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 41-44 and 47-56 are currently pending. Claims 47-49, 55 and 56 have been amended by Applicants’ amendment filed 12-10-2025. No claims have been added or cancelled by Applicant’s amendment filed 12-10-2025.
Applicant's election with traverse of Group III, claims 47-49, directed to a fiber optic scanner mounted with a slide bearing fluorescent beads; and the election of Species with traverse of:
Species (A): wherein the single specific species of non-natural polymer of formula (ii) is:
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(claim 47); in the reply filed June 19, 2024 was previously acknowledged.
Claims 41-46 and 50-54 were previously withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on June 19, 2024.
The restriction requirement is deemed proper and is 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 47-49, 55 and 56 are under consideration to which the following grounds of rejection are applicable.
Priority
The instant application filed February 2, 2021 is a CON of US Patent Application 15461455, filed March 16, 2017 (now abandoned); which is a CON of 35 U.S.C. 371 national stage filing of International Application No. PCT/US2015/050306, filed September 16, 2015; which claims priority to US Provisional Patent Application 62050922, filed September 16, 2014.
Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120 as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed applications: US Provisional Patent Application 62/050922, filed September 16, 2014 fails to provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for one or more claims of this application. The specific method steps recited in independent claims 47 and 55 do not have support for at least: bifurcated light path having two fiber optic bundles; fluorescently labeled beads; input aperture; a scanning source configured to scan a beam of radiation along a path; wherein the scanning source is configured to provide and maintain the beam of radiation perpendicular to the planar surface; processor configured to process the two channels of the light signal detected by the photodetector to select respective active ones of affixed non-natural polymers; beads comprising the affixed non-natural polymers of a distinct bioactive monomer; a band pass filter configured to split the light signal as emitted from the imager stage into two channels; processing the collected two channels of the light detected; and processor configured to calculate a ratio. Therefore, the priority date for the presently claimed invention is September 16, 2015, the filing date of International Patent Application WO2016053621 (PCT/US2015/050306).
Applicants are invited to specifically indicate the location of the cited phrase pertinent to claims 47 and 55 of the instant application.
Response to Arguments
Applicant’s arguments filed December 10, 2025 have been fully considered but they are not persuasive (in part). Applicants essentially assert that: (a) Applicant maintains that the provisional filing supports the "planar surface for supporting a sample comprising a slide", "bifurcated light path having two fiber optic bundles", "fluorescently labeled beads", "photodetector", and "processor", at least at page 6
including Figure 6 that shows various components of the fiber optic scanner and cites to reference 9 that describes the FAST system, page 7 describing bead scanning via a fluorescent based assay, and page 15 describing fluorescent detection of beads, among other locations (Applicant Remarks, pg. 8, Priority).
Regarding (a), please see the Examiner’s previous response to this same argument regarding US provisional patent application 62050922, in the Office Action mailed August 12, 2025. Additionally, instant the as-filed Specification and original claims do not teach: (i) a scanning source that is configured to provide and scan (or to provide and maintain) a beam of radiation; (ii) a processor configured to select respective non-natural polymers among the affixed non-natural polymers based on the processed two channels of light; and/or (iii) a processor configured to calculate a ratio of the two channels and to select respective non-natural polymers among the affixed non-natural polymers based on the ratio to process the two channels of the light signal detected by the photodetector.
Withdrawn Objections/Rejections
Applicants’ amendment and arguments filed December 10, 2025 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.
Maintained Objections/Rejections
Claim Interpretation: The fiber optic scanner of claim 47 is interpreted to comprise: an imager stage having a planar surface, two fiber optic bundles, an input aperture, an output aperture, a scanning source, a band pass filter, a photodetector, and a processor as recited. The Examiner has interpreted the term “comprising affixed non-natural polymers treated with a fluorescently labeled target agent” as recited in amended claim 47, line 4 to be encompassed by the phrase “configured to support a slide beading beads comprising affixed…target agent.”
The “picking system” recited in claims 48 and 56 is interpreted to refer to any systems that is capable of selecting a non-natural polymer and delivering to a well plate including: automated handling systems, a researcher/operator, FACS, FAST system, a fluorometer, fluorescence spectrophotometer, a microscope, a mass spectrometer, HPLC, FTIR spectrometer, NIR spectrometer, etc.
The fiber optic scanner of claim 55 is interpreted to comprise: an imager stage having a planar surface; two fiber optic bundles; an input aperture; an output aperture; a scanning source; a band pass filter; a photodetector; and a processor as recited.
The term “affixed non-natural polymer” is interpreted to refer to any non-natural polymer comprising a monomer of dihydroisoquinolinone that coats, attaches, and/or is fastened to any part of a bead, slide, substrate and/or surface.
Claim Rejections - 35 USC § 112(b)
The rejection of claims 47-49, 55 and 56 is maintained 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.
Claims 47-49, 55 and 56 are indefinite because the claims appear to recite both a product and process in the same claim. The examiner cautions that according to the MPEP 2173.05(p)(II) states that a single claim which claims both an apparatus and the method steps of using the apparatus is indefinite under 35 U.S.C. 112(b). PXL Holdings v. Amazon.com, Inc., 430 F.2d 1377, 1384, 77 USPQ2d 1140, 1145 (Fed. Cir. 2005); Ex parte Lyell, 17 USPQ2d 1548 (Bd. Pat. App. & Inter. 1990) (claim directed to an automatic transmission workstand and the method of using it held ambiguous and properly rejected under 35 U.S.C. 112(b)). For example, claims 47 and 55 recite: “an imager stage having a planar surface configured to support a slide bearing fluorescent beads in line 3”; and “a band pass filter configured to split the light signal as emitted from the imager stage into two channels” in lines 14-15; while claims 47 and 55 also recite: “affixed non-natural polymers treated with a fluorescently labeled target agent” in line 4; “a spot of illumination provided by the scanning source provides a light signal which is received by the input aperture of each of the two fiber optic bundles and transmitted via the bifurcated light path to the output aperture” in lines 10-13; and “the processed two channels of light” in line 20. Such claims can also be rejected under 35 U.S.C. 101 based on the theory that the claim is directed to neither a “process” nor a “machine,” but rather embraces or overlaps two different statutory classes of invention set forth in 35 U.S.C. 101 which is drafted so as to set forth the statutory classes of invention in the alternative only. Id. at 1551.
Claims 47 and 55 are indefinite for the recitation of the term “a scanning source is configured to provide and scan a beam of radiation” such as recited in claim 47, line 8 because it is unclear what the scanning source is ‘configured to’ do given that claim 47 recites several different configurations for the scanning source. Instant claim 47, lines 9-11 recite that the scanning source is configured to: (i) provide and maintain a beam of radiation; (ii) provide a spot of illumination; and (iii) provide a light signal such that it is unclear what the scanning source is configured to do and, thus, the metes and bounds of the claim cannot be determined.
Claims 47, 48 and 55 are indefinite for the recitation of the term “and “to select respective non-natural polymer among the affixed non-natural polymers” such as recited in claim 47, lines 19-20 because: (i) the instant as-filed Specification and original claims do not teach that that the processor is configured to select a non-natural polymer, and/or that the processor calculates (or is configured to calculate) two channels of the light signal detected by the photodetector ratio or a channel ratio; (ii) there are no non-natural polymers present in the fiber optic arrays of claims 47 and 55; and (iii) it is unclear how a processor selects a non-natural polymer. The processor is likely to select a bead based on an emitted or detected signal (e.g., fluorescence), and would not select a non-natural polymer itself (see, as-filed Specification, paragraph [85]), such that it is completely unclear how a processor is configured to select a non-natural polymer and, thus, the metes and bounds of the claim cannot be determined.
Claim 47 is indefinite for the recitation of the term “the processed two channels of light” such as recited in claim 47, line 20. There is insufficient antecedent basis for the term “the processed two channels of light” in the claim because claim 47, line 18 recites the term “to process the two channels of the light signal detected.”
Claim 48 is indefinite for the recitation of the term “deliver to well plates” such as recited in claim 48, line 4 because claim 48 depends from claim 47, where claim 47 does not recite the presence of well plates and, thus, the metes and bounds of the claim cannot be determined.
Claim 48 is indefinite for the recitation of the term “the processor is further configured to calculate a ratio of the two channels” such as recited in claim 48, lines 7-8 because the as-filed Specification and original claims do not teach that the processor is configured to calculate a ratio of two channels, and/or to calculate a ratio of two channels of light and, thus, the metes and bounds of the claim cannot be determined.
Claim 48 is indefinite for the recitation of the term “generate a digital image of locations on the slide” such as recited in claim 48, line 10 because the as-filed Specification and original claims do not teach that the processor generates a digital image, such that it is unclear how a digital image of locations on a slide are generated and, thus, the metes and bounds of the claim cannot be determined.
Claims 55 and 56 are indefinite for the recitation of the term “to select respective non-natural polymers among the affixed non-natural polymers” and/or “the selected respective non-natural polymers among the affixed non-natural polymers” such as recited in claim 55, lines 19-20 because there are no non-natural polymers recited to be present in relation to the fiber optic scanner, such that it is not possible for the system to be configured to select something that is not present and, thus, the metes and bounds of the claim cannot be determined.
Claim 56 is indefinite for the recitation of the term “using a digital image of locations on the slide” such as recited in claim 56, lines 3 and 10 because claim 56 depends from claim 55, wherein claim 55 does not recite the presence of a slide and/or any digital images of locations on the non-existent slide and, thus, the metes and bounds of the claim cannot be determined.
Claim 56 is indefinite for the recitation of the term “and deliver the selected respective non-natural polymers to well plates for cleavage from the beads and sequencing” such as recited in claim 56, lines 4-5 because claim 56 depends from instant claim 55, wherein claim 55 does not recite well plates, beads, and/or sequencing devices and, thus, the metes and bounds of the claim cannot be determined.
Claim Rejections - 35 USC § 112(d)
The rejection of claim 56 is maintained, and claim 48 is newly rejected, under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 48 recites (in part): “a picking system configured to pick the selected respective non-natural polymers from the slide and deliver to well plates” such as recited in claim 48, lines 3-4 because claim 48 depends from claim 47, wherein claim 47 does not recite the presence of non-natural polymers and/or well plates. Thus, claim 48 is an improper dependent claims for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 56 recites (in part): “a picking system configured to pick the selected respective non-natural polymers from the slide using a digital image…and deliver to well plates for cleavage from the beads and sequencing” such as recited in claim 56, lines 1-5 because claim 56 depends from claim 55, wherein claim 55 does not recite the presence of a slide, well plates, non-natural polymers, beads, and/or a digital image. Thus, claim 55 is an improper dependent claims for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
Claim Rejections - 35 USC § 103
The rejection of claims 47-49, 55 and 56 is maintained under 35 U.S.C. 103 as being unpatentable over Reiner et. al. (hereinafter “Reiner”) (US Patent Application No. 20130309170, published November 21, 2013; of record) in view of Kuhn et al. (hereinafter “Khun”) (US Patent Application No. 20090317836, published December 24, 2009; of record); and further in view of Yongnian (Gao Yongnian Thesis; National University of Singapore, 2008, 1-140; of record) as evidenced by Ao et al. (hereinafter “Ao”) (Methods in Molecular Biology, Springer Protocols, Chapter 20, 2017, 235-246; of record); and Oosterom et al. (hereinafter “Oosterom”) (EJNIMMI Research, 2014, 4(56), 1-11; of record); and Al-Jobouri (Universal Journal of Biomedical Engineering, 2013, 1(1), 1-5; of record); Flusberg et al. (hereinafter “Flusberg”) (Nature Methods, 2005, 2(1), 941-950; of record); and Schmalzlin et al. (hereinafter “Schmalzlin”) (Sensors, 2014, 14, 21968-21980; of record); and VanDevender et al. (hereinafter “VanDevender”) (Physical Review Letters, 2010, 105, 1-4; of record); and Jennifer Waters (hereinafter “Waters”) (Journal of Cell Biology, 2009, 185(7), 1135-1148; of record); and Curry et al. (hereinafter “Curry”) (Proceedings of the 26th Annual International Conference of the IEEE EMBS, San Francisco, CA, USA, September 2004, 1-4; of record); and Liu et al. (hereinafter “Liu”) (Cytometry Part A, 2012, 81A, 169-175; of record).
Regarding claims 47-49, 55 and 56, Kuhn teaches compounds useful for targeting PARP1, and methods for using such compounds to detect and image cancer cells (Abstract). Reiner teaches detectable compounds that bind PARRP1; as well as, methods and materials for using such compounds to image cells containing PARP1 including cancer cells and cells that overexpress PARP1, wherein a compound of formula (I) can be used to detect or image a cancer cells through non-invasive imaging of the subject (interpreted as beads affixed on non-natural polymers, claims 47 and 55) (paragraph [0005]). Reiner teaches that the methods and compositions provide several advantages including the ability to assess therapeutic efficacy of cancer therapies including the ability to image PARP1 non-invasively at the whole body level, and to quantitate therapeutic inhibition, where the technology allows separate subjects into appropriate treatment groups for the detection of emerging resistance; demonstrating that fluorescently labeled PARP1 inhibitors can be used for cellular imaging, such that the compounds provided can function as detectable probes for whole-body PARP1 imaging; measuring inhibition of PARP1 by emerging therapeutic PARP1 inhibitors; and to identify useful imaging agents including in vivo (interpreted as beads affixed on non-natural polymers; and a scanning source, claims 47 and 55) (paragraphs [0006]-[0007]). Reiner teaches that the compound of Formula (I) is: P-Ln-Tm-D, wherein P is a PARP1 inhibitor; L is a linker; T has the structure of the molecules of paragraph [0009]; D is a detectable agent; m = 0 or 1; and n = 0 or 1 (interpreted as encompassing dihydroisoquinolinones, claims 47 and 55) (paragraph [0008]-[0009]). Reiner teaches that P is selected from the group consisting of benzamide, quinolone, dihydro-isoquinolinone, isoquinolinone, isoquinoline, etc. (interpreted as non-natural monomers including dihydroisoquinolinone, claims 47 and 55) (paragraph [0010]). Reiner teaches that cancers that can be detected and/or imaged by the compounds, compositions, and methods including, but are not limited to, cardiac cancers, lung cancers, gastrointestinal cancers, genitourinary tract cancers, liver cancers, bone cancers, nervous system cancers, gynecological cancers, hematologic cancers, and/or skin cancers including solid tumors (interpreted as cancers) (paragraph [0105]-[0117]). Reiner teaches in vivo and in vitro imaging including a compound of Formula (I) or Formula (2) imaged using in vivo laparoscopy and endomicroscopy for the facile, real-time imaging and localization of cancers labeled with a compound having a fluorescent detectable agent, wherein the compound can be imaged using fiber optic endomicroscopy; and imaging to assess the effect of an anti-cancer therapy on cells expressing PARP1 using the compounds described herein, where the subject is imaged prior to, during, and/or after treatment with the therapy, and the corresponding signal/images are compared (interpreted as in vitro and in vivo imaging; bioactive monomers; interpreting fiber optic endomicroscopy as a fiber optic scanner; and cells, claims 47 and 55) (paragraphs [0120]-[0121]). Reiner teaches that Figure 5A is a schematic illustrating the synthesis of 18F-AZD2281 (6); 18F-labeled TCO 3 and AZD2281-Tz (5) were combined and incubated for 3 minutes; magnetic TCO scavenger resin was added (interpreted as a non-natural polymer, claim 47), incubated for 5 minutes, and removed; purified 18F-AZD2281 was reconstituted and brought into an injectable volume; that Figure 5B illustrates the synthesis of the magnetic TCO-scavenger resin from amine decorated beads and NHS-activated TCO (1); that Figure 5C illustrates the synthesis of 18F-labeled TCO (3) that Figure 5D provides the structure of AZD2281 (4); that Figure 5E shows the synthesis and structure of 18F-AZD2281 (6); only one isomer shown); and that Figure 5F illustrates the radioactivity and absorption traces of the 18F -AZD2281 reaction mixture before and after purification with the magnetic TCO-scavenger resin (interpreted as fluorescent beads; and beads affixed to non-natural polymers, claims 47, 48 and 55) (paragraph [0035]). Figure 5A-F is shown below:
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Reiner teaches that the compositions and methods can be imaged using a variety of modalities that are known to one of skill in the art, wherein detection methods can include both imaging ex vivo and in vivo imaging methods such as immunohistochemistry, bioluminescence imaging (BLI), Magnetic Resonance Imaging (MRI), positron emission tomography (PET), Single-photon emission computed tomography (SPECT), electron microscopy, X-ray computed tomography, Raman imaging, optical coherence tomography, absorption imaging, thermal imaging, fluorescence reflectance imaging, fluorescence microscopy, fluorescence molecular tomographic imaging, nuclear magnetic resonance imaging, X-ray imaging, ultrasound imaging, photoacoustic imaging, lab assays, or in any situation where tagging, staining, imaging is required, such that one or more imaging techniques can be used in the methods provided herein (interpreted as encompassing a photodetector and processor; a scanning source configured to scan a beam of radiation along a path; input aperture; output aperture; and detectors with processors that calculate a ratio of two light signals, claims 47 and 55) (paragraph [0100]); wherein it is known that SPECT and bioluminescence can be used together for photographic and fluorescence imaging via a CCD camera, wherein an animal is illuminated by the light source via a fiber optic bundle and an MI-150 fiber optic illuminator comprising two optic fibers to detect excitation and emission of light as evidenced by Oosterom (Abstract; and pg. 1, col 2, Methods; pg. 2, Figure 1; and pg. 2, col 2, second full paragraph); it is known that techniques that use fiber optics in optical sensors include MRI as evidenced by Al-Jobouri (Abstract); and where it is known that Raman scattering is collected with fiber-coupled high performance astronomy spectrograph using an array of 20 X 20 multimode fibers linked to the camera port of a microscope, such that multiplexing is achieved using a fiber bundle to sample the optical image as evidenced by Schmalzlin (Abstract; and pg. 21969, last full paragraph); where it is known that fiber-optic fluorescence imaging systems include portable handheld microscopes, flexible endoscopes well suited for imaging within hollow tissue cavities and micro-endoscopes that allow minimally invasive high-resolution imaging deep within tissue including epifluorescence, one-photon FMS, fiber-bundle epifluorescence, confocal fluorescence, dual-axis fiber confocal, fiber-bundle confocal, two-photon fluorescence, multi-focal two-photon, and double-clad two-photon as evidenced by Flusberg (Abstract; and pg. 942, Table 1); and wherein it is known that integrated optical fibers can be used for detecting 280-nm fluorescence photons including a multimode high-NA UV-transparent quartz fiber, such that integrating multiple fibers to a single surface-electrode ion trap enables scalable readout of multiple qubits in trapped ion quantum information processing systems as evidenced by VanDevender (Abstract; pg. 1, col 2, first full paragraph; and pg. 4, col 1, last full paragraph). Reiner teaches that a PARP1 inhibitors can include any compound which inhibits or reduces the activation of PARP1, such as where PARP1 activation in response to DNA breaks and/or involved in cell death, wherein PARP1 inhibitors include compounds from various chemical classes including dihydroisoquinolinones (interpreted a dihydroisoquinolinone, claims 47 and 55) (paragraph [0049], lines 1-6). Reiner teaches that in vitro imaging methods, the compounds and compositions described can be used in a variety of in vitro assays including contacting a sample, such as a biological sample (e.g., a cell such as a cancer cell), with one or more compounds of Formula (1) or Formula (2); allowing the conjugates to interact with a biological target in the sample; optionally, removing unbound agents; illuminating the sample with light of a wavelength absorbable by a fluorophore of the agents; and detecting a signal emitted from fluorophore thereby to determine whether the agent has been activated by or bound to the biological target (interpreted as a sample; light signal; detection; bioactive monomers; and a scanning source, claims 47 and 55) (paragraph [0124]). Reiner teaches cellular uptake, binding or cellular localization of the agent can be assessed using techniques known in the art, including, for example, fluorescent microscopy, fluorescence-activated cell sorting (FACS) analysis, immunohistochemistry, immunoprecipitation, in situ hybridization and Forster resonance energy transfer (FRET) or fluorescence resonance energy transfer (interpreted as encompassing fiber optic imaging; and fluorescent beads, claims 47-49, 55 and 56) (paragraph [0125]), wherein it is known that background fluorescence, and the fluorescence of submicron beads can be detected in biological specimens by fluorescence microscopy including FRET and FRAP as evidenced by Waters (Abstract; pg. 1136, Figure 1; and pg. 1143, col 3, last partial paragraph). Reiner teaches a polystyrene resin (interpreted as polystyrene core, claim 49) (paragraph [0129], line 5). Reiner teaches that the sample can then be viewed using an appropriate detection device such as a fluorescent microscope equipped with appropriate filters matched to the optical properties of a fluorescent agent, wherein fluorescence microscopy of cells in culture or scintillation counting is also a convenient means for determining whether uptake and binding has occurred; and that samples include tissues, tissue sections and other types of samples, wherein other detection methods include flow cytometry, immunoassays, hybridization assays, and microarray analysis (interpreted as fiber optics, a sample; a photodetector; interpreting the microscope as a scanning source; including an ordered array; and encompassing a processor, claims 47, 55 and 56) (paragraph [0126]). Reiner teaches that HT1080 cells were labeled with AZD2281 fluorophore conjugate in cell culture medium and imaged on an inverted epifluorescence microscope using a heated stage (interpreted as an imager stage; interpreting the microscope stage to be a planar surface; and a scanning source, claims 47 and 55) (paragraph [0196], lines 1-5). Reiner teaches that images in vessels were taken using a 20 X water immersion objective on a laser scanning confocal microscope (interpreted as a scanning source, claim 47) (paragraph [0198], lines 5-7). Reiner teaches that 4-amino pyridines are immobilized on a solid support such as magnetic materials, dextrans, polystyrenes, latex, biological macromolecules (interpreted as a bead containing a polystyrene core, claim 49) (paragraph [0082], lines 10-12). Reiner teaches that the “linker” can comprise atoms or groups of atoms including polyethylene glycol (PEG) (interpreted as PEG copolymer, claim 49) (paragraph [0058], lines 1-5). Reiner teaches that for AZD2281-TCO IC50 assays, MDA-MB-436 cells (500 μL, 80.000 cells/mL) were seeded into glycerin treated 8-well chamber slides, and allowed to attach overnight (interpreted as an slides; and an ordered array, claims 47, 48 and 55) (paragraph [0145], lines 1-4). Reiner teaches UV detectors and radio-detector connected in series; as well as, dual-wavelength UV-vis detectors and a flow-through gamma detector in series (interpreted as detectors with processors that calculate a ratio of two light signals including a background light and light signal, claims 47, 55 and 56) (pg. 25, paragraph [0153]). Reiner teaches that a compound having a fluorescent detectable agent can be detected by traditional fluorescence imaging techniques allowing for the facile tracking of the compounds by fluorescence microscopy or flow cytometry using methods known in the art, such as described in US 2005/0249668, the content of which is incorporated by reference in its entirety (interpreted as detecting fluorescence such as a fluorescent bead, claims 47 and 55) (paragraph [0099]). Reiner teaches that that for anatomic reference of PET signal, x-rays were projected over 360 degrees to create a computed tomographic (CT) image; and x-rays were incident on a CCD detector containing 2048 transaxial and 3072 axial pixels, which were calibrated using 70 dark and 70 light images processed through a Shepp-Logan filter and reconstructed using a filtered back projection algorithm (interpreted as scanning, filtering, detecting, and multi-channel processing, claims 47 and 55) (paragraph [0190]). Reiner teaches that the images in each channel were captured using identical acquisition parameters; and for each image, both cell structures and nuclei structures have been obtained using the appropriate fluorescence filters and appropriate excitation signal levels to avoid collecting auto-fluorescence; and the collected data was then pre-processed with Cellprofiler, wherein the fluorescence signal for the total cell and the signal in the nuclear area was calculated using the corresponding mask as a spatial filter; the two signals were normalized for their total areas, the ratio of fluorescent signal in the cytosol region over the signal in the nuclear region was calculated, background subtraction was performed on the normalized signal using the cell’s negative masks (interpreted as calculating a ratio of two channels, claims 55 and 56) (paragraph [0147]). Reiner teaches that detecting a detectable agent comprises using histochemistry, fluorescence detection, chemiluminescence detection, bioluminescence detection, magnetic resonance imaging, nuclear magnetic resonance imaging, positron emission tomography, single-photon emission computed tomography, X-ray imaging, X-ray computed tomography, ultrasound imaging, or photoacoustic imaging (interpreting laser ultrasound as fiber optic scanner; and including scanning sources; photodetectors’ band pass filters, etc., claims 47 and 55) (pg. 36, col 1, claim 13).
Reiner does not specifically exemplify a stage adjacent to fiber optic bundles (claim 48, in part); and a polystyrene bead core with a PEG graft co-polymer (claim 49).
Regarding 48 (in part), Kuhn teaches analyzing the cell population by cell attachment to the substrate, scanning the cell population on the substrate by fiber optic array, and imaging the cells by digital microscopy using relocation (interpreted as an ordered array, claim 48) (paragraph {0012], lines 10-14). Kuhn teaches method for detecting circulating tumor cells in a mammalian subject; and for diagnosing metastatic cancer or early stage cancer (Abstract). Kuhn teaches in Figure 1; a fiber optic array scanning technology (FAST) (paragraph [0020]; and Figure 1). Figure 1 is shown below:
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Kuhn teaches that the FAST technology has been used for high speed detection of CTCs in peripheral blood of stage IV breast cancer patients, wherein FAST scanning enables efficient imaging of CTCs with ADM so that 10 ml of blood containing about 60 million white blood cells can be evaluated in 80 minutes; such that technology improvements that should enable this scan time to be reduced by over 75%; and that high resolution ADM images are further used for CTC identification, such that the results support using this instrument for point-of-care patient screening, monitoring and management (interpreted as the fiber optic scanner, scanning source, photodetector, processor; bifurcated light source; fiber optic bundle; a circular beam of radiation; and all components as recited in instant claims 47 and 55, claims 47-49, 55 and 56) (paragraph [0038]), wherein the FAST cytometer is known to comprise a fiber optic bundle that is wide and thin on one end and round on the other, where the bundle contains over 40,000 fibers in close proximity to the fluorescence to maximize capture of emissions, a numerical aperture, where fluorescence is transmitted from a 1 cam diameter round end, passed through a dichromatic mirror that splits the beam into two wavelength regions, and is filtered by double cavity emission filters and detected by photomultiplier tubes as evidenced by Liu (pg. 171, col 1, last partial paragraph; and col 2, first partial paragraph). Kuhn teaches that automated digital microscopy (ADM) in combination with fiber-optic array scanning technology (FAST) is a reliable method for detection of cancer cells in blood and an important tool for diagnosis and monitoring of solid tumors in early stages, wherein FAST applies laser printing techniques to the rare-cell detection problem, such that with FAST cytometry, laser-printing optics are used to excite 300,000 cells per second, and emission is collected in an extremely wide field of view, enabling a 500-fold speed-up over ADM with comparable sensitivity and superior specificity, such that he combination of FAST enrichment and ADM imaging (interpreted as the fiber optic scanner, scanning source, photodetector, and processor of instant claim 47, claim 47) (paragraph [0039]), where the structure of the fiber-optic array scanning technology (FAST) is known in the art as evidenced by Ao (pg. 246, Figure 1) as shown below:
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Kuhn teaches that the method utilizes an imager apparatus capable of rapid and accurate detection of rare cells in circulation utilizing fiber-optic array scanning technology (FAST) comprises an imager apparatus for imaging a generally planar surface; a linearly translating stage linearly translates the surface in a first direction, a fiber optic bundle has a first end of parallel first fiber ends arranged to define a linear input aperture disposed perpendicular to the first direction and parallel to the surface, wherein the fiber optic bundle further has a second end defining a generally circular output aperture, such that each first fiber end optically communicates with the generally circular output aperture, a scanning radiation source linearly scans a radiation beam along the generally planar surface below the input aperture, such that the radiation beam interacts with the surface to produce a light signal that is collected by the input aperture and transmitted by the fiber optic bundle to the output aperture, a photodetector is arranged to detect the light signal at the generally circular output aperture, a rastering processor communicates with the imager stage and the scanning radiation source to coordinate the scanning of the radiation beam and the linear translation of the surface to effectuate a rastering of the radiation beam on the surface (interpreted as the fiber optic scanner, scanning source, photodetector, band pass filters configured to split light; interpreting FAST to be a picking systems; and processor of instant claims 47 and 55, claims 47-49, 55 and 56) (paragraph [0047]); wherein the fluorescence-based IVFC set up comprises F1 and F2 band pass filters as illustrated in Figure 3 as evidenced by Ao (pg. 254, Figure 3); and wherein doubled bandpass filters are used to provide out-of-band stop efficiencies of greater than 1:1010 as evidenced by Curry (pg. 1267, Figure 1; and pg. 1268, col 2, first partial paragraph). Kuhn teaches that a sample can be prepared as a biological monolayer by drawing a sample of a biological fluid including, but not limited to, blood or parts of blood from a subject including a mono layer of cells (paragraph [00048], lines 1-5). Kuhn teaches that useful labels in the present invention include magnetic beads (e.g. Dynabeads™), fluorescent dyes such as fluorescein isothiocyanate, Texas red, rhodamine, and the like; radiolabels; and other imaging agents such as microbubbles (interpreted as fluorophore label, claims 47 and 55) (paragraph [0081]). Kuhn teaches that the emission from the fluorescent probes is filtered by using standard dichroic filters before detection in a photomultiplier (interpreted as a band pass filter, claims 47 and 55) (paragraph [0042]). Kuhn teaches that detected fluorescent objects are analyzed with software filter operations to differentiate rare cells from false positives; and a second filter analyzes the ratio between the intensities of the fluorescence from different channels to eliminate homogeneous dye aggregates, a common artifact of immuno-fluorescence staining (interpreting the filter to include a band pass filter; and analyzing a ratio as calculating a ratio of signals, claims 47 and 55) (paragraph [0046]).
It would be prima facie obvious for one of ordinary skill in the art to before the effective filing date of the claimed invention to modify the method of imaging and detecting cancer cells including by fluorescence detection and fiber optic endomicroscopy as exemplified by Reiner to include the fiber-optic array scanning technology and cytometry as taught by Kuhn with a reasonable expectation of success in reliably detecting and/or identifying tumor cells in a sample from a subject including in the early stages of cancer; in conducting in vitro and/or in vivo imaging prior to, during, and/or after treatment with a cancer therapeutic for the detection and quantification of cancer cells; and/or for use in testing the efficacy of a cancer treatment including inhibitors of PARP1 such as dihydroisoquinolinones.
The combined references of Reiner and Kuhn do not specifically exemplify a PEG graft co-polymer (claim 49).
Regarding claim 49, Yongnian teaches the combinatorial synthesis of bioactive compounds (pg. v, first full paragraph, line 1). Yongnian teaches that Tentagel resin was originally synthesized by the polymerization of ethylene oxide on cross-linked polystyrene already derivatized with tetraethylene glycol to give polyethylene glycol chains that consist of polyethylene glycol attached to cross-linked polystyrene through an ether link, and combines the benefits of the soluble polyethylene glycol support (Figure 1.7) with insolubility and handling characteristics of the polystyrene beads (pg. 10, last partial paragraph; and pg. 11, first partial paragraph). Yongnian teaches that Figure 1.7 illustrates a TentaGel resin having a polyethylene glycol chain grafted onto a crosslinked polystyrene backbone (interpreted as a PEG graft copolymer surface, claim 49) (pg. 11, Figure 1.7). Yongnian teaches that optimized TentaGel grafted resins generally carry polyethylene glycol chains of about 3kDa in size, accounting for about 70-80% of the beads by weigh, where it is remarkable that the cross-linked polystyrene backbone is sufficiently flexible to accommodate the polyethylene glycol and flex further still to permit the synthesis of peptides or other organic molecules (pg.. 11, first full paragraph). Yongnian teaches compound 3,4-dihydroisoquinoline N-oxide (4-12f) (interpreted as a dihydroiso-quinolinone derivative, claims 47 and 55) (pg. 114, first full paragraph).
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 increasing the imaging speed of fiber optic array scanning technology as exemplified by Kuhn, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the in vitro and in vivo imaging methods such as fluorescence imaging and/or fiber optic endomicroscopy before, during and/or after treatment with a therapy as disclosed by Reiner to include the fiber-optic array scanning technology method as taught by Kuhn; and the TantaGel resin comprising polyethylene glycol side-chains crosslinked to polystyrene as taught by Yongnian with a reasonable expectation of success in producing resins with improved flexibility and handling characteristics to which an array of PARP1 inhibitors can be bound including dihydroisoquinolinone monomers, such that cancer cells can be quickly and sensitively imaged and/or quantified by fiber optic array scanning technology including to assess the therapeutic efficacy of cancer therapies; and/or in using FAST with cancer therapeutics including PARP1 inhibitors such as dihydroisoquinolinone compounds as detectable probes for the non-invasive imaging, detection and/or quantification of therapeutic efficacy such as related to PARP1 inhibition or expression in a cell and/or in subject including at the whole body level.
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 December 10, 2025 have been fully considered but they are not persuasive. Applicants essentially assert that: (a) the Reiner reference does not teach the fiber optic scanner including the specifically claimed components configured to scan fluorescent beads affixed to non-natural polymers as claimed (Applicant Remarks, pg. 13, first full paragraph); (b) Kuhn does not appear to teach a fiber optic scanner including the specifically claimed components configured to scan fluorescent beads affixed to non-natural polymers as claimed, where Kuhn describes scanning blood cells to image CTCs (Applicant Remarks, pg. 13, second full paragraph); (c) Reiner does not teach a band pass filter or splitting light into two channels as recited in the instant claims, nor the processor circuitry configured to process the channels by calculating a ratio of the two light channels (Applicant Remarks, pg. 13, last partial paragraph and pg. 14, first partial paragraph); (d) the Office Action does not provide any alleged motivation for further modifying the Reiner reference with the alleged teachings in the additionally recited secondary references (Applicant Remarks, pg. 14, first partial paragraph, last 3 lines); (e) independent claims 47 and 55 recites claim limitations at the very least reciting components that are “configured” to perform such claim limitations, such as in claim 47, which recites "an imager stage having a planar surface configured to support a slide bearing fluorescent beads" (Applicant Remarks, pg. 14, last partial paragraph); and (f) claims 48 and 56 have been amended to recite that the processor circuitry is configured to generate a digital image of locations on the slide of the selected respective non-natural polymers, and the picking system (Applicant Remarks, pg. 15, last full paragraph).
Regarding (a)-(c), please see the Examiner’s response to Applicant’s same arguments in the Office Action mailed August 12, 2025; as well as, the Examiner’s interpretation of the claim language. In addition, it is noted that the instant claims, the instant as-filed Specification, and the original claims do not teach or recite the term “processor circuitry.” Moreover, the instant as-filed Specification and the original claims do not teach that the processor is configured to process the two channels of the light signal, to calculate a ratio of the two channels, and/or to select respective non-natural polymers among affixed non-natural polymers. The claims remain rejected.
Regarding (d), please see the discussion supra regarding the Examiner’s response to Applicant’s arguments. As indicated in MPEP 2124:
In certain circumstances, references cited to show a universal fact need not be available as prior art before applicant’s filing date. In re Wilson, 311 F.2d 266, 135 USPQ 442 (CCPA 1962). Such facts include the characteristics and properties of a material or a scientific truism. Some specific examples in which later publications showing factual evidence can be cited include situations where the facts shown in the reference are evidence "that, as of an application’s filing date, undue experimentation would have been required, In re Corneil, 347 F.2d 563, 568, 145 USPQ 702, 705 (CCPA 1965), or that a parameter absent from the claims was or was not critical, In re Rainer, 305 F.2d 505, 507 n.3, 134 USPQ 343, 345 n.3 (CCPA 1962), or that a statement in the specification was inaccurate, In re Marzocchi, 439 F.2d 220, 223 n.4, 169 USPQ 367, 370 n.4 (CCPA 1971), or that the invention was inoperative or lacked utility, In re Langer, 503 F.2d 1380, 1391, 183 USPQ 288, 297 (CCPA 1974), or that a claim was indefinite, In re Glass, 492 F.2d 1228,1232 n.6, 181 USPQ 31, 34 n.6 (CCPA 1974), or that characteristics of prior art products were known, In re Wilson, 311 F.2d 266, 135 USPQ 442 (CCPA 1962)." In re Koller, 613 F.2d 819, 824 n.5, 204 USPQ 702, 706 n.5 (CCPA 1980) (quoting In re Hogan, 559 F.2d 595, 605 n.17, 194 USPQ 527, 537 n.17 (CCPA 1977) (emphasis in original)). See also Amgen Inc. v. Sanofi, 872 F.3d 1367, 1375, 124 USPQ2d 1354, 1359 (Fed. Cir. 2017).
Applicant’s assertion that the Office Action does not provide any alleged motivation for further modifying the Reiner reference with the alleged teachings in the additionally recited secondary references, is not found persuasive. The rejection is based on the combined references of Reiner and Kuhn, wherein the additionally cited references are evidentiary references. These references come after the phrase “as evidenced by,” such that they do not further modify the Reiner reference. Thus, the claims remain rejected.
Regarding (e), regarding claim 47, a preamble is generally not accorded any patentable weight where it merely recites the purpose of a process or the intended use of a structure, and where the body of the claim does not depend on the preamble for completeness but, instead, the process steps or structural limitations are able to stand alone. See In re Hirao, 535 F.2d 67, 190 USPQ 15 (CCPA 1976) and Kropa v. Robie, 187 F.2d 150, 152, 88 USPQ 478, 481 (CCPA 1951). The term “a fiber optic scanner mounted with a slide beading beads” is recited in the preamble of claims 47 and 55, such that no slide and/or beads are recited in the body of either claim. Thus, this term "an imager stage having a planar surface configured to support a slide bearing fluorescent beads" is not given patentable weight because it merely recites an intended use of the structure. Thus, the claims remain rejected for the reasons of record.
Regarding (f), please see the discussion supra regarding the Examiner’s response to Applicant’s arguments including what is taught or recited (and what is not taught or recited) in the instant claims, as-filed Specification, and/or originally filed claims (e.g., whether processor circuitry configured to generate a digital image of locations on the slide of the selected respective non-natural polymers; the picking system; calculation of ratios, etc.). Moreover, please see the Examiner’s interpretation of the claims including that the “picking system” as recited in instant claims 48 and 56 is interpreted to refer to any systems that is capable of selecting a non-natural polymer and delivering to a well plate including: automated handling systems, a researcher/operator, FACS, FAST system, a fluorometer, fluorescence spectrophotometer, a microscope, a mass spectrometer, HPLC, FTIR spectrometer, NIR spectrometer, etc. Reiner teaches in vivo imaging, fluorescence microscopy, PET, electron microscopy, MRI, CT, X-ray, SPECT, ultrasound imaging, FACS, FRET, etc., while Kuhn teaches systems such as FAST, FACS, high resolution imaging, image analysis, etc. (e.g., picking systems and configured to generate digital images). The combined references of Reiner and Kuhn teach all of the limitations of the claims.
The Examiner notes that Kuhn teaches the same SRI fiber-optic scanner as described in the instant as-filed Specification, while Reiner teaches a host of different fiber-optic scanners. The Examiner suggests that Applicant simplify the claims to recite the components of the fiber-optic scanner (e.g., modifying and/or removing ‘configured to’ language), and to include either a unique “picking system” or unique beads comprising specific/novel bioactive monomers.
Conclusion
Claims 47-49, 55 and 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