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 .
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. GB 2019912.1, filed on 16 Dec 2020.
Specification
The abstract of the disclosure is objected to because of undue length, exceeding the 150 word limit. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
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 13 recites the limitation “the photosensitiser" in line 3 and “the pre-activator reagent” in line 4. There is insufficient antecedent basis for this limitation in the claim.
The limitations “the photosensitiser” and “the pre-activator reagent” is not cited prior in claim 13. The examiner recommends correcting the limitations to “a photosensitiser” and “a pre-activator reagent” for continued prosecution of the claim.
Claims 14 and 15 are additionally rejected by the 35 USC § 112 rejection for being dependent on claim 13.
Claim 14 recites the limitation "the set of local regions" in line 3. There is insufficient antecedent basis for this limitation in the claim.
The limitations “the set of local regions” is not cited prior in claim 13 or 14. The examiner recommends correcting the limitations to “a set of local regions” for continued prosecution of the claim.
Claim 15 recites the limitation "t" in line 1 and “the reporter reagent” in line 3. There is insufficient antecedent basis for this limitation in the claim.
The limitations “the system” and “the reporter reagent” is not cited prior to claim 13 or 15. The examiner recommends correcting the limitations to “a system” and “a reporter reagent” for continued prosecution of the claim.
Claim Rejections - 35 USC § 102
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 (i.e., changing from AIA to pre-AIA ) 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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 13-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bosse et al. (WO 2017091609 A1, as cited in the IDS).
Regarding claim 13, Bosse et al. teaches a device for detecting an analyte in a sample (see Abstract, disclosing methods, systems, and apparatus for single analyte detection or multiplexed analyte detection.), the device comprising: a substrate (see Abstract, Fig. 1, hollow polymer optic fiber 106) having an optical component (see Abstract, ‘acceptor bead’ dye) and a binding component (see Abstract, Fig. 1, first binding partner 108), where the optical component and the binding component are attached to a surface of the substrate (see Abstract, [0011], Fig. 1, hollow polymer fiber 106 doped with ‘acceptor bead’ dye and first binding partner 108 bound to an interior surface of the fiber), the photosensitiser (see Abstract, Fig. 1, 'donor bead' dye 114 (e.g., phthalocyanine)) being capable of generating reactive oxygen species from the pre-activator reagent upon absorption of electromagnetic radiation (see Abstract, [0004], disclosing a sample solution containing donor beads, which are photosensitizers which can convert ambient oxygen to an excited and reactive form of oxygen, singlet oxygen, upon illumination at 680nm.), and the optical component being capable of changing from a first optical state to a second optical state on reaction with the reactive oxygen species (see [00132]-[00133], Fig. 1, disclosing that the acceptor dye doped hollow polymer optic fiber 106 upon exposure to excitation light 102 (e.g. laser excitation at a wavelength of 680 nm), the donor bead releases singlet oxygen 116, which causes emissions of light from the acceptor dye doped fiber 106, the wavelength of the emitted light 104 is distinguishable from the excitation light 102.), and wherein the substrate has a deuterium-enriched layer on the surface thereof (see [00235]-[00236], disclosing prior to excitation, the fibers are stimulated with singlet oxygen by immersing them in a solution comprising sodium molybdate and hydrogen peroxide in deuterium oxide D2O (which would provide a deuterium-enriched layer on the surface of the substrate or fiber).).
Regarding claim 14, Bosse et al. teaches the device as claimed in claim 13, comprising a cartridge, wherein the substrate is within the cartridge, and wherein the device further comprises a detector for detecting the set of local regions having the second optical state on the substrate (see [0019], disclosing fiber bundles used for multiplexed detection of analytes are arranged in a cartridge comprising multiple fiber bundles (i.e. substrate), where each bundle can be used for detection of a different analyte. Further see [0016], disclosing the system comprising multiple detectors and optical filter combinations that distinguishably detect emission light at different particular wavelengths, each corresponding to a particular fiber in the bundle, and, therefore, a particular analyte captured by the fiber.).
Regarding claim 15, Bosse et al. teaches the system for detecting an analyte in a sample (see Abstract, disclosing methods, systems, and apparatus for single analyte detection or multiplexed analyte detection.), comprising: the device as claimed in claim 13; and the reporter reagent (see Abstract, Fig. 1, ‘donor bead’ dye 114) and the pre-activator reagent (see [0004], ambient oxygen) for forming a mixture comprising the sample, the reporter reagent comprising a photosensitiser (see [0004], disclosing donor beads comprise a photosensitizer, for example, phthalocyanine.) being capable of generating reactive oxygen species from the pre-activator reagent upon absorption of electromagnetic radiation (see Abstract, [0004], photosensitizers can convert ambient oxygen to an excited and reactive form of oxygen, singlet oxygen, upon illumination at 680nm.).
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.
Claims 1-3, 5, 7-8, and 10-11 are rejected under 35 U.S.C. 103 as being unpatentable over Bosse et al.
Regarding claim 1, Bosse et al. teaches methods, systems, and apparatus for single analyte detection or multiplexed analyte detection (see Bosse et al., Abstract). A sample solution containing analytes and donor beads (i.e. a reporter reagent) is analyzed by introducing it into the hollow polymer fiber optic (i.e. a substrate) doped with ‘acceptor bead’ dye (i.e. an optical component, comprising e.g., thioxene, anthracene, rubrene, and/or lanthanide chelates) and/or ‘donor bead’ dye (e.g., phthalocyanine) that carry a signal generated by the dopant via singlet oxygen channeling (see Bosse et al., [0011], Abstract, Fig. 1). The donor bead comprises a photosensitizer such as phthalocyanine, which converts ambient oxygen (a pre-activator reagent) to an excited and reactive form of oxygen, singlet oxygen, upon illumination at 680nm.
Bosse et al. additionally teaches a first binding partner bound to the interior of the surface of the fiber, which binds to analytes of interest. The second binding partner immobilized on the surface of the donor beads also binds to the analyte, and is introduced to the fiber surface. The donor beads now introduced and bound to the fiber are within proximity of the acceptor dye, and when illuminated with excitation light, the donor beads generate singlet oxygen and is channeled to the acceptor bead dye, where it eventually causes emission of detectable fluorescent light, allowing to obtain quantitative information of one or more analytes in the sample (see Bosse et al., [0003], Abstract).
While Bosse et al. doesn’t explicitly teach irradiating the device with electromagnetic radiation for absorption by the reporter reagent, thereby forming a set of local regions of the optical component having the second optical state on the substrate, wherein, prior to irradiating, the substrate is contacted with a deuterium-enriched fluid, and/or the substrate is provided with a deuterium-enriched layer on the surface thereof; Bosse et al. does teach in another example that the fibers doped with a chemiluminescent singlet oxygen acceptor (e.g. thioxene, e.g. C28 thioxene) and a fluorescent compound (e.g. an europium chelate) in response to singlet oxygen, are stimulated with singlet oxygen by immersing them in a solution comprising sodium molybdate and hydrogen peroxide in deuterium oxide D2O (which would provide a deuterium-enriched layer on the surface of the substrate or fiber). The D2O generates a steady state concentration of singlet oxygen over a period of time as the hydrogen peroxide is catalytically converted to molecular oxygen, where the singlet oxygen intensity is sufficient enough to generate measurable light output from singlet oxygen responsive reagents (see Bosse et al., [00232], [00236]). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the hollow polymer fiber optic doped with an acceptor and donor beads and immerse it into the sodium molybdate and hydrogen peroxide in deuterium oxide solution, as it would have the benefit of the D2O extending the lifetime of the singlet oxygen that the donor beads produce when exposed to excitation light (see Bosse et al. [00236]).
Regarding claim 2, Bosse et al. teaches characterization of emission of light produced from a polymer optic fiber doped with an acceptor dye composition comprising a chemiluminescent singlet oxygen acceptor and a fluorescent compound in response to singlet oxygen. The doped fiber is then stimulated with singlet oxygen by immersing them in a solution comprising sodium molybdate and hydrogen peroxide in deuterium oxide. The solution generates a steady state concentration of singlet oxygen over a period of time as hydrogen peroxide is catalytically converted to molecular oxygen, and deuterium oxide is used to extend the lifetime of these singlet oxygen, to allow for reaction of the acceptor beads to produces UV emissions, which excite the fluorescent dye and emit light, without the presence of an external excitation light (see [00232], [00235]-[00236], [00238]).
While Bosse et al. does not explicitly teach that donor beads (a reporter reagent) are present in the doped fibers, Bosse et al. does teach that in the preparation of the hollow polymer optical fibers doped with acceptor and/or donor bead dye compositions (see Bosse et al. [0011]). The example performed with the deuterium oxide solution is also specified to be ran without an external excitation light, where otherwise the donor beads that’s excited by the light would generate its own singlet oxygen and cause the acceptor bead dye to fluoresce without contact with the deuterium oxide solution (see Bosse et al., [00235]). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the fiber substrate doped with both a donor and acceptor dye prior to immersing the fiber in the deuterium oxide solution, with the benefit of the D2O extending the lifetime of the singlet oxygen that the donor beads produce when exposed to excitation light (see Bosse et al. [00236]).
Regarding claim 3, Bosse et al. teaches the exact limitations of claim 3. Specifically, Bosse et al. teaches the method as claimed in claim 2, wherein the deuterium-enriched fluid comprises deuterium oxide (see [00236], disclosing the different fibers were stimulated with singlet oxygen by immersing them in a solution comprising sodium molybdate and hydrogen peroxide in deuterium oxide (D2O)).
Regarding claim 5, Bosse et al. teaches the exact limitations of claim 5. Specifically, Bosse et al. teaches the method as claimed in claimed in claim 1, wherein the reactive oxygen species is singlet oxygen (see [0004], disclosing donor beads comprise a photosensitizer, for example, phthalocyanine, which converts ambient oxygen to an excited and reactive form of oxygen, singlet oxygen, upon illumination at 680 nm.).
Regarding claim 7, Bosse et al. teaches the exact limitations of claim 7. Specifically, Bosse et al. teaches the method as claimed in claim 1, wherein the optical component in the first optical state absorbs light at one or more first wavelengths and in the second optical state absorbs light at one or more second wavelengths, where the first and second wavelengths are different (see [0058], [00165], disclosing the system comprising a first excitation source and a second excitation source, where both wavelengths correspond to a first and second donor dye composition (e.g. with which a first polymer optic fiber and/or first donor particle is doped), where the second excitation wavelength is different from the first excitation wavelength. The system may further comprise different optical filters having different transmittances are transparent and opaque to different wavelengths of light and may be used depending on the particular excitation sources that are used to illuminate a fiber and/or fiber bundle, as well as the different particular acceptor dye compositions with which either the fibers and/or acceptor beads are doped.).
Regarding claim 8, Bosse et al. teaches the exact limitations of claim 8. Specifically, Bosse et al. teaches the method as claimed in claim 1, wherein the optical component in the first optical state is fluorescent and in the second optical state is non-fluorescent or the optical component in the first optical state is non-fluorescent and in the second optical state is fluorescent (see [00125], disclosing the chemiluminescent singlet oxygen acceptor (from the 'acceptor bead' dye) reacts with singlet oxygen, and produces ultraviolet light. The fluorescent compound (i.e. dye component) is excited by the ultraviolet light produced by the chemiluminescent singlet oxygen acceptor via its reaction with singlet oxygen, and emits fluorescent light. The transfer of energy from the chemiluminescent singlet oxygen acceptor to the fluorescent compound excites the fluorescent compound, resulting in the emission of fluorescent light.).
Regarding claim 10, Bosse et al. teaches the exact limitations of claim 10. Specifically, Bosse et al. teaches the method as claimed in claim 1,wherein steps (i) and (ii) take place in the absence of wash steps (see [0004], disclosing the AlphaScreen® assay utilizing two bead types, donor beads and acceptor beads, and that the proximity-dependent chemical energy transfer is the basis for AlphaScreen®'s homogeneous nature, such that no washing steps are required, unlike ELISA assays, electrochemiluminescence, and flow cytometry assays, thereby offering a significant advantage.).
Regarding claim 11, Bosse et al. teaches the process 1400 for collection as sample 1420, preparing and introducing sample solutions into a bundle of polymer optic fibers, by dipping the fibers into the sample solution, where beads bound to the analyte of interest are drawn into the interior of the fiber via capillary forces. The fibers can then be stimulated with singlet oxygen by immersing them in a solution comprising sodium molybdate and hydrogen peroxide in deuterium oxide D2O. In some embodiments, the sample is a liquid that is mixed with the detection mixture (i.e. the beads), and in others, the sample is a solid sample that is crushed and/or dissolved as to be homogenized prior to adding the detection mixture (see [00216]-[00217], [00235]-[00236], Fig. 14).
While Bosse et al. doesn't explicitly teach that the sample is unprocessed, liquid samples do not go use further steps such as filtration or dilution, beyond having the detection reagents (i.e. donor beads) mixed with the sample, and the immersion of the fibers into the solution comprising sodium molybdate and hydrogen peroxide in deuterium oxide. Only the solid samples would need to be homogenized as it would only be possible to perform the assay while it is dissolved and/or crushed. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to assume that no further steps of processing the liquid sample is needed prior to adding it onto the substrate or fiber and subsequent immersion by the deuterium solution (see [00216]-[00217], [00235]-[00236], Fig. 14).
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Bosse et al. as applied to claim 1 above, and further in view of Song et al. (CN 107741417 A).
Regarding claim 4, Bosse et al. teaches a solution comprising sodium molybdate and hydrogen peroxide in deuterium oxide which is used to immerse fibers (which would provide a deuterium-enriched layer on the surface of the substrate or fiber) (see Bosse et al., [00236]).
Bosse et al. fails to teach wherein the deuterium-enriched layer comprises a deuterium-enriched polymer, such as a deuterium-enriched protein layer, or a deuterium-enriched polysaccharide layer.
However, in the analogous art of in-situ method for fast detecting cell biological process, Song et al. teaches a method for in-situ fast detecting cell biological processes, where the cells may be labeled by a deuterium-containing substance. The deuterium containing substance is a substance containing the deuterium element, including, but not limited to: deuterium substituted nucleic acid, deuterated deuterium substituted amino acid, deuterium-substituted fatty acid, deuterated protein or other deuterated organic metabolic substrate mixtures and so on (see Song et al., [0006], [0008], [0010]). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the deuterium oxide solution of Bosse et al. to further incorporate deuterated protein (as taught by Song et al.), for the benefit of being able to obtain the biochemical process, properties, and function related information pertaining to a target cell with the deuterium marker, allowing for tests to be performed in drug susceptibility of bacterial infections, environmental microorganism metabolism, human cell detection, and other biological and medical applications (see Song et al., Abstract).
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Bosse et al. as applied to claim 1 above, and further in view of Cretich et al. (“Digital detection of biomarkers assisted by nanoparticles: application to diagnostics”, as cited in the IDS).
Regarding claim 6, Bosse et al. teaches that the system requires an excitation light source and a detector. The detector for a hand-held or lab bench detector can include, for example, a charge-coupled device (CCD), a photomultiplier tube (PMT) and/or avalanche photodiode (APD). Existing detector systems can be used or adapted for use in reading signals from the hollow fibers described herein, e.g., monochromator-based absorbance, fluorescence, and/or luminescence detectors/readers (see Bosse et al., [00129]).
Bosse et al. fails to teach that the detector is optical microscopy.
However, in the analogous art of "Digital detection of biomarkers assisted by nanoparticles: application to diagnostics", Cretich et al. teaches that a fluorescence microscope (optical microscope with a fluorescent component) is used to determine the concentration of the analyte, by observing different populations of beads for a positive signal for active enzyme activity associated with the target analyte (see Cretich et al., Microfluidic compartments, Encapsulation of single molecules in nanodroplets by emulsion, Fig. 2). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the detector of Bosse et al. to further incorporate a fluorescence microscope (as taught by Cretich et al.), for the benefit reducing the required reagent and sample volumes needed to perform assays, which in turn improves assaying time enabled by confinement of nano-droplets by 6 times compared to standard ELISA, as well as improve the limit of detection by two orders of magnitude in comparison to standard ELISA (see Cretich et al., Encapsulation of single molecules in nanodroplets by emulsion).
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Bosse et al. as applied to claim 1 above, and further in view of Marcus et al. (US PG-Pub 20190195858 A1).
Regarding claim 9, Bosse et al. teaches that the acceptor dye doped hollow polymer optic fiber 106 upon exposure to excitation light 102 (e.g. laser excitation at a wavelength of 680 nm), the donor bead releases singlet oxygen 116, which causes emissions of light from the acceptor dye doped fiber 106 (see Bosse et al., [00132]-[00133], Fig. 1).
Bosse et al. fails to teach wherein the change from the first optical state to the second optical state is irreversible.
However, in the analogous art of separations of rare cells and genomic analysis thereof, Marcus et al. teaches a photo-convertible protein, a polypeptide sequence used for tracking cells, which changes its molecular structure or three-dimension folding confirmation upon exposure to light or other electromagnetic radiation, e.g. UV or visible light, resulting in an altered physical property such as a change in fluorescence. This change may be reversible, or irreversible dependent on the photoconvertible protein used, with examples that transition to a red fluorescence being Dendra2, IrisFP, tdEosFP, mEos2, PA-Cherryl, mKikGR, Fast-FT, Medium-FT, and Slow-FT (see Marcus et al., [0042]). In some embodiments, a photoconvertible dye may also be used, citing that it can also be used to track individual cells in vivo using a commercial lipophilic membrane dye that exhibits a permanent florescence shift, or photoconversion, after light exposure (see Marcus et al., [0047]). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the acceptor bead dyes of Bosse et al. to incorporate an irreversible photoconvertible protein or dye (as taught by Marcus et al.), for the benefit of being able to identify and track cells of interest with the permanently changed fluorescent marker following the application of light onto these cells, where the light or other electromagnetic radiation source can be directed to locations other than those of the charted coordinates directed to specified cells (see Marcus et al., [0045]).
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Bosse et al., as applied to claim 1 above, and further in view of Chan-Hui (US PG-Pub 20040229380 A1).
Regarding claim 12, Bosse et al. teaches illuminating fibers with excitation light, causing the donor beads to get excited, and results in the emission of light from the acceptor dye doped fibers (see [0015]).
Bosse et al. fails to teach wherein the device is irradiated with electromagnetic radiation for more than 1 second.
However, in the analogous art of ErbB heterodimers as biomarkers, Chan-Hui et al. teaches a length of time for irradiating a photosensitizer, dependent on the nature of the photosensitizer, the nature of the cleavable linkage, the power of the source of irradiation, and its distance from the sample, and so forth. The period of irradiation may be less than about a microsecond to as long as about 10 minutes, where the intensity and length of irradiation should be sufficient to excite at least 0.1% of the photosensitizer molecules, to preferably, substantially all of the photosensitizer molecules (see Chan-Hui et al., [0122]). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the excitation light of Bosse et al. to incorporate a time component for irradiation (as taught by Chan-Hui et al.), for the benefit of ensuring that the irradiation is intense enough for the photosensitizers to produce sufficient singlet oxygen in a practical time duration (see Chan-Hui et al., [0122]).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Tracy C Colena whose telephone number is (571)272-1625. The examiner can normally be reached Mon-Thus 8:00am-5:00pm.
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/TRACY CHING-TIAN COLENA/Examiner, Art Unit 1797
/ROBERT J EOM/Primary Examiner, Art Unit 1797