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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/04/2024. The submission is following the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 49, 50 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claims 49 and 50, the term “the locations” and “the first and second parts of the tissue sample” lack proper antecedent basis.
Claim Rejections - 35 USC § 103
5. 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, 4, 18, 23, 28, 33, 51 are rejected under 35 U.S.C. 103 as being unpatentable over Franjic et al., (US 2018/0180550 A1) in view of Freudiger et al., (US 2016/0178439 A1).
Regarding claim 1, Franjic et al., disclose a system for multimodal imaging of tissue samples comprising:
a white light imaging system (the probe PV 34, Fig.3, and paragraph [0073], “PV probe is a 2D PV probe, which is a bright field microscope with a camera”) configured to provide a white light image of a field of view of a tissue sample on the histology slide ([0055], probe PV (shown in FIG. 3) is configured to provide …a image of sample 18; and Fig. 9A, [0073], “the PV probe provides a 2D projection image of a 3D surface of a sample 122”, and [0111], “a snapshot of the sample is captured by the white light camera”);
a user interface ([0055], “a user can mark a set 39 of images of sample sections of interest…by using computer user interface techniques”, and Fig. 9A, [0092], “A user interacts with the computer 110 through a computer display 118, keyboard 112, mouse 116”) operable to receive user input specifying a region of interest (ROI) on the tissue sample (paragraph [0109], “the user selects the points for the Raman scan based on the image presented on the white light camera”);
a Raman spectroscopy system (140, Fig. 9A) comprising a light source (142) operable to generate an excitation beam (see Fig. 9A and [0094], “A coupled Raman probe 140 is used to excite sample 122 using a fiber coupled narrow line-width laser source 142”), and
a scanner (“the optical probe Pi contains an optical scanner”, [0052]) operable to scan the excitation beam over the ROI ([0052], “Another example is with scanning optical probes (such as OCT) where the optical probe Pi contains an optical scanner… where the position of optical scanner mirrors dictate the position of the excitation laser beam”; and/or paragraph [0116], “Once one point has been scanned, the system moves the sample to an the next selected point for Raman scanning”), and
a spectrometer (a spectrometer 144, Fig.9A) coupled to receive Raman scattered light resulting from interaction of the excitation beam and the tissue sample ([0094], “a spectrometer 144 collects and transfers the corresponding Raman signal”); the Raman spectroscopy system (140) configured to perform Raman spectroscopy on the ROI to obtain Raman spectra (Fig. 9, [0109], “the user selects the points for the Raman scan based on the image presented on the white light camera at step 1124”, paragraph [0116], “a Raman spectrum graph is acquired…for all the selected points”, showing Raman analysis is performed on the selected points ); and a display connected to display a Raman spectrogram and/or an image of the ROI acquired by the Raman spectroscopy system ([0105], “ the data can be reviewed by the user, and/or saved for export” and the [0055], the image of sample is shown on a computer display).
Although Franjic et al., disclose the tissue sample slide for histological analysis, [0057], and the multi-modal imaging system disclosed is for use in pathology labs [0119], Franjic et al., do not explicitly disclose the tissue slide as the histology-stained slide as claimed. Popp et al., disclose a system for multimodal imaging of a tissue sample comprising histology-stained slide (paragraph [0112], “Tissues can be…deposited on a cuvette or slide, dried, stained” for “the performance of histology, pathology, and/or morphological analysis”. Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Franjic et al., by incorporating the histology-stained slide, as taught by Freudiger et al., to provide higher optical imaging quality, and thus improving the overall information content of the multi-modal imaging process.
Regarding claim 4, Franjic et al., in view of Freudiger et al., as discussed in claim 1, Franjic et al., disclose the Raman spectroscopy system comprising a coherent anti-Stokes Raman scattering (CARS) system (paragraph [0082], “CARS” as a variant of the Raman probes used in the system) configured to generate a hyperspectral or multispectral Raman image of at least the ROI ([0085], “hyperspectral imaging (HSI)”, as a modality that combines imaging and spectroscopy to “generates a three-dimensional (3-D) dataset of spatial and spectral information”) and the spectrometer (144) is integrated with the CARS system ([0082], the Raman probe 140, which can be a CARS probe and [0094], the probe is coupled to 144).
Regarding claim 18, Franjic et al., in view of Freudiger et al., as discussed in claim 1, Franjic et al., disclose the Raman spectroscopy system (140, Fig. 9A of Franjic et al.) being arranged to receive the Raman scattered light ([0094], “A coupled Raman probe 140… collects and transfers the corresponding Raman signal to a spectrometer 144”) that is emitted in a backward direction on a side of the slide ([0090], “distal” refers to the end of the optical fiber closest to a sample” and [0094], A coupled Raman probe 140 is a fiber coupled, showing that the fiber Raman probe emits light and collects the backscattered light from the same tip) that is the same as a side of the slide (see Fig.9A, the probes and the sample are on the same side of the frame 152, and the light is collected by the probe head, see [0094], which is on the same side of the sample) on which the excitation beam is incident (see Fig.9A, [0094] and [0103], the Raman probe 140 uses the same fiber coupled probe tip for both excitation and collection on the same side of the sample). Franjic et al., do not explicitly disclose the tissue sample slide as the histology-stained slide as claimed. Freudiger et al., disclose a system for multimodal imaging of a tissue sample comprising histology-stained slide (paragraph [0112], “Tissues can be…deposited on a cuvette or slide, dried, stained” for “the performance of histology, pathology, and/or morphological analysis”. Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Franjic et al., by incorporating the histology-stained slide, as taught by Freudiger et al., to provide higher optical imaging quality, and thus improving the overall information content of the multi-modal imaging process.
Regarding claim 23, Franjic et al., in view of Freudiger et al., as discussed in claim 1,
Franjic et al., disclose a controller configured to obtain spectra from the spectrometer in coordination with operation of the scanner ([0116], “the system moves the sample to the next selected point for Raman scanning (step 1240). Thereafter, a Raman spectrum graph is acquired (step 1234)”) and to associate each of the spectra with a location within the ROI ([0063]-[0065], “The relative physical positions of feature 52 for recorded images can be easily measured”) wherein the controller comprises a data store containing process information ( [0078], “the sample information within the control software where that information will be linked to acquired data”) and the controller is configured to identify one or more components of the obtained spectra of the Raman scattered light based on the process information ([0103], “reviews the data, and based on the feedback may decide to terminate the session by unloading the sample; or to define and analyze new sampling regions of interest”). Franjic et al., do not disclose the chemical and/or stains as claimed. Freudiger et al., disclose the chemical and/or stains (paragraph [0112], “Tissues can be deposited on a cuvette or slide, dried, stained”) In combination, the controller would comprise a data store containing process information that characterizes Raman spectra of processing chemicals and/or stains and the controller would be configured to identify one or more components of the obtained spectra of the Raman scattered light that correspond to the processing chemicals and/or stains based on the process information as claimed. Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Franjic et al., by incorporating the histology-stained slide, as taught by Freudiger et al., to provide a better analysis the specific spot, and thus improving the overall information content of the multi-modal imaging process.
Regarding claim 33, Franjic et al., disclose a method for multimodal imaging of a tissue sample slide (Fig.9A) , the method comprising: imaging the slide with a white light imaging system (the probe PV 34, Fig.3, and paragraph [0073], “PV probe is a 2D PV probe, which is a bright field microscope with a camera”) to provide a white light image of a field of view of a tissue sample on the slide ([0055], probe PV (shown in FIG. 3) is configured to provide …an image of sample 18; and Fig. 9A, [0073], “the PV probe provides a 2D projection image of a 3D surface of a sample 122”, and [0111], “a snapshot of the sample is captured by the white light camera”); and displaying the white light image to a user ([0105], “ the data can be reviewed by the user, and/or saved for export” and the [0055], the image of sample is shown on a computer display);
receiving by a user interface user input specifying a region of interest (ROI) on the tissue sample ([0071], [0072] and [0109]“a user, she/he can indicate sample sections of interest Vs1′, Vs2′ via direct user input through a graphics user interface (GUI), voice input, or text input” based on the displayed image); based on the user input, operating a Raman spectroscopy system to obtain Raman spectra for a portion of the tissue sample corresponding to the ROI ([0109], “After the sample is placed under the white light camera, the user can select the point to do the Raman measurement and select the scan parameters for the points selected”, and paragraph [0116], “a Raman spectrum graph is acquired…for all the selected points”); and, displaying a Raman spectrogram and/or an image of the ROI acquired by the Raman spectroscopy system ([0094] and [0103], the system collects and transfers the corresponding Raman signal from a spectrometer and The user then reviews the data on the computer display).
Franjic et al., do not explicitly disclose the tissue slide as the histology-stained slide as claimed. Popp et al., disclose a system for multimodal imaging of a tissue sample comprising histology-stained slide (paragraph [0112], “Tissues can be…deposited on a cuvette or slide, dried, stained” for “the performance of histology, pathology, and/or morphological analysis”. Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Franjic et al., by incorporating the histology-stained slide, as taught by Freudiger et al., to provide higher optical imaging quality, and thus improving the overall information content of the multi-modal imaging process.
Regarding claims 28 and 51, Franjic et al., in view of Freudiger et al., as discussed in claims 1 and 33, Franjic et al., disclose the user interface (116, Fig.9A) comprising a pointing device ([0092], “mouse 116, and potentially by using any other computer interacting peripheral device available on the market.”) operable to specify the ROI ([0109], “the user selects the points for the Raman scan based on the image presented on the white light camera”) by drawing a boundary of the ROI on the white light image ([0055], “The image 38 of sample 18 is shown on a computer display 37 where a user can mark a set 39 of images”).
Claim 12, 41 are rejected under 35 U.S.C. 103 as being unpatentable over Franjic et al., in view of Freudiger et al., and in view of Bennett et al., (US 2004/0090621 A1).
Regarding claims 12 and 41, Franjic et al., in view of Freudiger et al., as discussed in claims 1 and 33, do not disclose the spectrometer being a virtual slit spectrometer and the scanner causes the Raman scattered light to be scanned back and forth along a virtual slit of the spectrometer as claimed. Bennett et al., disclose the spectrometer being a virtual slit spectrometer (paragraphs [0028] and [0029], “this analysis gives one-dimensional confocality in the vertical direction and acts as a “virtual slit”) and the scanner causes the Raman scattered light to be scanned back and forth ([0035], “This is achieved by the position of the slit being able to move horizontally, perpendicular to the optical path. This may be achieved by a motor 25 in FIG. 1. As the position of the slit changes, light scattered from different points on the sample become able to pass through the slit”) along a virtual slit of the spectrometer ([0040], “The slit on the spatial filter and the “virtual slit” of the CCD will move synchronously with the scanning laser beam”). Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Franjic et al., and Freudiger et al., by utilizing the teaching of Bennett et al., to make the measurement faster and clearer.
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Franjic et al., in view of Freudiger et al., and in view of Mahajan et al., (US 2023/0093989).
Regarding claim 24, Franjic et al., in view of Freudiger et al., as discussed in claim 23, do not disclose the controller being configured to remove the components of the obtained spectra of the Raman scattered light that correspond to the processing chemicals and/or stains as claimed. Mahajan et al., disclose a controller being configured to remove the components of the obtained spectra of the Raman scattered light ([0029], “the chemical and/or material specific information of the sample 300 may be determined based on the change in intensity” and [0033], “The elastic scattering component may be filtered out of the further scattered light 203…using a wavelength filter “) that correspond to the processing chemicals and/or stains ([0032], “the chemical and/or material specific information of the sample 300”). Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Franjic et al., and Freudiger et al., by utilizing the teaching of Mahajan et al., to provide the accuracy of tissue analysis performed by the system.
Claim 49 is rejected under 35 U.S.C. 103 as being unpatentable over Franjic et al., in view of Freudiger et al., and in view of Cohen et al., (US 2011/0313284 A1).
Regarding claim 49, Franjic et al., in view of Freudiger et al., as discussed in claim 33, although Franjic et al., disclose creating a mapping that indicates locations of corresponding features ([0063]-[0065], “The relative physical positions of feature 52 for recorded images can be easily measured”, wherein the mapping comprises a transformation comprising a rotation and/or a translation ([0053], “coordinate transformation equations”. Franjic et al., do not disclose features that are shown in both of the first and second parts of the tissue sample, as claimed. Cohen et al., disclose creating a mapping that indicates the locations of corresponding features that are shown in both of the first and second parts of the tissue sample ([0094], the registration module 300 processes relative positions to produce a mapped output of tissue), wherein the mapping comprises a transformation comprising a rotation and/or a translation ([0099], “a point can be “transformed” to corresponding point “) which takes a point on the first part of the tissue sample to a corresponding point on the second part of the tissue sample ([0091] and [0099], maps from a target (tissue) to an inner surface, the cavity or remaining tissue). Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Franjic et al., and Freudiger et al., by utilizing the teaching of Cohen et al., to improve spatial accuracy of tissue localization.
Claim 50 is rejected under 35 U.S.C. 103 as being unpatentable over Franjic et al., in view of Freudiger et al., and in view of Filkins et al., (US 2010/0301230 A1).
Regarding claim 50, Franjic et al., in view of Freudiger et al., as discussed in claim 33, Franjic et al., disclose a coordinate mapping system using white light images to select ROIs and transform points ([0067], [0109]), and creating a mapping that indicates the locations of corresponding features ([0063]-[0065], “The relative physical positions of feature 52 for recorded images can be easily measured”. However, Franjic et al., do not disclose the feaures that are shown in both of the first and second parts of the tissue sample , wherein creating the mapping comprises processing low magnification white light images as claimed. Filkins et al., disclose creating a mapping comprising a features that are shown in both of the first and second parts of the tissue sample ([0035], “a stage 15 to hold a tissue sample 17 mounted on a solid support” and [0033], “scan imaging of a TMA 30 starting from the test well on the bottom left 32 and moving back and forth across the rows”), and
creating the mapping comprises processing low magnification white light images (“different magnifications ”, [0035]) of the first and second parts of the tissue sample to locate coordinate pairs that indicate positions of structures present in both of the first and second parts of the tissue sample( [0034], “categorizes the images and generates one or more match filters based on a correlation factor”). Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Franjic et al., and Freudiger et al., by utilizing the teaching of Filkins et al., to reduce the scan time and getting better improvement in efficiency.
Claim 52 is rejected under 35 U.S.C. 103 as being unpatentable over Franjic et al., in view of Freudiger et al., and in view of Popp et al., (US 2021/0223183 A1).
Regarding claim 52, Franjic et al., in view of Freudiger et al., as discussed in claim 33, Franjic et al., disclose without removing the histology stained slide from an apparatus ([0091], “A sample 122 is placed on a sample holder 120 which is attached to a motorized positioning”, showing the sample is not removed from the apparatus during the multimodal imaging) comprising the white light imaging system ( [0073], bright field microscope with a camera) and the Raman spectroscopy system (140), imaging the tissue sample using one or more additional imaging modality ([0078], “any type of bio-imaging probe and any possible mode of operation of such a probe known to a person skilled in the art may be used”), the additional imaging modality selected from the group consisting of: reflectance confocal imaging ([0093], “example of the PB probes... include confocal microscopy probes”); and second harmonic generation imaging ([0088], “second-harmonic generation (SHG)”. Franjic et al., do not disclose the additional imaging modality selected from the group consisting of two-photon fluorescence imaging as claimed. Popp et al., disclose the additional imaging modality selected from the group consisting of two-photon fluorescence imaging ([0078], “two-photon excitation fluorescence (TPEF), second harmonic generation (SHG) or another freely selectable optical effect.”). Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Franjic et al., and Freudiger et al., by utilizing the teaching of Popp et al., to provide more accuracy in sample evaluation.
Allowable Subject Matter
6. Claims 14, 16, 17, 19, 21, 26,27, are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Regarding claim 14, the prior art fails to disclose the Raman spectroscopy system being arranged to receive the Raman scattered light that is emitted in a forward direction on a side of the histology-stained slide opposite to a side of the histology stained slide on which the excitation beam is incident.
Claims 16, 17 depend on claim 14.
Regarding claim 19, the prior art fails to disclose the Raman scattered light being guided to pass through the scanner and to be descanned by the scanner.
Regarding claim 21, the prior art fails to disclose the system being configured to collect: a forward component of the Raman scattered light that is emitted in a forward direction on a side of the histology stained slide opposite to a side of the histology stained slide on which the excitation beam is incident, and a backward component of the Raman scattered light that is emitted on a side of the histology stained slide that is the same as a side of the histology stained slide on which the excitation beam is incident, to combine the forward and backward components of the Raman scattered light and to direct the combined forward and backward components of the Raman scattered light into the spectrometer and the system comprises an optical reflector arranged to redirect one of the forward and backward components of the Raman scattered light to pass though the histology stained slide before reaching the spectrometer.
Regarding claim 26, the prior art fails to disclose a controller configured to obtain spectra from the spectrometer in coordination with operation of the scanner and to associate each of the spectra with a location within the ROI, wherein the tissue sample comprises a first part and a second part, the first part of the tissue sample being on the histology stained slide and the second part of the tissue sample being on a second slide wherein the white light imaging system is configured to image the first part of the tissue sample on the histology stained slide, the Raman spectroscopy system is configured to obtain the Raman spectrogram and/or image from the second part of the tissue sample and the controller is configured to create a mapping that indicates the locations of corresponding features that are shown in both of the first and second parts of the tissue sample and the mapping comprises a transformation comprising a rotation and/or a translation which takes a point on the first part of the tissue sample to a corresponding point on the second part of the tissue sample.
Regarding claim 27, the prior art fails to disclose a controller configured to obtain spectra from the spectrometer in coordination with operation of the scanner and to associate each of the spectra with a location within the ROI, wherein the tissue sample comprises a first part and a second part, the first part of the tissue sample being on the histology stained slide and the second part of the tissue sample being on a second slide wherein the white light imaging system is configured to image the first part of the tissue sample on the histology stained slide, the Raman spectroscopy system is configured to obtain the Raman spectrogram and/or image from the second part of the tissue sample, the controller is configured to create a mapping that indicates the locations of corresponding features that are shown in both of the first and second parts of the tissue sample and the controller is configured to generate the mapping by processing low magnification white light images of the first and second parts of the tissue sample to locate coordinate pairs that indicate positions of structures present in both of the first and second parts of the tissue sample.
Conclusion
7. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAI THI NGOC TRAN whose telephone number is (571)272- 3456. The examiner can normally be reached Monday-Friday: 9:00-5:30pm.
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/M.T.T./Examiner, Art Unit 2878
/GEORGIA Y EPPS/Supervisory Patent Examiner, Art Unit 2878