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 .
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 6/12/2025 and 6/12/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Rejections - 35 USC § 102
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 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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-6 and 9-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chen (WO 2021/146597 A1).
Regarding claim 1, Chen discloses a multiphoton microscopy system (Figs.1-3B), including:
a) a laser light source 115 configured to generate an excitation light having a first wavelength range including an excitation wavelength of a biological sample (pars.0115 and 0134);
b) an optical system 110 configured to direct the excitation light to the biological sample and configured to receive an emission light emitted by the biological sample in response to the excitation light; and
c) a detection module configured to receive the emission light from the optical system 110 and configured to:
i) separate the emission light into at least a first detection light including a second wavelength range, a second detection light including a third wavelength range, a third detection light including a fourth wavelength range, a fourth detection light including a fifth wavelength range, and a fifth detection light including a sixth wavelength range (via dichroic beamsplitters 130, 135, 140, etc. (pars.0120 and 0134-0139, particularly par.0137 which states that eight or more detection channels and corresponding dichroic selection may be provided as desired); and
ii) direct the first through fifth detection lights to a first through fifth detector, respectively (pars.0115 and 0136-0139).
With respect to claim 2, Chen further discloses that the first through fifth detectors are configured to simultaneously visualize the biological sample (par.0136) via the first through fifth different imaging modalities, respectively.
Examiner’s Note #1: The general recitation of imaging modalities is, at best, an intended use. No distinguishable structure to perform such a vague function is claimed. As broadly as claimed, the disclosure of Chen is equally capable.
With respect to claim 3, Chen anticipates the claim at least because, as broadly as claimed, Chen is equally capable of performing the claimed imaging modalities. Specifically, Chen anticipates the positively set forth structures and arrangements of parent claims 1 and 2. In addition, Chen does state that the device is capable of imaging complex fluorescence phenomena from biological samples (par.0075).
With respect to claim 4, Chen further discloses that the detection module is further configured to separate the emission light into a sixth detection light including a seventh wavelength range corresponding to fluorescence, and to direct the sixth detection light to a sixth detector (par.0137).
Examiner’s Note #2: the recitation of two-photon autofluorescence is, at best, an intended use. Chen is equally capable of performing the claimed imaging modalities insofar as Chen anticipates the positively set forth structures and arrangements of claim 4 and parent claim 1. In addition, Chen states two-photon fluorescence as possible analysis mode (par.0075).
With respect to claim 5, Chen further discloses that the laser light source includes a near-infrared pulsed laser source configured to generate the excitation light (par.0242-0243) and an optical fiber configured to deliver the excitation light to the optical system 110 (par.0243).
With respect to claim 6, Chen further discloses that the emission light is a supercontinuum light signal including wavelengths from 340 nm to 740 nm (par.0120, first dichroic splitter 130 passes one or more spectral bands including near UV, the entire visible spectrum, and near IR; also see pars.0247-0248).
Regarding claim 9, Chen discloses a detection module for a microscopy system (Figs.1-3B), including:
a) an optical input 110 configured to receive an emission light, where the emission light corresponds to illumination emitted by a biological sample in response to irradiation with an excitation light;
b) a beam separator 130, 135 and 140 configured to split the emission light into a first detection light, a second detection light, a third detection light, a fourth detection light, and a fifth detection light (via dichroic beamsplitters 130, 135, 140, etc. (pars.0120 and 0134-0139, particularly par.0137 which states that eight or more detection channels and corresponding dichroic selection may be provided as desired); and
c) first through fifth detectors 120 configured to receive the first through fifth detection lights, respectively (pars.0115 and 0135-0139).
With respect to claim 10, Chen further discloses that the first through fifth detectors are configured to simultaneously visualize the biological sample (par.0136) via the first through fifth different imaging modalities, respectively.
Examiner’s Note #3: The general recitation of imaging modalities is, at best, an intended use. No distinguishable structure to perform such a vague function is claimed. As broadly as claimed, the disclosure of Chen is equally capable.
With respect to claim 11, Chen anticipates the claim at least because, as broadly as claimed, Chen is equally capable of performing the claimed imaging modalities. Specifically, Chen anticipates the positively set forth structures and arrangements of parent claims 9 and 10. In addition, Chen does state that the device is capable of imaging complex fluorescence phenomena from biological samples (par.0074).
With respect to claim 12, Chen further discloses that the detection module is further configured to separate the emission light into a sixth detection light including a seventh wavelength range corresponding to fluorescence, and to direct the sixth detection light to a sixth detector (par.0137).
Examiner’s Note #4: the recitation of two-photon autofluorescence is, at best, an intended use. Chen is equally capable of performing the claimed modalities insofar as Chen anticipates the positively set forth structures and arrangements of claim 12 and parent claim 9. In addition, Chen states two-photon fluorescence as a possible analysis mode (par.0075).
With respect to claim 13, Chen further discloses that the emission light is a supercontinuum light signal including wavelengths from 340 nm to 740 nm (par.0120, first dichroic splitter 130 passes one or more spectral bands including near UV, the entire visible spectrum, and near IR).
With respect to claim 14, Chen further discloses that the first through fifth detectors are photomultiplier tubes (pars.0079 and 0367).
Regarding claim 15, Chen discloses a multiphoton microscopy method (Figs.1-3B), including:
a) illuminating a biological sample with an excitation light having a first wavelength range including an excitation wavelength of the biological sample (via source 115 and objective 110; see at least pars.0115 and 0134);
b) receiving an emission light emitted by the biological sample in response to the excitation light (via objective 110), where the emission light includes a supercontinuum (par.0120, first dichroic splitter 130 passes one or more spectral bands including one or more of near UV and blue, green to red and near IR; also see pars.0247-0248);
c) separating the emission light into at least a second through sixth wavelength range (via dichroic beamsplitters 130, 135, 140, etc. (pars.0120 and 0134-0139, particularly par.0137 which states that eight or more detection channels and corresponding dichroic selection may be provided as desired); and
d) simultaneously detecting the second through sixth wavelength ranges by first through fifth detectors, respectively (pars.0115 and 0136-0139).
With respect to claim 16, Chen further discloses that the first through fifth detectors respectively correspond to different imaging modalities (par.0136).
Examiner’s Note #5: absent any method steps establishing a process for performing the different imaging modalities beyond the currently-claimed method steps, Chen anticipates.
With respect to claim 17, Chen anticipates the claim, absent any method steps setting forth performing any of each of the modalities. All that is required by the claim are the illumination, receiving, separating and simultaneously detecting steps of parent claim 15.
With respect to claim 18, Chen further discloses separating the emission light into a seventh wavelength range (par.0137) corresponding to a two-photon excited long-wavelength autofluorescence (pars.0074 and 0247-0248: it is understood in the art that an unspecified molecule that undergoes two-photon long-wavelength autofluorescence will likely fall within the disclosed range of measured wavelengths/bands); and simultaneously detecting the seventh wavelength range by a sixth detector (par.0137).
With respect to claim 19, Chen further discloses outputting first through fifth images of the biological sample from the first through fifth detectors, respectively (pars.0078, 0114, 0379; also see Fig.38).
With respect to claim 20, Chen further discloses detecting a biomarker based on at least one of the first through fifth images (par.0473).
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 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 7 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Chen, as applied to claim 1 above, in view of Boppart (US 2022/0228987 A1).
With respect to claim 7, Chen does not specifically disclose post-acquisition image processing.
Boppart teaches the practice of simultaneous multi-band fluorescence imaging of a biological sample, where the images from each wavelength band are co-registered for subsequent comparison (Figs.4a-e). In this manner, meaningful spatial comparisons may be made in order to determine critical characteristics of the biological tissue (pars.0073-0075).
It would have been obvious to one of ordinary skill in the art at the time of the invention for Chen to co-register the output first through fifth images in order to efficiently and accurately analyze the sample, as taught by Boppart.
With respect to claim 8, neither Chen nor Boppart specifically teach any particular denoising methodology for the output images.
However, the skilled artisan readily recognizes the growing prevalence of employing supervised and unsupervised modeling of complex processes, including image denoising of both background and systemic artifacts, in order to rapidly improve the image quality for higher-precision diagnosis and pathology.
It would have been obvious to one of ordinary skill in the art at the time of the invention for Chen to apply a self-supervised denoising model to at least one of the first through fifth output images in order to improve the analytical value of the images in very little time, as known in the art.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure: the remaining prior art (see attached PTO-892) either further establishes the state of the art of multi-wavelength fluorescence imaging, autofluorescence imaging, and/or are US patent family members of previously-cited prior art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to THOMAS R ARTMAN whose telephone number is (571)272-2485. The examiner can normally be reached Monday-Thursday 10am-6:30pm.
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THOMAS R. ARTMAN
Primary Examiner
Art Unit 2884
/THOMAS R ARTMAN/ Primary Examiner, Art Unit 2884