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 .
Response to Amendment
This Office Action is in response to Applicant’s amendment/response filed on 16 January 2026, which has been entered and made of record.
Response to Arguments
Applicant’s arguments have been fully considered but they are moot in view of the new grounds of rejection that are presented in this Office Action in response to the claim amendments.
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.
Claims 1, 2, 5, and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Chukka et al. (US 2016/0321809; hereinafter “Chukka”) in view of Schie et al. (US 11,599,738; hereinafter “Schie”).
Regarding claim 1, Chukka discloses An image processing method for binarization of a multi-value cell image (“analysis of digitized images of tissue samples,” para. 2; “obtain a final binary image mask,” para. 109), the method comprising: a step of acquiring a frequency-component extraction image that extracts a predetermined high-frequency component, higher than a frequency of a background, corresponding to a subcellular structure of a cell from the converted cell image (“obtaining a gradient magnitude image … may help distinguish foreground regions where the stain contribution is very faint but have higher gradient magnitude as compared to smoother background regions with lower gradient magnitude,” para. 109; “the gradient magnitude image is computed from a grayscale image obtained from the color image, and then using Gaussian first derivatives along x and y axes, using kernels with a standard deviation,” para. 120; the gradient magnitude image of Chukka teaches the claimed frequency-component extraction image because a gradient is a rate of change in an image which teaches a spatial frequency); a step of acquiring a first image by binarizing the converted cell image, and a second image by binarizing the frequency-component extraction image (“applying OTSU thresholding on each of the soft-weighted foreground image and gradient magnitude image to obtain a binary mask image for the soft-weighted foreground image and a binary mask image for the gradient magnitude image,” para. 109); and a step of generating a binary image of the cell image by combining the first image and the second image (“OR-combining the two binary masks to obtain a final binary image mask (final foreground image mask or foreground image mask),” para. 109). Fig. 14A illustrates an original cell image “HE image,” and a soft-weighted version of the original HE image is binarized in the left column (corresponding to the claimed binarization of the converted cell image), and a gradient magnitude image of the HE image is binarized in the right column (corresponding to the claimed binarization of the frequency-component extraction image), and the two binary images are combined into a final binary mask.
Chukka does not disclose a step of extracting a background brightness distribution in the cell image; a step of converting pixel values of pixels in the cell image into relative values relative to the background brightness distribution.
In the same art of analyzing cell images, Schie teaches a step of extracting a background brightness distribution in the cell image; a step of converting pixel values of pixels in the cell image into relative values relative to the background brightness distribution (“a background estimate is obtained from the overview picture by blurring with a strength that essentially removes the objects, and the overview image is replaced by its difference to the background estimate prior to conversion into the binary image … all further operations then proceed only from this difference image,” col. 5, lines 20-30; “The original overview image 200 [of Fig. 1] is offset in the next step 106 by subtraction, or by pointwise dividing, with the background estimation,” col. 10, lines 35-45). This also teaches the claimed step of acquiring a first image by binarizing the converted cell image because the background-subtracted image of Schie (step 106 of Fig. 1) is directly converted into a binary image (step 110 of Fig. 1).
Before the effective filing date of the claimed invention, it would have been obvious to one having ordinary skill in the art to apply the teachings of Schie to Chukka. The motivation would have been to “improve the examination of a plurality of distributed objects” (Schie, col. 1, lines 50-55).
Regarding claim 2, the combination of Chukka and Schie renders obvious wherein a background image representing the background brightness distribution is generated by filtering the cell image to remove the cell in the cell image in the step of extracting a background brightness distribution (“a background estimate is obtained from the overview picture by blurring with a strength that essentially removes the objects,” Schie, col. 5, lines 20-30; see claim 1 for motivation to combine).
Regarding claim 5, the combination of Chukka and Schie renders obvious wherein the pixel values of the pixels in the cell image are converted into the relative values by dividing the pixel values of the pixels in the cell image by pixel values of pixels in the background image in the step of converting pixel values of pixels in the cell image into relative values relative to the background brightness distribution (“The overview image can then be divided pointwise prior to conversion into the binary image through the normalized background estimate,” Schie, col. 5, lines 35-45; “The original overview image 200 [of Fig. 1] is offset in the next step 106 by subtraction, or by pointwise dividing, with the background estimation,” col. 10, lines 35-45; see claim 1 for motivation to combine).
Regarding claim 11, it is rejected using the same citations and rationales described in the rejection of claim 1, with the additional limitations of An image processing apparatus comprising: at least one processor (“the systems include a processor,” Chukka, para. 11).
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over the combination of Chukka and Schie, and further in view of Suzuki (US 2017/0071562).
Regarding claim 3, the combination of Chukka and Schie does not disclose wherein the filtering the cell image to remove the cell is median filter for a kernel size corresponding to a size of the cell in the cell image.
In the same art of image filtering, Suzuki teaches a median filter for a kernel size corresponding to a size of the [object to be removed] in the image (“a median filter with a kernel of 25 pixels can remove ‘impulsive’ small regions smaller than or equal to 12 pixels,” para. 88).
Before the effective filing date of the claimed invention, it would have been obvious to one having ordinary skill in the art to apply the median filtering techniques of Suzuki to the cell removal in the cell image of the combination of Chukka and Schie. The motivation would have been “clinically important findings … can be improved” (Suzuki, abstract).
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over the combination of Chukka and Schie, and further in view of Alderson et al. (US 2002/0159648; hereinafter “Alderson”).
Regarding claim 4, the combination of Chukka and Schie does not disclose wherein the step of extracting a background brightness distribution includes a step of reducing the cell image, a step of filtering the reduced cell image to remove the cell in the reduced cell image, and a step of increasing the background image after being subjected to the step of filtering the reduced cell image to remove the cell back to a size of the cell image before being subjected to the step of reducing the cell image.
In the same art of image filtering, Alderson teaches wherein the step of extracting a background brightness distribution includes a step of reducing the image (“down-sampling filter,” para. 65), a step of filtering the reduced image to remove [objects] in the reduced image (“the spatial frequency of the gradient data to removed from the frame of image data … applying a median filter to an array of down-sampled super-pixels,” para. 65), and a step of increasing the background image after being subjected to the step of filtering the reduced image to remove the [objects] back to a size of the image before being subjected to the step of reducing the image (“applying up-sampling to the blurred array of pixels to generate up-sampled data,” para. 71).
Before the effective filing date of the claimed invention, it would have been obvious to one having ordinary skill in the art to apply the teachings of Alderson to the cell images for removing cells in the combination of Chukka and Schie. The motivation would have been “details corresponding to objects … can be difficult or impossible to detect if the low-frequency background gradient is not removed” (Alderson, para. 5).
Claims 6-8 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of Chukka and Schie, and further in view of Nie et al. (US 2020/0279126; hereinafter “Nie”).
Regarding claim 6, the combination of Chukka and Schie does not disclose wherein the step of acquiring a frequency-component extraction image includes a step of generating a first smoothed image and a second smoothed image that have different frequency characteristics by smoothing the cell image, and a step of generating the frequency-component extraction image based on difference between the first smoothed image and the second smoothed image.
In the same art of analyzing cell images, Nie teaches wherein the step of acquiring a frequency-component extraction image includes a step of generating a first smoothed image and a second smoothed image that have different frequency characteristics by smoothing the cell image, and a step of generating the frequency-component extraction image based on difference between the first smoothed image and the second smoothed image (“difference of Gaussian (DoG) filtering is used to identify such cell-like structures. In general, difference of Gaussians is a feature enhancement algorithm that involves the subtraction of one blurred version of an original image from another, less blurred version of the original,” para. 105).
Before the effective filing date of the claimed invention, it would have been obvious to one having ordinary skill in the art to apply the teachings of Nie to the combination of Chukka and Schie. The motivation would have been for “feature enhancement” (Nie, para. 105).
Regarding claim 7, the combination of Chukka, Schie, and Nie renders obvious wherein the step of acquiring a frequency-component extraction image includes a step of selecting a parameter set, which includes a first parameter for generating the first smoothed image and a second parameter for generating the second smoothed image, from sets of predetermined parameters (“the blurred images are obtained by convolving the original grayscale images with Gaussian kernels having differing standard deviations,” Nie, para. 105; see claim 6 for motivation to combine).
Regarding claim 8, the combination of Chukka, Schie, and Nie renders obvious wherein the smoothing is Gaussian filtering; and parameters of the smoothing are standard deviations of the Gaussian filtering (“the blurred images are obtained by convolving the original grayscale images with Gaussian kernels having differing standard deviations,” Nie, para. 105; see claim 6 for motivation to combine).
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over the combination of Chukka and Schie, and further in view of Kent et al. (US 2011/0045993; hereinafter “Kent”).
Regarding claim 9, the combination of Chukka and Schie does not disclose wherein the subcellular structure of the cell is a filipodia of the cell.
In the same art of analyzing cellular structures, Kent teaches wherein the subcellular structure of the cell is a filipodia of the cell (“processing the image to identify objects in the image,” para. 142; “When the objects are cells, the step of determining may be measurement of … filipodia,” para. 95).
Before the effective filing date of the claimed invention, it would have been obvious to one having ordinary skill in the art to apply the teachings of Kent to the combination of Chukka and Schie. The motivation would have been to “yield valuable prognostic, diagnostic and therapeutic information” (Kent, para. 8).
Allowable Subject Matter
Claim 10 is allowed. The following is a statement of reasons for the indication of allowable subject matter: The known prior art does not teach or suggest, when considered in the context of the remaining limitations of the claim, wherein the first image includes a first threshold image that is acquired by binarizing the cell image with a first threshold, and a second threshold image that is acquired by binarizing the cell image with a second threshold smaller than the first threshold; and the step of generating a binary image of the cell image includes a step of removing a mismatch part of the second image that does not match with the second threshold image from the second image, and a step of combining the first threshold image with the second image from which the mismatch part, which does not match with the second threshold image, is removed.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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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/RYAN MCCULLEY/Primary Examiner, Art Unit 2611