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
Request for Continued Examination Under 37 CFR 1.1143
A request for continued examination (RCE) under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant’s submission mailed on July 8, 2025 has been entered.
New claims 22 and 23 are acknowledged. Claims 1-9, 22 and 23 are pending in the instant application.
Accordingly, claims 1-9, 22 and 23 have been examined on the merits as detailed below:
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Response to Arguments
Applicant's Amendment and Response filed July 8, 2025 has been considered. Communications, rejections and/or objections not reiterated from the previous Office Action mailed April 28, 2025 are hereby withdrawn. Any arguments addressing said rejections and/or objections are moot. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application.
Information Disclosure Statement
The information disclosure statement (IDS) filed on June 2, 2026 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Claim Rejections - 35 USC § 103
In the previous Office Action mailed April 28, 2025, claims 1-9 were rejected under U.S.C. 103 as being obvious over WO 2016/168386 (submitted on the IDS filed March 15, 2022) in view of Park et al. (Gels, Vol. 4, No. 2, pages 1-15, March 2018) (submitted on the IDS filed March 15, 2022) and further in view of Pregibon et al. (EP 2576839 B1, published April 10, 2013) (submitted and made of record in the Office Action mailed November 8, 2024). This rejection is withdrawn in view of Applicant’s Arguments filed June 30, 2025 and in favor of the new 35 USC 103 rejection presented below:
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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 1-9, 22 and 23 are rejected under U.S.C. 103 as being obvious over U.S. Patent No. 8778848 to Lin, Shengrong et al. (hereinafter, “Lin”) in view of Pong et al. (Langmuir 2006, 22, 3851-3857).
The claims are drawn to a method, comprising: applying a hydrogel to a surface of a substrate; grafting primers to the applied hydrogel; and before or after grafting the primers, introducing plasmonic nanostructures to the applied hydrogel, whereby the plasmonic nanostructures covalently or non-covalently bond to the applied hydrogel.
Lin is relevant and relied upon in its entirety. Lin teaches patterned flow-cells useful for nucleic acid analysis. Lin particularly teaches and describes a method comprising applying a continuous gel layer (hydrogel) to a surface of a substrate and grafting primers to the applied gel layer.
Lin teach a method of preparing a surface comprising (i) providing a substrate having metal regions and interstitial regions, (ii) contacting the substrate with a polymerizable material and polymerizing it to form a continuous gel layer (hydrogel), and (iii) attaching nucleic acid analytes, including primers from which DNA clusters are grown to the gel layer. In some embodiments, fluorescent labeled probes are hybridized to the primers (i.e. optical labels) and detection is measured by fluorescence imaging. Lin further teaches that the metal regions enhance gel mass and analyte attachment over those regions, evidencing the intended cooperative function of metals in optical and structural proximity to the primer-grafted hydrogel.
Additionally, Lin contemplates additional surface functionalization steps applied to the gel layer after polymerization, but does not necessarily teach introducing plasmonic nanostructures to the applied hydrogel such that the nanostructures bind to the plasmonic nanostructures.
Pong et al. teach and report changes in the structure and thermoresponsive behavior of acrylamide hydrogels when gold nanostructures are synthesized within the hydrogel matrix. For example, Pong et al. teach synthesizing gold nanostructures within an acrylamide hydrogel matrix by infusion of gold ions followed by chemical reduction, whereby the gold nanostructures are bound with the hydrogel.
Regarding those claims that recite, wherein the plasmonic nanostructures are located within a signal enhancing proximity distance of an optical label, wherein the signal enhancing proximity distance is from 0 nm to 100 nm or from 0.1 nm to 25 nm, it should be noted that the combination of the Lin and Pong et al. references teaches gold nanostructures embedded within a hydrogel that also has primers grafted to it (with optical labels attached during sequencing). The labels will necessarily be within 0 nm to 100 nm of the nanostructure because hydrogel layer thickness in flow-cell sequencing are typically 10-200 nm as evidenced by Anger et al. (2006, Phys. Rev. Lett. 96, 113002 (1-4)). Applicant is reminded that the in situ grown nanostructures of Pong et al. are distributed throughout the matrix.
Before the effective filing date of the claimed invention, hydrogels on substrates with grafted primers were known. See Lin. Also, before the effective filing date of the claimed invention, gold nanostructures binding to hydrogels was known. See Pong et al. Nanoparticle-enhanced sequencing is an obvious technique based on what was taught in the prior art. It therefore would have been obvious to devise the methods of the claimed invention using the teachings and suggestions of the prior art of Lin in view of Pong et al.
A person of ordinary skill in the art would have been motivated to modify the teachings of Lin by introducing gold nanostructures according to the method of Pong et al. since both references concern hydrogel composites bearing or proximate to metals for optical signal enhancement. The combination of Lin with Pong et al. involves the application of a known nanoparticle-embedding technique (Pong et al.) to a known hydrogel-on-substrate platform (Lin) and the result – a hydrogel layer with bound gold nanostructures – is predictable from the teachings of the combined references. See KSR Intl’l Co. v. Teleflex Inc., 550 U.S. 398 (2007). Also, see MPEP § 2143(A).
A person of ordinary skill in the art devising Lin’s metal-patterned flow cell would have been motivated and expected reasonable success to incorporate Pong et al. functional gold nanostructure synthesis for the purpose of having metals in optical proximity to the gel layer for selective analyte attachment and signal enhancement. Pong et al. teaches a uniform way to achieve metal-gel optimal proximity by distributing nanostructures throughout the gel. The result, a primer-grafted hydrogel with bound gold nanostructures usable for sequence-format detection is therefore predictable and obvious.
Therefore, a person of ordinary skill in the art would have found the instant invention prima facie obvious.
Non-Statutory 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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-9, 22 and 23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 26-31 of U.S. Patent No. 12152237 B2 (hereinafter, “’237 Patent”). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims embrace and encompass claims 26-31 of the ‘237 Patent.
The claims of the ‘237 Patent are drawn to a method, comprising: preparing a plurality of functionalized plasmonic nanostructures, wherein each of the functionalized plasmonic nanostructures includes: a plasmonic nanostructure core; a polymeric hydrogel attached to the plasmonic nanostructure core, the polymeric hydrogel having a thickness ranging from about 10 nm to about 200 nm; a plurality of two primers that together seed and amplify a template nucleic acid strand, the plurality of two primers being attached to side chains of the polymeric hydrogel, wherein at least some of the plurality of primers are attached to the polymeric hydrogel at different distances from the plasmonic nanostructure core; and a mechanism to anchor each of the functionalized plasmonic nanostructures to capture sites of a flow cell; and dispersing the functionalized plasmonic nanostructures throughout a liquid carrier.
The claims of the present invention are drawn to a method, comprising: applying a hydrogel to a surface of a substrate; grafting primers to the applied hydrogel; and before or after grafting the primers, introducing plasmonic nanostructures to the applied hydrogel, whereby the plasmonic nanostructures covalently or non-covalently bond to the applied hydrogel.
The present claims embrace, encompass and overlap in scope with claims 26-31 of the ‘237 Patent. The limitations and structural requirements of the instant claims are provided in the supporting disclosure of the issued Patent as certain preferred embodiments.
A terminal disclaimer disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of U.S. Patent No. 12152237 is required, or some other appropriate action.
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Claims 1-9, 22 and 23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 11938475 B2 (hereinafter, “’475” Patent”) in view of Pong et al. (Langmuir 2006, 22, 3851-3857).
Although the claims at issue are not identical, they are not patentably distinct from each other because the applications are directed to overlapping subject matter. The reference claims are directed to a method, comprising: applying a functionalized coating layer in depressions of a patterned flow cell substrate, wherein the depressions are separated by interstitial regions and wherein the patterned flow cell substrate includes a bonding region; grafting a primer to the functionalized coating layer to form a grafted functionalized coating layer in the depressions; applying a non-grafted hydrogel on at least the grafted functionalized coating layer, the non-grafted hydrogel being selected from the group consisting of crosslinked polyacrylamide, an agarose gel, and crosslinked polyethylene glycol; and bonding a lid to the patterned flow cell substrate at the bonding region, thereby defining a flow channel between the patterned flow cell substrate and the lid. A suitable substrate of the ‘475 Patent is a metal.
The ’475 Patent does not teach plasmonic nanostructures applied and bound to the hydrogel.
Pong et al. is relied upon supra.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to modify the teachings of the ’475 Patent by introducing gold nanostructures according to the method of Pong et al. since both references concern hydrogel composites bearing or proximate to metals for optical signal enhancement. The combination of the ’475 Patent with Pong et al. involves the application of a known nanoparticle-embedding technique (Pong et al.) to a known hydrogel-on-substrate platform (‘475 Patent) and the result – a hydrogel layer with bound gold nanostructures – is predictable from the teachings of the combined references. See KSR Intl’l Co. v. Teleflex Inc., 550 U.S. 398 (2007). Also, see MPEP § 2143(A).
A person of ordinary skill in the art devising the ’475 Patent flow cells with hydrogel coating would have been motivated and expected reasonable success to incorporate Pong et al. functional gold nanostructure synthesis for the purpose of having metals in optical proximity to the gel layer for selective analyte attachment and signal enhancement. Pong et al. teaches a uniform way to achieve metal-gel optimal proximity by distributing nanostructures throughout the gel. The result, a primer-grafted hydrogel with bound gold nanostructures usable for sequence-format detection is therefore obvious.
The claims of the ’475 Patent in view of Pong et al. overlaps in scope and fully embraces that which is claimed in the instant invention.
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Claims 1-9, 22 and 23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 10919033 B2 (hereinafter, “’033” Patent”) in view of Pong et al. (Langmuir 2006, 22, 3851-3857).
Although the claims at issue are not identical, they are not patentably distinct from each other because the applications are directed to overlapping subject matter. The reference claims are directed to a flow cell, comprising: a patterned substrate including depressions separated by interstitial regions and including a bonding region; sequencing surface chemistry attached to each of the depressions, the sequencing surface chemistry including: a functionalized coating layer; and a primer grafted to the functional coating layer; a non-grafted hydrogel on at least the sequencing surface chemistry, the non-grafted hydrogel selected from the group consisting of crosslinked polyacrylamide, an agarose gel, and crosslinked polyethylene glycol; a lid attached to the patterned substrate at the bonding region; and a flow channel defined between the patterned substrate and the lid. It would have been obvious to use the flow cell of the ’033 Patent in the methods of the present invention for the purpose of devising a functionalized coating layer applied in depressions of a patterned flow cell substrate; the depressions are separated by interstitial regions; a primer is grafted to the functionalized coating layer to form a grafted functionalized coating layer in the depressions; a hydrogel is applied on at least the grafted functionalized coating layer. A suitable substrate of the ‘033 Patent is a metal.
The ’033 Patent does not teach plasmonic nanostructures applied and bound to the hydrogel.
Pong et al. is relied upon supra.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to modify the teachings of the ’033 Patent by introducing gold nanostructures according to the method of Pong et al. since both references concern hydrogel composites bearing or proximate to metals for optical signal enhancement. The combination of the ’475 Patent with Pong et al. involves the application of a known nanoparticle-embedding technique (Pong et al.) to a known hydrogel-on-substrate platform (’033 Patent) and the result – a hydrogel layer with bound gold nanostructures – is predictable from the teachings of the combined references. See KSR Intl’l Co. v. Teleflex Inc., 550 U.S. 398 (2007). Also, see MPEP § 2143(A).
A person of ordinary skill in the art devising the ’033 Patent flow cells with hydrogel coating would have been motivated and expected reasonable success to incorporate Pong et al. functional gold nanostructure synthesis for the purpose of having metals in optical proximity to the gel layer for selective analyte attachment and signal enhancement. Pong et al. teaches a uniform way to achieve metal-gel optimal proximity by distributing nanostructures throughout the gel. The result, a primer-grafted hydrogel with bound gold nanostructures usable for sequence-format detection is therefore obvious.
The claims of the ’033 Patent in view of Pong et al. overlaps in scope and fully embraces that which is claimed in the instant invention.
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Claims 1-9, 22 and 23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 11841310 B2 (hereinafter, “’310” Patent”) in view of Pong et al. (Langmuir 2006, 22, 3851-3857).
Although the claims at issue are not identical, they are not patentably distinct from each other because the applications are directed to overlapping subject matter. The reference claims are directed to a flow cell, comprising: a substrate consisting of a material selected from the group consisting of epoxy siloxane, glass, modified glass, nylon, ceramics/ceramic oxides, silica (silicon oxide SiO2), fused silica, silica-based materials, aluminum silicate, silicon nitride (Si3N4), and inorganic glasses; a lid; a flow channel defined between the lid and the substrate; a patterned electrode directly positioned on the substrate and in the flow channel, wherein the patterned electrode has walls that define depressions in the flow channel, wherein the substrate defines a bottom of the depressions, wherein the depressions are separated by interstitial regions, and wherein the interstitial regions are defined by a surface of the patterned electrode that is exposed to the flow channel; a functionalized surface of the substrate exposed at the bottom of each of the depressions, the functionalized surface including a polymer layer attached to silane groups or hydroxyl groups attached to the substrate; and a primer grafted to a functional group of the polymer layer in each of the depressions. It would have been obvious to use the flow cell of the ‘310 Patent in the methods of the present invention for the purpose of devising a functionalized coating layer applied in depressions of a patterned flow cell substrate; the depressions are separated by interstitial regions; a primer is grafted to the functionalized coating layer to form a grafted functionalized coating layer in the depressions; a hydrogel is applied on at least the grafted functionalized coating layer. A suitable substrate of the ‘310 Patent is a metal.
The ’310 Patent does not teach plasmonic nanostructures applied and bound to the hydrogel.
Pong et al. is relied upon supra.
It would have been obvious to one of ordinary skill in the art at the time the invention was made to modify the teachings of the ’310 Patent by introducing gold nanostructures according to the method of Pong et al. since both references concern hydrogel composites bearing or proximate to metals for optical signal enhancement. The combination of the ’310 Patent with Pong et al. involves the application of a known nanoparticle-embedding technique (Pong et al.) to a known hydrogel-on-substrate platform (’310 Patent) and the result – a hydrogel layer with bound gold nanostructures – is predictable from the teachings of the combined references. See KSR Intl’l Co. v. Teleflex Inc., 550 U.S. 398 (2007). Also, see MPEP § 2143(A).
A person of ordinary skill in the art devising the ’310 Patent flow cells with hydrogel coating would have been motivated and expected reasonable success to incorporate Pong et al. functional gold nanostructure synthesis for the purpose of having metals in optical proximity to the gel layer for selective analyte attachment and signal enhancement. Pong et al. teaches a uniform way to achieve metal-gel optimal proximity by distributing nanostructures throughout the gel. The result, a primer-grafted hydrogel with bound gold nanostructures usable for sequence-format detection is therefore obvious.
The claims of the ’310 Patent in view of Pong et al. overlaps in scope and fully embraces that which is claimed in the instant invention.
Conclusion
No claims are allowable at this time.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Terra C. Gibbs whose telephone number is 571-272-0758. The Examiner can normally be reached from 8 am - 5 pm M-F.
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/TERRA C GIBBS/Primary Examiner, Art Unit 1635
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