DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 3/5/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Election/Restrictions
Applicant’s election without traverse of group III (claim 10) in the reply filed on 4/23/2026 is acknowledged.
Claim Status
Claims 1-14 are pending with claims 10-12 being examined and claims 1-9 and 13-14 are withdrawn.
Claim Objections
Claim 10 is objected to because of the following informalities: the acronym “CSUCNPs” in line 18 on page 8 of 12 is not abbreviated in independent claim 10. The Examiner suggests to amend the claim 10 to read “core-shell upconversion nanoparticles (CSUCNPs)” in lines 9-10. Appropriate correction is required.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Scherr et al (US 20210187508 A1; hereinafter “Scherr”) in view of Halbert et al (US 20190317099 A1; hereinafter “Halbert”) in view of Chen et al (CN 113588618 A; hereinafter “Chen”).
Regarding claim 10, Scherr teaches a microfluidic biosensing platform (Scherr; Fig. 2B), the microfluidic biosensing platform comprising an upconversion luminescence biosensor (Scherr; Fig. 2D; para [119]; photosensors), and a microfluidic chip (Scherr; Fig. 2B; para [71]; a microfluidic device);
the microfluidic chip being configured as a reaction platform for the upconversion luminescence biosensor and a sample to be tested (Scherr; Fig. 3A; para [100]; a method and application of the high efficiency encapsulation of gel bead particles for phenotypically analyzing the proteins, lipids, carbohydrates or nucleic acids from a single cell), and being configured to integrate mixing, reaction, separation and detection of the upconversion luminescence biosensor and the sample to be tested (Scherr; Fig. 3A depicts the mixing, reaction, separation which is collected in the reservoir, and detection of the drops);
the upconversion luminescence biosensor comprising core-shell upconversion nanoparticles (Scherr; para [51]; a collection of hydrogel beads to which each are attached a unique oligonucleotide sequence) and magnetic nanoparticles (Scherr; para [54]; the capture molecules may be selected from the group comprising magnetic particles); the core-shell upconversion nanoparticles being combined with the magnetic nanoparticles (Scherr; Fig. 2B; para [51, 54]; magnetic colloidal particles with specific capture molecules can be incorporated into the hydrogel bead and be useful in selective capture and subsequent magnetic separation of specific ligands or molecules from a heterogeneous mixture…the capture molecules may be selected from the group comprising magnetic particles, nanoparticles); surfaces of the core-shell upconversion nanoparticles being modified with an EDC aptamer sequence (Scherr; para [96]; Hydrogel beads with poly A or oligo-specific capture sequences containing unique barcode sequences);
the microfluidic chip comprising a first injection pool, a second injection pool, a first channel, a second channel and a detection pool (Scherr; Fig. 2B, 5; first injection pool corresponds to the inlet for RT mix, the second injection pool corresponds to the sample cell inlet, the first channel is interpreted as the channel before the oil channels, the detection pool corresponds to the channel which the cells are detected as seen in Fig. 5 between the oil channel and sorter device; second channel is interpreted as the channel in which cells are sorted);
the first injection pool being configured for injection of the upconversion luminescence biosensor (Scherr; Fig. 2B; para [110]; Hydrogel beads with photolabile poly T or oligo-specific capture sequences containing unique barcode sequences are introduced into a drop forming region with cells, cell lysis buffer and a reverse transcriptase (RT) enzyme); the second injection pool being configured for injection of the sample to be tested (Scherr; Fig. 2B; cell inlet); the first channel being arc-shaped (Scherr; Fig. 2B; Examiner notes a part of the channel is arc represented by the curved channels before mixing with the cells); an inlet of the first channel communicating with the first injection pool and the second injection pool (Scherr; Fig. 5; the first channel is interpreted as the channel where the first injection pool and the second injection pool meet); the first channel being configured for mixing and reaction of the upconversion luminescence biosensor and the sample to be tested after the upconversion luminescence biosensor and the sample to be tested enter the first channel (Scherr; Fig. 5; samples are mixed ); the second channel communicating with an outlet of the first channel (Scherr; Fig. 5), and being configured for magnetic separation of the upconversion luminescence biosensor after the reaction is finished (Scherr; Fig. 5; interpreted as the channel that comprises the unsorted cells); and the detection pool communicating with an outlet of the second channel (Scherr; Fig. 5; Examiner notes the samples that are detected are led to the sorted channel) being configured for enhanced luminescence-based quantitative detection of EDCs (Scherr; Fig. 5; interpreted as the where the laser detects the fluorescence);
and separately injecting the plurality of EDCs standard solutions into the microfluidic chip together with the upconversion luminescence biosensor to complete mixing, reaction, separation and detection of the upconversion luminescence biosensor and EDCs (Scherr; Fig. 3A depicts the mixing, reaction, separation which is collected in the reservoir, and detection of the drops);
subjecting the microfluidic chip to standing to complete bridging flocculation and sedimentation of shedding CSUCNPs (Scherr; Fig. 5); collecting a fluorescence spectrum of a CSUCNPs interface formed during the sedimentation in the detection pool by using a fluorescence spectrometer; wherein fluorescence signal characteristic values are characteristic fluorescence intensities of the upconversion luminescence biosensor for specific recognition of EDCs (Scherr; Fig. 5; para [101, 119]; the fluorescently-labeled antibodies bind to the secreted molecules wherein the fluorescent signal is localized onto the hydrogel bead if the capture reagent is specific to the secreted product and the magnitude of the fluorescence signal is proportional to the labeled molecules localized on bead surface or in the hydrogel structure); and
injecting a sample solution to be tested into the microfluidic chip together with the upconversion luminescence biosensor followed by detection in the fluorescence spectrometer to collect a fluorescence signal characteristic value (Scherr; Fig. 5; para [119]).
Scherr does not teach an endocrine disrupting chemicals (EDCs) detection method using the microfluidic biosensing platform, and the upconversion luminescence biosensor for specifically recognizing EDCs; and surfaces of the magnetic nanoparticles being modified with a sequence complementary to the EDC aptamer sequence.
However, Halbert teaches an endocrine disrupting chemicals (EDCs) detection method (Halbert; Abstract; Examiner notes that the broadest reasonable interpretation of diagnosis, prognostic, or theranostic readout may be related to cancer or other diseases would impact endocrine levels) using a microfluidic biosensing platform, the microfluidic biosensing platform comprising an upconversion luminescence biosensor for specifically recognizing EDCs (Halbert; para [57]; the substrate comprises a magnetic bead and the different substrate comprises a non-magnetic bead, or the substrate comprises a non-magnetic bead and the different substrate comprises a magnetic bead), and surfaces of the magnetic nanoparticles being modified with a sequence complementary to the EDC aptamer sequence (Halbert; FIGS. 11F-H show functionalized magnetic beads). It would have been obvious to one of ordinary skill in the art before the effective filing date to have modified the microfluidic biosensing platform of Scherr to detect EDCs as taught by Halbert, because Halbert teaches that the sample may be cancer cells (Halbert; para [32]). Further, it would have been obvious to one of ordinary skill in the art before the effective filing date to have modified the magnetic nanoparticles to be modified with the sequence complementary to the EDC aptamer sequence as taught by Halbert, because Halbert teaches the aptamer binds to the vesicle (Halbert; para [113]).
Modified Scherr does not teach the detection method comprising: preparing a plurality of EDCs standard solutions varying in concentration, wherein concentrations of the plurality of EDCs standard solutions are selected from 0-250 ng/mL; and subjecting logarithmic values of the concentrations of the plurality of EDCs standard solutions and fluorescence signal characteristic values to linear fitting to establish a standard curve for quantification of EDCs; substituting the fluorescence signal characteristic value into the standard curve to calculate EDCs content in the sample solution to be tested.
However, Chen teaches an analogous art of an up-conversion luminescence biosensor (Chen; Abstract) comprising steps of preparing a plurality of EDCs standard solutions varying in concentration, wherein concentrations of the plurality of EDCs standard solutions are selected from 0-250 ng/mL (Chen; page 5, para [3]; the concentration range of the diethylstilbestrol standard 0.05-500ng/ml); and subjecting logarithmic values of the concentrations of the plurality of EDCs standard solutions and fluorescence signal characteristic values to linear fitting to establish a standard curve for quantification of EDCs (Chen; Fig. 4 page 11, para [4]); substituting the fluorescence signal characteristic value into the standard curve to calculate EDCs content in the sample solution to be tested (Chen; Fig. 4). It would have been obvious to one of ordinary skill in the art before the effective filing date have modified the steps of modified Scherr to teaches the models as taught by Chen, because Chen teaches that accounts for different concentrations (Chen; page 7, para [2]).
Allowable Subject Matter
Claims 11-12 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter: the prior art fails to teach “the EDC aptamer sequence consists of SEQ ID NO:1, and the sequence complementary to the EDC aptamer sequence consists of SEQ ID NO:2” of claim 11 and “the EDC aptamer sequence consists of SEQ ID NO:3, and the sequence complementary to the EDC aptamer sequence consists of SEQ ID NO:4” of claim 12. The Examiner notes that amending the independent claim 10 to comprise the dependent claim 11 or 12 may raise a 112(b) rejection. Specifically, if the EDCs are diethylstilbestrol, then it would be unclear as to how the EDCs could be bisphenol A as well. The same rejection would apply to the limitations of “the EDC aptamer sequence and the sequence complementary to the EDC aptamer sequence”.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Austin Q Le whose telephone number is (571)272-7556. The examiner can normally be reached Monday - Friday 9am - 5pm.
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/A.Q.L./Examiner, Art Unit 1796
/MATTHEW D KRCHA/Primary Examiner, Art Unit 1796
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