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 .
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1 – 3 is/are rejected under 35 U.S.C. 103 as being unpatentable Xu (US 10,151,701 B2; cited in the IDS), and further in view of Mano (US 2009/0250628 A1, cited in the IDS).
With respect to independent claim 1, Xu teaches A method for excitation spectral microscopy, the method comprising:
(a) providing one or more subjects with a plurality of components as shown in Fig. 12; see column 7, lines 1 - 37 for imaging;
(b) labeling dye-labeled cell samples in column 7, line 38 one or more components of the subject with a unique fluorophore label;
(c) selectively exciting each fluorophore with an excitation beam synchronously with an acquired frame of an imaging device in column 4, lines 40 – 50 and column 7, lines 49 - 55;
(e) quantifying a local abundance of each unique fluorophore at each pixel of the frame in column 8, lines 27 – 40; and
(f) rendering a fluorophore-decomposed micrograph of the labeled subject from the quantified abundance of each fluorophore as shown in Figs. 3A – 3B; in column 6, lines 51 – 55.
Xu, however, is silent with (d) switching excitation beam wavelength with each successive frame of said imaging device.
Mano, a pertinent art, teaches in paragraph [0038] switching excitation beam with a tunable filter 12A. In view of this, it would be obvious at the time of the claimed invention was filed to modify the teaching of Xu in order to speedy acquire a plurality of fluorescence images having different wavelength bands (see paragraph [0005] of Mano). This is in consistency with the Supreme Court Decision of the KSR. V. International Co.: applying a known technique to a known device (method or product) ready for improvement to yield predictable results.
With respect to dependent claim 2, Xu teaches in column 7, lines 1 – 4 wherein said subject comprises one or more fixed cells or one or more living cells.
With respect to dependent claim 3, Xu is silent with wherein said excitation beam comprises a beam profile of a bandwidth, intensity and range of one or more wavelengths that are optimized for exciting a specific fluorescent label.
Mano teaches in Fig. 2A and in paragraphs [0040 – 0057] the limitation of claim 3. In view of this, it would be obvious at the time of the claimed invention was filed to modify the teaching of Xu modified by Mano in order to match the emission characteristics of the light source with the absorption characteristics of the fluorescent material. This is in consistency with the Supreme Court Decision of the KSR. V. International Co.: applying a known technique to a known device (method or product) ready for improvement to yield predictable results.
Claim(s) 4 is/are rejected under 35 U.S.C. 103 as being unpatentable over Xu modified by Mano, and further in view of Buzby (US 2009/0061439 A1).
The teaching of Xu modified by Mano has been discussed above.
With respect to dependent claim 4, Xu is silent with wherein said fluorescent label is at least one member of the group consisting of LipidSpot 488, SYBR Gold, CF514, ATTO 532, ATTO 542 and CF568.
Buzby, a pertinent art, teaches ATTO 532 as a labeler. In view of this, it would be obvious at the time of the claimed invention was filed to modify the teaching of Xu modified by Mano in order to label desired fluorophores with a known material. This is in consistency with the Supreme Court Decision of the KSR. V. International Co.: applying a known technique to a known device (method or product) ready for improvement to yield predictable results.
Claim(s) 5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Xu modified by Mano, and further in view of Dube (US 2008/0075380 A1).
The teaching of Xu modified by Mano has been discussed above.
With respect to dependent claim 5, Xu is silent with wherein said fluorescent label is at least one member of the group consisting of SYBR Green, Mito-PhiYFP, WGA-CF532, LysoBrite Orange, and tdTomato-ER3.
Dube, a pertinent art, teaches SYBR Green in paragraph [0061] as a labeler. In view of this, it would be obvious at the time of the claimed invention was filed to modify the teaching of
Xu modified by Mano in order to label desired fluorophores with a known material. This is in consistency with the Supreme Court Decision of the KSR. V. International Co.: applying a known technique to a known device (method or product) ready for improvement to yield predictable results.
Claim(s) 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Xu modified by Mano, and further in view of Wachman (US 9,412,005 B2; cited in the IDS).
The teaching of Xu modified by Mano has been discussed above.
With respect to dependent claim 6, Xu teaches in column 8, lines 27 – 35 wherein quantification of the local abundance of each fluorophore comprises: measuring excitation spectra of one or more fluorophore labels from a singly labeled sample; but is silent with linearly unmixing an excitation spectrum of every pixel based on the excitation spectrum of each fluorophore using singly labeled samples.
Wachman, a pertinent art, teaches in Abstract linearly unmixing of the spectral image set. In view of this, it would be obvious at the time of the claimed invention was filed to modify the teaching of Xu modified by Mano in order to reduce or eliminate false positive results (see column 6, lines 33 – 34 of Wachman). This is in consistency with the Supreme Court Decision of the KSR. V. International Co.: applying a known technique to a known device (method or product) ready for improvement to yield predictable results.
Claim(s) 7 – 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mano, and further in view of Wachman2 (US 8,110,159 B2; cited in the IDS) and McCarthy (2009/0280559 A1).
With respect to independent claim 7, Mano teaches an apparatus for excitation spectral microscopy see paragraph [0003], comprising:
(a) a microscope with an excitation beam input and an image output as shown in Fig. 1; see paragraph [0023];
(b) a multispectral illumination source operably coupled to the excitation beam input of the epifluorescence microscope, configured to produce excitation beams with controlled wavelengths see paragraph [0024]; in Fig. 1;
(c) an imaging device coupled to the image output of the epifluorescence microscope see paragraph [0033];
(d) one or more processors 37 in Fig. 1 operably connected to the multispectral illumination source and to the imaging device; and
(e) a non-transitory memory storing executable instructions that, if executed by the one or more processors, configure the apparatus to:(i) control wavelength range of the excitation beam; (ii) synchronize actuation of the excitation beam with capture of the image output by the imaging device; and (iii) analyze captured excitation spectral images see paragraphs [0035 and 0067].
Mano is silent with and epifluorescence microscope and said imaging device capturing image output frame by frame with a controllable frame rate.
Wachman2, a pertinent art, teaches in paragraph [0056] an epifluorescence microscope and McCarthy teaches in paragraph [0030] controller controls the frame rate. In view of these, it would be obvious at the time of the claimed invention was filed to modify the teaching of Mano in order to control frame rate in a known epifluorescence microscope. This is in consistency with the Supreme Court Decision of the KSR. V. International Co.: applying a known technique to a known device (method or product) ready for improvement to yield predictable results.
With respect to dependent claim 8, Mano teaches in paragraph [0038] wherein said instructions when executed by the processor further perform steps comprising: creating one or more preset excitation profiles of a bandwidth, an intensity and a wavelength; and switching the excitation between a plurality of preset wavelength profiles in successive image frames.
With respect to dependent claim 9, Mano teaches in paragraph [0025] wherein said excitation profile comprises: an excitation beam profile of a bandwidth, intensity and range of one or more wavelengths that are optimized for exciting a specific fluorescent label.
With respect to dependent claim 10, as discussed above McCarthy teaches in paragraph [0030] wherein said instructions when executed by the processor further perform steps comprising: controlling a frame rate of the imaging device.
Claim(s) 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mano modified by Wachman2 and McCarthy, and further in view of Xu.
The teaching of Mano modified by Wachman2 and McCarthy has been discussed above.
With respect to dependent claim 11, Mano is silent with wherein said instructions when executed by the processor further perform steps comprising: quantifying a local abundance of a fluorescence of a fluorophore at each pixel of a frame; and rendering a fluorophore-decomposed micrograph of a labeled subject from the quantified abundance of the fluorophore.
As in the rejection justification discussed above, Xu teaches the limitation of claim 11.
In view of this, it would be obvious at the time of the claimed invention was filed to modify the teaching of Mano modified by Wachman2 and McCarthy in order to calculate amount of desired fluorophores. This is in consistency with the Supreme Court Decision of the KSR. V. International Co.: applying a known technique to a known device (method or product) ready for improvement to yield predictable results.
Claim(s) 12 and 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mano modified by Wachman2 and McCarthy, and further in view of Wu (US 10,386,300 B2; cited in the IDS).
The teaching of Mano modified by Wachman2 and McCarthy has been discussed above.
With respect to dependent claim 12, Mano is silent with wherein said multispectral illumination source comprises: a white light source; a polarizer positioned downstream of the light source; an acousto-optic tunable filter (AOTF) positioned downstream of the polarizer for receiving a polarized beam from the light source; and a second polarizer positioned downstream of the AOTF for receiving a polarized excitation beam from the AOTF, the second polarizer downstream of the excitation beam input of the epifluorescence microscope.
Wachman2 teaches in Abstract an acousto-optic tunable filter (AOTF) and Wu, a pertinent art, teaches a white light source 1310; a first and a second polarizer see column 48, line 60 – column 49, line 9. In view of these, it would be obvious at the time of the claimed invention was filed to modify the teaching of Mano modified by Wachman2 and McCarthy in order to transmit excitation light. This is in consistency with the Supreme Court Decision of the KSR. V. International Co.: applying a known technique to a known device (method or product) ready for improvement to yield predictable results.
With respect to dependent claim 15, Mano silent with wherein said imaging device further comprises: an RF synthesizer coupled to imaging device and to the AOTF and configured to select one or more excitation wavelengths for scanning; and wherein the imaging device and processor are configured to control the RF synthesizer to apply an RF frequency to the AOTF on a frame-by-frame basis; and wherein said RF synthesizer is configured for synchronized control of the excitation wavelength for each image frame.
Wachman2 teaches AOTF in Fig. 6 (see column 13, lines 44 – 45) and an RF synthesizer coupled to imaging device and the AOTF wherein the imaging device and processor are configured to control the RF synthesizer to apply an RF frequency to the AOTF on a frame-by-frame basis; and wherein said RF synthesizer is configured for synchronized control of the excitation wavelength for each image frame see Fig. 4, Column 7, lines 7 - 12. In view of this, it would be obvious at the time of the claimed invention was filed to modify the teaching of Mano modified by Wachman2 and McCarthy in order to avoid requiring a complicated and expensive bank of RF drivers rather than a single RF driver (see column 3, lines 52 – 53 of Wachman2). This is in consistency with the Supreme Court Decision of the KSR. V. International Co.: applying a known technique to a known device (method or product) ready for improvement to yield predictable results.
Claim(s) 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mano modified by Wachman2 and McCarthy, and further in view of Ginestet (US 6,225,626; cited in the IDS).
The teaching of Mano modified by Wachman2 and McCarthy has been discussed above.
With respect to dependent claim 13, Mano is silent with wherein said epifluorescence microscope further comprises a single band filter cube.
Ginestet, a pertinent art, teaches in column 6, lines 63 – 67 a single band filter cube. In view of this, it would be obvious at the time of the claimed invention was filed to modify the teaching of Mano modified by Wachman2 and McCarthy in order to pass desired emissions or excitation beams. This is in consistency with the Supreme Court Decision of the KSR. V. International Co.: applying a known technique to a known device (method or product) ready for improvement to yield predictable results.
Claim(s) 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mano modified by Wachman2 and McCarthy, and further in view of Xu2 (US 10,151,701 B1; cited in the IDS.
The teaching of Mano modified by Wachman2 and McCarthy has been discussed above.
With respect to dependent claim 14, Mano is silent with wherein said epifluorescence microscope further comprises an objective lens with a back focal plane positioned for receiving an excitation beam from the second polarizer.
Xu2, a pertinent art, teaches an objective lens 16 an a back focal plane in column 5, lines 46 – 62. In view of this, it would be obvious at the time of the claimed invention was filed to modify the teaching of Mano modified by Wachman2 and McCarthy in order to reduce or block excitation light. This is in consistency with the Supreme Court Decision of the KSR. V. International Co.: applying a known technique to a known device (method or product) ready for improvement to yield predictable results.
Claim(s) 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mano, and further in view of Wachman2 (US 8,110,159 B2; cited in the IDS)
With respect to independent claim 16, as discussed above Mano modified by Wachman2 teaches system for excitation spectral imaging, the system comprising: (a) an excitation light source configured to produce an excitation beam with a controlled wavelength, intensity and bandwidth; (b) an epifluorescence microscope with an objective coupled to the excitation light source configured to illuminate a target field with an excitation beam; and(c) an imaging device with a controller operably coupled to the excitation light source, the imaging device configured for frame-by-frame imaging of the target field at a different excitation wavelength for each frame.
Claim(s) 17 - 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mano modified by Wachman2, and further in view of Wu.
The teaching of Mano modified by Wachman2 has been discussed above.
With respect to dependent claim 17, Mano is silent with wherein said excitation light source comprises: a white light source; a polarizer positioned downstream of the white light source; an acousto-optic tunable filter (AOTF) positioned downstream of the polarizer for receiving a polarized beam from the white light source; a second polarizer positioned downstream of the AOTF for receiving a polarized excitation beam from the AOTF, the second polarizer downstream of an excitation beam input of the epifluorescence microscope; and a single bandpass filter positioned downstream of an output of the epifluorescence microscope providing said excitation beam.
As discussed above in view of teaching of Mano modified by Wachman2 and Wu, the limitation of claim 17 would be obvious in order to reduce or block excitation light from propagating into detection system. This is in consistency with the Supreme Court Decision of the KSR. V. International Co.: applying a known technique to a known device (method or product) ready for improvement to yield predictable results.
With respect to dependent claim 18, as discussed above Mano modified by Wachman2 and Wu teaches wherein said imaging device with a controller comprises: an RF synthesizer coupled to the AOTF and imaging device controller; wherein the image capture device controller is configured to control the RF synthesizer to apply an RF frequency to the AOTF on a frame-by-frame basis; and wherein said RF synthesizer is configured for synchronized control of the excitation wavelength, intensity, and bandwidth for each image frame.
With respect to dependent claim 19, as discussed above Mano modified by Wachman2 and Wu teaches wherein said imaging device controller is configured to control the RF synthesizer for frame-by-frame imaging at a different excitation wavelength for each frame according to one of a plurality of fluorophore excitation profiles of a bandwidth, intensity and range of one or more wavelengths that are optimized for exciting a specific fluorescent label.
Claim(s) 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Mano modified by Wachman2 and Wu, and further in view of McCarthy.
The teaching of Mano modified by Wachman2 and Wu has been discussed above.
With respect to dependent claim 20, Mano is silent with wherein said imaging device controller is further configured to control a frame rate of image acquisition of the imaging device.
McCarthy teaches in paragraph [0030] controller controls the frame rate. In view of these, it would be obvious at the time of the claimed invention was filed to modify the teaching of Mano in order to control frame rate in a known epifluorescence microscope. This is in consistency with the Supreme Court Decision of the KSR. V. International Co.: applying a known technique to a known device (method or product) ready for improvement to yield predictable results.
Conclusion
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KIHO KIM, Ph.D.
Primary Examiner
Art Unit 2884
/Kiho Kim/ Primary Examiner, Art Unit 2884