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 .
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 11/12/25 is acknowledged.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 12 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 12, the claim recites “an RNA target forms a heteroduplex with a trigger DNA to initiate amplification” in an apparatus claim. This limitation is indefinite as the claim provides no context for the subject matter of the claim and how it is related to the claimed invention. The limitation appears to recite a phenomenon, yet it is unclear how this phenomenon relates to the claimed invention.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1-4, 6, 8-14, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Hu (WO 2018/231962) in view of Geissler (Polymer Micropillar Arrays for Colorimetric DNA Detection, 2020), Zhang (Molecular Imprinting with Functional DNA, 2019) and Koster (Fibers Coated with Molecularly Imprinted Polymers for Solid-Phase Microextraction, 2001).
Regarding Claims 1, 2, 8, and 11, Hu teaches a sensor (referred to as 3D porous photonic cell structure 100, used as a colorimetric sensor) for detecting an analyte of interest in a fluid sample (see abstract, [0067] and Figure 1b), the sensor comprising:
a structure comprising a plurality of walls (such as base substrate 110 and cell structure 100’s side walls) that define a plurality of air gaps (referred to as air voids/pores 105) in the structure (see Figure 1B and [0068]), wherein each wall of the plurality walls includes a plurality of surfaces (base substrate and cell structure each has multiple surfaces);
a functional layer, wherein the functional layer is coated on the plurality of walls (referred to as layer 115); para. [0021]), wherein the functional layer comprises a binding material to bind to the analyte of interest (an analyte contacts the molecularly imprinted polymer and becomes disposed within a cavity; para. [0016]);
a material coating (hydrophobic layer 112; para. [0087]) the plurality of the walls providing an initial surface energy for at least a portion of the plurality of surfaces of the plurality of walls (As described below, upon absorbing a target analyte(s) of interest, the MIP coatings 115 modify the wettability of the surfaces upon which they are coated to a degree great enough to overcome the initial hydrophobicity of the surfaces and thereby allow infiltration of a fluid containing the target analyte(s) of interest into (e.g., via a fluid inlet 117) the air voids/pores 105 that are coated with the MIP materials 115. Para. [0087]),
wherein the initial surface energy of at least the portion of the plurality of surfaces of the plurality of walls provided by the material coating changes when analyte of interest is present (see [0064]-[0068], [0087]-[0091] and [0123]), and
wherein the plurality of walls coated with the functional layer are fabricated from a micropillar array, a nanopillar array, or a combination thereof (See Fig. 8).
Hu does not disclose the device comprises at least one amplification initiator to amplify the analyte of interest after extraction and the functional layer further comprises an extraction component to extract an analyte of interest.
With respect to using an amplification initiator, analogous art Geissler teaches a sensor (Abstract; Fig. 1b) for detecting an analyte of interest in a fluid sample, the sensor comprising:
a structure comprising a plurality of walls (Fig. 1b) that define a plurality of air gaps (interpreted as the space between pillars) in the structure, wherein each wall of the plurality walls includes a plurality of surfaces (each pillar has multiple surfaces);
a functional layer (interpreted as the agent/reagent used to functionalize/modify/coating the surface of the pillar material), wherein the functional layer is coated on the plurality of walls (referred to oxide formed from the oxidized substrate during oxygen plasma exposure; Micropillar array substrates were exposed to oxygen plasma for 2 min at a pressure of 50 mTorr, a power of 100 W, and a gas flow of 20 sccm, activating structured and planar portions of the surface alike. Freshly oxidized substrates…Surface Modification and Spotting),
wherein the functional layer comprises a binding material to bind to the analyte of interest (oligonucleotide probes, Probes were dissolved in DI water to provide concentrations of 200 μM. Spotting was done by transferring ∼200 nL of oligo probe solution onto the pillar array…The substrate was placed on a hot plate at 95 °C for 3–10 min to complement the binding process. Surface Modification and Spotting; Fig. 1a);
wherein the functional layer comprises an extraction component includes an oxide coating layer (referred to oxide formed from the oxidized substrate during oxygen plasma exposure; Micropillar array substrates were exposed to oxygen plasma for 2 min at a pressure of 50 mTorr, a power of 100 W, and a gas flow of 20 sccm, activating structured and planar portions of the surface alike. Freshly oxidized substrates…Surface Modification and Spotting); and
at least one amplification initiator to amplify the analyte of interest after extraction (oligonucleotide primers, Multiplex PCR).
Furthermore, Zhang discloses MIP can be further functionalized or incorporated with DNA aptamer to improve specificity and binding. In particular, Zhang discloses MIP-DNA aptamer (in which Hu also discloses aptamer can be incorporated with MIP, para. [0086]) is capable of specifically recognized certain target DNA strand through complementary binding (In addition to DNA aptamers, imprinting using double-strand DNA was also reported.55 By anchoring one of the strands as a monomer and removing the other strand as the target, the generated DNA-MIPs specifically recognized the target DNA strand through complementary binding. Furthermore, a single nucleotide (e.g., polymerizable 2′-deoxyuridine, dU) was also used as a monomer to imprint deoxyadenosine (dA).56 The “tailored” MIP had specificity for the Watson–Crick paired dA, but not other nucleotides (e.g., dG or dC). Para. 8, 4.1 DNA Aptamers as Macromonomers).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date to have further modified the MIP of Hu with DNA-aptamers as taught by Zhang and incorporating amplification initiator/primers as taught by Geissler to derive the claimed invention. Doing so allows the device of Hu to be able to detect a specific strand in a target DNA molecule.
Regarding the limitation of functional layer further comprises an extraction component to extract an analyte of interest, Hu discloses the substrate can be made of insulative material such as silica, titanium oxide but does not explicitly disclose oxide coating as extraction component (para. [0087]). In an analogous art, Koster discloses silica fibers (interpreted as the oxide coating of claim 11) can be coated with MIPS to improve extraction characteristics under various condition (Abstract). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date to have incorporated silica/oxide coating to the MIP of the device of Hu to derive the claimed invention, doing so achieves selective extraction of polar molecule from biological samples (To achieve selective extraction of brombuterol from human urine, MIP-coated fibers were washed with acetonitrile after the extraction. Clean extracts and yields of ∼45% were obtained, demonstrating the suitability of MIP-coated fibers for the analysis of biological samples. Koster, Abstract).
Regarding claim 3, Modified Hu discloses the claimed invention as discussed above in claim 2. Geissler discloses the binding of the of the binding material (probe) binding the amplicon (Fig. 1a; Result and Discussion, para. 2). The discussion of the change in the initial surface energy is due to amplicons binding to the binding material on at least the portion of the plurality of surfaces of the plurality of walls preventing a fluid sample comprising the analyte of interest from exiting the plurality of air gaps after amplification is a recitation of intended use as the analyte of interest is not recited as part of the invention.
The intended use recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See In re Casey, 152 USPQ 235 (CCPA 1967) and In re Otto, 136 USPQ 458,459 (CCPA 1963). Moreover, Hu discloses the change in the initial surface energy is due to analyte of interest (amplicon is essentially an analyte of interest after amplification) binding with the binding material in solution on at least the portion of the plurality of surfaces of the plurality of the wall (… upon absorbing a target analyte(s) of interest, the MIP coatings 115 modify the wettability of the surfaces upon which they are coated to a degree great enough to overcome the initial hydrophobicity of the surfaces and thereby allow infiltration of a fluid containing the target analyte(s) of interest into (e.g., via a fluid inlet 117) the air voids/pores 105 that are coated with the MIP materials 115. Para. [0087]), preventing a fluid sample comprising the analyte of interest from exiting the plurality of air gaps (Fig 14B; In contrast, with reference to FIGURE 14B, a fluid 140 Γ that contains the analyte of interest causes a wettability of the sensor surface to change due to the binding of analytes to the sensor surface. As such, a full fluid penetration or partial penetration into the grooves 1310 is triggered; para. [0125]).
Regarding claim 4, Modified Hu discloses the claimed invention as discussed above in claim 1. Geissler discloses the binding of the of the binding material (probe) binding the amplicon (Fig. 1a; Result and Discussion, para. 2). The discussion of the change in the initial surface energy is due to amplicons binding to the binding material on at least the portion of the plurality of surfaces of the plurality of walls preventing a fluid sample comprising the analyte of interest from exiting the plurality of air gaps after amplification is a recitation of intended use as the analyte of interest is not recited as part of the invention.
The intended use recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See In re Casey, 152 USPQ 235 (CCPA 1967) and In re Otto, 136 USPQ 458,459 (CCPA 1963). Moreover, Hu discloses the change in the initial surface energy is due to analyte of interest (amplicon is essentially an analyte of interest after amplification) binding with the binding material in solution on at least the portion of the plurality of surfaces of the plurality of the wall (… upon absorbing a target analyte(s) of interest, the MIP coatings 115 modify the wettability of the surfaces upon which they are coated to a degree great enough to overcome the initial hydrophobicity of the surfaces and thereby allow infiltration of a fluid containing the target analyte(s) of interest into (e.g., via a fluid inlet 117) the air voids/pores 105 that are coated with the MIP materials 115. Para. [0087]), preventing a fluid sample comprising the analyte of interest from exiting the plurality of air gaps (Fig 14B; In contrast, with reference to FIGURE 14B, a fluid 140 Γ that contains the analyte of interest causes a wettability of the sensor surface to change due to the binding of analytes to the sensor surface. As such, a full fluid penetration or partial penetration into the grooves 1310 is triggered; para. [0125]).
Regarding claim 6, Modified Hu discloses the claimed invention as discussed above in claim 1. The limitation is an intended use recitation as the limitation is directed to how a phenomenon of a device is used to determine a property of the sample. The intended use recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See In re Casey, 152 USPQ 235 (CCPA 1967) and In re Otto, 136 USPQ 458,459 (CCPA 1963). Moreover, Hu discloses the change of surface energy can be used to determine a concentration of the analyte of interest (para. [0126]).
Regarding claim 9, Modified Hu discloses the claimed invention as discussed above in claim 1. Geissler discloses the extraction and amplification are conducted on the functional layer via a combination of solution base and solid base amplification mechanism (The PCR product (50 μL) was denatured by heating at 100 °C for 10 min, snap-chilled on ice, and mixed with 250 μL ice-cold 1X hybridization solution containing 50% formamide (Sigma-Aldrich). The mixture was pipetted onto the micropillar substrate and incubated at 45 °C for 20–30 min. Detection Assay).
Regarding claim 10, Modified Hu discloses the claimed invention as discussed above in claim 1. The discussion of the analyte of interest is a recitation of intended use as the analyte of interest is not recited as part of the invention.
The intended use recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See In re Casey, 152 USPQ 235 (CCPA 1967) and In re Otto, 136 USPQ 458,459 (CCPA 1963). The apparatus of Geissler is identical to the presently claimed structure and therefore, would have the ability to perform the use recited in the claim. Moreover, Geissler discloses the analyte of interest is DNA.
Regarding claim 12-14 and 16, Geissler discloses the claimed invention as discussed above in claim 1. The discussion of the analyte of interest is a recitation of intended use as the analyte of interest is not recited as part of the invention.
The intended use recitation of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. See In re Casey, 152 USPQ 235 (CCPA 1967) and In re Otto, 136 USPQ 458,459 (CCPA 1963). The apparatus of Geissler is identical to the presently claimed structure and therefore, would have the ability to perform the use recited in the claim.
Claim(s) 5 and 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hu in view of Geissler, Zhang, and Koster as discussed above in claim 6, and further in view of Barcelo (WO 2021262163).
Regarding claim 5, Modified Hu discloses the claimed invention as discussed above in claim 1. None of the arts cited disclose multiple amplification initiator are immobilized on at least the portion of the plurality of walls in spatial separated zones to enable multiplex detection. Analogous art, Barcelo discloses a plasmonic substrate comprising nanopillars (para. [0016]; Figs. 2-6). Specifically, Barcelo discloses different primers can be immobilized at different locations in order to detect different molecules (As a result, different primers may be dispensed on desired locations 710 to detect different target molecules. For example, a first primer may functionalize the location 710i to detect DNA. A second primer may functionalize the location 7102 to detect RNA, and so forth. Thus, selective functionalization may enable multiplexing to detect different target molecules on a single plasmonic substrate. Para. [0072]). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date to have immobilized multiple amplification initiators on a portion of the plurality of walls of the device of Modified Hu to derive the claimed invention. Doing so enables multiplex detection of different target molecule in a single run (Barcelo, para. [0073]).
Regarding claim 15, Modified Hu discloses the claimed invention as discussed above in claim 1. None of the arts cited discloses using a reverse primer. Analogous art Barcelo that reverse primer can be used complementary to the forward primers used in the amplification (para. [0034], [0036], [0041]). It would have been obvious to one of ordinary skill in the art before the effective filing date to have utilized reverse primers in conjunction of forward primers in the device of Modified Hu to derive the claimed invention, doing so enable exponential amplification (the two primers defined the boundaries of the amplicon, and with both primers present, amplification is exponential because each newly synthesized complementary strand becomes a template in subsequent cycles).
Claim(s) 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Hu in view of Geissler, Zhang, and Koster as discussed above in claim 6, and further in view of Billard (The Allele-Specific Probe and Primer Amplification Assay, a New Real-Time PCR Method for Fine Quantification of Single-Nucleotide Polymorphisms in Pooled DNA, 2012).
Regarding claim 7, Modified Hu discloses the claimed invention as discussed above in claim 6. Geissler does not explicitly disclose using an allele specific primer as amplification initiator (comprising a variable base and a matching base.
In an analogous art, Bilard discloses a colorimetric method of conducting PCR for quantification of SNP in DNA sample using an allele-specific primer as amplification initiator (We describe here a new real-time PCR method, the allele-specific probe and primer amplification assay (ASPPAA PCR). This method makes use of mixtures of allele-specific minor groove binder (MGB) TaqMan probes and allele-specific primers for the fine quantification of SNPs from a pool of DNA extracted from a mixture of conidia. Abstract).
As the amplification from Geissler is conducted separately before the amplicon were fed to the colorimetric device (neither does the claim explicitly requiring the amplification initiator to be explicitly attach to the device), it would have been obvious to one of ordinary skill in the art before the effective filing date to have utilize the allele-specific primers of the kit from the disclosure of Bilard for amplification reaction to the device of Modified Hu to derive the claimed invention. Doing so allows for the device of Modified Hu being configured to detect SNP.
Conclusion
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/M.H./ Examiner, Art Unit 1758 /LYLE ALEXANDER/ Supervisory Patent Examiner, Art Unit 1797