DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Response to Amendment
This action is in response to the remarks filed on 3/9/2026. The amendments filed on 3/9/2026 have been entered. Accordingly, claims 1-8 have been cancelled, claims 9-31 remain pending. Claim 11 was previously withdrawn pursuant to election restriction.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 9-10, 12-15 and 18-31 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Petrich et al (US20030160182) in view of Brenner (US20060270919) and Boyden et al (US20080059070) further in view of Boyden ‘795 (US 20080058795, cited in the IDS) and Kusano (JP2008096266A).
Regarding the claim 9, Petrich teaches a method for fluorescence-based imaging of a target to detect contamination (“method for detecting ingesta or fecal contamination on an object or surface using fluorescent spectroscopy is disclosed.” [0003]) comprising:
illuminating the target with excitation light emitted by an excitation light source of a handheld imaging device (see e.g., re-produced fig. 3 below and the associated pars.) and having at least one wavelength or wavelength band causing to fluoresce (“device is used to emit UV or visible light having an appropriate wavelength onto the object to be examined, causing any feces or ingesta which may be present to fluoresce” [0003]);
detecting fluorescence emissions with an image detector of the handheld imaging device (“hand-held, lightweight and portable apparatus and method for detecting ingesta or fecal contamination on an object or surface using fluorescent” [0003]);
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illuminating the target with white light emitted by a white light source of the handheld imaging device (“illuminated with UV or visible light having a wavelength between 300-600 nm, preferably between about 400 to 440 nm or between about 510 to 600 nm, and most preferably between about 410-430 nm and/or between about 520-540 nm, and fluorescent light emissions having a wavelength between about 660 to 680 nm are then detected” [0009]);
detecting reflections from the target in response to illumination of the target with the white light (see e.g., re-produced fig. 3 below and the associated pars. along with [0009]);
identifying a presence of colonies of bacteria contaminating the target based (“detect the presence of such contamination, optionally including further steps to identify the source of any contamination” abst; “the present invention may aid in objectively identifying the presence of contaminant” [0038]), at least in part, detected fluorescence emissions of at least the selected object (“object is illuminated with UV or visible light having a wavelength effective to elicit fluorescence of feces at a wavelength between about 660 to 680 nm, which fluorescent light emissions having a wavelength between about 660 to 680 run are then detected by a detector. The emission of fluorescent light having wavelengths between about 660 to 680 nm is an indication of the presence of ingesta or fecal material on the protein source or other object” [0015]; “the system illuminates the object to be examined with blue light 120 in the 380-470 nm range. If fecal contamination or ingesta is present on the object, the feces will fluoresce at approximately 675 nm, +/−10 nm, where such fluorescence can then be visibly detected” [0033]), and
displaying a representation of contaminated target indicative of the presence of the colonies of bacteria contaminating the target(“a display monitor 119, …Indicator 118 may include a signal for when the fluorescent intensity at the measured 660-680 nm range has exceeded a predetermined threshold value. Signals may include for example, audible alarms, visible lights or LEDs, or any combination of the above. … aid in objectively identifying the presence of contaminant” [0038]; “presenting or storing a graphical display of fluorescent spectra intensity. For example, FIGS. 5(a)-(d) depict the illumination source and resulting emission spectra created by the use of present invention connected to a printer.” [0040])
cleaning the target and outputting a representation of a cleaned target (“The process for detecting ingesta and feces on the washed surface may then be repeated, followed by additional washing and/or disinfection steps if necessary, until all traces of ingesta or feces have been removed or destroyed. A variety of wash solutions or disinfectants are known in the art and are suitable for use herein and include but are not limited to pressurized water or steam sprays, organic acids, chlorinated water, inorganic acids, detergents, and treatment with radiation. Once the object has been determined to be free of contamination as evidenced by the lack of fluorescence at the described range, the object may be returned to use, or prepared for consumption if the item is a food item, such as meat” [0034]), and
wherein the target is selected from the group consisting of a food product, a food- preparation surface, a food-handling surface, a food packaging surface, an area in a food processing plant, an area in a food production facility, and a food-equipment surface (“detecting the ingesta or feces from any green-plant-eating animal or person that may be present on the surface of an object, such as on cuts of meat of wild or domestic meat producing animals, including but not limited to facultatively herbivorous or plant-eating mammals and birds such as bovine, poultry, porcine, ovine, caprine, equine, and ratites, especially cattle and calves, hogs, chickens, turkeys, sheep, and goats. It is to be understood that the word “object” as used in this Specification is meant to include both meat products and non-meat items” [0029]).
Petrich does not point out the specifics of labelling a selected biomarker at the target with at least one fluorescing contrast agent; and co-registering the representation of the contaminated target and the representation of the cleaned target.
However, in the same field of endeavor, Brenner teaches a method of, and system for, assaying for selected constituents in liquid mixtures confined by corresponding containing structures having relatively small electromagnetic absorption in at least one transmission wavelength range for transmissions of electromagnetic radiation therethrough, including in vivo assaying for a presence of selected constituents in bloodstreams in circulatory system passageways in mammalian bodies (abst). Methods can be used with a body supported bloodstream biomarker evaluation system for such assaying with this system being provided on a substrate supporting a first electromagnetic radiation emitter capable of emitting evaluation electromagnetic radiation of wavelengths in the transmission wavelength range and also capable of emitting evaluation electromagnetic radiation of wavelengths in the absorption spectra range of that fluorophore having an overlapping emission spectra peak distribution [0018].
It would have been obvious to an ordinary skilled in the art before the invention was made to modify the method and/or device of the modified combination of reference(s) as outlined above with labelling a selected biomarker at the target with at least one fluorescing contrast agent as taught by because it allows for continuous monitoring which in turn providing real-time, or near real-time, information feedback include the measurement ([0003] of Brenner).
The above noted combination does not seem point out the specifics of displaying a representation of the target indicative of the presence of contamination on the target, wherein the representation of the target spatially co-registers fluorescence emission data and reflection data and; co-registering the representation of the contaminated target and the representation of the cleaned target.
However, in the same field of endeavor, Boyden teaches autofluorescence location can be updated by registering the detected autofluorescence location relative to other, updatable, location information. In one example, the detected autofluorescence location is registered relative to fiducials on or within the individual. Then, the location of the fiducials is updated, and the site of the autofluorescence location at such time can be predicted based upon its known registration relative to the fiducial locations. In another example, the detected autofluorescence location is registered relative to features within an image of a related portion of the individual. Then, the image is updated and the location of the autofluorescence location at such time can be predicted based upon its known registration relative to the image features [0098].
It would have been obvious to an ordinary skilled in the art before the invention was made to modify the method and/or device of the modified combination of reference(s) as outlined above with displaying a representation of the target indicative of one or more of the presence, location, and quantity of contamination on the target, wherein the representation of the target spatially co-registers fluorescence emission data and reflection data as taught by Boyden because speed and accuracy are paramount ([0373] of Boyden).
Further, as noted above, combination teaches all the limitations of the claims including "identifying one or more of a presence, a location, and a quantity of colonies of bacteria contaminating the target based, at least in part, on the detected fluorescence emissions of at least the selected biomarker; and displaying a representation of the target indicative of one or more of the presence, the location, and the quantity of the colonies of bacteria contaminating the target, wherein the representation of the target spatially co- registers fluorescence emission data and reflection data”. Yet, in an interpretation, if one argues (which the office does not concede), the Boyden ‘795 reference is brought in to clearly and factually show the teachings of these limitations as well.
In the same field of endeavor, Boyden ‘795 teaches electromagnetic energy selected to induce a fluorescent response from a target area in the lesion; a sensor 120 configured to detect the fluorescent response; control circuitry 130 coupled to the sensor 120 and responsive to identify the target area [0036]. Pathogens, such as, for example, a chemical dye or an antibody or aptamer conjugated to a fluorescent tag. Pathogens may include bacteria, fungi and/or viruses [0167]. The device emits electromagnetic energy at wavelengths sufficient to cause fluorescence of reagents added to the lumen to selectively detect pathogens, such as, for example, a chemical dye or an antibody or aptamer conjugated to a fluorescent tag. Pathogens may include bacteria, fungi and/or viruses. A lumen may include that associated with blood vessels, the urogenital tract, and the respiratory tract, for example. The untethered luminal device detects the autofluorescence or reagent-induced fluorescence [0209].
In illustrative embodiments, a first input includes dara representative of one or more characteristics of one or more targets and/or one or more diseases and/or disorders. In illustrative embodiments, a first input includes data representative of the target fluorescent response. Data representative of the target fluorescent response may include, but is not limited to, one or more measurements of electromagnetic energy, and/or one or more measurements of one or more temporal-spatial locations of the target fluorescent response. As used herein, the term "temporal-spatial locations" may include one or more temporal locations and/or one or more spatial locations. Data representative of a target fluorescent response may include, but is not limited to, a clustering of fluorescent responses that would otherwise be considered a normal response in the absence of clustering, or with limited clustering, or non-significant clustering. In illustrative embodiments, clustering might include cells forming a plaque, bacterial cells forming a colony, blood cells forming a clot, malaria-infected red blood cells aggregating, among others [0303].
Determining the graphical illustration of the first possible dataset for inclusion in a display element of a graphical user interface. In illustrative embodiments, determining a graphical illustration of the first possible dataset includes, but is not limited to, determining a graphical illustration of data representative of one or more characteristics of one or more targets associated with one or more diseases and/or disorders [0328]. In illustrative embodiments of an optional determining operation 460, 470, and/or 480, determining a graphical illustration of the first possible dataset includes, but is not limited to, performing an analysis of one or more elements of the first possible dataset to determine the location of the target area; and determining the graphical illustration based on the analysis [0329].
It would have been obvious to an ordinary skilled in the art before the invention was made to modify the method and/or device of the modified combination of reference(s) as outlined above with identifying one or more of a presence, a location, and a quantity of colonies of bacteria contaminating the target based, at least in part, on the detected fluorescence emissions of at least the selected biomarker; and displaying a representation of the target indicative of one or more of the presence, the location, and the quantity of the colonies of bacteria contaminating the target, wherein the representation of the target spatially co- registers fluorescence emission data and reflection data as taught by Boyden because speed and accuracy are paramount ([0373] of Boyden).
The above noted combination does not seem point out the specifics of co-registering the representation of the contaminated target and the representation of the cleaned target.
However, in the same field of endeavor, Kusano teaches non-tissues such as blood, feces, and food are targeted and specific microorganisms are captured therefrom (pg. 2). biological sample analyzing apparatus 100, the luminescent image and the bright field image and / or the fluorescent image of the sample S, which is a biological sample including a microorganism having a bioluminescent protein, are captured and captured. Since the ecology of microorganisms is analyzed based on a superimposed image obtained by superimposing a luminescent image and a bright-field image and / or a fluorescence image, microorganisms in a biological sample such as a thick living tissue are identified as the microorganisms. In a state where the biological sample is present without being removed from the biological sample, it can be clearly captured with a simple apparatus configuration without damaging the biological sample. It is possible to analyze (know) accurately and in detail the behavior, morphology, localization, life and death of microorganisms in a biological sample. In other words, by superimposing the luminescent image and the bright field image and / or the fluorescence image, the light signal from the thick biological sample can be measured with high sensitivity without any damage to the tissue without background, As a result, ecology such as the behavior, morphology, localization, life and death of microorganisms in the biological sample can be analyzed accurately and in detail.
The biological sample analyzer 100, the luminescent image and the bright field image and / or the fluorescence image are captured over time, and the captured luminescence image and the bright field image and / or the fluorescence image are superimposed. Because changes in the ecology of microorganisms are analyzed based on multiple superimposed images, microorganisms in a biological sample such as a thick living tissue can be present in the biological sample without removing the microorganism from the biological sample. In this state, the biological sample can be clearly captured with a simple apparatus configuration without damaging the biological sample, and as a result, the change in the ecology of microorganisms in the biological sample, specifically the behavior of microorganisms in the biological sample, Localization, life and death, proliferation, reduction, etc. can be analyzed (tracked) accurately and in detail over time. In other words, by observing the image of the light signal in a time-lapse manner, the light signal from a thick biological sample can be measured (tracked) over time with high sensitivity and no background damage. As a result, biological changes such as behavior, localization, life / death, proliferation, and decrease of microorganisms in a biological sample can be analyzed accurately and in detail over time (pg. 4).
It would have been obvious to an ordinary skilled in the art before the invention was made to modify the method and/or device of the modified combination of reference(s) as outlined above with co-registering the representation of the contaminated target and the representation of the cleaned target as taught by Kusano because biological sample can be measured (tracked) over time with high sensitivity and no background damage. As a result, biological changes such as behavior, localization, life / death, proliferation, and decrease of microorganisms in a biological sample can be analyzed accurately and in detail over time (pg. 4 of Kusano).
Regarding the claim 10, Petrich teaches all the limitations of the claims except for comparing fluorescence emission band(s) of the at least the selected biomarker to a predetermined look-up table of fluorescence emission spectra or fluorescence emission band(s) of biomarkers.
However, in the same field of endeavor, Brenner teaches absorptions can also be compared to absorption in other tissues shown previously in FIG. 3. The simplest approach is to use radiation at a single wavelength, 660 nm from emitters 26 for instance, and assume that the location with the least amount of backscattered light (corresponding to high absorption in red blood) as measured by photodetectors 30 [0078].
It would have been obvious to an ordinary skilled in the art before the invention was made to modify the method and/or device of the modified combination of reference(s) as outlined above with comparing fluorescence emission band(s) of the at least one biomarker as taught by because it allows for continuous monitoring which in turn providing real-time, or near real-time, information feedback include the measurement ([0003] of Brenner).
Regarding the claim 12, Petrich teaches all the limitations of the claims except for labelling the selected biomarker at the target comprises labelling the selected biomarker with an exogenous, bacteria-specific contrast agent.
However, in the same field of endeavor, Brenner teaches [0039] The signals of the reacted and unreacted antibodies are separated in wavelength to thereby be separately detectable, so it is not necessary to flush away the unreacted material.
[0040] Such dyes must be capable of operating in the wavelength range in which relatively little absorption occurs in the human body being assayed or monitored so that this range can constitute an electromagnetic radiation transmission window for the body. This is termed a “therapeutic window” and is commonly understood to range from around 600 nm to 1400 nm as is indicated in the plot in the graph of FIG. 3.
[0041] Dyes are now available in which the absorption and emission occurs in the red and near infrared portions of the electromagnetic radiation spectrum which is within this therapeutic window. For instance, the cyanine class of dyes are available from the 450 nm to 900 nm range, and exhibit high molar extinction coefficients (>150,000 M−1 cm−1) and good fluorescence quantum yields (up to 50%). The Alexa Fluor dyes from Molecular Probes (Eugene, Oreg.) and the CyDye™ series from Amersham—Pharmacia Biotechnology (Piscataway, N.J.) are two commercially available series of dyes that encompass the wavelength range of interest. Dyes absorbing and emitting in the red and near-IR have been applied to a whole blood immunoassay in the Triage System (Biosite Incorporated, San Diego, Calif.). In that system, the excitation energy of the donor dye is 670 nm, while the emission light of the acceptor dye is 760 nm.
It would have been obvious to an ordinary skilled in the art before the invention was made to modify the method and/or device of the modified combination of reference(s) as outlined above with labelling the selected biomarker with an exogenous, bacteria-specific contrast agent as taught by because it allows for continuous monitoring which in turn providing real-time, or near real-time, information feedback include the measurement ([0003] of Brenner).
Regarding the claims 13 and 15, Petrich teaches the exogenous, bacteria-specific contrast agent is configured to make visible one or more of Listeria monocytogenes, Enterobacter sakazakii, Campylobacter coli, Campylobacter jejuni, Campylobacter lari, coliform bacteria, all bacteria of the E. coli species, Salmonella, all bacteria of the Staphylococcus aureus species, all bacteria of the Staphylococcus genus, and Pseudomonas aeruginosa (“contamination of meat with feces or ingesta is the primary source of contamination of meat and poultry with particularly onerous pathogens, including Campylobacter spp., Escherichia coli” [0006]; “food-borne illnesses caused by six common bacterial pathogens, Campylobacter spp., Clostridium perfringens, Escherichia coli 0157:H7, Listeria monocytogenes, Salmonella spp., and Staphylococcus aureus” [0005]).
Regarding the claim 14, Petrich teaches determining a presence of colonies of bacteria contaminating the target based (“detect the presence of such contamination, optionally including further steps to identify the source of any contamination” abst; “the present invention may aid in objectively identifying the presence of contaminant” [0038]), at least in part, detected fluorescence emissions of at least the selected object (“object is illuminated with UV or visible light having a wavelength effective to elicit fluorescence of feces at a wavelength between about 660 to 680 nm, which fluorescent light emissions having a wavelength between about 660 to 680 run are then detected by a detector. The emission of fluorescent light having wavelengths between about 660 to 680 nm is an indication of the presence of ingesta or fecal material on the protein source or other object” [0015]; “the system illuminates the object to be examined with blue light 120 in the 380-470 nm range. If fecal contamination or ingesta is present on the object, the feces will fluoresce at approximately 675 nm, +/−10 nm, where such fluorescence can then be visibly detected” [0033]),
Further, in the same field of endeavor, Boyden ‘795 teaches electromagnetic energy selected to induce a fluorescent response from a target area in the lesion; a sensor 120 configured to detect the fluorescent response; control circuitry 130 coupled to the sensor 120 and responsive to identify the target area [0036]. Pathogens, such as, for example, a chemical dye or an antibody or aptamer conjugated to a fluorescent tag. Pathogens may include bacteria, fungi and/or viruses [0167]. The device emits electromagnetic energy at wavelengths sufficient to cause fluorescence of reagents added to the lumen to selectively detect pathogens, such as, for example, a chemical dye or an antibody or aptamer conjugated to a fluorescent tag. Pathogens may include bacteria, fungi and/or viruses. A lumen may include that associated with blood vessels, the urogenital tract, and the respiratory tract, for example. The untethered luminal device detects the autofluorescence or reagent-induced fluorescence [0209].
In illustrative embodiments, a first input includes dara representative of one or more characteristics of one or more targets and/or one or more diseases and/or disorders. In illustrative embodiments, a first input includes data representative of the target fluorescent response. Data representative of the target fluorescent response may include, but is not limited to, one or more measurements of electromagnetic energy, and/or one or more measurements of one or more temporal-spatial locations of the target fluorescent response. As used herein, the term "temporal-spatial locations" may include one or more temporal locations and/or one or more spatial locations. Data representative of a target fluorescent response may include, but is not limited to, a clustering of fluorescent responses that would otherwise be considered a normal response in the absence of clustering, or with limited clustering, or non-significant clustering. In illustrative embodiments, clustering might include cells forming a plaque, bacterial cells forming a colony, blood cells forming a clot, malaria-infected red blood cells aggregating, among others [0303].
Determining the graphical illustration of the first possible dataset for inclusion in a display element of a graphical user interface. In illustrative embodiments, determining a graphical illustration of the first possible dataset includes, but is not limited to, determining a graphical illustration of data representative of one or more characteristics of one or more targets associated with one or more diseases and/or disorders [0328]. In illustrative embodiments of an optional determining operation 460, 470, and/or 480, determining a graphical illustration of the first possible dataset includes, but is not limited to, performing an analysis of one or more elements of the first possible dataset to determine the location of the target area; and determining the graphical illustration based on the analysis [0329].
It would have been obvious to an ordinary skilled in the art before the invention was made to modify the method and/or device of the modified combination of reference(s) as outlined above with identifying one or more of a presence, a location, and a quantity of colonies of bacteria contaminating the target based, at least in part, on the detected fluorescence emissions of at least the selected biomarker; and displaying a representation of the target indicative of one or more of the presence, the location, and the quantity of the colonies of bacteria contaminating the target, wherein the representation of the target spatially co- registers fluorescence emission data and reflection data as taught by Boyden because speed and accuracy are paramount ([0373] of Boyden).
Regarding the claim 18, Petrich teaches bacteria, fungi, yeast, spores, virus, microbes, parasites, connective tissues, tissue components, exudates, pH, blood vessels, reduced nicotinamide adenine dinucleotide (NADH), flavin adenine dinucleotide (FAD), microorganisms, vascular endothelial growth factor (VEGF), endothelial growth factor (EGF), epithelial growth factor, epithelial cell membrane antigen (ECMA), hypoxia inducible factor (HIF-1), carbonic anhydrase IX (CAIX), laminin, fibrin, fibronectin, fibroblast growth factor, transforming growth factors (TGF), fibroblast activation protein (FAP), tissue inhibitors of metalloproteinases (TIMPs), nitric oxide synthase (NOS), inducible and endothelial NOS, lysosomes in cells, macrophages, neutrophils, lymphocytes, hepatocyte growth factor (HGF), anti-neuropeptides, neutral endopeptidase (NEP), granulocyte-macrophage colony stimulating factor (GMCSF), neutrophil elastases, cathepsins, arginases, fibroblasts, endothelial cells and keratinocytes, keratinocyte growth factor (KGF), macrophage inflammatory protein-2 (MIP-2), macrophage inflammatory protein-2 (MIP-2), and macrophage chemoattractant protein-1(MCP-1), polymorphonuclear neutrophils (PMN), macrophages, myofibroblasts, interleukin-1 (IL-1), tumour necrosis factor (TNF), nitric oxide (NO), c-myc, beta-catenin, endothelial progenitor cells (EPCs), matrix metalloproteinases (MMPs) and MMP inhibitors (“contamination of meat with feces or ingesta is the primary source of contamination of meat and poultry with particularly onerous pathogens, including Campylobacter spp., Escherichia coli” [0006]; “food-borne illnesses caused by six common bacterial pathogens, Campylobacter spp., Clostridium perfringens, Escherichia coli 0157:H7, Listeria monocytogenes, Salmonella spp., and Staphylococcus aureus” [0005]).
Further Brenner also teaches wherein the selected biomarker is chosen from the group consisting of: bacteria, fungi, yeast, spores, virus, microbes, parasites, connective tissues, tissue components, exudates, pH, blood vessels, reduced nicotinamide adenine dinucleotide (NADH), flavin adenine dinucleotide (FAD), microorganisms, vascular endothelial growth factor (VEGF), endothelial growth factor (EGF), epithelial growth factor, epithelial cell membrane antigen (ECMA), hypoxia inducible factor (HIF-1), carbonic anhydrase IX (CAIX), laminin, fibrin, fibronectin, fibroblast growth factor, transforming growth factors (TGF), fibroblast activation protein (FAP), tissue inhibitors of metalloproteinases (TIMPs), nitric oxide synthase (NOS), inducible and endothelial NOS, lysosomes in cells, macrophages, neutrophils, lymphocytes, hepatocyte growth factor (HGF), anti-neuropeptides, neutral endopeptidase (NEP), granulocyte-macrophage colony stimulating factor (GMCSF), neutrophil elastases, cathepsins, arginases, fibroblasts, endothelial cells and keratinocytes, keratinocyte growth factor (KGF), macrophage inflammatory protein-2 (MIP-2), macrophage inflammatory protein-2 (MIP-2), and macrophage chemoattractant protein-1(MCP-1), polymorphonuclear neutrophils (PMN), macrophages, myofibroblasts, interleukin-1 (IL-1), tumour necrosis factor (TNF), nitric oxide (NO), c-myc, beta-catenin, endothelial progenitor cells (EPCs), matrix metalloproteinases (MMPs) and MMP inhibitors (“showing the effect of antigens, 13, on antibodies, 14, to an arm of which a dye, 15, or fluorophore 1, is attached and to another arm of which another dye, 16, or fluorophore 2, is attached through an extra Protein A or G, 17, directly bound to that antibody second arm. Proteins 17 serve to keep fluorophores 1 and 2, or the dyes, sufficiently separated as positioned with respect to corresponding antibody 14.” [0039]).
Regarding the claim 19, Petrich teaches illuminating the target with a light source emitting light having a wavelength between about 400 nm and about 450 nm (“system illuminates the object to be examined with blue light 120 in the 380-470 nm range” [0033]).
Regarding the claim 20, Petrich teaches filtering emissions responsive to illumination of the target with one or more filters configured to permit optical signals having wavelengths corresponding to bacterial fluorescence to pass through the one or more filters to the image detector of the handheld device (“light emitting mechanism has an integrated filter element 160 which allows passage of the light indicating fecal contamination. Such element 160 can be mounted on the housing 113 of the light emitting system, or simply positioned at any point between the object to be examined and the detection system to be used.” [0035]).
Regarding the claim 21, Petrich teaches the wavelengths corresponding to bacterial fluorescence include wavelengths of one or more of 490 nm to about 550 nm and wavelengths above 600 nm (“surface of the carcass is illuminated with UV or visible light having a wavelength between 300-600 nm, preferably between about 400 to 440 nm or between about 510 to 600 nm, and most preferably between about 410-430 nm and/or between about 520-540 nm,” [0009]).
Regarding the claim 22, Petrich teaches determining the one or more of the presence, location, and quantity of contamination on the illuminated target comprises displaying the detected fluorescence emissions on a display of the handheld imaging device or a display configured to receive transmissions from the handheld device (see fig. 3 and the associated pars).
Further, in the same field of endeavor, Boyden ‘795 teaches electromagnetic energy selected to induce a fluorescent response from a target area in the lesion; a sensor 120 configured to detect the fluorescent response; control circuitry 130 coupled to the sensor 120 and responsive to identify the target area [0036]. Pathogens, such as, for example, a chemical dye or an antibody or aptamer conjugated to a fluorescent tag. Pathogens may include bacteria, fungi and/or viruses [0167]. The device emits electromagnetic energy at wavelengths sufficient to cause fluorescence of reagents added to the lumen to selectively detect pathogens, such as, for example, a chemical dye or an antibody or aptamer conjugated to a fluorescent tag. Pathogens may include bacteria, fungi and/or viruses. A lumen may include that associated with blood vessels, the urogenital tract, and the respiratory tract, for example. The untethered luminal device detects the autofluorescence or reagent-induced fluorescence [0209].
In illustrative embodiments, a first input includes dara representative of one or more characteristics of one or more targets and/or one or more diseases and/or disorders. In illustrative embodiments, a first input includes data representative of the target fluorescent response. Data representative of the target fluorescent response may include, but is not limited to, one or more measurements of electromagnetic energy, and/or one or more measurements of one or more temporal-spatial locations of the target fluorescent response. As used herein, the term "temporal-spatial locations" may include one or more temporal locations and/or one or more spatial locations. Data representative of a target fluorescent response may include, but is not limited to, a clustering of fluorescent responses that would otherwise be considered a normal response in the absence of clustering, or with limited clustering, or non-significant clustering. In illustrative embodiments, clustering might include cells forming a plaque, bacterial cells forming a colony, blood cells forming a clot, malaria-infected red blood cells aggregating, among others [0303].
Determining the graphical illustration of the first possible dataset for inclusion in a display element of a graphical user interface. In illustrative embodiments, determining a graphical illustration of the first possible dataset includes, but is not limited to, determining a graphical illustration of data representative of one or more characteristics of one or more targets associated with one or more diseases and/or disorders [0328]. In illustrative embodiments of an optional determining operation 460, 470, and/or 480, determining a graphical illustration of the first possible dataset includes, but is not limited to, performing an analysis of one or more elements of the first possible dataset to determine the location of the target area; and determining the graphical illustration based on the analysis [0329].
It would have been obvious to an ordinary skilled in the art before the invention was made to modify the method and/or device of the modified combination of reference(s) as outlined above with identifying one or more of a presence, a location, and a quantity of colonies of bacteria contaminating the target based, at least in part, on the detected fluorescence emissions of at least the selected biomarker; and displaying a representation of the target indicative of one or more of the presence, the location, and the quantity of the colonies of bacteria contaminating the target, wherein the representation of the target spatially co- registers fluorescence emission data and reflection data as taught by Boyden because speed and accuracy are paramount ([0373] of Boyden).
Regarding the claim 23, Petrich teaches wherein displaying a representation of the target indicative of one or more of the presence, location, and quantity of contamination on the target includes displaying an image of a location and/or biodistribution of bacteria, microorganisms, selected biomarker(s), and/or pathogens detected on the illuminated target on a display of the handheld device or a display configured to receive transmissions from the handheld device (“A processor 117, such as a CPU, controls the operation of the system, including receiving signals from an activation device 116, such as a user keypad. Processor 117 receives a signal from the detection device 130 and transmits it to a result indicator 118, or a display monitor 119, or an external network or employee ID reader (not shown), or any combination thereof. Indicator 118 may include a signal for when the fluorescent intensity at the measured 660-680 nm range has exceeded a predetermined threshold value. Signals may include for example, audible alarms, visible lights or LEDs, or any combination of the above. Thus, as taught herein, the present invention may aid in objectively identifying the presence of contaminant.” [0038]).
Further, in the same field of endeavor, Boyden ‘795 teaches electromagnetic energy selected to induce a fluorescent response from a target area in the lesion; a sensor 120 configured to detect the fluorescent response; control circuitry 130 coupled to the sensor 120 and responsive to identify the target area [0036]. Pathogens, such as, for example, a chemical dye or an antibody or aptamer conjugated to a fluorescent tag. Pathogens may include bacteria, fungi and/or viruses [0167]. The device emits electromagnetic energy at wavelengths sufficient to cause fluorescence of reagents added to the lumen to selectively detect pathogens, such as, for example, a chemical dye or an antibody or aptamer conjugated to a fluorescent tag. Pathogens may include bacteria, fungi and/or viruses. A lumen may include that associated with blood vessels, the urogenital tract, and the respiratory tract, for example. The untethered luminal device detects the autofluorescence or reagent-induced fluorescence [0209].
In illustrative embodiments, a first input includes dara representative of one or more characteristics of one or more targets and/or one or more diseases and/or disorders. In illustrative embodiments, a first input includes data representative of the target fluorescent response. Data representative of the target fluorescent response may include, but is not limited to, one or more measurements of electromagnetic energy, and/or one or more measurements of one or more temporal-spatial locations of the target fluorescent response. As used herein, the term "temporal-spatial locations" may include one or more temporal locations and/or one or more spatial locations. Data representative of a target fluorescent response may include, but is not limited to, a clustering of fluorescent responses that would otherwise be considered a normal response in the absence of clustering, or with limited clustering, or non-significant clustering. In illustrative embodiments, clustering might include cells forming a plaque, bacterial cells forming a colony, blood cells forming a clot, malaria-infected red blood cells aggregating, among others [0303].
Determining the graphical illustration of the first possible dataset for inclusion in a display element of a graphical user interface. In illustrative embodiments, determining a graphical illustration of the first possible dataset includes, but is not limited to, determining a graphical illustration of data representative of one or more characteristics of one or more targets associated with one or more diseases and/or disorders [0328]. In illustrative embodiments of an optional determining operation 460, 470, and/or 480, determining a graphical illustration of the first possible dataset includes, but is not limited to, performing an analysis of one or more elements of the first possible dataset to determine the location of the target area; and determining the graphical illustration based on the analysis [0329].
It would have been obvious to an ordinary skilled in the art before the invention was made to modify the method and/or device of the modified combination of reference(s) as outlined above with identifying one or more of a presence, a location, and a quantity of colonies of bacteria contaminating the target based, at least in part, on the detected fluorescence emissions of at least the selected biomarker; and displaying a representation of the target indicative of one or more of the presence, the location, and the quantity of the colonies of bacteria contaminating the target, wherein the representation of the target spatially co- registers fluorescence emission data and reflection data as taught by Boyden because speed and accuracy are paramount ([0373] of Boyden).
Regarding the claim 24, Petrich teaches comprising storing, archiving, cataloguing, or retrieving from storage the displayed image maps of the target (“the output signal from the photodetector may be relayed to a recording instrument, such as an oscilloscope, desktop computer, hard drive, printer or any other device known in the art for presenting or storing a graphical display of fluorescent spectra intensity” [0040]).
Regarding the claim 25, Petrich teaches all the claimed limitations except for comparing previously calculated fluorescence intensities of the target.
However, in the same field of endeavor, Boyden teaches autofluorescence location can be updated by registering the detected autofluorescence location relative to other, updatable, location information. In one example, the detected autofluorescence location is registered relative to fiducials on or within the individual. Then, the location of the fiducials is updated, and the site of the autofluorescence location at such time can be predicted based upon its known registration relative to the fiducial locations. In another example, the detected autofluorescence location is registered relative to features within an image of a related portion of the individual. Then, the image is updated and the location of the autofluorescence location at such time can be predicted based upon its known registration relative to the image features [0098].
Fluorescence maxima may be compared at various emission wavelengths, for example, 444, 469, 481, 486, 545, 609, and 636 nm following excitation at 337 nm and 400 nm [0203].
It would have been obvious to an ordinary skilled in the art before the invention was made to modify the method and/or device of the modified combination of reference(s) as outlined above with comparing previously calculated fluorescence intensities of the target as taught by Boyden because speed and accuracy are paramount ([0373] of Boyden).
Regarding the claim 26, Petrich teaches cleaning the target (“Upon detection of ingesta or fecal contamination, the object may be washed,” [0034]), and
subsequent to the cleaning of the target, determining and displaying the presence, location, or quantity of contamination on the cleaned target based on the detected fluorescence and reflectance emissions of at least the selected object (“. Processor 117 receives a signal from the detection device 130 and transmits it to a result indicator 118, or a display monitor 119” [0038]).
Petrich does not point out the specifics of labelling a selected biomarker at the target with at least one fluorescing contrast agent.
However, in the same field of endeavor, Brenner teaches a method of, and system for, assaying for selected constituents in liquid mixtures confined by corresponding containing structures having relatively small electromagnetic absorption in at least one transmission wavelength range for transmissions of electromagnetic radiation therethrough, including in vivo assaying for a presence of selected constituents in bloodstreams in circulatory system passageways in mammalian bodies (abst). Methods can be used with a body supported bloodstream biomarker evaluation system for such assaying with this system being provided on a substrate supporting a first electromagnetic radiation emitter capable of emitting evaluation electromagnetic radiation of wavelengths in the transmission wavelength range and also capable of emitting evaluation electromagnetic radiation of wavelengths in the absorption spectra range of that fluorophore having an overlapping emission spectra peak distribution [0018].
It would have been obvious to an ordinary skilled in the art before the invention was made to modify the method and/or device of the modified combination of reference(s) as outlined above with labelling a selected biomarker at the target with at least one fluorescing contrast agent as taught by because it allows for continuous monitoring which in turn providing real-time, or near real-time, information feedback include the measurement ([0003] of Brenner).
Further, in the same field of endeavor, Kusano also teaches non-tissues such as blood, feces, and food are targeted and specific microorganisms are captured therefrom (pg. 2). biological sample analyzing apparatus 100, the luminescent image and the bright field image and / or the fluorescent image of the sample S, which is a biological sample including a microorganism having a bioluminescent protein, are captured and captured. Since the ecology of microorganisms is analyzed based on a superimposed image obtained by superimposing a luminescent image and a bright-field image and / or a fluorescence image, microorganisms in a biological sample such as a thick living tissue are identified as the microorganisms. In a state where the biological sample is present without being removed from the biological sample, it can be clearly captured with a simple apparatus configuration without damaging the biological sample. It is possible to analyze (know) accurately and in detail the behavior, morphology, localization, life and death of microorganisms in a biological sample. In other words, by superimposing the luminescent image and the bright field image and / or the fluorescence image, the light signal from the thick biological sample can be measured with high sensitivity without any damage to the tissue without background, As a result, ecology such as the behavior, morphology, localization, life and death of microorganisms in the biological sample can be analyzed accurately and in detail.
The biological sample analyzer 100, the luminescent image and the bright field image and / or the fluorescence image are captured over time, and the captured luminescence image and the bright field image and / or the fluorescence image are superimposed. Because changes in the ecology of microorganisms are analyzed based on multiple superimposed images, microorganisms in a biological sample such as a thick living tissue can be present in the biological sample without removing the microorganism from the biological sample. In this state, the biological sample can be clearly captured with a simple apparatus configuration without damaging the biological sample, and as a result, the change in the ecology of microorganisms in the biological sample, specifically the behavior of microorganisms in the biological sample, Localization, life and death, proliferation, reduction, etc. can be analyzed (tracked) accurately and in detail over time. In other words, by observing the image of the light signal in a time-lapse manner, the light signal from a thick biological sample can be measured (tracked) over time with high sensitivity and no background damage. As a result, biological changes such as behavior, localization, life / death, proliferation, and decrease of microorganisms in a biological sample can be analyzed accurately and in detail over time (pg. 4).
It would have been obvious to an ordinary skilled in the art before the invention was made to modify the method and/or device of the modified combination of reference(s) as outlined above with co-registering the representation of the contaminated target and the representation of the cleaned target as taught by Kusano because biological sample can be measured (tracked) over time with high sensitivity and no background damage. As a result, biological changes such as behavior, localization, life / death, proliferation, and decrease of microorganisms in a biological sample can be analyzed accurately and in detail over time (pg. 4 of Kusano).
Regarding the claim 27, Petrich teaches identifying a change in one or more of a presence, a location, a population, a distribution, a colonization, a contamination, a critical colonization, and an extent of bacteria, fungus, yeast, and other microorganisms present in the target based at least in part on a comparison of the previously calculated fluorescence intensities of the target and the newly calculated fluorescence intensities of the target (“Upon detection of ingesta or fecal contamination, the object may be washed, disinfected or otherwise treated to remove ingesta or feces from the surface thereof. The process for detecting ingesta and feces on the washed surface may then be repeated, followed by additional washing and/or disinfection steps if necessary, until all traces of ingesta or feces have been removed or destroyed. A variety of wash solutions or disinfectants are known in the art and are suitable for use herein and include but are not limited to pressurized water or steam sprays, organic acids, chlorinated water, inorganic acids, detergents, and treatment with radiation. Once the object has been determined to be free of contamination as evidenced by the lack of fluorescence at the described range, the object may be returned to use, or prepared for consumption if the item is a food item, such as meat.” [0034]).
Regarding the claim 28, Petrich teaches all the claimed limitations except for the representation of the target comprises fluorescence intensity data displayed in combination with reflectance intensity data.
However, in the same field of endeavor, Boyden teaches autofluorescence induced by excitation wavelengths of 365, 385, 405, 420, 435, and 450 nm may be combined with diffuse reflectance spectroscopy to detect pre-malignant and malignant lesions in the oral mucosa [0202]. Autofluorescence location can be updated by registering the detected autofluorescence location relative to other, updatable, location information. In one example, the detected autofluorescence location is registered relative to fiducials on or within the individual. Then, the location of the fiducials is updated, and the site of the autofluorescence location at such time can be predicted based upon its known registration relative to the fiducial locations. In another example, the detected autofluorescence location is registered relative to features within an image of a related portion of the individual. Then, the image is updated and the location of the autofluorescence location at such time can be predicted based upon its known registration relative to the image features [0098].
Fluorescence maxima may be compared at various emission wavelengths, for example, 444, 469, 481, 486, 545, 609, and 636 nm following excitation at 337 nm and 400 nm [0203].
It would have been obvious to an ordinary skilled in the art before the invention was made to modify the method and/or device of the modified combination of reference(s) as outlined above with representation of the target comprises fluorescence intensity data displayed in combination with reflectance intensity data as taught by Boyden because speed and accuracy are paramount ([0373] of Boyden).
Regarding the claim 29, Petrich teaches all the claimed limitations except for fluorescence red-blue-green (RBG) ratio data displayed in combination with reflectance RBG ratio data.
However, in the same field of endeavor, Boyden teaches the fluorescence intensity of normal mucosa may be greater than that of abnormal areas, while the ratio of red fluorescence (635 nm) to blue fluorescence (455-490 nm) intensities may be greater in abnormal areas [0183]. The fluorescence intensity of normal mucosa may be greater than that of abnormal areas, while the ratio of red fluorescence (635 nm) to blue fluorescence (455-490 nm) intensities may be greater in abnormal areas [0202].
It would have been obvious to an ordinary skilled in the art before the invention was made to modify the method and/or device of the modified combination of reference(s) as outlined above with fluorescence red-blue-green (RBG) ratio data displayed in combination with reflectance RBG ratio data as taught by Boyden because speed and accuracy are paramount ([0373] of Boyden).
Regarding the claim 30, Petrich teaches a method for fluorescence-based imaging of a target to detect contamination (“method for detecting ingesta or fecal contamination on an object or surface using fluorescent spectroscopy is disclosed.” [0003]) comprising:
illuminating the target with excitation light emitted by an excitation light source of (see e.g., re-produced fig. 3 below and the associated pars.) and having at least one wavelength or wavelength band causing to fluoresce (“device is used to emit UV or visible light having an appropriate wavelength onto the object to be examined, causing any feces or ingesta which may be present to fluoresce” [0003]);
detecting fluorescence emissions with an image detector of a handheld imaging device (“hand-held, lightweight and portable apparatus and method for detecting ingesta or fecal contamination on an object or surface using fluorescent” [0003]);
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filtering optical signals responsive to illumination of the target including the at least one fluorescing object with the excitation light, the at least one optical filter being configured to enable optical signals having a wavelength corresponding to bacterial fluorescence to pass through the at least one optical filter (“light emitting mechanism has an integrated filter element 160 which allows passage of the light indicating fecal contamination. Such element 160 can be mounted on the housing 113 of the light emitting system, or simply positioned at any point between the object to be examined and the detection system to be used.” [0035]);
illuminating the target with white light emitted by a white light source of the handheld imaging device (“illuminated with UV or visible light having a wavelength between 300-600 nm, preferably between about 400 to 440 nm or between about 510 to 600 nm, and most preferably between about 410-430 nm and/or between about 520-540 nm, and fluorescent light emissions having a wavelength between about 660 to 680 nm are then detected” [0009]);
detecting reflections from the target in response to illumination of the target with the white light (see e.g., re-produced fig. 3 below and the associated pars. along with [0009]);
determining in real time one or more of a presence, a location, and a quantity of contaminating the target based on the detected fluorescence emissions of at least the selected object (“object of the invention is to provide an improved real-time method and lightweight and portable apparatus to detect fecal contamination” [0018]; “the system illuminates the object to be examined with blue light 120 in the 380-470 nm range. If fecal contamination or ingesta is present on the object, the feces will fluoresce at approximately 675 nm, +/−10 nm, where such fluorescence can then be visibly detected” [0033]), and
Petrich does not point out the specifics of labelling a selected biomarker at the target with at least one fluorescing contrast agent.
However, in the same field of endeavor, Brenner teaches a method of, and system for, assaying for selected constituents in liquid mixtures confined by corresponding containing structures having relatively small electromagnetic absorption in at least one transmission wavelength range for transmissions of electromagnetic radiation therethrough, including in vivo assaying for a presence of selected constituents in bloodstreams in circulatory system passageways in mammalian bodies (abst). Methods can be used with a body supported bloodstream biomarker evaluation system for such assaying with this system being provided on a substrate supporting a first electromagnetic radiation emitter capable of emitting evaluation electromagnetic radiation of wavelengths in the transmission wavelength range and also capable of emitting evaluation electromagnetic radiation of wavelengths in the absorption spectra range of that fluorophore having an overlapping emission spectra peak distribution [0018].
It would have been obvious to an ordinary skilled in the art before the invention was made to modify the method and/or device of the modified combination of reference(s) as outlined above with labelling a selected biomarker at the target with at least one fluorescing contrast agent as taught by because it allows for continuous monitoring which in turn providing real-time, or near real-time, information feedback include the measurement ([0003] of Brenner).
The above noted combination does not seem point out the specifics of displaying a representation of the target indicative of one or more of the presence, location, and quantity of contamination on the target, wherein the representation of the target spatially co-registers fluorescence emission data and reflection data.
However, in the same field of endeavor, Boyden teaches autofluorescence location can be updated by registering the detected autofluorescence location relative to other, updatable, location information. In one example, the detected autofluorescence location is registered relative to fiducials on or within the individual. Then, the location of the fiducials is updated, and the site of the autofluorescence location at such time can be predicted based upon its known registration relative to the fiducial locations. In another example, the detected autofluorescence location is registered relative to features within an image of a related portion of the individual. Then, the image is updated and the location of the autofluorescence location at such time can be predicted based upon its known registration relative to the image features [0098].
It would have been obvious to an ordinary skilled in the art before the invention was made to modify the method and/or device of the modified combination of reference(s) as outlined above with displaying a representation of the target indicative of one or more of the presence, location, and quantity of contamination on the target, wherein the representation of the target spatially co-registers fluorescence emission data and reflection data as taught by Boyden because speed and accuracy are paramount ([0373] of Boyden).
Further, as noted above, combination teaches all the limitations of the claims including " determining, in real-time, one or more of a presence, a location, and a quantity of colonies of bacteria contaminating the target based on the detected fluorescence emissions of at least the selected biomarker by spatially co-registering fluorescence intensity data of at least the pre-selected biomarker relative to reflectance data from the target, and displaying a representation of the target, wherein the representation of the target comprises the fluorescence intensity data and reflectance data”. Yet, in an interpretation, if one argues (which the office does not concede), the Boyden ‘795 reference is brought in, in an effort to provide compact prosecution, and to clearly and factually show the teachings of these limitations as well.
In the same field of endeavor, Boyden ‘795 teaches electromagnetic energy selected to induce a fluorescent response from a target area in the lesion; a sensor 120 configured to detect the fluorescent response; control circuitry 130 coupled to the sensor 120 and responsive to identify the target area [0036]. Pathogens, such as, for example, a chemical dye or an antibody or aptamer conjugated to a fluorescent tag. Pathogens may include bacteria, fungi and/or viruses [0167]. The device emits electromagnetic energy at wavelengths sufficient to cause fluorescence of reagents added to the lumen to selectively detect pathogens, such as, for example, a chemical dye or an antibody or aptamer conjugated to a fluorescent tag. Pathogens may include bacteria, fungi and/or viruses. A lumen may include that associated with blood vessels, the urogenital tract, and the respiratory tract, for example. The untethered luminal device detects the autofluorescence or reagent-induced fluorescence [0209].
In illustrative embodiments, a first input includes dara representative of one or more characteristics of one or more targets and/or one or more diseases and/or disorders. In illustrative embodiments, a first input includes data representative of the target fluorescent response. Data representative of the target fluorescent response may include, but is not limited to, one or more measurements of electromagnetic energy, and/or one or more measurements of one or more temporal-spatial locations of the target fluorescent response. As used herein, the term "temporal-spatial locations" may include one or more temporal locations and/or one or more spatial locations. Data representative of a target fluorescent response may include, but is not limited to, a clustering of fluorescent responses that would otherwise be considered a normal response in the absence of clustering, or with limited clustering, or non-significant clustering. In illustrative embodiments, clustering might include cells forming a plaque, bacterial cells forming a colony, blood cells forming a clot, malaria-infected red blood cells aggregating, among others [0303].
Determining the graphical illustration of the first possible dataset for inclusion in a display element of a graphical user interface. In illustrative embodiments, determining a graphical illustration of the first possible dataset includes, but is not limited to, determining a graphical illustration of data representative of one or more characteristics of one or more targets associated with one or more diseases and/or disorders [0328]. In illustrative embodiments of an optional determining operation 460, 470, and/or 480, determining a graphical illustration of the first possible dataset includes, but is not limited to, performing an analysis of one or more elements of the first possible dataset to determine the location of the target area; and determining the graphical illustration based on the analysis [0329].
It would have been obvious to an ordinary skilled in the art before the invention was made to modify the method and/or device of the modified combination of reference(s) as outlined above with identifying one or more of a presence, a location, and a quantity of colonies of bacteria contaminating the target based, at least in part, on the detected fluorescence emissions of at least the selected biomarker; and displaying a representation of the target indicative of one or more of the presence, the location, and the quantity of the colonies of bacteria contaminating the target, wherein the representation of the target spatially co- registers fluorescence emission data and reflection data as taught by Boyden because speed and accuracy are paramount ([0373] of Boyden).
The above noted combination does not seem point out the specifics of co-registering the representation of the contaminated target and the representation of the cleaned target.
However, in the same field of endeavor, Kusano teaches non-tissues such as blood, feces, and food are targeted and specific microorganisms are captured therefrom (pg. 2). biological sample analyzing apparatus 100, the luminescent image and the bright field image and / or the fluorescent image of the sample S, which is a biological sample including a microorganism having a bioluminescent protein, are captured and captured. Since the ecology of microorganisms is analyzed based on a superimposed image obtained by superimposing a luminescent image and a bright-field image and / or a fluorescence image, microorganisms in a biological sample such as a thick living tissue are identified as the microorganisms. In a state where the biological sample is present without being removed from the biological sample, it can be clearly captured with a simple apparatus configuration without damaging the biological sample. It is possible to analyze (know) accurately and in detail the behavior, morphology, localization, life and death of microorganisms in a biological sample. In other words, by superimposing the luminescent image and the bright field image and / or the fluorescence image, the light signal from the thick biological sample can be measured with high sensitivity without any damage to the tissue without background, As a result, ecology such as the behavior, morphology, localization, life and death of microorganisms in the biological sample can be analyzed accurately and in detail.
The biological sample analyzer 100, the luminescent image and the bright field image and / or the fluorescence image are captured over time, and the captured luminescence image and the bright field image and / or the fluorescence image are superimposed. Because changes in the ecology of microorganisms are analyzed based on multiple superimposed images, microorganisms in a biological sample such as a thick living tissue can be present in the biological sample without removing the microorganism from the biological sample. In this state, the biological sample can be clearly captured with a simple apparatus configuration without damaging the biological sample, and as a result, the change in the ecology of microorganisms in the biological sample, specifically the behavior of microorganisms in the biological sample, Localization, life and death, proliferation, reduction, etc. can be analyzed (tracked) accurately and in detail over time. In other words, by observing the image of the light signal in a time-lapse manner, the light signal from a thick biological sample can be measured (tracked) over time with high sensitivity and no background damage. As a result, biological changes such as behavior, localization, life / death, proliferation, and decrease of microorganisms in a biological sample can be analyzed accurately and in detail over time (pg. 4).
It would have been obvious to an ordinary skilled in the art before the invention was made to modify the method and/or device of the modified combination of reference(s) as outlined above with co-registering the representation of the contaminated target and the representation of the cleaned target as taught by Kusano because biological sample can be measured (tracked) over time with high sensitivity and no background damage. As a result, biological changes such as behavior, localization, life / death, proliferation, and decrease of microorganisms in a biological sample can be analyzed accurately and in detail over time (pg. 4 of Kusano).
Regarding the claim 31, the above combination teaches all the limitations of the claims including labelling a selected biomarker at the target with at least one fluorescing contrast agent comprises labelling one or more biomarkers selected to identify, in combination, only viable Listeria monocytogenes.
Specifically, in the same field of endeavor, Boyden ‘795 teaches electromagnetic energy selected to induce a fluorescent response from a target area in the lesion; a sensor 120 configured to detect the fluorescent response; control circuitry 130 coupled to the sensor 120 and responsive to identify the target area [0036]. Pathogens, such as, for example, a chemical dye or an antibody or aptamer conjugated to a fluorescent tag. Pathogens may include bacteria, fungi and/or viruses [0167]. Pathogens commonly associated with gastrointestinal disorders include bacteria, such as certain strains of Escherichia coli (e.g. Escherichia coli 0157:H7), various strains of Salmonella, Vibrio cholera, Campylobacter, Listeria monocytogenes [0194]. The device emits electromagnetic energy at wavelengths sufficient to cause fluorescence of reagents added to the lumen to selectively detect pathogens, such as, for example, a chemical dye or an antibody or aptamer conjugated to a fluorescent tag. Pathogens may include bacteria, fungi and/or viruses. A lumen may include that associated with blood vessels, the urogenital tract, and the respiratory tract, for example. The untethered luminal device detects the autofluorescence or reagent-induced fluorescence [0209].
It would have been obvious to an ordinary skilled in the art before the invention was made to modify the method and/or device of the modified combination of reference(s) as outlined above with labelling a selected biomarker at the target with at least one fluorescing contrast agent comprises labelling one or more biomarkers selected to identify, in combination, only viable Listeria monocytogenes as taught by Boyden because speed and accuracy are paramount ([0373] of Boyden).
Claims 16-17 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Petrich et al (US20030160182) in view of Brenner (US20060270919), Boyden, Boyden ‘795 and Kusano, and further in view of King et al (US20040014202).
Regarding the claim 16, the above combination teaches all the limitations of the claims except for differentiating based on the fluorescence emissions of at least the selected biomarker.
However, in the same field of endeavor, King teaches differentiating multiple detectable signals by excitation wavelength. The apparatus can include a light source that can emit respective excitation light wavelengths or wavelength ranges towards a sample in a sample retaining region, for example, in a well. The sample can contain two or more detectable markers, for example, fluorescent dyes, each of which can be capable of generating increased detectable emissions when excited in the presence of a target component (abst).
It would have been obvious to an ordinary skilled in the art before the invention was made to modify the method and/or device of the modified combination of reference(s) as outlined above with differentiating based on the fluorescence emissions of at least the selected biomarker as taught by because it is desirable to create a less expensive apparatus and method of determining the composition of a sample using fluorescent dyes ([0003] of King).
Regarding the claim 17, Petrich teaches different bacterial strains include Staphylococcus aureus and Pseudomonas aeruginosa (“food-borne illnesses caused by six common bacterial pathogens, Campylobacter spp., Clostridium perfringens, Escherichia coli 0157:H7, Listeria monocytogenes, Salmonella spp., and Staphylococcus aureus” [0005]).
Response to Arguments
Applicant’s arguments have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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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/SERKAN AKAR/ Primary Examiner, Art Unit 3797
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