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 02/25/2022 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been 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 4, 8, and 12 is 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.
Claim 4 recites the claim limitation “wherein the first irradiation unit includes a scanning unit configured to scan the cells with the light”, in lines 5-6 of the claim. It is unclear and therefore indefinite which “light” is considered “the light”, because claim 4 now recites 2 forms of light: the illumination light, that is explicitly claimed in claim 3, or the irradiation light that is claimed in claim 1, from which claim 4 depends . The examiner assumes that the first light detector emits the irradiation light that creates the photoacoustic effect in the cells.
Claims 8, 12 are rejected because they inherit deficiencies by nature of its/their dependency on claim 4.
Claim Rejections - 35 USC § 103
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1, 2, 15-18, and 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over US20190142277 to Tokita et al. “Tokita”, in view of Non-Patent Literature (NPL): “In vivo Ultrasound and Photoacoustic Monitoring of Mesenchymal Stem Cells Labeled with Gold Nanotracers” to Nam et al. “Nam”, and further in view of NPL: “Development of a stem cell tracking platform for ophthalmic applications using ultrasound and photoacoustic imaging” to Kubelick et al. “Kubelick”.
Regarding claim 1 and 20, Tokita (et al.) teaches a device (Fig. 1, photoacoustic measurement apparatus) and method (Paragraph 0009) for evaluating melanin (Paragraph 0031) in a mole or nevus on the surface of an object (Paragraph 0060), which would read on pigment-containing cells (i.e. melanin containing tissue cells), the device comprising:
a first irradiation unit (Fig. 2, 3b, light source, with fiber optic cable 3c; Paragraph 0067) configured to irradiate cells (tissue cells of the mole or nevus) with light
a first detection unit (acoustic wave probe 1, Fig. 2; Paragraph 0069) configured to detect photo-acoustic waves (Paragraph 0069, photoacoustic wave generated at the focal position can be detected), and
a processor (processing unit 2, Paragraph 0052, Fig. 1)
wherein the processor is configured to output an evaluation result relevant to the pigment-containing cells, based on intensity of the photo-acoustic waves detected by the first detection unit (Paragraph 0051, The processing unit 2 includes a unit that amplifies an electric signal acquired by the acoustic wave probe 1 and converts the electric signal into a digital signal, and a unit that acquires object information such as a light absorption coefficient and oxygen saturation inside the object (generating unit) based on the converted digital signal (photoacoustic signal; wherein what is also calculated can be a melanin concentration, Paragraph 0031).
However, Tokita does not disclose the device is used for evaluating the progression of differentiation of stem cells, wherein the method comprises the cells are in vessels, and wherein the photoacoustic signals are generated from cells irradiated with light.
Nam teaches evaluating progression of differentiation of mesenchymal stem cells (MSCs) using photoacoustic imaging. Nam teaches a longitudinal in vitro and in vivo photoacoustic imaging of mesenchymal stem cells (Pages 5-6). Nam teaches acquiring the photoacoustic image and spectra at 750 nm. The samples were Au NT (gold Nanotracers) labeled MSCs in PEGylated fibrin gels. The in vitro photoacoustic study was performed over a one week period in a 24 well plate (Page 5, MSCs were cultured in the PEGylated fibrin gels in the 24 well plate over the 1 week period, with photoacoustic performed at day 1, 4, and 7, during the culturing, which reads on performing photoacoustic of the sample in a vessel, and hence irradiating the cells in a vessel). For the in-vivo study, the Au NT loaded MSCs in PEGylated fibrin gel were injected into the LGAS of the Lewis rat to study differentiation (Page 6, “Longitudinal in vivo monitoring…” Section), with samples taken at days 3, 7, and 10. As discussed in Fig. 1, the PEGylated fibrin gels promote MSC differentiation toward a vascular cell type, thus contributing to regeneration, and both MSC distribution and neovascularization can be monitored using a multimodality approach that includes photoacoustic imaging. As seen in Fig. 6, the photoacoustic signal amplitudes and the images from the three days of measurements, in vivo, showed the uptake, indicated by the decrease of Au NT MSCs, and therefore the differentiation of MSCs into vascular cell type. This reads on the evaluation of the differentiation of the stem cells based on the photoacoustic intensities and images obtained.
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the Tokita’s invention, wherein the device and method of Tokita are used to evaluate the progression of differentiation of stem cells, wherein the method comprises the cells are in vessels, and wherein the photoacoustic signals are generated from cells irradiated with light, as taught by Nam, in order to noninvasively understand the role of delivered stem cells in stem cell therapeutics, by being able to longitudinally assess the stem cell behaviors with sufficient spatial resolution and penetration depth. (Nam, Abstract)
However, the modifications of Tokita and Nam do not disclose the differentiation is from pluripotent stem cells to pigment-containing cells, wherein the cells are irradiated in a melanin absorption wavelength band, wherein the results are relevant to the progression of the differentiation of the cells to the pigment-containing cells.
Kubelick teaches a multimodality approach to stem cell tracking in ophthalmic applications (Title). Kubelick teaches that induced pluripotent stem cells and MSCs have been found to renormalize intraocular pressure and restore the trabecular meshwork (TM) (Page 3812, bottom of right column to Page 3813, top of left column). Therefore Kubelick teaches a method of tracking stem cells in the anterior segment of the eye (Page 3812, right column, “In this work…”). Kubelick uses a very similar method as Nam (described above) of using gold nanospheres (AuNSs) to label MSCs. Samples of the AuNS-MSCs were prepared in a tissue-mimicking gelatin phantom for photoacoustic imaging was performed at 700 nm (bottom of Page 3814, to the top of Page 3815). Kubelick also injected the AuNS-MSCs into a porcine eye for ex vivo photoacoustic imaging (Page 3815, left column) at 680 nm. The ex-vivo imaging was performed fully submerged in a vessel (See Page3815, left column, and Supplemental S1) . The wavelengths for all the photoacoustic studies were chosen because melanin is the predominant endogenous absorber in the anterior eye (Page 3816, left column), and as seen in the ex-vivo photoacoustic images in Fig. 3, the photoacoustic signals for the AuNS-MSCs slowly disappears, with only melanin photoacoustic signals remaining at the end of the time series. This shows that AuNS-MSCs and melanin, and the transition from one signal to the other can be observed. Additionally, Kubelick also teaches evaluation of the photoacoustic signal to determine cell concentrations (Page 3821, bottom of left column to top of right column).
Therefore, It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the apparatus and method of Tokita and Nam, wherein the differentiation is from pluripotent stem cells to pigment-containing cells, wherein the cells are irradiated in a melanin absorption wavelength band, wherein the results are relevant to the progression of the differentiation of the cells to the pigment-containing cells, as taught by Kubelick, since Kubelick teaches that MSCs behave similarly to pluripotent stem cells in the eye, and from the preliminary data of Kubelick that uses similar sample preparation techniques as Nam, that a longitudinal study for stem cell uptake into melanin containing tissue, and therefore cells, was possible, it would be obvious that investigating the differentiation of pluripotent cells into melanin (pigment) containing cells would be similarly viable to perform.
Regarding claim 2, the modifications of Tokita, Nam, and Kubelick disclose all the features of claim 1 above.
Tokita teaches wherein the first irradiation unit includes a scanning unit (See Fig. 2, scanning stage 9a) configured to scan the cells with the light (the probe 101 is constructed to be movable by the scanning stage 9a, thereby measurement can be performed while moving the light irradiation position on the object, Paragraph 0072), wherein the processor is configured to output a photo-acoustic image based on the intensity of the photo-acoustic waves detected by the first detection unit and an irradiation position of the light when detecting the photo-acoustic waves with the intensity (displays information acquired by the processing unit 2, Paragraph 0058; such as a two dimensional image from the photoacoustic signal, Paragraph 0063).
Regarding claim 15, the modifications of Tokita, Nam, and Kubelick disclose all the features of claim 1 above.
As disclosed in the claim 1 rejection above, Kubelick teaches the center wavelength of light for the in vitro experiments was 700 nm (bottom of Page 3814, to the top of Page 3815), and 680 for the ex-vivo experiment (Page 3815, left column).
Regarding claim 16, the modifications of Tokita, Nam, and Kubelick disclose all the features of claim 1 above.
As disclosed in the claim 1 rejection above, Tokita teaches wherein the evaluation result includes information relevant to an amount of melanin to be contained in the cells, which is estimated on the basis of the intensity of the photo-acoustic waves (melanin concentration, Paragraph 0031).
Regarding claim 17, the modifications of Tokita, Nam, and Kubelick disclose all the features of claim 1 above.
As disclosed in the claim 1 rejection above, Nam teaches the culture vessel as being a well plate (Page 5, MSCs were cultured in the PEGylated fibrin gels in the 24 well plate over the 1 week period, with photoacoustic performed at day 1, 4, and 7, during the culturing, which reads on performing photoacoustic of the sample in a vessel, and hence irradiating the cells in a vessel).
Regarding claim 18, the modifications of Tokita, Nam, and Kubelick disclose all the features of claim 1 above.
Tokita teaches where the cells are moles or nevus with melanin (Paragraph 0031, Paragraph 0060). A nevus is a cluster of melanocytes.
Claim(s) 3, 4, 11, and 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tokita, in view of Nam, and further in view of Kubelick, as applied to claim 1 above, and further in view of US20150247999 to Ntziachristos et al. “Ntziachristos”.
Regarding claim 3, the modifications of Tokita, Nam, and Kubelick disclose all the features of claim 1 above.
Tokita teaches a second detection unit configured to detect observation light from the cells irradiated with the illumination light (Fig. 2, camera 8a, Paragraph 0075).
However, Tokita does not disclose a second irradiation unit to irradiate the illumination light.
Ntziachristos teaches a second irradiation unit to irradiate the illumination light (Paragraph 0091, Fig. 2d, the arrangement of the scanning light 3 with the wide field illumination light 2s). Further Ntziachristos also teaches a optical light source for the illumination light configured to detect fluorescence (Paragraph 0045). Ntziachristos teaches superimposing optical image with the optoacoustic (i.e. photoacoustic) image, especially with fluorescence images (Paragraph 0016).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the combination of Tokita, Nam, and Kubelick, wherein the illumination light is from a second irradiation unit, as taught by Ntziachristos, in order to allow collecting of opto-acoustic [i.e. photoacoustic] with optical signals in parallel (Paragraph 0092). Further, It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the combination, wherein the optical camera is configured to detect fluorescence, and superimposing the fluorescence optical image with the optoacoustic image, in order to be able to take advantage of fluorescent tags that can stain functional and molecular processes (Paragraph 0002). Further, adding fluorescent capabilities to optical detectors only requires adding a filter (Paragraph 0085). Superimposing the optical image with the optoacoustic image allows combining the contrast unique to each imaging modality, such as fluorescence’s high resolution with optoacoustics depth scaling (Paragraphs 00015 and 0018).
Regarding claim 4, the modifications of Tokita, Nam, and Kubelick disclose all the features of claim 1 above.
Tokita discloses a second detection unit configured to detect observation light from the cells irradiated with the illumination light (Fig. 2, camera 8a, Paragraph 0075), wherein the first irradiation unit includes a scanning unit configured to scan the cells with the light, and (the probe 101 is constructed to be movable by the scanning stage 9a, thereby measurement can be performed while moving the light irradiation position on the object, Paragraph 0072).
However, Tokita does not disclose the evaluation result includes differentiation rate information relevant to a rate of differentiated cells in the vessel to the total cells in the vessel,. which is calculated on the basis of the intensity of the photo-acoustic waves detected by the first detection unit, an irradiation position of the light when detecting the photo-acoustic waves with the intensity, and a cell image based on the observation light detected by the second detection unit.
Kubelick teaches wherein the evaluation result includes differentiation rate information relevant to a rate of differentiated cells in the vessel to the total cells in the vessel, which is calculated on the basis of the intensity of the photo-acoustic waves detected by the first detection unit, an irradiation position of the light when detecting the photo-acoustic waves with the intensity, and a cell image based on the observation light detected by the second detection unit (Kubelick, see Fig. 2, Photoacoustic signal vs. Cell Nuclei Count. Plot, with known total cell numbers, Page 3818, right column, with photoacoustic images over the time series for differentiation, Fig. 3, wherein the photoacoustic signal intensity and location, can be extracted per pixel of the photoacoustic image, would read on the relevant rate information, since cell count over time can be extracted from the plot in Fig. 2, per time point per pixel position, and when taken for each of the time points, would determine a rate of differentiation as a function of cell count).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the combination of Tokita, Nam, and Kubelick, wherein the evaluation result includes differentiation rate information relevant to a rate of differentiated cells in the vessel to the total cells in the vessel, which is calculated on the basis of the intensity of the photo-acoustic waves detected by the first detection unit, an irradiation position of the light when detecting the photo-acoustic waves with the intensity, and a cell image based on the observation light detected by the second detection unit, in order to be able to be able to track the stem cells longitudinally (i.e. track them over time) (Page 3821, right column).
However, Tokita does not disclose a second irradiation unit to irradiate the illumination light.
Ntziachristos teaches a second irradiation unit to irradiate the illumination light (Paragraph 0091, Fig. 2d, the arrangement of the scanning light 3 with the wide field illumination light 2s).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the combination of Tokita, Nam, and Kubelick, wherein the illumination light is from a second irradiation unit, as taught by Ntziachristos, in order to allow collecting of opto-acoustic [i.e. photoacoustic] with optical signals in parallel (Paragraph 0092).
Regarding claim 11, the modifications of Tokita, Nam, Kubelick, and Ntziachristos disclose all the features of claim 3 above.
Tokita discloses an objective lens with the camera 8a that reads on the second detector (See Fig. 2, lens in front of camera 8a with a horizontal optical axis). Additionally, as disclosed in the claim 3 rejection, Ntziachristos teaches the second irradiation unit as Fig. 2D, Ref. 2’s which point substantially down in the nearly the same direction as the scanning light (light source for photoacoustic). Therefore based on what has already been taught in claim 3, the second irradiation unit would intersect with the optical axis of the objective lens).
Regarding claim 12, the modifications of Tokita, Nam, Kubelick, and Ntziachristos disclose all the features of claim 4 above.
Tokita discloses an objective lens with the camera 8a that reads on the second detector (See Fig. 2, lens in front of camera 8a with a horizontal optical axis). Additionally, as disclosed in the claim 3 rejection, Ntziachristos teaches the second irradiation unit as Fig. 2D, Ref. 2’s which point substantially down in the nearly the same direction as the scanning light (light source for photoacoustic). Therefore based on what has already been taught in claim 3, the second irradiation unit would intersect with the optical axis of the objective lens).
Claim(s) 5, 6, 13, and 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tokita, in view of Nam, and further in view of Kubelick, as applied to claim 1 above, and further in view of Ntziachristos , and further in view of US 2020/0239827 to Sasaki et al. “Sasaki”.
Regarding claim 5, the modifications of Tokita, Nam, and Kubelick disclose all the features of claim 1 above.
Tokita discloses a second detection unit configured to detect observation light from the cells irradiated with the illumination light (Fig. 2, camera 8a, Paragraph 0075), wherein the first irradiation unit includes a scanning unit configured to scan the cells with the light, and (the probe 101 is constructed to be movable by the scanning stage 9a, thereby measurement can be performed while moving the light irradiation position on the object, Paragraph 0072).
However, Tokita does not disclose a second irradiation unit to irradiate the illumination light.
Ntziachristos teaches a second irradiation unit to irradiate the illumination light (Paragraph 0091, Fig. 2d, the arrangement of the scanning light 3 with the wide field illumination light 2s).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the combination of Tokita, Nam, and Kubelick, wherein the illumination light is from a second irradiation unit, as taught by Ntziachristos, in order to allow collecting of opto-acoustic [i.e. photoacoustic] with optical signals in parallel (Paragraph 0092).
However, the modifications of Tokita, Nam, Kubelick, and Ntziachristos do not explicitly disclose the evaluation result includes progression degree information relevant to a differentiation progression degree of each of the cells which is calculated on the basis of the intensity of the photo-acoustic waves detected by the first detection unit, an irradiation position of the light when detecting the photo-acoustic waves with the intensity, and a cell image based on the observation light detected by the second detection unit.
Sasaki teaches in a similar field of endeavor of a erythrocyte culture monitoring device (Abstract), wherein the erythrocytes are produced from ES cells (Fig. 7, starting point of the flow chart, wherein ES cells = embryonic stem cells, Paragraph 0003). Sasaki teaches irradiating a monochromatic light onto the culture solution W in the culture container 11, a photodetector detects the amount of monochromatic light transmitted through the culture solution (Paragraph 0027). Sasaki further teaches monitoring the differentiation of the erythrocytes from the ES cells from the irradiation of the monochromatic light (Paragraph 0044), and the controller 7 evaluates the degree of increase based on temporal change in the amount of transmitted light detected by the photodetector (Paragraph 0045). Sasaki also discloses that by using an imaging optical system, a culture-solution image can be obtained (Paragraph 0093), wherein based on a change in the image acquired by the imaging optical system, it is possible to detect the state/progression of the cells (Paragraph 0095).
Therefore, It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the combination of Tokita, Nam, Kubelick, and Ntziachristos, wherein the evaluation result includes progression degree information relevant to a differentiation progression degree of each of the cells which is calculated on the basis of the intensity of the photo-acoustic waves detected by the first detection unit, an irradiation position of the light when detecting the photo-acoustic waves with the intensity, and a cell image based on the observation light detected by the second detection unit, since the method of Tokita, Nam, Kubelick, and Ntziachristos are all techniques based on light irradiation, and as disclosed in the claim 1 rejection, Kubelick teaches a decreasing result (decreasing photoacoustic intensity) as the stem cell differentiates (and is up taken by the melanin rich tissue). Therefore, based on the teachings of Sasaki (See Paragraph 0100-0102 of Sasaki), the amount of the end product (in the instant case melanin containing cells) can be imaged temporally (resulting in a “melanin” image) and compared with the photoacoustic image of the stem cells to determine the degree of progression of each stem cell in the image.
Regarding claim 6, the modifications of Tokita, Nam, Kubelick, Ntziachristos, and Sasaki disclose all the features of claim 5 above.
As disclosed in the claim 5 rejection above, comparison of the “melanin” image with the photoacoustic image of the stem cell would read on the on the claimed image. The 2D points of the photoacoustic image would show the stem cells an there position in the region of interest, while the “melanin” image would show accumulation of the differentiation of the stem cells into melanin containing cells.
Regarding claims 13, the modifications of Tokita, Nam, Kubelick, Ntziachristos, and Sasaki disclose all the features of claim 5 above.
Tokita discloses an objective lens with the camera 8a that reads on the second detector (See Fig. 2, lens in front of camera 8a with a horizontal optical axis). Additionally, as disclosed in the claim 3 rejection, Ntziachristos teaches the second irradiation unit as Fig. 2D, Ref. 2’s which point substantially down in the nearly the same direction as the scanning light (light source for photoacoustic). Therefore based on what has already been taught in claim 3, the second irradiation unit would intersect with the optical axis of the objective lens).
Regarding claims 14, the modifications of Tokita, Nam, Kubelick, Ntziachristos, and Sasaki disclose all the features of claim 6 above.
Tokita discloses an objective lens with the camera 8a that reads on the second detector (See Fig. 2, lens in front of camera 8a with a horizontal optical axis). Additionally, as disclosed in the claim 3 rejection, Ntziachristos teaches the second irradiation unit as Fig. 2D, Ref. 2’s which point substantially down in the nearly the same direction as the scanning light (light source for photoacoustic). Therefore based on what has already been taught in claim 3, the second irradiation unit would intersect with the optical axis of the objective lens).
Claim(s) 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tokita, in view of Nam, further in view of Kubelick and Ntziachristos as applied to claim 3 above, and further in view of NPL: “Label-free characterization of living human induced pluripotent stem cells by subcellular topographic imaging technique using full-field quantitative phase microscopy coupled with interference reflection microscopy” to Sugiyama et al. “Sugiyama”.
Regarding claim 7, the modifications of Tokita, Nam, Kubelick, and Ntziachristos disclose all the features of claim 3 above.
Tokita teaches a filter on the second detection unit (See Fig. 2, Ref. 8b, optical filter of camera 8a).
However, the modifications of Tokita, Nam, Kubelick, and Ntziachristos do not disclose wherein the filter is a phase filter for a phase contrast observation.
Sugiyama teaches a similar method and apparatus of a label-free method of characterizing pluripotent stem cells (Title), using optical detection (interference reflection microscopy, Title). Sugiyama teaches using a phase grating (G) in front of the CCD sensor of the detector (See Fig. 1) that results in a quantitative phase image (which reads on the instant phase contrast observation) (Page 4).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the combination of Tokita, Nam, Kubelick, and Ntziachristos, wherein the second detection unit includes a phase film for a phase contrast observation, in order to obtain an optical image that provides information regarding cellular structure, height of the cell, and adherent surface, for intact cells in cultured conditions (Page 9). As discussed by Sugiyama (Page 9), many of these features provide differentiation between stem cell states (Page 9).
Claim(s) 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tokita, in view of Nam, further in view of Kubelick and Ntziachristos, as applied to claim 4 above, and further in view of Sugiyama.
Regarding claim 8, the modifications of Tokita, Nam, Kubelick, and Ntziachristos disclose all the features of claim 4 above.
Tokita teaches a filter on the second detection unit (See Fig. 2, Ref. 8b, optical filter of camera 8a).
However, the modifications of Tokita, Nam, Kubelick, and Ntziachristos do not disclose wherein the filter is a phase filter for a phase contrast observation.
Sugiyama teaches a similar method and apparatus of a label-free method of characterizing pluripotent stem cells (Title), using optical detection (interference reflection microscopy, Title). Sugiyama teaches using a phase grating (G) in front of the CCD sensor of the detector (See Fig. 1) that results in a quantitative phase image (which reads on the instant phase contrast observation) (Page 4).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the combination of Tokita, Nam, Kubelick, and Ntziachristos, wherein the second detection unit includes a phase film for a phase contrast observation, in order to obtain an optical image that provides information regarding cellular structure, height of the cell, and adherent surface, for intact cells in cultured conditions (Page 9). As discussed by Sugiyama (Page 9), many of these features provide differentiation between stem cell states (Page 9).
Claim(s) 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tokita, in view of Nam, further in view of Kubelick, further in view of Ntziachristos, and further in view of Sasaki, as applied to claim 5 above, and further in view of Sugiyama.
Regarding claim 9, the modifications of Tokita, Nam, Kubelick, Ntziachristos, and Sasaki disclose all the features of claim 5 above.
Tokita teaches a filter on the second detection unit (See Fig. 2, Ref. 8b, optical filter of camera 8a).
However, the modifications of Tokita, Nam, Kubelick, Ntziachristos, and Sasaki do not disclose wherein the filter is a phase filter for a phase contrast observation.
Sugiyama teaches a similar method and apparatus of a label-free method of characterizing pluripotent stem cells (Title), using optical detection (interference reflection microscopy, Title). Sugiyama teaches using a phase grating (G) in front of the CCD sensor of the detector (See Fig. 1) that results in a quantitative phase image (which reads on the instant phase contrast observation) (Page 4).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the combination of Tokita, Nam, Kubelick, Ntziachristos, and Sasaki, wherein the second detection unit includes a phase film for a phase contrast observation, in order to obtain an optical image that provides information regarding cellular structure, height of the cell, and adherent surface, for intact cells in cultured conditions (Page 9). As discussed by Sugiyama (Page 9), many of these features provide differentiation between stem cell states (Page 9).
Claim(s) 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tokita, in view of Nam, further in view of Kubelick, further in view of Ntziachristos, and further in view of Sasaki, as applied to claim 6 above, and further in view of Sugiyama.
Regarding claim 10, the modifications of Tokita, Nam, Kubelick, Ntziachristos, and Sasaki disclose all the features of claim 6 above.
Tokita teaches a filter on the second detection unit (See Fig. 2, Ref. 8b, optical filter of camera 8a).
However, the modifications of Tokita, Nam, Kubelick, Ntziachristos, and Sasaki do not disclose wherein the filter is a phase filter for a phase contrast observation.
Sugiyama teaches a similar method and apparatus of a label-free method of characterizing pluripotent stem cells (Title), using optical detection (interference reflection microscopy, Title). Sugiyama teaches using a phase grating (G) in front of the CCD sensor of the detector (See Fig. 1) that results in a quantitative phase image (which reads on the instant phase contrast observation) (Page 4).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the combination of Tokita, Nam, Kubelick, Ntziachristos, and Sasaki, wherein the second detection unit includes a phase film for a phase contrast observation, in order to obtain an optical image that provides information regarding cellular structure, height of the cell, and adherent surface, for intact cells in cultured conditions (Page 9). As discussed by Sugiyama (Page 9), many of these features provide differentiation between stem cell states (Page 9).
Claim(s) 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tokita, in view of Nam, and further in view of Kubelick, as applied to claim 1 above, and further in view of NPL: “Retinal pigment epithelial phenotype induced in human adipose tissue-derived mesenchymal stromal cell” to Vossmerbaeumer et al. “Vossmerbaeumer”.
Regarding claim 19, the modifications of Tokita, Nam, and Kubelick disclose all the features of claim 1 above.
As disclosed in the claim 1 rejection above, both Nam and Kubelick disclosed the stem cell as MSCs.
However, the modifications of Tokita, Nam, and Kubelick do not disclose wherein the pigment-containing cells include retinal pigmentary epithelial cells.
Vossmerbaeumer teaches MSCs that differentiate into retinal pigment epithelial cells (Page 177, Title and Introduction).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the combination of Tokita, Name, and Kubelick wherein the MSCs of Nam and Kubelick differentiated into pigment containing cells that include retinal pigmentary epithelial cells, as taught by Vossmerbaeumer, in order to synthesize a therapeutic that can aid in macular degeneration (Page 178, Introduction, first paragraph).
Conclusion
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/MT/Examiner, Art Unit 3798
/KEITH M RAYMOND/Supervisory Patent Examiner, Art Unit 3798