having a . . . shape suggesting a well for water” or “an open space extending vertically though floors of a structure.” Accordingly, we construe “well” in the claims on appeal to mean a space having a shape suggesting a well for water, i.e., a discrete concave feature having a surface opening. Finally, we are not persuaded by the Examiner’s assertion that Appellant did not dispute the Examiner’s construction of the term during prosecution. Ans. 23. Although the Appeal Brief may not include any new or non-admitted evidence, see 37 C.F.R. § 41.37(c)(2), Appellant’s arguments with respect to the construction of the term “well” is not new “evidence.” ii. Pitch The Examiner “has interpreted the term ‘a pitch between the first set of wells and the second set of wells is less than about 0.4[]µm[’] to include a flat surface of a base having no pitch.” Ans. 3. We are not persuaded. The Specification states that, “the term ‘pitch,’ when used in reference to features of an array, is intended to refer to the center-to-center spacing for adjacent features” and “refers to spacing in the xy dimension.” Spec. 11:1-3. Accordingly, “a pitch between each of the first set of wells and each adjacent well of the second set of wells is less than 0.4 µm” means that the distance between the center of a well in the first set Appeal 2020-005167 Application 15/471,730 8 and the center of any adjacent well in the second set, is less than 0.4 µm. This construction does not encompass “a flat surface of a base having no pitch,” at least because a flat surface does not contain any concave features and thus does not have any “wells” as we have construed that term.7 B. Anticipation by Barnard (claims 1, 3, 7, 9, 11-13, 21, 22) 1. Issue The Examiner finds that Barnard teaches all of the limitations of claim 1. Ans. 4-6. Appellant first contends that the Examiner erred as a matter of law because the Examiner admits that she “does not believe Barnard teaches all elements of independent claim 1 explicitly or implicitly.” Appeal Br. 5. Appellant also contends that Barnard does not teach “different sets of wells with different depths and/or . . . pitch between the different set of wells . . . in the particular arrangement of independent claim 1.” Id. at 7. More specifically, Appellant contends that Barnard does not teach the recited height difference between the bottoms of a first and second sets of wells, because [Barnard’s] examples of well depths does not indicate using multiple well depths together, particularly where a first set of wells is at a first height and a second, interleaved set of wells is at a second height such that the height difference between the sets of interleaved wells along the z axis is greater than 0.5 μm and less than 25 μm. 7 We further note that having no pitch (i.e., a pitch of zero) would mean that the center of a well in the first set of wells is at the same spot as the center of an adjacent well of the second set of wells. The Examiner has not cited any persuasive evidence that such an interpretation is consistent with one those skilled in the art would reach. In re Cortright, 165 F.3d at 1358. Appeal 2020-005167 Application 15/471,730 9 Appeal Br. 7-8. Appellant further contends that Barnard does not teach the limitation that “a pitch between the first set of wells and the second set of wells is less than 0.4 μm” and that the Examiner erred in construing this limitation as including “a flat surface of a base having no pitch.” Id. at 8-9. Finally, Appellant contends that, even if Barnard discloses all of the limitations of claim 1, “the recitation of values for well depth and/or values for well pitch are multiple distinct teachings and the Office’s combinations of the different parts to meet several different elements of independent claim 1 are also in error.” Id. at 9-10. The issue with respect to this rejection is whether a preponderance of evidence supports the Examiner’s determination that Barnard teaches all of the limitations of claim 1 as recited in that claim. 2. Analysis We agree with Appellant that the Examiner has not established a prima facie case that Barnard discloses all of the limitations of claim 1 arranged or combined in the same way as recited in the claim. We reproduce Barnard’s Figures 2B, 4, and 6A below to facilitate our analysis. Appeal 2020-005167 Application 15/471,730 10 Barnard Fig. 2B (annotations added). Figure 2B of Barnard shows a fluorescent image of a “substrate modified to have gel material in the wells,” obtained after “polishing [the planar surface of the solid support] and hybridization to fluorescently labeled oligonucleotides.” Barnard ¶¶ 6, 13. Barnard Figs. 4, 6A. Figure 4 “shows high resolution fluorescence microscope images of nanowell substrates showing patterned gel features on the nanowell substrate.” Id. ¶ 15. Figure 6A shows “a multi-color merge of patterned clusters in a . . . sequencing run with a 750 nm pitch nanowell substrate.” Id. ¶ 17. “peak” “valley” FIG.4 FIG. 2B NILTS 750 nm pitch 550 nm wells NILT 5 1.5 µm pitch 550 nm wells FIG. 6A Appeal 2020-005167 Application 15/471,730 11 In response to Appellant’s arguments that Barnard does not disclose the limitations regarding height difference and pitch between the wells, the Examiner interprets a “peak” in Barnard’s Figure 2B as z1 and an adjacent “valley” as z2. Ans. 19. Citing to Figure 4 and paragraph 56 of Barnard, the Examiner further asserts that Barnard teaches “550 nm wells having a 750 nm pitch (corresponding to an elevation greater than 0.5 μm)” and also teaches that “the depth of each well can be at least 0.1 micron, 1 micron, 100 microns or more.” Id.; see also id. at 4. The Examiner concludes that, accordingly, “based on the broadest reasonable interpretation of the claim language, Barnard . . . teach[es] a height[ difference between z1 and] z2, along the z axis[, that] is greater than 0.5 μm and less than 25 μm.” Id. at 19. The Examiner further argues that Figures 4 and 6A of Barnard teach “a 750 nm pitch nanowell substrate, when z1 is a peak and z2 is an adjacent valley, such that a pitch of 750 [nm] measured valley to valley in Barnard . . . is actually a pitch of 375 [nm] measured peak to valley (corresponding to a pitch of less than 0.4 μm,” i.e., “less than 0.5 μm, and less than about [0.]4 μm.” Id. at 19. We are not persuaded. As an initial matter, the Examiner does not persuasively show that the cited paragraphs and figures are part of the same embodiment or are otherwise “directly related to each other by the teachings of [Barnard].” In re Arkley, 455 F.2d 586, 587 (CCPA 1972) (explaining that, for an anticipation rejection to be proper, the reference must “clearly and unequivocally disclose the claimed [invention] or direct those skilled in the art to the [invention] without any need for picking, choosing, and combining various disclosures not directly related to each other by the teachings of the cited reference”). To anticipate, however, “it is not enough Appeal 2020-005167 Application 15/471,730 12 that the prior art reference . . . includes multiple, distinct teachings that the artisan might somehow combine to achieve the claimed invention.” Net MoneyIN, Inc. v. VeriSign, Inc., 545 F.3d 1359, 1371 (Fed. Cir. 2008). Furthermore, the Examiner’s prima facie case for anticipation appears to rely on the construction of the term “well” as encompassing a “peak” depicted in Figure 2B. As discussed above, we conclude that such a construction of “well” is unreasonably broad. Accordingly, for the reasons discussed above, we reverse the Examiner’s rejection of claim 1 as anticipated by Barnard. We reverse the rejection of claims 3, 7, 9, 11-13, 21, and 22, which depend directly or indirectly from claim 1, for the same reasons. C. Anticipation by Law (claims 1, 3, 9, 11-13, 21, 22) 1. Issue The Examiner finds that Law teaches all of the limitations of claim 1. Ans. 6-7. Appellant first contends that the Examiner “admits that Law . . . fails to disclose all elements of independent claim 1” and that an anticipation rejection is therefore inappropriate. Appeal Br. 10. Appellant further contends that the rejection relies on an unreasonably broad interpretation of the terms “a first set of wells,” “a second set of wells,” and pitch. Id. at 14- 15. Appellant further contends that the Examiner has not established a prima facie case that Law teaches the height difference or pitch limitations of claim 1. Id. at 12-16. The issue with respect to this rejection is whether a preponderance of evidence supports the Examiner’s determination that Barnard teaches all of the limitations of claim 1 as recited in that claim. Appeal 2020-005167 Application 15/471,730 13 2. Analysis We agree with Appellant that the Examiner has not established a prima facie case that Law discloses all of the limitations of claim 1 arranged or combined in the same way as recited in the claim. We reproduce Law’s Figure 3 below to facilitate our analysis. Law Fig. 3. Figure 3 depicts “some of the different topographical formations that were fabricated.” Id. ¶ 116. In response to Appellant’s arguments that Law does not teach the height difference and pitch limitations of claim 1, the Examiner cites Law’s Figure 3 and paragraph 116 and asserts that Law teaches “a 2 μm line (Figs. 3a and 3c), a 1 μm dimple (Fig. 3e), and 2 μm pillars (Figure 3f) (corresponding to greater than 0.5 μm and less than 25 μm).” Ans. 22. The ~igure 3 Appeal 2020-005167 Application 15/471,730 14 Examiner asserts Law also teaches that “the size of the structures can be customized to meet particular requirements, and . . . the height of the topographic formation can be in the microscale from about 1 μm to about 10 μm.” Id. The Examiner asserts that, accordingly, “based on the broadest reasonable interpretation of the claim language, Law . . . teaches all of the limitations of the claims including a first bottom at a first elevation, z1, and the second bottom at a second elevation, z2, along the z-axis is greater than 0.5 μm and less than 25 μm.” Id. We are not persuaded. As an initial matter, it is not clear whether the dimensions quoted from Figure 3 and paragraph 116 refer to the height of the topographical feature or something else such as the diameter. Compare Law ¶ 116 with ¶ 117 (explicitly describing height). In this regard, we note that “if a reference is ambiguous and can be interpreted so that it may or may no[t] constitute an anticipation of an appellant’s claims, an anticipation rejection under 35 U.S.C. § 102 based upon the ambiguous reference is improper.” In re Brink, 419 F.2d 914, 917 (CCPA 1970). Furthermore, the claim recites a height difference greater than 0.5 μm and less than 25 μm. It is not clear which two dimensions the Examiner is comparing to arrive at the “greater than 0.5 μm and less than 25 μm” limitation. To the extent the Examiner is comparing the “height” of the topographical feature to the surface of the substrate, the Examiner has not persuasively shown how the surface of the substrate may be considered a “well” so as to make up “a . . . set of wells” under the construction of “well” as set forth earlier in the opinion. To the extent that the Examiner is comparing the dimensions of the different topographical features (e.g., the line or pillars to the dimple), the Appeal 2020-005167 Application 15/471,730 15 Examiner also has not explained how topographical features such as lines or pillars would be considered “wells.” Moreover, the Examiner has not persuasively shown that all of the topographical formations are fabricated on the same base or substrate. In particular, although Law teaches that “[a] wide range of different topographies . . . could be incorporated on a single substrate,” Law ¶ 108, and teaches Figure 3 shows “some of the different topographical formations that were fabricated”, id. ¶ 116, Law does not explicitly teach incorporating the particular topographies cited by the Examiner on a single substrate. Moreover, even if Law teaches incorporating all of the topographical formations in Figure 3 on the same substrate, the Examiner has not cited to any teaching in Law that these formations are interleaved with one another, as recited in the claims. As discussed above, picking, choosing, and combining different disclosures in the reference not directed related to each other by the reference itself is improper in an anticipation rejection. In re Arkley, 455 F.2d at 587. For the same reason, we are not persuaded that Law’s general disclosure in paragraphs 55 and 56 of the height ranges of its topographical formations (e.g., “from about 1 micron to about 10 microns,” etc.) suffices to establish a prima facie case of anticipation. Such disclosure does not in itself teach an embodiment comprising all of the limitations of claim 1 arranged in the manner recited in the claim, even if it may, when combined with other disclosures in the reference, render claim 1 obvious. With respect to the pitch limitations of claim 1, the Examiner asserts: Law et al. teach in Example 1, making a topographical structure including gratings, pillars, and dimples (interpreted as wells including a first set of wells and a second set of wells), wherein the substrate can be comprised of silicon, glass, polymers, and Appeal 2020-005167 Application 15/471,730 16 metals (interpreting the pores of the substrate as wells), and wherein in step (a) of Figure 1c, PDMS is spin-coated onto the silicon substrate, thus, interpreted by the Examiner as providing a polymer layer comprising pores (interpreting polymer pores as wells including sets of wells having a pitch of less than 0.4 μm). Moreover, Law et al. teach in Figure 4(a) . . . an interleaved pattern of wells, wherein z1 is 0 nm and z2 is 123.4 nm and, thus, indicating a pitch of less than 0.4 μm. . . . Furthermore, Law et al. teach that that the size of the structures can be customized to meet particular requirements, and that the pitch can be in the nanoscale and can be selected from the group consisting of about 100 nm to about 500 nm (See, paragraphs [0054]; and [0057]). Thus, based on the broadest reasonable interpretation of the claim language Law et al. teach all of the limitations of the claim language. Ans. 24. We are not persuaded. As we understand the Examiner’s position, the Examiner first asserts that Law discloses substrates made of porous polymers, and asserts that the pores within the polymers are wells that inherently have a pitch of less than 0.4 µm. However, the Examiner has not provided any explanation why a pore within a polymer would read on a well as recited in the claim. Moreover, assuming that pores reads on wells, we note that “[i]nherency may not be established by probabilities or possibilities,” Scaltech Inc. v. Retec/Tetra L.L.C., 178 F.3d 1378, 1384 (Fed. Cir. 1999), and the Examiner has not provided any explanation why the pores of Lam’s substrate will necessarily form a first and second set of wells having the recited height difference and pitches. Neither are we persuaded by the Examiner’s assertion that “Law et al. teach in Figure 4(a) . . . an interleaved pattern of wells, wherein z1 is 0 nm Appeal 2020-005167 Application 15/471,730 17 and z2 is 123.4 nm and, thus, indicating a pitch of less than 0.4 μm.” Ans. 24. We reproduce Law’s Figure 4 below to facilitate our analysis. Figure 4 “shows a range of topographical formations with different heights,” including “(a) 250 nm line 250 nm space gratings with 120 nm height; (b) 250 nm pillars, 500 nm pitch with 250 nm height; [and] (c) 1 µm pitch mirolens with 90 nm sag.” Law ¶ 117. The Examiner provides no persuasive argument why the height of a topographical feature would indicate anything about pitch. Indeed, given that there appears to be five line/space sets in 2.50 µm of distance in Figure 4(a), the pitch would appear to be 0.5 µm rather than less than 0.4 µm. To the extent the Examiner’s position is that the “line” is the first set of wells and the “space” is the second set of wells - and hence the pitch between the two sets of “wells’ is 0.25 µm (i.e., half of 0.5 µm) - we are not persuaded because, as discussed above, the Examiner has not persuasively explained why a “line” would be considered a “well” within the meaning of claim 1. (b) (c) ' ,n ---------- 8- N! '' .~ . -------,---~~- 0 :i. ~ ~.o i . S 10 .0 Figur e 4 Appeal 2020-005167 Application 15/471,730 18 Finally, we are not persuaded by the Examiner’s citation to Law’s disclosures that “the size of the structures can be customized to meet particular requirements” and that “pitch . . . can be selected from the group consisting of about 100 nm to about 500 nm,” because, while such disclosures may be relevant to an obviousness rejection, they require picking, choosing, and combining various disclosures to arrive at the claim, which is not appropriate in an anticipation rejection. In re Arkley, 455 F.2d at 587. Accordingly, for the reasons set forth above, we reverse the Examiner’s rejection of claim 1 as anticipated by Law. We reverse the rejection of claims 3, 9, 11-13, 21, and 22, which depend directly or indirectly from claim 1, for the same reasons. D. Anticipation by Chou (claims 1, 3, 7, 9, 11-13, 21, and 22) 1. Issue The Examiner finds that Chou teaches all of the limitations of claim 1. Ans. 8-9. Appellant contends that the rejection relies on an unreasonably broad construction of “wells” as encompassing the pillars disclosed in Chou. Appeal Br. 16. Appellant further contends that, even if Chou’s pillars could be construed as wells, the Examiner “has still failed to establish that Chou discloses a second set of wells.” Id. The issue with respect to this rejection is whether a preponderance of evidence supports the Examiner’s assertion that Chou discloses all of the limitations of claim 1 arranged in the same way as recited in the claim. 2. Analysis Appeal 2020-005167 Application 15/471,730 19 We agree with Appellant that the Examiner has not established a prima facie case that Chou discloses all of the limitations of claim 1 arranged or combined in the same way as recited in the claim. We reproduce Figures 1A and 1B below to facilitate our analysis. Chou, Figs. 1A & 1B. Figures 1A and 1B “schematically illustrate some features of [an] embodiment of [Chou’s] nanodevice,” which is designed to “enhance a luminescence signal (e.g.[,] a fluorescence signal) and detection sensitivity of biological and chemical assays.” Spec. 1:14-18; 2:6-9. The Examiner asserts that substrate 110 (as labeled in Fig. 1A) reads on the “base of the solid support” as recited in claim 1; metallic discs 130 on top of the pillars 115 (as labeled in Figs. 1A & 1B) read on “a first set of wells” at “a first elevation, z1”; and the metallic back-plane 150 (as labeled in Figs. 1A & 1B) at the foot of the pillar reads on “a second set of wells” at “a second elevation, z2.” Ans. 26. The Examiner cites to Figure 7C, reproduced below, to support the assertion that Chou’s “pillar array [has] a 200 nm pitch (interpreted as a pitch of less than 0.4 µm): Chou Fig. 7. Figure 7c is a “[s]canning electron micrograph (SEM) of [disk- coupled dots-on-pillar antenna array (D2PA)] with 200 nm period (overview A }115 Appeal 2020-005167 Application 15/471,730 20 and cross-section),” with “gold nanodots rest[ing] on the silica nano-pillar sidewalls.” Id. at 2:21-31. We agree with Appellant that the Examiner has not persuasively explained how the metallic discs on top of Chou’s pillars are “wells” as we have construed that term. Likewise, we are not persuaded that the metallic back-plane 150 may be considered a “set of wells.” As shown in Figure 1A, the metallic back-plane 150 appears to be a continuous flat sheet (i.e., there are no individual “wells” separated from other wells). Because we are not persuaded that the either the metallic discs on top of Chou’s pillars or the metallic back-plane is a set of wells, we are also not persuaded that Chou teaches the limitations in claim 1 regarding the pitches of the sets of wells. The Examiner asserts that Chou also teaches a molecular adhesion layer 160 comprising “an inner surface that is attached to the nanodevice and an outer (exterior[)] surface[] that can be bound to capture agents,” which may be in the form of “multi-molecular layers of thin film of a polymer.” Ans. 26. The Examiner “interpret[s] the pores of the polymer film as a set of wells[, with] a pitch of less than 0.4 µm.” Id. We are not persuaded for the reasons already discussed above: The Examiner does not persuasively explain how pores within a polymer film is a set of wells as we have construed the phrase above; neither has the Examiner provided any persuasive explanation of why, even if such pores may be considered a set of wells within the meaning of the claims, they would inherently meet the other limitations of the claims such as the recited pitch limitations and height differences between two sets of wells. Accordingly, for the reasons discussed above, we reverse the Examiner’s rejection of claim 1 as anticipated by Chou. We reverse the Appeal 2020-005167 Application 15/471,730 21 rejection of claims 3, 7, 9, 11-13, 21, and 22, which depend directly or indirectly from claim 1, for the same reasons. E. Obviousness over Barnard (claims 1, 3, 7, 9, 11-13, 21, and 22) 1. Issue The Examiner finds that Barnard teaches all of the limitations of claim 1 and that the claims are no more than a “combin[ation of] prior art elements according to known methods to yield predictable results.” Ans. 11. The Examiner concludes that, in view of the benefits of providing an array of wells in a solid support as exemplified by Barnard et al., it would have been prima facie obvious for one of skill in the art before the effective filing date of the claimed invention to modify the gel patterned surface in the array of wells in a solid support separated by interstitial regions in the method of making and using the array as disclosed by Barnard et al. to include combinations of sets of wells that comprise a single species of target nucleic acid and differ in size, depth, pitch, area, and/or volume as disclosed by Barnard et al. with a reasonable expectation of success in determining which layouts, patterns and/or designs of the wells accommodate a desired throughput, resolution, analyte composition, and/or analyte reactivity for downstream use of the substrate including genomics analysis, gene expression analysis and/or RNA sequencing; for carrying out reactions on the analytes in the wells; distinguishing at least a subset of target analytes that interact with one or more probes and/or to distinguish the wells having a target nucleic acid species that binds to at least one probe. Id. at 11-12. Appellant contends that the Examiner has not “articulate[d] a reason with rational underpinning why one would modify Barnard to arrive at the elements of independent claim 1.” Appeal Br. 18; Reply Br. 6-8. Appeal 2020-005167 Application 15/471,730 22 The issue with respect to this rejection is whether a preponderance of evidence supports the Examiner’s assertion that a skilled artisan would have had reason to combine the teachings of Barnard to arrive at the invention recited in claim 1. 2. Findings of Fact 1. Barnard teaches “an array that includes a solid support having a surface, the surface having a plurality of wells . . . separated from each other by interstitial regions on the surface.” Barnard ¶ 5. 2. Barnard teaches that the wells of its array may contain gel material, which can “in turn be attached to an analyte of interest, such as a nucleic acid.” Barnard ¶ 19. 3. Barnard teaches that “patterned array of nucleic acids in gel- containing wells provides multiple advantages for DNA sequencing” and that “[e]xamples of advantages compared to random arrays (i.e.[,] arrays having a random pattern of features) include increased density of feature packing, increased control and tuning of feature density using concentration- independent template seeding, reduced processing requirements for image registration and increased ease of signal extraction.” Barnard ¶ 21; see also id. ¶ 19 (teaching that its array “provides advantages when carrying out reactions on the analytes and/or detecting the analytes,” including, e.g., distinguishing the individual features of the array “with relative ease due to the discrete pattern created by the gel-containing wells”). 4. Barnard teaches that, for its array comprising wells, “each well can have any volume that is capable of confining a liquid” and that “[t]he minimum or maximum volume can be selected . . . to accommodate the throughput (e.g.[,] multiplexity), resolution, analyte composition, or analyte Appeal 2020-005167 Application 15/471,730 23 reactivity expected for downstream uses of the substrate.” Barnard ¶ 55; see also id. ¶ 85 (teaching that “size or volume of the wells . . . can be adjusted to influence the purity of analytes captured”). 5. Barnard teaches that “[t]he area occupied by each well opening on a surface can be selected based upon similar criteria as those set forth above for well volume,” that “[t]he depth of each well can be at least 0.1 µm, 1 µm, 10 µm, 100 µm or more,” and that, “[a]lternatively or additionally, the depth can be at most 1x103 µm, 100 µm, 10 µm, 1 µm, 0.1 µm or less.” Barnard ¶ 56. 6. Barnard teaches that “[m]any different layouts of wells or other concave features may be envisaged, including regular, repeating, and non- regular patterns.” Barnard ¶ 57. 7. Barnard teaches that “repeating pattern,” when used in reference to wells on a surface, means that the relative locations of a subset of wells in one region of the surface is the same as the relative locations of a subset of wells in at least one other region of the surface. Thus, the relative locations for wells in one region of a repeating pattern are generally predictable from the relative locations of wells in another region of the repeating pattern. The subset used for the measure will generally include at least 3 wells but can include at least, 4, 5, 6, 10 or more wells. Exemplary repeating patterns include rectilinear patterns and hexagonal patterns. A repeating pattern can include multiple repetitions of a sub-pattern. Barnard ¶ 41. 8. Barnard teaches that “[a] pattern of wells can be characterized in terms of the average pitch (i.e.[,] center-to-center spacing) for the wells.” Barnard ¶ 58. Barnard teaches that “the average pitch can be, for example, at least 10 nm, 0.1 μm, 0.5 μm, 1 μm, 5 μm, l0 μm, 100 μm or more. Alternatively or additionally, the average pitch can Appeal 2020-005167 Application 15/471,730 24 be, for example, at most 100 μm, 10 μm, 5 μm, 1 μm, 0.5 μm[,] 0.1 μm or less. Of course, the average pitch for a particular pattern of wells can be between one of the lower values and one of the upper values selected from the ranges above. Id. 3. Analysis We agree with the Examiner that claim 1 is obvious over Barnard. Barnard teaches “an array that includes a solid support having a surface, the surface having a plurality of wells . . . separated from each other by interstitial regions on the surface.” FF1. Barnard further teaches that the wells in its array may have different characteristics (e.g., volume, size of well opening, and depth), as well as different layouts, including regular and repeating layouts. FF4-FF7. Thus, Barnard suggests a solid support of its array comprising “a first set of wells interleaved with a second set of wells,” as recited in claim 1. With respect to the limitations regarding the elevations of the first and second set of wells and the height difference between the two elevations, Barnard teaches that “[t]he depth of each well can be at least 0.1 µm, 1 µm, 10 µm, 100 µm or more,” and that, “[a]lternatively or additionally, the depth can be at most 1x103 µm, 100 µm, 10 µm, 1 µm, 0.1 µm or less.” FF5. Similarly, with respect to the limitations regarding pitch, Barnard teaches that “[a] pattern of wells can be characterized in terms of the average pitch (i.e.[,] center-to-center spacing) for the wells” and that the average pitch can be “at least 10 nm, 0.1 μm, 0.5 μm, 1 μm, 5 μm, l0 μm, 100 μm or more” and that, “[a]lternatively or additionally, the average pitch can be, for example, at most 100 μm, 10 μm, 5 μm, 1 μm, 0.5 μm[,] 0.1 μm or less.” FF8. Thus, Barnard suggests ranges of height differences and pitches Appeal 2020-005167 Application 15/471,730 25 between wells that overlaps the recited height difference of “greater than 0.5 μm and less than 25 μm” and recited pitches of at most 0.5 μm or less than 0.4 μm. The disclosure of such overlapping ranges suffices to establish a prima facie case of obviousness as to the limitations regarding height difference and pitch and shifts the burden to the Appellant to show that they would not have been obvious. In re Peterson, 315 F.3d 1325, 1330 (Fed. Cir. 2003). Appellant has not provided persuasive evidence that the recited ranges of height difference and pitches exhibits unexpected results or are otherwise non-obvious. Finally, although Barnard does not explicitly teach the limitation that the only the analyte in the first set of wells (and not the analyte in the second set of wells) is optically distinguishable when an optical detector is focused for a first focal plane, Barnard renders prima facie obvious an array having the recited height difference that would inherently meet this limitation. Moreover, in light of Barnard’s teaching that characteristics of the wells may be selected to optimize, e.g., throughput and resolution, we find that a skilled artisan would have optimized the height difference between the first and second set of wells to arrive at the recited claim limitation. Appellant contends that the Examiner has not articulated a reason to combine the elements of Barnard to arrive at the claimed invention. Appeal Br. 17-18; Reply Br. 6-8. We are not persuaded for reasons already discussed above. Barnard teaches that various characteristics of the well, such as volume and the area occupied by well opening on the surface (and hence also the depth), can be selected to accommodate specific analytical parameters including “throughput (e.g.[,] multiplexity) and resolution.” FF4, FF5. Thus, we find Appeal 2020-005167 Application 15/471,730 26 that Barnard discloses the general conditions of a claim and establishes that characteristics such as height and pitch are result-effective variables. See In re Applied Materials, Inc., 692 F.3d 1289, 1297 (Fed. Cir. 2012) (“A recognition in the prior art that a property is affected by the variable is sufficient to find the variable result-effective.”). Accordingly, the specifically recited patterning of the wells, including the heights and pitches of the first and second set of wells, merely expresses the optimum or workable ranges that a skilled artisan would have arrived at by routine experimentation. “[T]he discovery of an optimum value of a variable in a known process is normally obvious.” In re Antonie, 559 F.2d 618, 620, 195 USPQ 6, 8 (CCPA 1977); see also Applied Materials, 692 F.3d at 1297 (“[G]enerally, a claim to a product does not become nonobvious simply because the patent specification provides a more comprehensive explication of the known relationships between the variables and the affected properties.”). As discussed above, Appellant has not provided persuasive evidence to the contrary. Accordingly, for the reasons discussed above, we affirm the Examiner’s rejection of claim 1 as obvious over Barnard. Claims 3, 7, 9, 11-13, 21, and 22, which were not separately argued, fall with claim 1. F. Obviousness over Law and Barnard 1, 3, 7, 9, 11-13, 21, and 22) 1. Issue The Examiner finds that Law teaches all of the limitations of claim 1, except that it does not “specifically teach a first set of wells interleaved with a second set of wells.” Ans. 13. The Examiner concludes that, in view of the benefits of providing an array of wells in a solid support as exemplified by Barnard et al., it would have been prima facie obvious for one of skill in the art . . . to modify the Appeal 2020-005167 Application 15/471,730 27 wells, dimples, pillars, and trenches of the patterned microarray of structures having a plurality of different topographies on a single substrate including wells of different heights in the method of making arrays for cell assays as disclosed by Law et al. to include the gel material and/or to select specific areas and/or densities of wells as taught by Barnard et al. with a reasonable expectation of success in creating a low-cost, scalable, and high- throughput customizable microarrays having different topographies on a single substrate for the detection, reaction, and/or analysis of analyte, wherein the microarrays accommodate a desired throughput, resolution, analyte composition, and/or analyte reactivity for downstream use of the substrate. Moreover, it would have been prima facie obvious before the effective filing date of the claimed invention to use the nano-print technology as disclosed by Law et al. to create a plurality of wells in an array comprising gel material in a selected area as taught by Barnard et al. with a reasonable expectation of success in in creating a low-cost, scalable, and high-throughput customizable microarrays having different topographies on a single substrate that can accommodate a desired throughput, resolution, analyte composition, and/or analyte reactivity for downstream use of the substrate including genomics analysis, gene expression analysis and/or RNA sequencing; for carrying out reactions on the analytes in the wells; distinguishing at least a subset of target analytes that interact with one or more probes; and/or to distinguish the wells having a target nucleic acid species that binds to at least one probe. Ans. 14-15. 2. Findings of Fact 9. Law teaches that “the main obstacle facing cell-topographical studies is the lack of a single surface possessing a large range of different topographies, such as different heights, dimensions and feature shapes, in order to facilitate fast microscopy-based screening and subsequent analysis of the data generated.” Law ¶ 3. 10. Law teaches “an array for cell assays comprising . . . an array of Appeal 2020-005167 Application 15/471,730 28 structure on a substrate, each of said structures having a pre-defined topography thereon, and wherein at least one structure has a different topography from at least one other structure.” Law Abstract; see also id. ¶ 72 (teaching “an ordered array of structures on [a] substrate”), ¶ 75 (explaining that the structure may be a circle, a square, or any arbitrary shape or size, and that size of the structures can be customized to meet particular requirements). 11. Law teaches that “the topographical formations may comprise . . . wells” having diameters in the microscale or nanoscale. Law ¶¶ 66-67. 12. Law teaches that “[t]he various topographies include . . . complex three-dimensional hierarchical structures.” Law ¶ 108; see also id. ¶ 110 (describing using a sequential imprinting process to create hierarchical structures), ¶ 124 (describing a hierarchical structure of 2 µm line, 2 µm space + 250 nm line, 250 nm space), ¶ 130 (describing various hierarchical structures including a structure of 2 µm line and 2 µm space + 250 nm diameter holes). 13. Law teaches that the height of the topographical formations may be in the microscale (e.g., from about 1 micron to about 10 microns) or in the nanoscale (e.g., from about 10 nm to about 1000 nm). Law ¶¶ 55-56; see also id. ¶ 117 (describing Figure 4 as showing “a range of topographical formations with different heights, including, e.g., gratings with 120 nm height, pillars with 250 nm height, and microlens with 90 nm sag). 14. Law teaches that, where topographical formations may have an associated pitch, the pitch may be in the microscale (e.g., from about 0.5 microns to about 15 microns) or in the nanoscale (e.g., from about 100 nm to about 1000 nm). Law ¶ 57. Appeal 2020-005167 Application 15/471,730 29 3. Analysis We agree with the Examiner that claim 1 is obvious over Law and Barnard. Law teaches an array comprising structures on a substrate, which reads on an array comprising “a solid support having an exterior surface,” as recited in claim 1. FF10. Law also teaches that the structures of its array have a pre-defined topography and that such topography may comprise wells. FF11. While Law teaches using wells in its array, Law does not explicitly teach a first set of wells interleaved with a second set of wells. Nevertheless, Law teaches that the structures of its array may have “three- dimensional hierarchical structures” that combine different topographical features such as lines having different dimeters or lines/space and holes (i.e., wells). FF10-FF12. Law also teaches that the height of the topographical formations in its array may be in the microscale (e.g., from about 1 micron to about 10 microns) or in the nanoscale (e.g., from about 10 nm to about 1000 nm). FF13. We find that Law’s teaching of three-dimensional hierarchical structures suggests a structure comprising two sets of wells having different elevations, as recited in claim 1. In addition, given these teachings, and given Barnard’s suggestion of repeating patterns of wells with different depths (discussed above), we find that the combination of Law and Barnard renders obvious the limitations relating to “a first set of wells interleaved with a second set of wells” and the limitations relating to elevations and height difference of the first and second set of wells. Law further teaches that, where topographical formations may have an associated pitch, the pitch may be in the microscale (e.g., from about 0.5 microns to about 15 microns) or in the nanoscale (e.g., from about 100 nm to Appeal 2020-005167 Application 15/471,730 30 about 1000 nm). FF14. Thus, Law suggests wells having pitches that overlaps the recited range of pitches (i.e., “at most 0.5 μm” and “less than 0.4 μm”) and renders these limitations prima facie obvious. Finally, although Law and Barnard do not explicitly teach the limitation that the only the analyte in the first set of wells (and not the analyte in the second set of wells) is optically distinguishable when an optical detector is focused for a first focal plane, the cited combination of references renders prima facie obvious an array having the recited height difference that would inherently meet this limitation. Moreover, in light of Barnard’s teaching that characteristics of the wells may be selected to optimize, e.g., throughput and resolution, and Law’s teaching that a single surface possessing a range of topographies of different heights and dimensions would be useful to facilitate fast microscopy-based screening in, e.g., cell-topographical studies, FF9, we find that a skilled artisan would have optimized the height difference between the first and second set of wells to arrive at the recited claim limitation. Appellant contends that “the Office failed to articulate a reason with rational underpinning regarding why one would modify Law in view of Barnard or even how one would modify Law in view of Barnard to arrive at the elements of independent claim 1.” Appeal Br. 19; see also Reply Br. 6- 8. We are not persuaded for the reasons already discussed. In summary: Law teaches that an array comprising topographies of different dimensions, including wells, is useful for facilitating fast microscopy-based screening and data analysis. FF9. Barnard also teaches an array comprising wells and teaches that “[m]any different layouts of wells . . . may be envisaged,” including interleaved patterns of wells having different depths (i.e., wells Appeal 2020-005167 Application 15/471,730 31 having different elevations from the base). FF5-FF7; see also Barnard Fig. 2B. Barnard teaches that the dimensions of the wells are result-effective variables for, among other things, throughput (e.g.[,] multiplexity) and resolution, FF4, and Barnard and/or Law teaches elevations/height differences and/or pitches of the wells that are in the ranges of those claimed. Thus, a skilled artisan would have had reason to modify an array comprising a first set of wells interleaved with a second set of wells having different elevations, as suggested by the combination of Law and Barnard, to arrive at the height difference and pitches recited in claim 1, in order to achieve the desired/optimum throughput and resolution. Accordingly, for the reasons discussed above, we affirm the Examiner’s rejection of claim 1 as obvious over Law and Barnard. Claims 3, 7, 9, 11, 13, 21, and 22, which are not separately argued, fall with claim 1. CONCLUSION In summary: Claim(s) Rejected 35 U.S.C. § Reference(s)/ Basis Affirmed Reversed 1, 3, 7, 9, 11, 13, 21, 22 102(a)(1), 102(a)(2) Barnard 1, 3, 7, 9, 11, 13, 21, 22 1, 3, 9, 11, 13, 21, 22 102(a)(1), 102(a)(2) Law 1, 3, 9, 11, 13, 21, 22 1, 3, 7, 9, 11, 13, 21, 22 102(a)(1), 102(a)(2) Chou 1, 3, 7, 9, 11, 13, 21, 22 1, 3, 7, 9, 11, 13, 21, 22 103 Barnard 1, 3, 7, 9, 11, 13, 21, 22 1, 3, 7, 9, 11, 13, 21, 22 103 Law, Barnard 1, 3, 7, 9, 11, 13, 21, 22 Overall Outcome 1, 3, 7, 9, 11, 13, 21, 22 Appeal 2020-005167 Application 15/471,730 32 TIME PERIOD FOR RESPONSE No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a). See 37 C.F.R. § 1.136(a)(1)(iv). AFFIRMED