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
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office Action has been withdrawn pursuant to 37 CFR 1.114. Applicant’s submission filed on April 29, 2026 has been entered.
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, 48, 55 and 56 have been amended by Applicants’ amendment filed 04-29-2026. No claims have been added or canceled by Applicants’ amendment filed 04-29-2026.
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Claims 41-46 and 50-54 were previously withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.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 was deemed proper and was made FINAL.
The claims will be examined insofar as they read on the elected species.
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.
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: the as-filed Specification and original claims filed February 2, 2021 do not teach or recite fail 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 components recited in independent claims 47 and 55 do not have support for at least: the processor configured to process the two channels of the light signal detected by the photodetector and to select respective ones of the beads on the slide based on the processed two channel of the light signal. Moreover, 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 of the two channels of a light signal. Therefore, the priority date for the presently claimed invention is February 2, 2021, the filing date of US Patent Application 17/165,293.
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 April 29, 2026 have been fully considered but they are not persuasive (in part). Applicants essentially assert that: (a) 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 which includes 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 Actions mailed February 2, 2026 and August 12, 2025. As well as, the priority discussion supra. The Examiner respectfully requests that Applicant point to where the teachings can be found in the as-filed Specification or the claims as originally filed.
Withdrawn Objections/Rejections
Applicants’ amendment and arguments filed April 29, 2026 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 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 lines 3-4”; and “a scanning source configured to provide and scan a beam of radiation along a path” in lines 9-10; while claims 47 and 55 also recite: “affixed non-natural polymers treated with a fluorescently labeled target agent” in line 4; “the beam of radiation 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” claims 47 and 55, lines 12-14; “as emitted from the imager stage” in claims 47 and 55, line 15; “based on the processed two channels of the light signal” in claim 47, line 21; and “based on the ratio to process the two channels of the light signal detected by the detector” in claim 55, line 21. 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 “the light signal as emitted from the imager stage” such as recited in claim 47, line 15 because claim 47, line 12 recites that the scanning source provides a light signal, such that it is unclear how the light signal is emitted from the imager stage. Moreover, the imager stage is not recited to comprise an emitted light signal and, thus, the metes and bounds of the claim cannot be determined.
Claims 47, 48, and 56 are indefinite for the recitation of the term “selected respective ones of the beads” such as recited in claim 47, line 20. There is insufficient antecedent basis for the term “ones of the beads” in the claim because claim 47, line 1 recites the term “a slide bearing beads.” Moreover, the term “ones of the beads” is odd and confusing because it is unclear what the term refers to, including whether the term “ones of the beads” refers to selecting a single bead, to selecting a plurality of beads, or whether the term refers to something else and, thus, the metes and bounds of the claim cannot be determined.
Claims 48 and 56 are indefinite for the recitation of the terms “well plates” and “picking system” such as recited in claim 48, lines 3-4 because the claims are directed to a fiber-optic scanner and not, for example, to a fiber-optic scanning system, such that the as-filed Specification and original claims do not teach that the fiber-optic scanner itself comprises “well plates” and/or a “picking system”, which appear to be separate devices and, thus, the metes and bounds of the claim cannot be determined.
Claims 48 and 55 are indefinite for the recitation of the term “processor is [further] configured to calculate a ratio of the two channels of the light signal” 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 the two channels of the light signal and, thus, the metes and bounds of the claim cannot be determined.
The rejection of claim 48 is maintained, and claim 56 is newly rejected as being indefinite for the recitation of the term “generate a digital image of locations on the slide of the selected respective ones of the beads” such as recited in claim 48, lines 9-10 because the as-filed Specification and original claims do not teach that the processor is configured to generate a digital image of locations of beads on the slide, such that it is unclear how a digital image of such locations is generated and, thus, the metes and bounds of the claim cannot be determined.
Claim 56 is indefinite for the recitation of the term “the slide comprising the beads” such as recited in claim 56, line 3. There is insufficient antecedent basis for the term “the slide comprising the beads” in the claim because claim 55, line 3 recites the term “a slide bearing beads.”
Claim 56 is indefinite for the recitation of the terms “for cleavage from the beads and sequencing” and “background light” such as recited in claim 56, lines 7-8 and 10 because claim 56 depends from claim 55, wherein claim 55 does not recite the presence of background light; as well as, the presence of nucleic acids, cleavage reagents, and/or sequencing devices and, thus, the metes and bounds of the claim cannot be determined.
Claim 56 is indefinite for the recitation of the term “a first channel representing background light and channel representing the light signal” such as recited in claim 56, line 10 because the channels are unclear given that there are two channels of a light signal comprising a first channel representing background light, and a channel (any channel ?) representing the light signal, although both channels are recited in claim 55 to represent a light signal. Moreover, the instant as-filed Specification does not teach a first channel and a channel and, thus, the metes and bounds of the claim cannot be determined.
Response to Arguments
Applicant’s arguments filed April 29, 2026 have been fully considered but they are not persuasive (in part). Applicants essentially assert that: (a) regarding that the processor is further configured “to generate a digital image of locations on the slide of the selected respective ones of the beads,” Applicant submits that paras 79-80 of the Specification provides express support for the claim language (Applicant Remarks, pg. 11, third full paragraph).
Regarding (a), the Examiner could not locate any teaching in paragraphs [79]-[80] of the as-filed Specification that the processor is configured to generate a digital image of locations on the slide including digital images of the selected respective ones of the beads. It is noted that paragraph [79] teaches that in the FAST process, blood samples are plated on a glass slide, labeled CTCs are scanned with the FAST system, that 60 seconds is needed to create a digital image, and that SRI international (e.g., Stanford Research Institute) has processed thousands of blood samples on the FAST system; while paragraph [80] teaches a location identified by the FAST system. Paragraph [80] teaches that once cells are identified by the FAST system, individual cells are picked from the slide and transferred to well-plates. Thus, the instant as-filed Specification does not teach a processor configured to generate a digital image of bead locations on a slide of selected respective ones of the beads. The claims remain rejected.
Claim Rejections - 35 USC § 112(d)
The rejection of claim 56 is maintained 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 56 recites (in part): “and deliver the selected respective ones of the beads to the well plates for cleavage from the beads and sequencing…a first channel representing background light and channel representing the light signal” such as recited in claim 56, lines 6-11 because claim 56 depends from claim 55, wherein claim 55 does not recite the presence of a slide comprising beads, a first channel, background light, a channel; as well as, the presence of nucleic acids, cleavage reagents, and/or sequencing devices. Thus, claim 56 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 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 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 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; fluorescent beads; and interpreting FACS as a picking system, 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). Kuhn teaches that once the rare cell or CTC has been localized the coverslip on the biological monolayer can be removed or the water soluble mounting media can be solubilized on each fluorescently stained slide (interpreting fluorescent staining as treatment with a fluorescent target agent, claims 47 and 55) (paragraph [0051], lines 1-4).
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 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]). 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 (e.g., 3H, 14C, 35S, 125I, 121 I, 112In, 99mTc); and other imaging agents such as microbubbles (for ultrasound imaging); 18F, 11C, 15O, (for positron emission tomography), 99"'TC, 111In (for single photon emission tomography), enzymes (e.g., horse radish peroxidase, alkaline phosphatase and others commonly used in an ELISA), and calorimetric labels such as colloidal gold or colored glass or plastic (e.g. polystyrene, polypropylene, latex, and the like) beads (interpreted as fluorophore label; and non-natural polymers treated with a fluorescently labeled target agent, 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]).
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 April 29, 2026 have been fully considered but they are not persuasive. Applicants essentially assert that: (a) Reiner does not teach a fiber-optic scanner (Applicant Remarks, pg. 13, first full paragraph); (b) Kuhn and Reiner does not teach a band pass filter as recited in claim 1 including calculating of the two channels (as split) to select beads (Applicant Remarks, pg. 13, last partial paragraph through pg. 14, first partial paragraph, lines 6-9); (c) the Office Action does not provide any alleged motivation for further modifying the Reiner reference with the alleged teachings in the additionally recited secondary reference (Applicant Remarks, pg. 14, first partial paragraph, lines 14-16); and (d) the combination of references do not teach the limitations as recited in claims 47 and 55 including each of the components that are “configured” to perform the claim limitations (Applicant Remarks, pg. 14, last partial paragraph through pg. 15, first partial paragraph).
Regarding (a), it is noted that none of the references has to teach each and every claim limitation. If they did, this would have been anticipation and not an obviousness-type rejection. One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Applicant’s assertion that Reiner does not teach a fiber-optic scanner, is not found persuasive. The instant rejection is based on the combined references of Reiner and Khun. Khun clearly teaches the fiber-optic array scanning technology (FAST), the same fiber-optic scanner used in the instant application. Thus, the claims remain rejected.
Regarding (b), please see the discussion supra regarding the teachings of Khun. Applicant’s assertion that Kuhn and Reiner does not teach a band pass filter as recited in claim 1 and/or splitting of the channel of light emitted using a band pass filter, nor calculating of the two channels to select beads, is not found persuasive. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26USPQ2d 1057 (Fed. Cir. 1993). Moreover, Applicant is reminded that the claims are directed to a product, and not to a method of using the product. Therefore, there is no splitting of emitted light, calculating of the two channels; or the selection of beads. The claims are directed to a fiber-optic scanner, wherein the as-filed Specification is directed to fiber-optic array scanning technology (FAST), which is exactly the same technology taught by Khun. As noted in MPEP 2112.01(I),
where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990) (underline added).
The fiber-optic scanning technology (FAST) taught in the as-filed Specification is the same technology used in the Khun reference, wherein the various components of fiber-optic scanners are known in the art, and they are obvious to one of ordinary skill in the art before the effective filing date of the claimed invention. For example, it is known in the art that FAST includes a band pass filter to split the emitted light into two or more channels (e.g. 520 nm and 580 nm), wherein one channel (e.g. 520nm light) represents background light and the other (e.g. 580nm) is our signal light as evidenced by Collins (paragraphs [05] and [20]). Therefore, the FAST scanner taught by Khun inherently comprises a band pass filter configured as recited in instant claims 47 and 55. Additionally, Reiner teaches viewing samples with appropriate filters including fluorescent filters; as well as, endomicroscopy (paragraphs [0101]; [0126] and [0147]), where it is known in the art that fiber-optic endomicroscopy comprises a band pass filter as evidenced by He (pg. 1, last full paragraph, lines 8-10). As indicated in MPEP 2112.01(I), Applicant has the burden of showing that the products recited in claims 47 and 55 and the prior art are not the same. The combined references teach all of the limitations of the claims. The claims remain rejected.
Regarding (c), 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 reference, is not found persuasive. The Office has clearly included the motivation on pg. 19 of the Office Action mailed February 2, 2026. Thus, the claims remain rejected.
Regarding (d), Applicant’s assertion that the combination of references do not teach the limitations as recited in claims 47 and 55 including each of the components that are “configured” to perform the claim limitations, is not found persuasive. As an initial matter, the instant as-filed Specification teaches only that the invention provides a library of beads configured for high-throughput drug screening (See; paragraphs [06] and [034]). Please see the teachings of Reiner and Khun for FAST and/or fiber-optic components and/or processes. Additionally, please see Collins (WO2016053621A1) or the instant published Specification US20210208157 for components of the fiber-optic scanning technology (FAST) and what may be configured to do.
New Objections/Rejections
Specification Objection
The disclosure is objected to because of the following informalities: the as-filed Specification, filed February 2, 2021, does not include the current status of US Patent Application No. 15461455 (now abandoned).
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a) – New Matter
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 47-49, 55 and 56 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
MPEP § 2163.II.A.3.(b) states, “when filing an amendment an applicant should show support in the original disclosure for new or amended claims” and “[i]f the originally filed disclosure does not provide support for each claim limitation, or if an element which applicant describes as essential or critical is not claimed, a new or amended claim must be rejected under 35 U.S.C. 112, para. 1, as lacking adequate written description”. According to MPEP § 2163.I.B, “While there is no in haec verba requirement, newly added claim limitations must be supported in the specification through express, implicit, or inherent disclosure” and “The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117”.
The claim contains subject matter that was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art (hereafter the Artisan), that the inventor(s), at the time the application was filed, had possession of the claimed invention. 37 CFR §1.118 (a) states that "No amendment shall introduce new matter into the disclosure of an application after the filing date of the application". Claims 47 and 55 recite in part: “a processor configured to process the two channels of the light signal detected by the photodetector and to select respective ones of the beads on the slide based on the processed two channel of the light signal” in claims 47 and 55 at lines 19-21. However, support was not found for these limitations in the as-filed Specification and/or the original claims.
Upon review of the instant as-filed Specification and original claims, support was not found for the microcapsules comprising a cell, a microbead, and one of a plurality of compounds attached to the microbead; a reaction involves the compound and a molecule associated with the cell; and/or identifying microbeads comprising a portion of the compounds that cause a selectable change in a product of the reaction as recited in instant claims 47 and 55. The instant as-filed Specification, filed February 2, 2021 teaches, for example: “a processor that processes the light signal detected by the photodetector” (paragraph [40]). No such corresponding teaching of a processor being configured to process specific data in order to select respective ones of the beads on a slide is taught by the instant as-filed Specification and/or the original claims.
A claim-by-claim analysis and for independent claims 47 and 55, and a component by component analysis regarding where support can be found for the broad teaching of the processor and how it is configured to carry out calculations, selecting beads on a slide, generating digital images of locations of beads on a slide, etc. in the originally filed specification is respectfully suggested. See MPEP § 2163 particularly § 2163.06.
Claims 47-49, 55 and 56 will remain rejected until Applicant cancels all new matter.
Conclusion
Claims 47-49, 55 and 56 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY M BUNKER whose telephone number is (313) 446-4833. The examiner can normally be reached on Monday-Friday (6am-2:30pm).
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/AMY M BUNKER/Primary Examiner, Art Unit 1684
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