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 .
DETAILED ACTION
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office Action.
Status of Claims
Claims 1, 2, 9, 14, 15 and 48-56 are currently pending. Claims 1 and 2 have been amended by Applicants’ amendment filed 02-24-2026. Claims 18-20, 22-24, 27, 30, 40-44 and 46 have been canceled by Applicant’s amendment filed 02-24-2026. Claims 48-56 have been added by Applicants’ amendment filed 02-24-2026.
Applicant's election without traverse of Group I, claims 1-3, 9, 14 and 15 directed to a method of inverting an oligonucleotide on a surface; and the election of Species without traverse as follows:
Species (A): wherein the first oligonucleotide comprises a free hydroxyl group (instant claim 2) (claim 2), in the reply filed on March 5, 2024 was previously acknowledged.
The restriction requirement is still deemed proper and is therefore made FINAL.
Claims 18-20, 22-24, 27, 30, 40-44 and 46 were previously withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 3 and 9 were previously withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim.
The restriction requirement was deemed proper and was made FINAL.
The claims will be examined insofar as they read on the elected species.
A complete reply to the final rejection must include cancellation of nonelected claims or other appropriate action (37 CFR 1.144) See MPEP § 821.01.
Therefore, claims 1, 2, 9, 14, 15 and 48-56 are under consideration to which the following grounds of rejection are applicable.
Priority
The present application filed September 18, 2020 is a 35 U.S.C. 371 national stage filing of International Application No. PCT/US2019/023245, filed on March 20, 2019; which claims the benefit of US Provisional Patent Application 62/646,279, filed March 21, 2018.
Withdrawn Objections/Rejections
Applicants’ amendment and arguments filed February 24, 2026 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Any rejection and/or
objection not specifically addressed below are herein withdrawn.
Claim Rejections - 35 USC § 102
The rejection of claims 1, 2, 14 and 15 is withdrawn under 35 U.S.C. 102(a1)/(a2) as being anticipated Zhou et al. (hereinafter “Zhou”) (US Patent No. 10391467, issued August 27, 2019; PCT publication date June 11, 2015; of record) as evidenced by Rehman et al. (hereinafter “Rehman”) (Nucleic Acids Research, 1999, 27(2), 649-655); and Mikkola (Beilstein J. Org. Chem., 2018, 14, 803-837); and Dong et al. (hereinafter “Dong”) (ACS Omega, 2019, 4, 3881-3886); and Kenny et al. (hereinafter “Kenny”) (BioTechniques, 2018, 25(3), 516-521).
Zhou does not specifically exemplify a quartz acceptor substrate.
In view of the withdrawn rejection, Applicant’s arguments are rendered moot.
Claim Rejections - 35 USC § 103
The rejection of claims 1, 2, 14 and 15 is withdrawn under 35 U.S.C. 103 as being unpatentable over Zhou et al. (hereinafter “Zhou”) (US Patent No. 10391467, issued August 27, 2019; PCT publication date June 11, 2015; of record) in view of Indermuhle et al. (hereinafter “Indermuhle”) (US Patent No. 10669304, issued June 2, 2020; effected filing date February 4, 2015; of record); as evidenced by Rehman et al. (hereinafter “Rehman”) (Nucleic Acids Research, 1999, 27(2), 649-655); and Mikkola (Beilstein J. Org. Chem., 2018, 14, 803-837); and Dong et al. (hereinafter “Dong”) (ACS Omega, 2019, 4, 3881-3886); and Kenny et al. (hereinafter “Kenny”) (BioTechniques, 2018, 25(3), 516-521).
The combined references of Zhou and Indermuhle do not specifically exemplify a quartz acceptor substrate.
In view of the withdrawn rejection, Applicant’s arguments are rendered moot.
Maintained Objections/Rejections
Claim Rejections - 35 USC § 112(b)
The rejection of claims 1, 2, 14 and 15 are maintained, and claims 48-56 are newly rejected, under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claim 1 is indefinite for the recitation of the term “said acrylamide solution or derivative thereof” such as recited in claim 1, line 29. There is insufficient antecedent basis for the term “said acrylamide solution or derivative thereof.” Moreover, claim 1, line 14 recites that the middle layer comprises polyacrylamide; such that the first oligonucleotide is not recited to be immobilized via an acrylamide solution or derivative thereof. Additionally, it is unclear how the first oligonucleotide can be immobilized to a solution (or a derivative of an acrylamide solution); and it is completely unclear as to the identity and/or structure encompassed by the term “derivative thereof” of an acrylamide solution and, thus, the metes and bounds of the claim cannot be determined.
Claims 53 and 54 are indefinite for the recitation of the term “full length” such as recited in claim 53, line 2 because it is unclear what structure and/or length the first oligonucleotide is being compared to, such that it is designated to be “full length.” It is unclear if claim 54 is intended to indicate that the entire oligonucleotide is transferred to the recipient substrate (e.g., is not truncated, or only partially transferred); or whether the term is meant to refer to something else and, thus, the metes and bounds of the claim cannot be determined.
Claims 2, 14, 15, 48-52, 55 and 56 are indefinite insofar as they ultimately depend from instant claim 1.
Claim Rejections - 35 USC § 103
Please Note: the references have been modified slightly in view of Applicant’s arguments and amendments, in the reply filed February 24, 2026.
The rejection of claims 1, 2, 14 and 15 is maintained, and claims 48-56 are newly rejected, under 35 U.S.C. 103 as being unpatentable over Zhou et al. (hereinafter “Zhou”) (US Patent No. 10391467, issued August 27, 2019; PCT publication date June 11, 2015; of record) in view of Indermuhle et al. (hereinafter “Indermuhle”) (US Patent No. 10669304, issued June 2, 2020; effected filing date February 4, 2015; of record); as evidenced by Rehman et al. (hereinafter “Rehman”) (Nucleic Acids Research, 1999, 27(2), 649-655; of record); and Mikkola (Beilstein J. Org. Chem., 2018, 14, 803-837; of record); and Dong et al. (hereinafter “Dong”) (ACS Omega, 2019, 4, 3881-3886; of record); and Kenny et al. (hereinafter “Kenny”) (BioTechniques, 2018, 25(3), 516-521; of record); and NIST (National Institute of Standards and Technology Chemistry WebBook, 2026, 1-3).
Regarding claim 1, Zhou teaches compositions for the fabrication of patterned arrays such as nucleotide arrays; and method for the transfer and reorientation of array components (interpreted as inverting an oligonucleotide, claim 1) (Abstract). Zhou teaches a method for transferring an array, comprising: (a) providing a substrate comprising a plurality of linker sites (interpreted as a acceptor substrate, claim 1b); (b) providing an array comprising a plurality of template oligonucleotides (interpreted as a first surface of a donor substrate comprising oligonucleotides, claim 1a); (c) applying reaction mix to said array, said reaction mix comprising enzyme, dNTPs, and a plurality of linker oligonucleotides comprising sequence complementary to an adaptor sequence appended to each of said plurality of template oligonucleotides and further comprising linker molecules capable of binding to said plurality of linker sites (interpreted as applying a reaction mixture, claim 1c); (d) conducting extension reactions of said plurality of said linker oligonucleotides using said plurality of template oligonucleotides as templates, thereby generating a plurality of extension products comprising said linker molecules (interpreted as an immobilization condition, claim 1d); (e) contacting said array with said substrate; and (f) linking said linker molecules of said plurality of extension products to said linker sites (interpreted as producing a transformed sandwich formation, claim 1d), wherein in some cases, said adaptor sequence is located at or near the 3' end of said template oligonucleotides; said adaptor sequence is located at or near the 5' end of said template oligonucleotides; the substrate can comprises polymer; said substrate comprises acrylamide or polyacrylamide; and/or the template array comprises at least 100 spots that are at most about 500 μm in size (col 3, lines 4-28). Zhou teaches that the template array is physically separated from each of the recipient arrays after synthesis of each of the recipient arrays including separation by increased temperature (interpreted as releasing the donor substrate, claim 1d) (col 2, lines 24-29). Zhou teaches that the composition comprises a surface, a polyacrylamide coating covalently bound to the surface; and at least one oligonucleotide coupled to the polyacrylamide coating, wherein oligonucleotides can be arranged on the array (template and/or recipient array) surface in 5’ to 3’ orientation, or in a 3’ to 5’ orientation (interpreting Fig. 2B as a 3’ to 5’ orientation; and as providing a first oligo in a 5’ to 3’ orientation, claim 1a and 1f) (col 18, lines 56-59). Zhou teaches that the oligo array for use as a template array can be fabricated by any method, wherein the substrate of the template array and the transfer array can be any appropriate material including, but not limited to, glass, silicon, and polymers (interpreted as silicon substrate, and encompassing quartz, claims 1 and 48) (col 19, lines 40-44 and 46-49). Zhou teaches that the oligos are incorporated into the polymer coatings (e.g., polyacrylamide coating) during the polymerization process, wherein for example, 5'-acrydite-modified oligonucleotides chains can be added during the acrylamide polymerization process to allow the incorporation of the oligonucleotides into the polymerizing polyacrylamide structure including oligonucleotides coupled to the polymer coating (e.g., polyacrylamide coating) at the 5' end (interpreted as an acrydite phosphoramidite reactive group, claim 1) (col 19, lines 5-13). Zhou teaches that Figure 2A illustrates a general schematic of enzymatic transfer by synthesis (ETS); while Figure 2B illustrates an enzymatic transfer resulting in the transfer resulting from a different orientation of the nucleic acids relative to the substrate (interpreted as a donor substrate; an acceptor substrate; donor surface is facing the acceptor surface; and arranging in a sandwich formation, claim 1a-c) (col 3, lines 49-52; and Figures 2A-B). Figures 2A and 2B are shown below:
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Zhou teaches that a substrate for the oligo array (i .e., template array) can comprise adaptors or oligos bound capable of binding to a region on a separate oligo, permitting bridge amplification or recombinase polymerase amplification of the separate oligo on the substrate, wherein the substrate can be seeded with oligos (i.e., primers) within known barcode sequences, followed by amplification to generate oligo regions (interpreted as adaptor-linked oligonucleotides, and amplification) (col 20, lines 3-10). Zhou teaches that the face-to-face gel transfer process (e.g., EIS or OIT) can significantly reduce the unit cost of fabrication while simultaneously flipping the oligo orientation (5' immobilized) which can have assay advantages such as allowing for the enzymatic extension of the 3' ends of the array bound oligos; and EIS or OIT can result in the transfer of a greater number or higher percentage of oligos of a desired or defined length (i.e., full-length oligo) from the template array to the recipient array including oligos comprising greater than 50 nucleotide bases without suffering from low yield or partial length products (col 20, lines 56-67; and col 21, lines 1-2). Zhou teaches that for enzymatic transfer methods, the immobilization of the oligonucleotides can reduce cross-contamination between array features (col 33, lines 63-65). Zhou teaches that the reaction mixture can be placed on the surface of the recipient array or embedded in a recipient surface; while In some cases, the reaction mixture is placed on the surface of the recipient array, or is embedded in the recipient surface, wherein the recipient surface can be a compatible gel layer; and the reaction mixture can comprise any reagent necessary to conduct enzymatic transfer by synthesis (EIS) (interpreted as the reaction mixture to be placed in-between the first surface of the donor substrate and the surface of the acceptor substrate, claim 1c) (col 28, line 5-11). Zhou teaches detecting the presence of a target nucleic acid sequence, as well as, SNP detection (col 17, lines 33-35; and col 33, lines 50-51). Zhou teaches that a transfer array, or recipient array, comprises oligomers that selectively hybridize or bind to aptamers on a template array, wherein immobilized oligomers, nucleotides, or primers can be complementary to adaptor regions on template polymers (interpreted as forming a first covalent bond and a second covalent bond, claim 1(d)) (col 24, lines 27-31). Zhou teaches that the oligonucleotides can comprise cleavable linkages including enzymatically cleavable linkages (interpreted as encompassing universally cleavable linkers; and revealing a 3’ hydroxyl group, claim 1) (col 11, lines 23-24), where it is known that the diester linkages bridging 3’-O of one nucleoside to the 5’-O of the next one are cleaved by a variety of enzymes as evidenced by Mikkola (pg. 803, col 1). Zhou teaches that oligonucleotides complementary to the adaptor sequence can be added and hybridized to the array components; and DNAse specific to double-stranded DNA can be used to digest the oligonucleotides; alternatively, one or more cleavable bases such as dU can be incorporated into the primer strand to be removed (interpreted as universally cleavable linkers; and revealing a 3’ hydroxyl group, claim 1) (col 23, lines 58-64), wherein an apurinic/apyrimidinic (AP) site such as the U base in a truncated primer is recognized and cleaved by endonuclease IV to generate a truncated primer with a 3’-OH as evidenced by Dong (Abstract; and pg. 3882, col 1). Zhou also teaches that the oligonucleotides are coupled to the polymer coating (e.g., polyacrylamide coating) at the 3' end; and/or some oligonucleotides are coupled to the polymer coating (e.g., polyacrylamide coating) at the 3' end and at the 5' end (interpreted as an acrydite phosphoramidite reactive group, claim 1) (col 19, lines 13-17), wherein the acrylamide group on the 5’-end of the oligonucleotide is added using an acrylamide phosphoramidite as evidenced by Rehman (pg. 651, Figure 1). Zhou teaches that the template and recipient surfaces can be biocompatible, such as polyacrylamide gels, modified polyacrylamide gels, PDMS, or any other biocompatible surfaces (e.g., silica, silicon, COC, and metals such as gold or chrome) (interpreting the polyacrylamide gel layer as a middle layer, claim 1) (col 27, lines 24-27). Zhou teaches that the template surface and/or the recipient surface used for transfer methods can comprise a polymer gel or coating on a substrate such as a polyacrylamide gel or a PDMS gel, wherein the polymer coating can have a range of thickness or widths including of about 0.0001 to 200 mm (interpreted as a donor and receptor substrate; the gel comprising the middle layer; an acrylamide solution; and encompassing a sandwich formation, claim 1) (col 30, lines 16-20 and 35-40). Zhou teaches that glass slides with a gel coating is prepared by functionalizing the glass slides with acrylamide monomers via a silanation solution such as (3-acrylamidopropyl)trimethoxysilane in ethanol and water, wherein the acrylamide gel mix is: (i) prepared using a 6% acrylamide gel mix (e.g., 50 μL 12% acrylamide gel mix, 45 μL DI water, 5 μL 5'-acrydite modified oligonucleotide primers (1 mM) vortexed to mix); (ii) activated (e.g., 1.3 μL of 5% ammonium persulfate and 1.3 μL of 5% TEMED are each added per 100 μL of gel mix and vortexed); (iii) gel mix is applied to a surface (e.g. silanized functionalized glass slide surface); (iv) evenly spread (e.g. by pressing with a cover slip or by spin coating), and (v) allowed to polymerize (interpreted as a donor and receptor substrate; the gel comprising the middle layer; an acrylamide solution; and encompassing a sandwich formation, claim 1) (col 32, lines 5-26). Zhou teaches that the 5’-acrydite modified primers can be capable of incorporation into a polymer gel (e.g., polyacrylamide) during polymerization (interpreted as an acrydite phosphoramidite reactive group, claim 1) (col 29, lines 9-12), wherein Acrydite is a proprietary phosphoramidite that is capable of free-radical copolymerization with acrylamide as evidenced by Kenney (pg. 516, col 2; second full paragraph).
Regarding claim 2, Zhou teaches that the term “primer” can refer to an oligonucleotide with a free 3’ hydroxyl group that is capable of hybridizing with a template nucleic acid or nucleic acid molecule such as a target polynucleotide, target DNA, target RNA or a primer extension product, and is also capable of promoting polymerization of a polynucleotide complementary to the template (interpreted as the first oligonucleotide comprises a free 3’ hydroxyl group, claim 2) (col 11, lines 36-42).
Regarding claims 14, 15 and 50, Zhou teaches that enzymatic transfer of a template array by ETS can be conducted as follows: (1) enzyme mix is prepared from water, buffer, BSA, dNTPs and Bst enzyme; (2) enzyme mix is applied to a recipient array (e.g., an acrylamide gel coated glass slide with coupled primers prepared as described; (3) a template array is placed face-to-face with the recipient array and allowed to react; (4) the template and recipient arrays are separate (e.g., loosened by application of SSC buffer and pulled apart with the aid of a razor blade) (interpreted as mechanical dicing); (5) the template array is rinsed with water and dried; and (6) the recipient array rinsed with SSC buffer (interpreting using a razor blade and a mechanical dicing process; and washing with SSC buffer as subsequently treating with a base, claims 14, 15 and 50) (col 28, lines 13-27). Zhou teaches that the gel was bound to the chips and the gel-chip substrates were removed from the clean flat surface with the aid of a razor blade or other implement if necessary, wherein gel chips were rinsed in water and excess gel from the chip edges was removed, and the gel chips used immediately or stored in saline-sodium citrate (SSC) buffer (interpreting using a razor blade and a mechanical dicing process; and Thermopol buffer as subsequently treating with a base, claims 14, 15 and 50) (col 34, lines 39-45). Zhou teaches that array surfaces can comprise barriers to prevent amplification of array components beyond their individual feature borders, wherein barriers can comprise physical borders, reaction borders, or other borders, such that borders can be fabricated by laser ablation of surface-coupled features (e.g. nucleic acids or other polymers); as well as, by light-activated protective groups, wherein light-activated protective groups can be coupled to nucleic acids across an entire array, and then only desired areas can be deprotected (interpreting laser ablation as a laser perforation process, claim 14) (col 33, lines 11-20).
Regarding claim 48, Zhou teaches that the oligo array for use as a template array can be fabricated by any method, wherein the substrate of the template array and the transfer array can be any appropriate material including, but not limited to, glass, silicon, and polymers (interpreting a silicon substrate to encompass a silicon wafer, and encompassing quartz, claims 1 and 48) (col 19, lines 40-44 and 46-49). Zhou teaches that the gel mix can be pipetted onto a silicon wafer (interpreted as a silicon wafer, claim 48) (col 34, lines 33-35).
Regarding claim 52, Zhou teaches that the oligos are incorporated into the polymer coatings (e.g., polyacrylamide coating) during the polymerization process, wherein for example, 5'-acrydite-modified oligonucleotides chains can be added during the acrylamide polymerization process to allow the incorporation of the oligonucleotides into the polymerizing polyacrylamide structure including oligonucleotides coupled to the polymer coating (e.g., polyacrylamide coating) at the 5' end (interpreting polymerization as an oligonucleotide immobilization condition, claims 1 and 52) (col 19, lines 5-13).
Regarding claims 53 and 54, Zhou teaches method, compositions, and systems for fabricating patterned oligonucleotide arrays that result in high quality full length probes in desired orientation and at low cost (interpreted as the oligonucleotide in an orientation is full length, claims 53 and 54) (col 1, lines 24-27). Zhou teaches that at least 40% of the recipient oligonucleotides are complementary or identical to a full-length oligonucleotide from the at least 1,000 different oligonucleotides (interpreted as the oligonucleotide in an orientation is full length, claims 53 and 54) (col 1, lines 52-55).
Regarding claims 55 and 56, Zhou teaches compositions for the fabrication of patterned arrays such as nucleotide arrays; and method for the transfer and reorientation of array components, wherein the recipient surface contains a copied oligonucleotide pattern that is complementary to the first surface (interpreted as the molecules forming a pattern on the donor substrate, claim 55) (Abstract; and col 1, lines 32-34).
Zhou does not specifically exemplify a quartz substrate (claim 1, in part); or the structure of the linker as recited in claim 49 (claim 49).
Regarding claims 1 (in part), Zhou ‘278 teaches a probe inversion processes for in situ synthesized arrays which can use universal linkers and commercially available building blocks and the incorporation of a universal cleavable linker phosphoramidite for use in releasing free 3 '-OH termini, incorporation of branched linkers with orthogonally protected, addressable functional groups for oligonucleotide synthesis and post-synthesis circularization, more efficient crosslinking chemistries for circularization steps utilizing commercially available reagents, and other improvements, wherein previous processes attempting probe inversion on in situ synthesized arrays involved a large number of special linkers, building blocks and reagents, which can make it impractical to use for large scale manufacturing of in situ synthesized arrays (interpreted as universal phosphoramidite linkers; and releasing and revealing a free 3’-hydroxyl , claim 1) (paragraph [0005]). Zhou ‘278 teaches the method comprising: providing a substrate with a plurality of branched linkers coupled to said substrate, wherein said substrate comprises a plurality of hydroxyalkyl groups, wherein each branched linker comprises (i) a first branch comprising a first alkyne and (ii) a second branch, wherein said second branch comprises a first cleavable linker coupled to a 3' end of a first oligonucleotide, and wherein a 5' end of said first oligonucleotide is coupled to a first azide group; and circularizing said first oligonucleotide by reacting said first azide group with a second alkyne, wherein said second alkyne is said first alkyne or a neighboring alkyne; wherein efficiency of said circularization increases when said second branch further comprises a capping moiety (paragraph [0006]). Zhou ‘278 teaches that the solid substrate can comprise SiO2, modified silicon, the top dielectric layer of a semiconductor integrated circuit chip, etc. (interpreting SiO2 as quartz, claim 1) (paragraph [0063], wherein SiO2 is quartz as evidenced by NIST (pg. 1). Zhou ‘268 teaches that the probes that are attached to the support are primarily full-length sequences (interpreted as full length, claims 53 and 54) (paragraph [0066]).
Regarding claim 49, Zhou ‘278 teaches a plurality of branched linkers coupled to said substrate via a first intermediate selected from the group consisting of the structures shown in Figures 1B, 2A-C and/or via a second intermediate selected from the group of structures in Figures 3A-C, wherein the method further comprises (c) cleaving said first cleavable linker, thereby decoupling said 3' end of said first oligonucleotide from said second branch, wherein said cleaving comprises deprotection with a base (interpreted as universal phosphoramidite cleavable linkers; a 3’-hydroxyl; the linker of claim 49 treatment with a base, claims 1, 2 and 49) (paragraphs [0007]; [0078]; and Figures 1, 2 & 3), wherein some linker structures illustrated in Figures 1B, 2 and 3 are shown below:
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wherein additional universal phosphoramidite linkers are known in the art as evidenced by Yagodkin (pg. 191, Scheme 4). Structure 2 of Scheme 4 is shown below:
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Regarding claim 51, Zhou ’278 teaches that the oligonucleotides were de-protected and cleaved from the cleavable linker (CL) sites using standard deprotection conditions, such as treatment with NH4OH (interpreted as releasing comprises treatment with a base; and NH4OH, claims 50 and 51) (paragraph [0100]).
It is prima facie obvious to combine prior art elements according to known methods to yield predictable results; the court held that, "…a conclusion that a 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 would have yielded nothing more than predictable results to one of ordinary skill in the art. KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1395 (2007); Sakraida v. AG Pro, Inc., 425 U.S. 273, 282, 189 USPQ 449, 453 (1976); Anderson’s-Black Rock, Inc. v. Pavement Salvage Co., 396 U.S. 57, 62-63, 163 USPQ 673, 675 (1969); Great Atlantic & P. Tea Co. v. Supermarket Equipment Corp., 340 U.S. 147, 152, 87 USPQ 303, 306 (1950)”. Therefore, in view of the benefits of using universal cleavable linkers for oligonucleotide probe inversion processes as exemplified by Zhou ‘278, it would have been prima facie obvious before the effective filing date of the claimed invention to modify the method of fabricating patterned oligonucleotide arrays using enzymatic transfer by synthesis or oligonucleotide immobilization transfer from a template surface as disclosed by Zhou to include the universal cleavable linkers including cleavable phosphoramidite linkers for oligonucleotide inversion processes for in situ synthesized arrays as taught by Zhou ‘278 with a reasonable expectation of success in selectively removing truncated sequences, while simultaneously inverting the orientation of the probe sequences; in reducing the number of special linkers, building blocks and/or reagents from the inversion process; and/or in releasing the transferred and reoriented array of copied oligonucleotides from the donor surface using ammonia, methyl amine, 1,2-diaminoethane, and/or potassium carbonate.
Thus, in view of the foregoing, the claimed invention, as a whole, would have been obvious to one of ordinary skill in the art at the time the invention was made. Therefore, the claims are properly rejected under 35 USC §103(a) as obvious over the art.
Response to Arguments
Applicant’s arguments filed February 24, 2026 have been fully considered but they are not persuasive. Applicants essentially assert that: (a) Zhou ‘268 does not teach: (i) a sandwich formation for inverting oligonucleotides, (ii) mechanical dicing or laser perforation of a substrate, nor (iii) an acceptor substrate that is quartz (Applicant Remarks, pg. 18, second full paragraph); and (b) combining the enzymatic transfer of Zhou with the oligonucleotide inversion on a single substrate of Zhou ‘268 would not arrive at the instant claims (Applicant Remarks, pg. 18, third full paragraph)
Regarding (a), although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26USPQ2d 1057 (Fed. Cir. 1993). Moreover, it is noted that none of the references has to teach each and every claim limitation. If they did, this would have been anticipation and not an obviousness-type rejection. 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). Additionally, MPEP 2112.01(I) states that:
where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Applicant’s assertion that Zhou ‘268 does not teach (i) a sandwich formation, is not found persuasive. As an initial matter, it is noted that the rejection is based on the combination of the Zhou reference and the Zhou ‘268 reference. The Examiner contends that the combined references of Zhou and Zhou ‘268 teach all of the limitations of the claims including a sandwich formation. For example –
Zhou teaches:
Patterned arrays comprising a transfer array, a polyacrylamide gel coating, and a recipient array; as well as, an array transfer process that can invert or preserve the orientation of the template nucleic acids (interpreted as a sandwich formation, claim 1) (col 7, lines 41-55; col 24, lines 32-37; col 25, lines 63-67; and col 26, lines 55-63).
Zhou ‘268 teaches:
Solid substrates can comprise polymer coatings or gels, such as a polyacrylamide gel or a PDMS gel (interpreted as a polyacrylamide middle layer, claim 1) (paragraph [0064]).
Applicant’s assertion that Zhou ‘268 does not teach mechanical dicing or laser perforation of a substrate, is not found persuasive.
Zhou teaches:
Array surfaces can comprise barriers including physical borders, reaction borders, or other borders, wherein borders can be fabricated by laser ablation of surface-coupled features (e.g. nucleic acids or other polymers), deprotecting light-activated protective groups including light-activated protective coupled to nucleic acids across an entire array (interpreted as mechanical or laser perforation, claim 1) (col 33, lines 11-20).
Using pre-diced silanized fused-silica substrate surfaces (interpreted as mechanical or laser perforation, claim 1) (col 36, lines 30-32).
The array can be a modified glass surface (interpreted as encompassing mechanical or laser modifications, claim 1) (col 29, lines 2-5).
Zhou ‘268 teaches:
Modified silicon (interpreted as encompassing mechanical or laser perforation, claim 1) (paragraph [0063]).
A surface can be modified with reagents (interpreted as encompassing mechanical or laser perforation, claim 1) (paragraph [0075]).
Applicant’s assertion that Zhou ‘268 does not teach an acceptor substrate that is quartz, is not found persuasive.
Zhou teaches:
The oligo array for use as a template array can be fabricated by any method, wherein the substrate of the template array and the transfer array can be any appropriate material including, but not limited to, glass, silicon, and polymers (interpreting a silicon substrate and any appropriate material to encompass quartz, claim 1) (col 19, lines 40-44 and 46-49).
Zhou ‘278 teaches:
The solid substrate can comprise SiO2, modified silicon, the top dielectric layer of a semiconductor integrated circuit chip, etc., wherein SiO2 is quartz as evidenced by NIST (interpreting SiO2 as quartz, claim 1) (paragraph [0063],
The combined references of Zhou and Zhou ‘268 teach all of the limitations of the claims. Thus, the rejection is maintained.
Regarding (b), please see the discussion supra regarding the Examiner’s response to Applicant’s arguments. MPEP 2123(I) states:
"The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. See In re Heck, 699 F.2d 1331, 1332-33,216 USPQ 1038, 1039 (Fed. Cir. 1983); In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275,277 (CCPA 1968); Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); and Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005) (underline added).
Applicant’s assertion that combining the enzymatic transfer of Zhou with the oligonucleotide inversion on a single substrate of Zhou ‘268 would not arrive at the instant claims, is not found persuasive. Zhou ‘268 is cited for teaching different silicon substrate surfaces including SiO2; as well as, the use of specific universal cleavable linkers, such as recited in claim 49. As noted in the instant rejection, by including the universal cleavable linkers including cleavable phosphoramidite linkers as taught by Zhou ‘278 in the method of Zhou, there is a reasonable expectation of success in selectively removing truncated sequences, and/or in releasing the transferred and reoriented array of copied oligonucleotides from the donor surface using ammonia, methyl amine, 1,2-diaminoethane, and/or potassium carbonate. Thus, the rejection is maintained.
Conclusion
Claims 1, 2, 14, 15 and 48-56 are rejected.
THIS ACTION IS MADE FINAL. 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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/AMY M BUNKER/
Primary Examiner, Art Unit 1684