DETAILED ACTION
Notice of AIA Status
The present application, filed on 11/23/2022, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
Claims 1-20 are pending.
Claims 17-20 are withdrawn.
Claims 1-13 and 15-16 are rejected.
Claims 9-10 and 14 are objected to.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-16, in the reply filed on 10/16/25 is acknowledged.
Claim Objections
Claims 9-10 are objected to because of the following informalities:
Claim 9 recites “the system of any of claim 1”. For the sake of clarity, consider rephrasing to ‘the system of any of claim 1’.
Claim 10 recites “the system of any of claim 1”. For the sake of clarity, consider rephrasing to ‘the system of any of claim 1’.
Claim 14 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. Appropriate correction is required.
Claim Rejections under 35 U.S.C. § 103
In the event the determination of the status of the application as subject to 35 U.S.C. §102 and §103 is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. §103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. §103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. §102(b)(2)(C) for any potential 35 U.S.C. §102(a)(2) prior art against the later invention.
Claims 1-7, 10-11, 13, and 15-16 are rejected under 35 U.S.C. § 103 as being unpatentable over Lim (US20100075374 cited by the applicant in the 5/23/23 Information Disclosure Statement by Applicant) in view of Chen (US20160230210).
As to claim 1, Lim (US20100075374) teaches a system, comprising:
a substrate holder (solid support in [0277]) comprising a porous matrix (porous polymer matrix in [0168], which recites “the bead (first surface) comprises a (strept)avidin …, coated onto a porous polymer matrix), the porous matrix (porous polymer matrix) comprising:
a first detectable agent (anti-p53 labeled with the Cy5 fluorophore in [0141]) configured to selectively couple to a first target moiety (C-terminal detection epitope tag) and to emit a first detectable signal (red signal in [0141]) upon fluorescence of the first detectable agent (anti-p53 labeled with the Cy5 fluorophore) (see [0141], which recites “2-color fluorescence overlays, whereby … the red corresponds to the C-terminal detection epitope tag probed with an anti-p53 antibody labeled with the Cy5 fluorophore”); and
a second detectable agent (anti-VSV antibody labeled with the Cy3 fluorophore in [0141]) configured to selectively couple to a second target moiety (N-terminal detection epitope tag) and to emit a second detectable signal (green signal in [0141]) different than the first detectable signal (red signal) upon fluorescence of the second detectable agent (anti-VSV antibody labeled with the Cy3 fluorophore) (see [0141], which recites “The images above are 2-color fluorescence overlays, whereby the green corresponds to the N-terminal detection epitope tag probed with an anti-VSV antibody labeled with the Cy3 fluorophore and the red corresponds to the C-terminal detection epitope tag probed with an anti-p53 antibody labeled with the Cy5 fluorophore”);
an excitation filter (different bandpass filter, see [0222], which recites “spectral information can be generated by collecting more than one image via different bandpass, longpass, or shortpass filters”);
an emission filter (520 nm emissions filter in [0855]).
Lim doesn’t teach a housing, optically coupled with the substrate holder, and shaped to optically couple with a radiation source and a radiation sensor and to optically isolate the radiation source and the radiation sensor;
an excitation filter, disposed in or on the housing, configured to receive excitation electromagnetic radiation from the radiation source and to transmit a first portion of the excitation electromagnetic radiation to the porous matrix; and
an emission filter, disposed in or on the housing, configured to receive emitted fluorescence electromagnetic radiation from the porous matrix and to transmit a second portion of the emitted fluorescence electromagnetic radiation, the second portion being different from the first portion.
In the analogous art of providing analytical systems, Chen (US20160230210) teaches a housing (instrument housing 105 in [0052]), optically coupled with a substrate holder (sample holder drawer [0052], which recites “system 100 comprises an instrument housing 105 and sample holder drawer 110 comprising base 300 and configured during use to receive, hold, or contain sample holder 305 and to position sample holder 305 to provide optical coupling thereof with optical system 400”) (see Fig. 5), and shaped to optically couple with a radiation source (radiation source 402 in [0037]) and a radiation sensor (optical sensor 408 in [0037]) and to optically isolate the radiation source (radiation source 402) and the radiation sensor (optical sensor 408) (see Fig. 1);
an excitation filter (excitation filter 430 in [0039]), disposed in or on the housing (instrument housing 105), configured to receive excitation electromagnetic radiation from the radiation source (radiation source 402) and to transmit a first portion of the excitation electromagnetic radiation to the biological sample (see [0039], which recites “excitation source 402 further comprises two or more excitation filters 430 moveable into and out of excitation optical path 412, for instance, used in combination with a broadband excitation source 402. In such embodiments, different excitation filters 430 may be used to select different wavelength ranges or excitation channels suitable for inducing fluorescence from a respective dye or marker within biological samples 310”) (see Fig. 1); and
an emission filter (emission filter 435 in [0048]), disposed in or on the housing (instrument housing 105), configured to receive emitted fluorescence electromagnetic radiation from the biological sample (see Fig. 1) and to transmit a second portion of the emitted fluorescence electromagnetic radiation (see Fig. 1), the second portion being different from the first portion (see [0050], which recites “Beamsplitter 420 is disposed along both excitation and emission optical paths 412, 417 and is configured to receive both first and second excitation beams 405 a, 405 b during operation. In the illustrated embodiment shown in FIG. 1, beamsplitter 420 is configured to transmit the excitation beams 405 and to reflect emissions from the biological samples 310. Alternatively, beamsplitter 420 may be configured to reflect the excitation beams and to transmit emissions from the biological samples 310”) (see Fig. 1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the system disclosed by Lim by incorporating the housing disclosed by Chen with a reasonable expectation of success such that the housing is optically coupled with the substrate holder, and shaped to optically couple with a radiation source and a radiation sensor and to optically isolate the radiation source and the radiation sensor; the excitation filter, is disposed in or on the housing, and is configured to receive excitation electromagnetic radiation from the radiation source and to transmit a first portion of the excitation electromagnetic radiation to the porous matrix; and the emission filter is disposed in or on the housing, and is configured to receive emitted fluorescence electromagnetic radiation from the porous matrix and to transmit a second portion of the emitted fluorescence electromagnetic radiation, the second portion being different from the first portion for the benefit of effectively protecting, with the housing, the internal optical components from environmental contamination while enabling selective passage of excitation and emission radiation from reliable fluorescence detection of the sample in the porous matrix without interference from external environmental light.
As to claim 2, Lim in view of Chen teaches the system of claim 1, wherein the excitation filter is a multiple- passband filter, and wherein the first portion comprises two non-contiguous excitation energy ranges corresponding to a first excitation wavelength range of the first detectable agent and a second excitation wavelength range of the second detectable agent, respectively (see [0039] of Chen, which recites “excitation filters 430 may comprise a plurality of filters that together provide a plurality of band passes suitable for fluorescing one or more of a SYBR® dye or probe, a FAM™ dye or probe, a VIC® dye or probe, a ROX™ dye or probe, or a TAMRA™ dye or probe”) (each of the fluorescent dyes SYBR® dye or probe, a FAM™ dye or probe, a VIC® dye or probe, a ROX™ dye or probe, or a TAMRA™ dye or probe have a distinct excitation energy range for example FAM excites near ~ 495nm, VIC near ~538nm, ROX near ~575 nm, etc, one non-contiguous from another).
As to claim 3, Lim in view of Chen teaches the system of claim 1, wherein the emission filter is a second multiple-passband filter (see [0222] of Lim, which recites The emitted light can be detected with a device that provides spectral information for the substrate, e.g., grating spectrometer, prism spectrometer, imaging spectrometer, or the like, or use of interference (bandpass) filters. Using a two-dimensional area imager such as a CCD camera, many objects may be imaged simultaneously. Spectral information can be generated by collecting more than one image via different bandpass, longpass, or shortpass filters (interference filters, or electronically tunable filters are appropriate). More than one imager may be used to gather data simultaneously through dedicated filters, or the filter may be changed in front of a single imager. Imaging based systems, like the Biometric Imaging system, scan a surface to find fluorescent signals”) and wherein the second portion comprises two non-contiguous emitted fluorescence energy ranges corresponding to the first detectable signal and the second detectable signal, respectively (see [0118] of Lim, which recites “proteins were applied to a microarray substrate by contact photo-transfer. The microarray substrate was further probed with a Cy5 labeled anti-p53 specific antibody. The internal tRNA mediated BODIPY-FL fluorescence labels as well as binding of the Cy5 labeled p53 antibody were imaged. The images were quantified to determine the integrated fluorescence intensities for each spot for both the red (Cy5) and green (BODIPY-FL) fluorescence signals and the ratios calculated”).
As to claim 4, Lim in view of Chen teaches the system of claim 3, wherein the two non-contiguous emitted fluorescence energy ranges comprise a first band in a wavelength range from about 500 nm to about 550 nm and a second band in a range from about 600 nm to about 650 nm (see [0118] of Lim, which recites “proteins were applied to a microarray substrate by contact photo-transfer. The microarray substrate was further probed with a Cy5 labeled anti-p53 specific antibody. The internal tRNA mediated BODIPY-FL fluorescence labels as well as binding of the Cy5 labeled p53 antibody were imaged. The images were quantified to determine the integrated fluorescence intensities for each spot for both the red (Cy5) and green (BODIPY-FL) fluorescence signals and the ratios calculated”) (Green light has a wavelength of approximately 495–570 nanometers (nm), while red light has a longer wavelength of approximately 620–750 nm”).
As to claim 5, Lim in view of Chen teaches the system of claim 1, wherein the excitation electromagnetic radiation is characterized by a continuous emission intensity distribution within a wavelength range from about 400 nm to about 700 nm (see [0008] of Chen, which recites “FIG. 3 is a normalized spectrum plot of various light sources, including a light source according to an embodiment of the present invention”).
As to claim 6, Lim in view of Chen teaches the system of claim 1, wherein the emitted fluorescence electromagnetic radiation is characterized by a biplexed intensity distribution comprising the first detectable signal and the second detectable signal (see [0118] of Lim, which recites “proteins were applied to a microarray substrate by contact photo-transfer. The microarray substrate was further probed with a Cy5 labeled anti-p53 specific antibody. The internal tRNA mediated BODIPY-FL fluorescence labels as well as binding of the Cy5 labeled p53 antibody were imaged. The images were quantified to determine the integrated fluorescence intensities for each spot for both the red (Cy5) and green (BODIPY-FL) fluorescence signals and the ratios calculated”).
As to claim 7, Lim in view of Chen teaches the system of claim 1 wherein the porous matrix (porous polymer matrix) further comprises reagents (amplification reagents in [0037] of Lim) to amplify a target nucleic acid molecule (template molecules in [0037] of Lim, which recites “b. mixing said beads and said template molecules in a first aliquot of said solution of amplification reagents so as to create a mixture”) and a positive control nucleic acid molecule (see [0037] of Lim, which recites e. contacting said manipulated beads with a second aliquot of said solution of amplification reagents under conditions such that at least a portion of said extended primers is amplified to create loaded beads comprising immobilized amplified nucleic acid and unloaded beads lacking amplified nucleic acid”).
As to claim 10, Lim in view of Chen teaches the system of any of claim 1, wherein the first detectable agent a (anti-p53 labeled with the Cy5 fluorophore) and the second detectable agent (anti-VSV antibody labeled with the Cy3 fluorophore) are colocalized on the porous matrix (porous polymer matrix) (see [0764] and Fig. 40 of Lim).
As to claim 11, Lim in view of Chen teaches the system of claim 1, further comprising an electronic device (instrument 100 in [0029] of Chen), wherein the electronic device (instrument 100) comprises the radiation source (radiation source 402) and the radiation sensor (optical sensor 408) (see Fig. 1 of Chen), and wherein the excitation filter (excitation filter 430) and the emission filter (emission filter 435) are positioned to optically couple with the radiation source (radiation source 402) and the radiation sensor (optical sensor 408), respectively (see Fig. 1 of Chen).
As to claim 13, Lim in view of Chen teaches the system of claim 11, further comprising a controller (controller 200 in [0029] of Chen) including one or more processors and a non-transitory computer readable memory (see [0031], which recites “data from electronic processor 200 (e.g., from optical system 400 and/or base 300) may be transferred to an external memory storage device, for example, an external hard drive, a USB memory module”) storing executable instructions that, when executed by the one or more processors, cause the one or more processors to execute operations, comprising:
generating the excitation electromagnetic radiation using the radiation source, the radiation source being optically coupled with the excitation filter to transmit the first portion of the excitation electromagnetic radiation to the porous matrix (see [0030], which recites “Electronic processor 200 may include electronic memory storage containing instructions … Electronic processor 200 may be configured, for example, to operate various components of optical system 400 or to obtain and/or process data provided by base 300. For example, electronic processor 200 may be used to obtain and/or process optical data provided by one or more photodetectors of optical system 400”);
detecting the first detectable signal and the second detectable signal using the second portion of the emitted fluorescence electromagnetic radiation received by the radiation sensor via the emission filter (see [0030], which recites “Electronic processor 200 may include electronic memory storage containing instructions … Electronic processor 200 may be configured, for example, to operate various components of optical system 400 or to obtain and/or process data provided by base 300. For example, electronic processor 200 may be used to obtain and/or process optical data provided by one or more photodetectors of optical system 400”); and
determining a differential emission value using the first detectable signal and the second detectable signal (see [0118] of Lim, which recites “The images were quantified to determine the integrated fluorescence intensities for each spot for both the red (Cy5) and green (BODIPY-FL) fluorescence signals and the ratios calculated”) (see also [0125] of Lim, which recites “The microarray substrate was further probed with a Cy5 labeled anti-p53 specific antibody. The internal tRNA mediated BODIPY-FL fluorescence labels (Green Fluorescence Channel) as well as binding of the Cy5 labeled p53 antibody (Red Fluorescence Channel) were imaged”).
As to claim 15, Lim in view of Chen teaches the system of claim 13, wherein the substrate holder (solid support) further comprises an electronic heating circuit (sample block assembly in [0033]) thermally coupled with the porous matrix (porous polymer matrix), wherein the electronic heating circuit (sample block assembly) is configured to heat the porous matrix (porous polymer matrix) (see [0033] of Chen, which recites “Base 300 may comprise a sample block assembly configured to control the temperature of sample holder 305 and/or biological samples 310. Sample block assembly 300 may comprise one or more of a sample block, a Peltier device or other apparatus for controlling or cycling temperature, and/or a heat sink (e.g., for aiding in stabilizing a temperature). Base 300 may comprise a thermal controller or thermal cycler, for example, to provide or perform a PCR assay”).
As to claim 16, Lim in view of Chen teaches the system of claim 15, wherein the non-transitory computer readable memory (a USB memory module) stores further instructions that, when executed by one or more processors (electronic processor 200) of the system, cause the one or more processors (electronic processors 200) to execute operations (see [0030] of Chen, which recites “Electronic processor 200 is configured to control, monitor, and/or receive data from optical system 400 and/or base 300”) comprising:
heating the porous matrix to a temperature and for a period of time sufficient to amplify a target nucleic acid above a limit of detection (see [0029] of Chen, which recites “system 100 may comprise a sequencing instrument, a polymerase chain reaction (PCR) instrument (e.g., a real-time PCR (qPCR) instrument and/or digital PCR (dPCR) instrument)”), wherein the limit of detection corresponds to a differential emission value greater than zero (see [0028] of Chen, which recites “When the reaction regions are subsequently thermally cycled in a PCR protocol, procedure, assay, process, or experiment, the reaction regions containing the one or more molecules of the target nucleotide sequence are greatly amplified and produce a positive, detectable detection signal, while those containing none of the target(s) nucleotide sequence are not amplified and do not produce a detection signal, or a produce a signal that is below a predetermined threshold or noise level”) .
Claim 8 is rejected under 35 U.S.C. § 103 as being unpatentable over Lim (US20100075374) in view of Chen (US20160230210) as applied to claim 7 further in view of Chiu (US20200362391).
As to claim 8, Lim in view of Chen teaches the system of claim 7, wherein the first detectable agent a first detectable agent (anti-p53 labeled with the Cy5 fluorophore) is a probe of an amplicon of the positive control nucleic acid molecule (see [0105] of Lim, which recites “contact photo-transfer of pre-formed protein-protein complexes from single 100 micron agarose beads by incorporated PC-biotin. Advanced 2 color fluorescence p53-MDM protein-protein interaction assay. Importantly, protein-protein complexes between MDM and p53 are formed prior to contact photo-transfer to activated microarray substrates. Both the “bait” proteins (MDM and GST) and the p53 probe were expressed in a cell-free reaction, each with appropriate tRNA mediated labels needed for the assay”).
Lim in view of Chen doesn’t teach that the second detectable agent is a probe of an amplicon of the target nucleic acid molecule.
In the analogous art of providing analytical systems, Chiu (US20200362391) teaches a probe of an amplicon of a target nucleic acid molecule (see [0176], which recites “A probe can be used to detect, identify, or quantify a target molecule directly or indirectly. For example, in dPCR, a probe can indirectly indicate the presence of a target molecule by through hybridization with an amplification product (e.g., an amplicon) of the target molecule”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the system disclosed by Lim in view of Chen by incorporating the probe disclosed by Chen with a reasonable expectation of success such that the second detectable agent is a probe of an amplicon of the target nucleic acid molecule for the benefit of effectively detecting, identify and quantify the target molecule (see [0176] of Chiu, which recites “A probe can be used to detect, identify, or quantify a target molecule directly or indirectly. For example, in dPCR, a probe can indirectly indicate the presence of a target molecule by through hybridization with an amplification product (e.g., an amplicon) of the target molecule”).
Claim 9 is rejected under 35 U.S.C. § 103 as being unpatentable over Lim (US20100075374) in view of Chen (US20160230210) as applied to claim 1 further in view of Jones (US20060040408).
As to claim 9, Lim in view of Chen teaches the system of any of claim 1.
Lim in view of Chen doesn’t teach that the porous matrix comprises non-woven glass fiber.
In the analogous art of analytical systems, Jones (US20060040408) teaches a porous matrix (see [0632], which recites “porous medium” may have uniform or non-uniform pores. Alternatively, it may comprise, for example, a “matrix” or a “network of fibers”) comprising non-woven glass fiber (see [0591], which recites “a matrix, more preferably a monolithic matrix, of glass fiber, non-woven polymer, or a combination thereof”).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the system disclosed by Lim in view of Chen such that the porous matrix comprises non-woven glass fiber as disclosed by Jones with a reasonable expectation of success for the benefit of effectively enabling controlled fluid communication while preventing particulate contamination and maintaining consistent analytical performance.
Claim 12 rejected under 35 U.S.C. § 103 as being unpatentable over Lim (US20100075374) in view of Chen (US20160230210) as applied to claim 11 further in view of DeJohn (US20140206412).
As to claim 12, Lim in view of Chen teaches the system of claim 11.
Lim in view of Chen doesn’t teach that the electronic device is a smart phone, wherein the radiation source is an electronic flash, and wherein the radiation sensor is a camera.
In the analogous art of providing analytical devices, DeJohn (US20140206412) teaches a smart phone (smartphone 206 in [0077]), a radiation source (light source 53 in [0077]) is an electronic flash (see [0077], which recites “a light source 53, such as a flash”) (the flash of the smartphone is an electronic flash because the smartphone is an electronic device) and a radiation sensor (CMOS sensors in [0077]) is a camera (rear facing camera 52 in [0077]) (CMOS (Complementary Metal-Oxide-Semiconductor) sensors are digital image sensors that convert light into electrical signals).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the system disclosed by Lim in view of Chen such that the electronic device is a smartphone with a reasonable expectation of success because The simple substitution of one known element for another is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007) (see MPEP § 2143, B.).
for the benefit of making the electronic device portable.
Allowable Subject Matter
Claim 14 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
As to claim 14, Lim in view of Chen teaches the system of claim 13, wherein Lim in view of Chen doesn’t teach generating a first gamma-corrected signal based on the first detectable signal and a second gamma-corrected signal based on the second detectable signal; and
determining a difference between the second gamma-corrected measurement and the first gamma-corrected measurement.
In the analogous art of providing analytical systems, Olanrewaju (Towards a portable and inexpensive lab-on-a-chip device for point of care applications”) teaches generating a first gamma-corrected signal based on a first detectable signal (see page 72, which recites “The next step in analyzing the CCD images gathered during real time PCR was to perform gamma correction to eliminate non-linear encoding of the images … . Choosing a scaling factor of 10 gave fluorescence values that were easy to work with while the application of the exponent (1.87) linearized the relationship between fluorescence and concentration of fluorophore in the PCR chamber”).
None of the cited prior art references, Lim, Chen, and Olanrewaju teaches or reasonably suggests and a second gamma-corrected signal based on the second detectable signal and determining a difference between the second gamma-corrected measurement and the first gamma-corrected measurement.
Conclusion
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/JONATHAN BORTOLI/ Examiner, Art Unit 1797