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 .
Response to Amendment
The Amendment filed September 30, 2025 has been entered. Claims 1-14 are pending.
Response to Arguments
Applicant's arguments filed September 30, 2025 have been fully considered but they are not persuasive.
On page 2, the applicant’s argument “the asserted measurement unit in Iketaki does not involve time-resolved measurement for distinguishing optical responses to the optical pulses with different center wavelengths arranged at predetermined time intervals included in the pulse train, as recited in claim 1” is not convincing. Iketaki explicitly discloses a system that performs time-resolved measurement to distinguish optical responses based on pulse train. Iketaki’s core innovation is using temporal separation (time-resolved detection). Iketaki teaches “A light irradiation unit configured to sequentially irradiate a sample with a plurality of light beams having different wavelengths as pulsed light”, “A sampling unit configured to acquire an optical response signal corresponding to the irradiated pulsed light from the light detection unit in synchronization with the irradiation of the pulsed light from the light irradiation unit” in [0028] . This is done using gate signals (G1, G2, G3) that are synchronized with the pulses signals (P1, P2, P3). The logic circuits (51, 52, 53) sample the detector’s output only during the time window when the response from a specific pulsed wavelength is expected ([0058]-[0060]). Time-resolved measurement means a measurement that distinguishes signals based on their time of arrival or a specific time window. Iketaki’s system does exactly this. The system measures the optical response from the sample within specific , predetermined time gates that synchronized to the pulsed excitation train ([0042]-[0043]).
On page 2, the applicant argues the prior art does not teach “time-resolved measurement on an optical response from a sample from irradiation of a pulse train arranged at predetermined time intervals, and performing batch linear unmixing on the time-resolved measurement data with respect to each optical pulse of the optical pulses” is not convincing. Radosevich teaches a processor configured to perform batch linear unmixing processing on the measurement data with respect to each optical pulse of the optical pulses on the basis of an excitation spectrum for every target included in the sample (page 2164, right col.: linear unmixing strategies can…. be applied to multispectral two-photon data. Images of Cn and Sn 2 can be calculated via a nonnegative least-squares fit to both “seeded” basis spectra, and basis spectra of intrinsic fluorophores measured in vitro., the batch linear unmixing is inherent as the fitting is performed after a complete wavelength scan data from images from 710-920 nm or each optical pulse). The combination of Radosevich’ s data processing ( batch linear unmixing) with Iketaki’s data acquisition method is a predictable and obvious step for a person of ordinary skill in the art seeking to improve multimodal imaging.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-2, 4-9 and 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Radosevich (2008. Hyperspectral in vivo two-photon microscopy of intrinsic contrast. Optics letters, 33(18), pp.2164-2166) in view of Iketaki (JP2012032183 A) .
Regarding claim 1, Radosevich teaches a sample observation device (Abstract), comprising: a light source (a Ti:sapphire laser) configured to output a pulse train in which multiple optical pulses with different center wavelengths are arranged at predetermined time intervals as excitation light (page 2164, right col.: the laser being tuned from 710 to 920 nm in 2 nm steps); an optical measurement device configured to perform measurement for distinguishing optical responses to the optical pulses with different center wavelengths included in the pulse train while scanning the sample, and to acquire measurement data with respect to the optical pulses (page 2164, right col.: ”Wavelength scans consisted of 400X400 pixel images captured in synchrony with the laser”, inherently obtaining measurement data for each distinct-wavelength as the sample is scanned); and a processor configured to perform batch linear unmixing processing on the measurement data with respect to each optical pulse of the optical pulses on the basis of an excitation spectrum for every target included in the sample (page 2164, right col.: linear unmixing strategies can…. be applied to multispectral two-photon data. Images of Cn and Sn 2 can be calculated via a nonnegative least-squares fit to both “seeded” basis spectra, and basis spectra of intrinsic fluorophores measured in vitro., the batch linear unmixing is inherent as the fitting is performed after a complete wavelength scan data from images from 710-920 nm or each optical pulse), but fails to disclose a measurement unit configured to perform time-resolved measurement for distinguishing optical responses to the optical pulses with different center wavelengths.
However, Iketaki from the same field of endeavor, teaches a measurement unit configured to perform time-resolved measurement for distinguishing optical responses to the optical pulses with different center wavelengths ([0042]-[0043] the response light of each color light of the polychromatic light can be detected without overlapping in the time domain, the sample can be observed with high accuracy).
Therefore, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to modify Radosevich by incorporating a measurement unit configured to perform time-resolved measurement for distinguishing optical responses to the optical pulses with different center wavelengths so the sample can be observed with high accuracy ([0043]).
Regarding claim 2, Radosevich, when modified by Iketaki teaches the sample observation device according to claim 1: wherein the light source generates the pulse train by temporally modulating the center wavelengths of the optical pulses generated from a single light source (page 2164, left col. : “Our integrated control software written in MATLAB allows synchronous tuning of the laser wavelength during imaging” in other words, the laser’s center wavelength is actively changed as a function of time).
Regarding claim 4, Radosevich, when modified by Iketaki teaches the sample observation device according to claim 1, wherein the processor retains an excitation spectrum of a region in the sample where only a specific target (page 2164, right col.: “Six seed regions were selected from this data set, targeting regions with distinctive morphology, The spectra extracted from these regions were then fit to the spectrum of every voxel” using regions with one specific target emitting light) emits light with respect to the multiple optical pulses included in the pulse train in advance (page 2164, right col.: “each voxel effectively contains a coarse nine-element excitation–emission map consisting of 720, 800, and 900 nm excitations and 350– 505, 505–560, and 560–650 nm emissions” therefore the system collects and retains an excitation profile for each target), and performs linear unmixing (a nonnegative least-squares fitting) processing on measurement data with respect to the optical pulses on the basis of the excitation spectrum (page 2164, right col.: “Images of Cn and Sn 2 can be calculated via a nonnegative least-squares fit to both “seeded” basis spectra, and basis spectra of intrinsic fluorophores measured in vitro”).
Regarding claim 5, Radosevich, when modified by Iketaki teaches the sample observation device according to claim 1, further comprising: an image generator configured to generate an observation image relating to a specific target on the basis of the measurement data on which the linear unmixing processing has been performed (page 2164, right col.: Unmixing results are shown at three different depths, with three unmixed components merged as red–green–blue (RGB), and three as a cyan– magenta–yellow (CMY) merges. These images reveal keratinocytes in the epidermis and the hair follicle sheath (yellow), fibrous structures in the dermis (red), hairs (blue), sebaceous glands (yellow), and hair follicle cysts (common in hairless mice—cyan)).
Regarding claim 6, Radosevich, when modified by Iketaki teaches The sample observation device according to claim 5, wherein the image generator generates a superimposed image in which observation images relating to the specific target are superimposed on each other (page 2164, right col.: Unmixing results are shown at three different depths, with three unmixed components merged as red–green–blue (RGB), and three as a cyan– magenta–yellow (CMY) merges. Figs. 1b-1c shows a superimposed image from target specific images).
Regarding claim 7, Radosevich, when modified by Iketaki teaches the sample observation device according to claim 1, wherein the optical measurement device includes a multi-channel detection unit configured to perform time-resolved measurement on the optical response from the sample (Iketaki: [0040]: a dedicated detector or detection channel for each pulse or each wavelength and those channels are used to time-gate (time-resolved measurement) the measure fluorescence signal).
Regarding claim 8, Radosevich teaches a sample observation method (Abstract), comprising: outputting a pulse train in which multiple optical pulses with different center wavelengths are arranged at predetermined time intervals as excitation light (page 2164, right col.: the laser being tuned from 710 to 920 nm in 2 nm steps); measuring measurement for distinguishing optical responses to the optical pulses with different center wavelengths included in the pulse train while scanning the sample with the excitation light, and acquiring measurement data with respect to the optical pulses (page 2164, right col.: ”Wavelength scans consisted of 400X400 pixel images captured in synchrony with the laser”, inherently obtaining measurement data for each distinct-wavelength as the sample is scanned); and processing batch linear unmixing processing on the measurement data with respect to each optical pulse of the optical pulses on the basis of an excitation spectrum for every target included in the sample (page 2164, right col.: linear unmixing strategies can…. be applied to multispectral two-photon data. Images of Cn and Sn 2 can be calculated via a nonnegative least-squares fit to both “seeded” basis spectra, and basis spectra of intrinsic fluorophores measured in vitro.), but fails to disclose measuring time-resolved measurement for distinguishing optical responses to the optical pulses with different center wavelengths.
However, Iketaki from the same field of endeavor, teaches measuring time-resolved measurement for distinguishing optical responses to the optical pulses with different center wavelengths ([0042]-[0043] the response light of each color light of the polychromatic light can be detected without overlapping in the time domain, the sample can be observed with high accuracy).
Therefore, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to modify Radosevich by incorporating measuring time-resolved measurement for distinguishing optical responses to the optical pulses with different center wavelengths so the sample can be observed with high accuracy ([0043]).
Regarding claim 9, Radosevich, when modified by Iketaki teaches the sample observation method according to claim 8, wherein in the outputting, the pulse train is generated by temporally modulating the center wavelengths of the optical pulses generated from a single light source (page 2164, left col. : “Our integrated control software written in MATLAB allows synchronous tuning of the laser wavelength during imaging” in other words, the laser’s center wavelength is actively changed as a function of time).
Regarding claim 11, Radosevich, when modified by Iketaki teaches the sample observation method according to claim 8, wherein in the processing, an excitation spectrum of a region in the sample where only a specific target (page 2164, right col.: “Six seed regions were selected from this data set, targeting regions with distinctive morphology, The spectra extracted from these regions were then fit to the spectrum of every voxel” using regions with one specific target emitting light) emits light with respect to the multiple optical pulses included in the pulse train is retained in advance (page 2164, right col.: “each voxel effectively contains a coarse nine-element excitation–emission map consisting of 720, 800, and 900 nm excitations and 350– 505, 505–560, and 560–650 nm emissions” therefore the system collects and retains an excitation profile for each target), and linear unmixing (a nonnegative least-squares fitting) processing is performed on measurement data with respect to the optical pulses on the basis of the excitation spectrum (page 2164, right col.: “Images of Cn and Sn 2 can be calculated via a nonnegative least-squares fit to both “seeded” basis spectra, and basis spectra of intrinsic fluorophores measured in vitro”).
Regarding claim 12, Radosevich, when modified by Iketaki teaches the sample observation method according to claim 8, further comprising: generating an observation image relating to a specific target on the basis of the measurement data on which the linear unmixing processing has been performed (page 2164, right col.: Unmixing results are shown at three different depths, with three unmixed components merged as red–green–blue (RGB), and three as a cyan– magenta–yellow (CMY) merges. These images reveal keratinocytes in the epidermis and the hair follicle sheath (yellow), fibrous structures in the dermis (red), hairs (blue), sebaceous glands (yellow), and hair follicle cysts (common in hairless mice—cyan)).
Regarding claim 13, Radosevich, when modified by Iketaki teaches the sample observation method according to claim 12, wherein in the generating, a superimposed image in which observation images relating to the specific target are superimposed on each other is generated (page 2164, right col.: Unmixing results are shown at three different depths, with three unmixed components merged as red–green–blue (RGB), and three as a cyan– magenta–yellow (CMY) merges. Figs. 1b-1c shows a superimposed image from target specific images).
Regarding claim 14, Radosevich, when modified by Iketaki teaches the sample observation method according to claim 8, wherein in the measuring, time-resolved measurement is performed on the optical response from the sample by multi-channel detection (Iketaki: [0040]: a dedicated detector or detection channel for each pulse or each wavelength and those channels are used to time-gate (time-resolved measurement) the measure fluorescence signal).
7. Claims 3 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Radosevich (2008. Hyperspectral in vivo two-photon microscopy of intrinsic contrast. Optics letters, 33(18), pp.2164-2166) in view of Iketaki (JP2012032183 A), further in view of Kazi (JP2005-241733A)
Regarding claim 3, Radosevich, when modified by Iketaki teaches the sample observation device according to claim 1, but fails to disclose wherein the light source generates the pulse train by using soliton self-frequency shift in which an output wavelength depends on an input intensity.
However, Kazi , from the same field of endeavor teaches wherein the light source generates the pulse train by using soliton self-frequency shift in which an output wavelength depends on an input intensity ([0026]).
Therefore, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to modify Radosevich and Iketaki by incorporating wherein the light source generates the pulse train by using soliton self-frequency shift in which an output wavelength depends on an input intensity for an efficient wavelength conversion ([0006]).
Regarding claim 10, Radosevich, when modified by Iketaki teaches the sample observation method according to claim 8, but fails to disclose wherein in the outputting, the pulse train is generated by using soliton self- frequency shift in which an output wavelength depends on an input intensity.
However, Kazi, from the same field of endeavor teaches wherein in the outputting, the pulse train is generated by using soliton self- frequency shift in which an output wavelength depends on an input intensity ([0026]).
Therefore, it would have been obvious to someone of ordinary skill in the art before the effective filing date of the claimed invention to modify Radosevich and Iketaki by incorporating wherein in the outputting, the pulse train is generated by using soliton self- frequency shift in which an output wavelength depends on an input intensity for an efficient wavelength conversion ([0006]).
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/MOHAMED DOUMBIA/Examiner, Art Unit 2877
/UZMA ALAM/Supervisory Patent Examiner, Art Unit 2877