DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 3/25/26 has been entered.
Response to Amendment
The remarks and claim amendments filed on 3/2/26 and 3/25/26 have been entered. Claims 14-17 are new. Claim 11 is canceled. The previous rejections of claims 1-10 and 12-13 have been withdrawn in light of Applicant’s amendments and remarks in the claim sets filed 3/2/26 and 3/25/26. Claims 14-17 are withdrawn from consideration as provided below. Accordingly Claims 1-10 and 12-13 are pending.
Election/Restrictions
Newly submitted claims 14-17 are directed to an invention that is independent or distinct from the invention originally claimed for the following reasons: Claim 14 requires features such a lens and prism for transmission and the process of detection and generation of the fluorescence substance change information for treatment progress varies from the process found in claims 1-13. The variances require(s) different field(s) of search(es) not previously considered.
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 14-17 are withdrawn from consideration as being directed to a non-elected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 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.
Claims 1-10 and 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Takeyama (U.S. 20020196337, December 26, 2002)(hereinafter, “Takeyama”) in view of Toida (JP 2011167344A, September 1, 2011)(hereinafter, “Toida”) and Biel et. al. (U.S. 20180250405, September 6, 2018)(hereinafter, “Biel”).
Regarding Claim 1,Takeyama teaches: A treatment support device (Fig. 1, weak light color imaging device, [0031]) comprising:
a spectrometer configured to detect, during photoimmunotherapy for killing cancer cells by irradiating a drug that contains a fluorescent substance and has been administered to a with therapeutic light in a specific wavelength band, signal waveforms of fluorescence emitted from the fluorescent substance of the drug excited by the therapeutic light (“…an excitation light source 22 (Hg--Xe lamp) for generating characteristic HpD fluorescence by irradiating excitation light, as used in photodynamic diagnosis (PDD), and a treatment light source 23 (excimer dye laser) for destroying cancer cells by irradiating treatment light, as using in photodynamic therapy (PDT).” [0033]; “FIG. 3 shows the fluorescence spectrum of HpD in different locations when excitation light is irradiated onto a body containing cancer cells, into which HpD has been injected… PDD is a diagnosis method which uses the characteristics of the HpD accumulated selectively in the cancer cells in this way to diagnose cancers by detecting fluorescence of the characteristic wavelength of HpD….excitation light is irradiated onto the subject A by an excitation light source 22, the fluorescence of the HpD is captured as images by the weak light color imaging device, and the observer is able to diagnose cancer cells in the peripheral region of the subject A, in other words, to perform PDD, by observing the fluorescence.” [0035]);
a processor configured to selectively acquire first signal information corresponding to light in a first wavelength band that is a wavelength band from the signal waveforms of fluorescence emitted from the fluorescent substance of the drug detected by the spectrometer, wherein the first wavelength band includes 770 nm, and generate first fluorescence change information that is information on a change in fluorescence intensity in the first wavelength band, based on acquired first signal information (“FIG. 3 shows the fluorescence spectrum of HpD in different locations when excitation light is irradiated onto a body containing cancer cells, into which HpD has been injected. As shown in this diagram, since the cancer cells (tumour) accumulate the HpD selectively, fluorescence having peaks at wavelengths 630 nm and 690 nm as characteristic of HpD is generated. However, in the peripheral region of the cancer cells, where the amount of HpD absorbed in low, the HpD fluorescence generated is of lower intensity than in the cancer cells. Since normal cells hardly accumulate HpD, there is virtually no HpD fluorescence. PDD is a diagnosis method which uses the characteristics of the HpD accumulated selectively in the cancer cells in this way to diagnose cancers by detecting fluorescence of the characteristic wavelength of HpD.” [0035]; “The RGB filter is constituted by filters which respectively transmit light of the three basic colors, red (R), green (G) and blue (B). FIG. 4 is a diagram showing the relationship between the wavelength of the light incident on the RGB filter and the transmissivity thereof; and it depicts respective wavelength transmission characteristics for the three filters, red, green and blue. The solid line indicate the wavelength transmission characteristics of the RGB filter when used in a standard CCD camera. IL can be seen that the transmissivity increases as the wavelength shortens, from red, through green to blue. These wavelength transmission characteristics are set in order to obtain an image which corresponds to the visual receptivity of humans, in such a manner that the colors of the obtained images correspond to the colors of the images as actually seen by the human eye. The single-dotted line indicates the wavelength transmission characteristics of an RGB filter 33 having raised transmissivity of components in the longer wavelength, red region…” [0038]; “The light amplifying tube 35…has extended sensitivity into the longer wavelength, infrared region, and as shown in the diagram, it has satisfactory gain for light between wavelengths of 100 nm and 900 nm. Therefore, it is capable of amplifying light of various wavelength components, from infrared to blue light, transmitted by the RGB filter 33.” [0041]. See Figs. 3-4 and 6);
with regards to limitation: and a display configured to output an indication of progress of a treatment based on irradiation of the therapeutic light, based on the first fluorescence change information, Takeyama further teaches: “The operator controls the endoscope 11 appropriately so as to find the subject A by means of the images displayed on the monitor 27. When the subject is discovered, the endoscope 11 makes a one-touch connection with the connection section for the endoscope 11 on the camera box 3. Thereby, the endoscope 11 faces the subject A, and the weak light from the subject A it is facing is guided by the image guide (not illustrated) of the endoscope 11 to the camera box 3. Thereafter, the subject A is observed by means of the weak light color imaging device” [0032]; “…both the image of the peripheral region of the subject A and the fluorescence of the HpD are readily discernable by the observer on the monitor 27 displaying the captured images, and therefore he or she can perform PDD easily. After establishing the location of cancer cells by means of PDD, the excitation light source 22 can be changed for a treatment light source 23, whereby PDT can be performed at that location.” [0058].
Takeyama does not explicitly teach a dye being IRDye700, the display providing an indication of progress and the signal waveforms includes two peaks where the second peak is excluded from the first peak and located on a shorter wavelength side from the signal waveforms of fluorescence, than the first peak and has a greater fluorescent intensity than the first peak.
Toida in the field of fluorescent endoscopy systems teaches: “…the monitor 14 displays three images: a color normal light image, a red fluorescent light image, and a red treatment light image. Thus, by displaying not only the normal light image and the treatment light image but also the fluorescence light image on the monitor 14, the progress of the PDT treatment can be confirmed by the change in the concentration of the photosensitive substance. Each image is shifted in time by one frame.”
Therefore, it would be obvious to one of ordinary skill in the art before the effective filing date of the invention to modify the display in Takeyama to provide an indication of progress as taught in Toida for the intended purpose of progress notification of treatment confirmation (Toida).
The combination of references does not teach the dye being IRDye700 and the signal waveforms includes two peaks where the second peak is located on a shorter wavelength side than the first peak and has a greater fluorescent intensity than the first peak.
Biel in the field of photoimmunotherapy systems teaches: “…the wavelength for irradiation is 600 nm to 850 nm, such as 660 nm to 740 nm.” [0005];“…the phthalocyanine dye includes IRDye 700DX (IR700).” [0031]; “Patients with head and neck cancer patients treated with a single administration of cetuximab-IRDye 700DX conjugate followed by irradiation to induce photoimmunotherapy (PIT) were assessed for tumor response.” [1027]; “Cetuximab-IRDye 700DX (CTX700) conjugate used to produce all dual conjugates described below was prepared substantially as described in Example 1. Briefly, cetuximab was reacted with 4 molar equivalents of IRDye 700DX NHS ester for 2 hours at pH=8.5, in the dark, at room temperature in a using through Amicon® Ultra Centrifugal Filter Units…” [1233]; See Figs. 22 and 24.
Therefore, it would be obvious to one of ordinary skill in the art before the effective filing date of the invention to further modify the combination of references to modify the dye to be IRDye700 and the signal waveforms includes two peaks where the second peak is located on a shorter wavelength side than the first peak and has a greater fluorescent intensity than the first peak as taught in Biel for “…improved performance for imaging or detection.” (Biel, [0003]).
Regarding Claim 2, the combination of Takeyama, Toida and Biel teach the claim limitations as noted above.
Takeyama further teaches: wherein the therapeutic light is light in the specific wavelength band includes a wavelength of 690 nm, wherein the signal waveforms of the fluorescence emitted from the fluorescent substance of the drug excited by the therapeutic light has a plurality of peaks, and wherein the first wavelength band includes the first peak positioned at 770 nm among the plurality of peaks in the signal waveforms of the fluorescence emitted from the fluorescent substance of the drug (“FIG. 3 shows the fluorescence spectrum of HpD in different locations when excitation light is irradiated onto a body containing cancer cells, into which HpD has been injected. As shown in this diagram, since the cancer cells (tumour) accumulate the HpD selectively, fluorescence having peaks at wavelengths 630 nm and 690 nm as characteristic of HpD is generated. However, in the peripheral region of the cancer cells, where the amount of HpD absorbed in low, the HpD fluorescence generated is of lower intensity than in the cancer cells. Since normal cells hardly accumulate HpD, there is virtually no HpD fluorescence. PDD is a diagnosis method which uses the characteristics of the HpD accumulated selectively in the cancer cells in this way to diagnose cancers by detecting fluorescence of the characteristic wavelength of HpD.” [0035]; “The RGB filter is constituted by filters which respectively transmit light of the three basic colors, red (R), green (G) and blue (B). FIG. 4 is a diagram showing the relationship between the wavelength of the light incident on the RGB filter and the transmissivity thereof; and it depicts respective wavelength transmission characteristics for the three filters, red, green and blue. The solid line indicate the wavelength transmission characteristics of the RGB filter when used in a standard CCD camera. IL can be seen that the transmissivity increases as the wavelength shortens, from red, through green to blue. These wavelength transmission characteristics are set in order to obtain an image which corresponds to the visual receptivity of humans, in such a manner that the colors of the obtained images correspond to the colors of the images as actually seen by the human eye. The single-dotted line indicates the wavelength transmission characteristics of an RGB filter 33 having raised transmissivity of components in the longer wavelength, red region…” [0038]; “The light amplifying tube 35…has extended sensitivity into the longer wavelength, infrared region, and as shown in the diagram, it has satisfactory gain for light between wavelengths of 100 nm and 900 nm. Therefore, it is capable of amplifying light of various wavelength components, from infrared to blue light, transmitted by the RGB filter 33.” [0041]. See Figs. 3-4 and 6).
Regarding Claim 3, the combination of Takeyama, Toida and Biel teach the claim limitations as noted above.
Takeyama further teaches: wherein the processor is configured to generate the first fluorescence change information based on a change in the signal waveforms due to an increase in an irradiation time of the therapeutic light in the first wavelength band of the signal waveforms of the fluorescence emitted from the fluorescent substance of the drug (“FIG. 3 shows the fluorescence spectrum of HpD in different locations when excitation light is irradiated onto a body containing cancer cells, into which HpD has been injected. As shown in this diagram, since the cancer cells (tumour) accumulate the HpD selectively, fluorescence having peaks at wavelengths 630 nm and 690 nm as characteristic of HpD is generated. However, in the peripheral region of the cancer cells, where the amount of HpD absorbed in low, the HpD fluorescence generated is of lower intensity than in the cancer cells. Since normal cells hardly accumulate HpD, there is virtually no HpD fluorescence. PDD is a diagnosis method which uses the characteristics of the HpD accumulated selectively in the cancer cells in this way to diagnose cancers by detecting fluorescence of the characteristic wavelength of HpD.” [0035]; “The RGB filter is constituted by filters which respectively transmit light of the three basic colors, red (R), green (G) and blue (B). FIG. 4 is a diagram showing the relationship between the wavelength of the light incident on the RGB filter and the transmissivity thereof; and it depicts respective wavelength transmission characteristics for the three filters, red, green and blue. The solid line indicate the wavelength transmission characteristics of the RGB filter when used in a standard CCD camera. IL can be seen that the transmissivity increases as the wavelength shortens, from red, through green to blue. These wavelength transmission characteristics are set in order to obtain an image which corresponds to the visual receptivity of humans, in such a manner that the colors of the obtained images correspond to the colors of the images as actually seen by the human eye. The single-dotted line indicates the wavelength transmission characteristics of an RGB filter 33 having raised transmissivity of components in the longer wavelength, red region…” [0038]; “The light amplifying tube 35…has extended sensitivity into the longer wavelength, infrared region, and as shown in the diagram, it has satisfactory gain for light between wavelengths of 100 nm and 900 nm. Therefore, it is capable of amplifying light of various wavelength components, from infrared to blue light, transmitted by the RGB filter 33.” [0041]. See Figs. 3-4 and 6).
Regarding Claim 4, the combination of Takeyama, Toida and Biel teach the claim limitations as noted above.
Takeyama further teaches: wherein the spectrometer is configured to detect a signal waveform of the light in the first wavelength band from the fluorescence emitted from the fluorescent substance of the drug by sequentially scanning fluorescence emitted from the fluorescent substance of the drug for each corresponding predetermined wavelength band, and wherein the processor is configured to acquire the signal waveform of the light in the first wavelength band detected by the spectrometer as the first signal information by sequentially scanning a fluorescence corresponding each predetermined wavelength band and to generate the first fluorescence change information based on the acquired signal waveform of the light in the first wavelength band (“FIG. 3 shows the fluorescence spectrum of HpD in different locations when excitation light is irradiated onto a body containing cancer cells, into which HpD has been injected. As shown in this diagram, since the cancer cells (tumour) accumulate the HpD selectively, fluorescence having peaks at wavelengths 630 nm and 690 nm as characteristic of HpD is generated. However, in the peripheral region of the cancer cells, where the amount of HpD absorbed in low, the HpD fluorescence generated is of lower intensity than in the cancer cells. Since normal cells hardly accumulate HpD, there is virtually no HpD fluorescence. PDD is a diagnosis method which uses the characteristics of the HpD accumulated selectively in the cancer cells in this way to diagnose cancers by detecting fluorescence of the characteristic wavelength of HpD.” [0035]; “The RGB filter is constituted by filters which respectively transmit light of the three basic colors, red (R), green (G) and blue (B). FIG. 4 is a diagram showing the relationship between the wavelength of the light incident on the RGB filter and the transmissivity thereof; and it depicts respective wavelength transmission characteristics for the three filters, red, green and blue. The solid line indicate the wavelength transmission characteristics of the RGB filter when used in a standard CCD camera. IL can be seen that the transmissivity increases as the wavelength shortens, from red, through green to blue. These wavelength transmission characteristics are set in order to obtain an image which corresponds to the visual receptivity of humans, in such a manner that the colors of the obtained images correspond to the colors of the images as actually seen by the human eye. The single-dotted line indicates the wavelength transmission characteristics of an RGB filter 33 having raised transmissivity of components in the longer wavelength, red region…” [0038]; “The light amplifying tube 35…has extended sensitivity into the longer wavelength, infrared region, and as shown in the diagram, it has satisfactory gain for light between wavelengths of 100 nm and 900 nm. Therefore, it is capable of amplifying light of various wavelength components, from infrared to blue light, transmitted by the RGB filter 33.” [0041]. See Figs. 3-4 and 6).
Regarding Claim 5, the combination of Takeyama, Toida and Biel teach the claim limitations as noted above.
Takeyama further teaches: wherein the first wavelength band is a band of 750 nm or more and 790 nm or less, wherein the processor is configured to selectively acquire, in addition to the first signal information corresponding to the therapeutic light in the first wavelength band, second signal information corresponding to light in a second wavelength band that is a wavelength band shorter than the first wavelength band and is a wavelength band of 700 nm or more and 730 nm or less, among the signal waveforms of the fluorescence emitted from the fluorescent substance of the drug, generate second fluorescence change information that is information on a change in fluorescence intensity in the second wavelength band, based on the acquired second signal information, and generate a treatment progress index that is an index of progress of treatment of the subject based on the first fluorescence change information and the second fluorescence change information (“FIG. 3 shows the fluorescence spectrum of HpD in different locations when excitation light is irradiated onto a body containing cancer cells, into which HpD has been injected. As shown in this diagram, since the cancer cells (tumour) accumulate the HpD selectively, fluorescence having peaks at wavelengths 630 nm and 690 nm as characteristic of HpD is generated. However, in the peripheral region of the cancer cells, where the amount of HpD absorbed in low, the HpD fluorescence generated is of lower intensity than in the cancer cells. Since normal cells hardly accumulate HpD, there is virtually no HpD fluorescence. PDD is a diagnosis method which uses the characteristics of the HpD accumulated selectively in the cancer cells in this way to diagnose cancers by detecting fluorescence of the characteristic wavelength of HpD.” [0035]; “The RGB filter is constituted by filters which respectively transmit light of the three basic colors, red (R), green (G) and blue (B). FIG. 4 is a diagram showing the relationship between the wavelength of the light incident on the RGB filter and the transmissivity thereof; and it depicts respective wavelength transmission characteristics for the three filters, red, green and blue. The solid line indicate the wavelength transmission characteristics of the RGB filter when used in a standard CCD camera. IL can be seen that the transmissivity increases as the wavelength shortens, from red, through green to blue. These wavelength transmission characteristics are set in order to obtain an image which corresponds to the visual receptivity of humans, in such a manner that the colors of the obtained images correspond to the colors of the images as actually seen by the human eye. The single-dotted line indicates the wavelength transmission characteristics of an RGB filter 33 having raised transmissivity of components in the longer wavelength, red region…” [0038]; “The light amplifying tube 35…has extended sensitivity into the longer wavelength, infrared region, and as shown in the diagram, it has satisfactory gain for light between wavelengths of 100 nm and 900 nm. Therefore, it is capable of amplifying light of various wavelength components, from infrared to blue light, transmitted by the RGB filter 33.” [0041]. See Figs. 3-4 and 6).
Regarding Claim 6, the combination of Takeyama, Toida and Biel teach the claim limitations as noted above.
Takeyama further teaches: wherein the second wavelength band includes a rising portion of the second peak positioned in a wavelength band shorter than 770 nm in wavelength, among a plurality of peaks in the signal waveforms of the fluorescence emitted from the fluorescent substance of the drug (“FIG. 3 shows the fluorescence spectrum of HpD in different locations when excitation light is irradiated onto a body containing cancer cells, into which HpD has been injected. As shown in this diagram, since the cancer cells (tumour) accumulate the HpD selectively, fluorescence having peaks at wavelengths 630 nm and 690 nm as characteristic of HpD is generated. However, in the peripheral region of the cancer cells, where the amount of HpD absorbed in low, the HpD fluorescence generated is of lower intensity than in the cancer cells. Since normal cells hardly accumulate HpD, there is virtually no HpD fluorescence. PDD is a diagnosis method which uses the characteristics of the HpD accumulated selectively in the cancer cells in this way to diagnose cancers by detecting fluorescence of the characteristic wavelength of HpD.” [0035]; “The RGB filter is constituted by filters which respectively transmit light of the three basic colors, red (R), green (G) and blue (B). FIG. 4 is a diagram showing the relationship between the wavelength of the light incident on the RGB filter and the transmissivity thereof; and it depicts respective wavelength transmission characteristics for the three filters, red, green and blue. The solid line indicate the wavelength transmission characteristics of the RGB filter when used in a standard CCD camera. IL can be seen that the transmissivity increases as the wavelength shortens, from red, through green to blue. These wavelength transmission characteristics are set in order to obtain an image which corresponds to the visual receptivity of humans, in such a manner that the colors of the obtained images correspond to the colors of the images as actually seen by the human eye. The single-dotted line indicates the wavelength transmission characteristics of an RGB filter 33 having raised transmissivity of components in the longer wavelength, red region…” [0038]; “The light amplifying tube 35…has extended sensitivity into the longer wavelength, infrared region, and as shown in the diagram, it has satisfactory gain for light between wavelengths of 100 nm and 900 nm. Therefore, it is capable of amplifying light of various wavelength components, from infrared to blue light, transmitted by the RGB filter 33.” [0041]. See Figs. 3-4 and 6).
Regarding Claim 7, the combination of Takeyama, Toida and Biel teach the claim limitations as noted above.
Takeyama further teaches: wherein the processor is configured to generate the second fluorescence change information, based on the change in the signal waveforms due to an increase in an irradiation time of the therapeutic light in the second wavelength band of the signal waveforms of the fluorescence emitted from the fluorescent substance of the drug (“FIG. 3 shows the fluorescence spectrum of HpD in different locations when excitation light is irradiated onto a body containing cancer cells, into which HpD has been injected. As shown in this diagram, since the cancer cells (tumour) accumulate the HpD selectively, fluorescence having peaks at wavelengths 630 nm and 690 nm as characteristic of HpD is generated. However, in the peripheral region of the cancer cells, where the amount of HpD absorbed in low, the HpD fluorescence generated is of lower intensity than in the cancer cells. Since normal cells hardly accumulate HpD, there is virtually no HpD fluorescence. PDD is a diagnosis method which uses the characteristics of the HpD accumulated selectively in the cancer cells in this way to diagnose cancers by detecting fluorescence of the characteristic wavelength of HpD.” [0035]; “The RGB filter is constituted by filters which respectively transmit light of the three basic colors, red (R), green (G) and blue (B). FIG. 4 is a diagram showing the relationship between the wavelength of the light incident on the RGB filter and the transmissivity thereof; and it depicts respective wavelength transmission characteristics for the three filters, red, green and blue. The solid line indicate the wavelength transmission characteristics of the RGB filter when used in a standard CCD camera. IL can be seen that the transmissivity increases as the wavelength shortens, from red, through green to blue. These wavelength transmission characteristics are set in order to obtain an image which corresponds to the visual receptivity of humans, in such a manner that the colors of the obtained images correspond to the colors of the images as actually seen by the human eye. The single-dotted line indicates the wavelength transmission characteristics of an RGB filter 33 having raised transmissivity of components in the longer wavelength, red region…” [0038]; “The light amplifying tube 35…has extended sensitivity into the longer wavelength, infrared region, and as shown in the diagram, it has satisfactory gain for light between wavelengths of 100 nm and 900 nm. Therefore, it is capable of amplifying light of various wavelength components, from infrared to blue light, transmitted by the RGB filter 33.” [0041]. See Figs. 3-4 and 6).
Regarding Claim 8, the combination of Takeyama, Toida and Biel teach the claim limitations as noted above.
Takeyama does not teach: wherein the processor is configured to calculate the treatment progress index based on calculating a ratio of the first fluorescence change information to the second fluorescence change information.
Toida in the field of fluorescent endoscopy systems teaches: “…As a result, the monitor 14 displays three images: a color normal light image, a red fluorescent light image, and a red treatment light image. Thus, by displaying not only the normal light image and the treatment light image but also the fluorescence light image on the monitor 14, the progress of the PDT treatment can be confirmed by the change in the concentration of the photosensitive substance. Each image is shifted in time by one frame. However, by shortening the frame acquisition period, each image can appear to be captured at the same time. For example, the acquisition period of 3 frames is preferably 33 msec.”
Therefore, it would be obvious to one of ordinary skill in the art before the effective filing date of the invention to modify the change information generation unit in Takeyama to calculate the treatment progress index as taught in Toida for the intended purpose of treatment progress (Toida).
Regarding Claim 9, the combination of Takeyama, Toida and Biel teach the claim limitations as noted above.
Takeyama further teaches: wherein the spectrometer is configured to detect each of a signal waveform of light in the first wavelength band and a signal waveform of light in the second wavelength band from the fluorescence emitted from the fluorescent substance by sequentially scanning a fluorescence emitted from the fluorescent substance of the drug for each corresponding predetermined wavelength band, and wherein the processor is configured to acquire the signal waveform of light in the second wavelength band detected by the spectrometer as the second signal information by sequentially scanning a fluorescence corresponding to each predetermined wavelength band, and generate the second fluorescence change information based on the acquired signal waveform of the light in the second wavelength band (“FIG. 3 shows the fluorescence spectrum of HpD in different locations when excitation light is irradiated onto a body containing cancer cells, into which HpD has been injected. As shown in this diagram, since the cancer cells (tumour) accumulate the HpD selectively, fluorescence having peaks at wavelengths 630 nm and 690 nm as characteristic of HpD is generated. However, in the peripheral region of the cancer cells, where the amount of HpD absorbed in low, the HpD fluorescence generated is of lower intensity than in the cancer cells. Since normal cells hardly accumulate HpD, there is virtually no HpD fluorescence. PDD is a diagnosis method which uses the characteristics of the HpD accumulated selectively in the cancer cells in this way to diagnose cancers by detecting fluorescence of the characteristic wavelength of HpD.” [0035]; “The RGB filter is constituted by filters which respectively transmit light of the three basic colors, red (R), green (G) and blue (B). FIG. 4 is a diagram showing the relationship between the wavelength of the light incident on the RGB filter and the transmissivity thereof; and it depicts respective wavelength transmission characteristics for the three filters, red, green and blue. The solid line indicate the wavelength transmission characteristics of the RGB filter when used in a standard CCD camera. IL can be seen that the transmissivity increases as the wavelength shortens, from red, through green to blue. These wavelength transmission characteristics are set in order to obtain an image which corresponds to the visual receptivity of humans, in such a manner that the colors of the obtained images correspond to the colors of the images as actually seen by the human eye. The single-dotted line indicates the wavelength transmission characteristics of an RGB filter 33 having raised transmissivity of components in the longer wavelength, red region…” [0038]; “The light amplifying tube 35…has extended sensitivity into the longer wavelength, infrared region, and as shown in the diagram, it has satisfactory gain for light between wavelengths of 100 nm and 900 nm. Therefore, it is capable of amplifying light of various wavelength components, from infrared to blue light, transmitted by the RGB filter 33.” [0041]. See Figs. 3-4 and 6).
Regarding Claim 10, the combination of Takeyama, Toida and Biel teach the claim limitations as noted above.
Takeyama further teaches: further comprising: an imaging sensor configured to image a distribution of the fluorescence emitted from the fluorescent substance of the drug excited by the therapeutic light, based on light in a wavelength band that includes the first wavelength band and the second wavelength band(“ A conventional weak light color imaging device is either a cold CCD color camera, or an astronomical 3 CCD color camera, or the like…” [0008]; “…a light amplifying tube 35 for amplifying the light transmitted by the RGB filter 33, and a CCD camera 37 for capturing images of light amplified by the light amplifying tube 35, by means of a relay lens 36.” [0036]; “The CCU 41 controls the RGB frame memory 42 and the scan converter 44 in the RGB control unit 4. The RGB frame memory 42 is controlled in such a manner that it reads out the respective image signals of the extended red (red including infrared), red, green, and blue wavelength components captured in time series by the CCD camera 37, in synchronism with a CCD charge read-out signal sent by the CCU 41, and it stores the respective image signals thus read out in respective corresponding video frame memories (VFM).” [0044]. See Fig. 1.),
with regards to limitation: wherein the display is configured to display at least one of the treatment progress index which is an index of the progress of the treatment based on the first fluorescence change information and the second fluorescence change information and a fluorescence distribution image showing the distribution of the fluorescence imaged by the image sensor, Takeyama further teaches: “The operator controls the endoscope 11 appropriately so as to find the subject A by means of the images displayed on the monitor 27. When the subject is discovered, the endoscope 11 makes a one-touch connection with the connection section for the endoscope 11 on the camera box 3. Thereby, the endoscope 11 faces the subject A, and the weak light from the subject A it is facing is guided by the image guide (not illustrated) of the endoscope 11 to the camera box 3. Thereafter, the subject A is observed by means of the weak light color imaging device” [0032]; “…both the image of the peripheral region of the subject A and the fluorescence of the HpD are readily discernable by the observer on the monitor 27 displaying the captured images, and therefore he or she can perform PDD easily. After establishing the location of cancer cells by means of PDD, the excitation light source 22 can be changed for a treatment light source 23, whereby PDT can be performed at that location.” [0058].
Takeyama does not explicitly teach the display providing progress notification.
Toida in the field of fluorescent endoscopy systems teaches: “…the monitor 14 displays three images: a color normal light image, a red fluorescent light image, and a red treatment light image. Thus, by displaying not only the normal light image and the treatment light image but also the fluorescence light image on the monitor 14, the progress of the PDT treatment can be confirmed by the change in the concentration of the photosensitive substance. Each image is shifted in time by one frame.”
Therefore, it would be obvious to one of ordinary skill in the art before the effective filing date of the invention to modify the display in Takeyama to provide progress notification as taught in Toida for the intended purpose of progress notification of treatment confirmation (Toida).
Regarding Claim 12, Takeyama teaches: A treatment support device (Fig. 1, weak light color imaging device, [0031]) comprising:
a spectrometer configured to detect fluorescence emitted from a fluorescent substance excited by a therapeutic light, wherein the therapeutic light is irradiated in a specific wavelength band onto a drug that contains the fluorescent substance and has been administered to a cancer patient to kill cancer cells by a photoimmunotherapy method (“…an excitation light source 22 (Hg--Xe lamp) for generating characteristic HpD fluorescence by irradiating excitation light, as used in photodynamic diagnosis (PDD), and a treatment light source 23 (excimer dye laser) for destroying cancer cells by irradiating treatment light, as using in photodynamic therapy (PDT).” [0033]; “FIG. 3 shows the fluorescence spectrum of HpD in different locations when excitation light is irradiated onto a body containing cancer cells, into which HpD has been injected… PDD is a diagnosis method which uses the characteristics of the HpD accumulated selectively in the cancer cells in this way to diagnose cancers by detecting fluorescence of the characteristic wavelength of HpD….excitation light is irradiated onto the subject A by an excitation light source 22, the fluorescence of the HpD is captured as images by the weak light color imaging device, and the observer is able to diagnose cancer cells in the peripheral region of the subject A, in other words, to perform PDD, by observing the fluorescence.” [0035]);
a processor configured to selectively acquire first signal information corresponding to light in a first wavelength band, the first wavelength band including a wavelength in a range of 750 nm to 790 nm from signal waveforms of the fluorescence emitted from the fluorescent substance detected by the spectrometer and generate first fluorescence change information on a change in fluorescence intensity in the first wavelength band, based on the acquired first signal information (“FIG. 3 shows the fluorescence spectrum of HpD in different locations when excitation light is irradiated onto a body containing cancer cells, into which HpD has been injected. As shown in this diagram, since the cancer cells (tumour) accumulate the HpD selectively, fluorescence having peaks at wavelengths 630 nm and 690 nm as characteristic of HpD is generated. However, in the peripheral region of the cancer cells, where the amount of HpD absorbed in low, the HpD fluorescence generated is of lower intensity than in the cancer cells. Since normal cells hardly accumulate HpD, there is virtually no HpD fluorescence. PDD is a diagnosis method which uses the characteristics of the HpD accumulated selectively in the cancer cells in this way to diagnose cancers by detecting fluorescence of the characteristic wavelength of HpD.” [0035]; “The RGB filter is constituted by filters which respectively transmit light of the three basic colors, red (R), green (G) and blue (B). FIG. 4 is a diagram showing the relationship between the wavelength of the light incident on the RGB filter and the transmissivity thereof; and it depicts respective wavelength transmission characteristics for the three filters, red, green and blue. The solid line indicate the wavelength transmission characteristics of the RGB filter when used in a standard CCD camera. IL can be seen that the transmissivity increases as the wavelength shortens, from red, through green to blue. These wavelength transmission characteristics are set in order to obtain an image which corresponds to the visual receptivity of humans, in such a manner that the colors of the obtained images correspond to the colors of the images as actually seen by the human eye. The single-dotted line indicates the wavelength transmission characteristics of an RGB filter 33 having raised transmissivity of components in the longer wavelength, red region…” [0038]; “The light amplifying tube 35…has extended sensitivity into the longer wavelength, infrared region, and as shown in the diagram, it has satisfactory gain for light between wavelengths of 100 nm and 900 nm. Therefore, it is capable of amplifying light of various wavelength components, from infrared to blue light, transmitted by the RGB filter 33.” [0041]. See Figs. 3-4 and 6);
and a display configured to display an indication of progress of a treatment based on the first fluorescence change information, Takeyama further teaches: “The operator controls the endoscope 11 appropriately so as to find the subject A by means of the images displayed on the monitor 27. When the subject is discovered, the endoscope 11 makes a one-touch connection with the connection section for the endoscope 11 on the camera box 3. Thereby, the endoscope 11 faces the subject A, and the weak light from the subject A it is facing is guided by the image guide (not illustrated) of the endoscope 11 to the camera box 3. Thereafter, the subject A is observed by means of the weak light color imaging device” [0032]; “…both the image of the peripheral region of the subject A and the fluorescence of the HpD are readily discernable by the observer on the monitor 27 displaying the captured images, and therefore he or she can perform PDD easily. After establishing the location of cancer cells by means of PDD, the excitation light source 22 can be changed for a treatment light source 23, whereby PDT can be performed at that location.” [0058].
Takeyama does not explicitly teach a dye being IRDye700 and the display providing an indication of progress.
Toida in the field of fluorescent endoscopy systems teaches: “…the monitor 14 displays three images: a color normal light image, a red fluorescent light image, and a red treatment light image. Thus, by displaying not only the normal light image and the treatment light image but also the fluorescence light image on the monitor 14, the progress of the PDT treatment can be confirmed by the change in the concentration of the photosensitive substance. Each image is shifted in time by one frame.”
Therefore, it would be obvious to one of ordinary skill in the art before the effective filing date of the invention to modify the display in Takeyama to provide progress notification as taught in Toida for the intended purpose of progress notification of treatment confirmation (Toida).
The combination of references does not teach the dye being IRDye700.
Biel in the field of photoimmunotherapy systems teaches: “…the wavelength for irradiation is 600 nm to 850 nm, such as 660 nm to 740 nm.” [0005];“…the phthalocyanine dye includes IRDye 700DX (IR700).” [0031]; “Patients with head and neck cancer patients treated with a single administration of cetuximab-IRDye 700DX conjugate followed by irradiation to induce photoimmunotherapy (PIT) were assessed for tumor response.” [1027]; “Cetuximab-IRDye 700DX (CTX700) conjugate used to produce all dual conjugates described below was prepared substantially as described in Example 1. Briefly, cetuximab was reacted with 4 molar equivalents of IRDye 700DX NHS ester for 2 hours at pH=8.5, in the dark, at room temperature in a using through Amicon® Ultra Centrifugal Filter Units…” [1233]; See Figs. 22 and 24.
Therefore, it would be obvious to one of ordinary skill in the art before the effective filing date of the invention to further modify the combination of references to modify the dye to be IRDye700 as taught in Biel for “…improved performance for imaging or detection.” (Biel, [0003]).
Regarding Claim 13, the combination of Takeyama and Toida teach the claim limitations as noted above.
Takeyama further teaches: wherein the processor is configured to selectively acquire first signal information corresponding to light in the first wavelength band including a wavelength of 770 nm (“FIG. 3 shows the fluorescence spectrum of HpD in different locations when excitation light is irradiated onto a body containing cancer cells, into which HpD has been injected. As shown in this diagram, since the cancer cells (tumour) accumulate the HpD selectively, fluorescence having peaks at wavelengths 630 nm and 690 nm as characteristic of HpD is generated. However, in the peripheral region of the cancer cells, where the amount of HpD absorbed in low, the HpD fluorescence generated is of lower intensity than in the cancer cells. Since normal cells hardly accumulate HpD, there is virtually no HpD fluorescence. PDD is a diagnosis method which uses the characteristics of the HpD accumulated selectively in the cancer cells in this way to diagnose cancers by detecting fluorescence of the characteristic wavelength of HpD.” [0035]; “The RGB filter is constituted by filters which respectively transmit light of the three basic colors, red (R), green (G) and blue (B). FIG. 4 is a diagram showing the relationship between the wavelength of the light incident on the RGB filter and the transmissivity thereof; and it depicts respective wavelength transmission characteristics for the three filters, red, green and blue. The solid line indicate the wavelength transmission characteristics of the RGB filter when used in a standard CCD camera. IL can be seen that the transmissivity increases as the wavelength shortens, from red, through green to blue. These wavelength transmission characteristics are set in order to obtain an image which corresponds to the visual receptivity of humans, in such a manner that the colors of the obtained images correspond to the colors of the images as actually seen by the human eye. The single-dotted line indicates the wavelength transmission characteristics of an RGB filter 33 having raised transmissivity of components in the longer wavelength, red region…” [0038]; “The light amplifying tube 35…has extended sensitivity into the longer wavelength, infrared region, and as shown in the diagram, it has satisfactory gain for light between wavelengths of 100 nm and 900 nm. Therefore, it is capable of amplifying light of various wavelength components, from infrared to blue light, transmitted by the RGB filter 33.” [0041]. See Figs. 3-4 and 6).
Response to Arguments
Applicant’s arguments regarding the pending amended claims are moot in view of the new grounds of rejections.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Bukesov et. al. U.S. 20210044079 teaches endoscopic laser systems for controlling laser energy delivered to a target based on spectroscopic feedback.
DaCosta et. al. U.S. 20200367818 teaches a system for tumor visualization and removal using multispectral fluorescence imaging.
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/AMAL ALY FARAG/Primary Examiner, Art Unit 3798
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