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
Applicant’s amendment filed on January 7, 2026 has been entered. Claims 1 – 3, 5 and 10 – 13 have been amended. No claims have been canceled. Claim 21 has been added. Claims 1 – 21 are still pending in this application, with claims 1, 11 and 20 being independent.
Response to Arguments
Applicant’s arguments with respect to claim(s) 1 – 21 have been considered but are moot because the new ground of rejection.
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.
Claim(s) 1, 4, 11, 14, 20 and 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Glass et al. (US Patent Application Publication 2022/0375606), hereinafter referred as Glass, in view of Spitzmueller et al. (WIPO Patent Application Publication WO 2023/175483), hereinafter referred as Spitzmueller.
Regarding claim 1, Glass discloses a computing apparatus ([0017 – 0018], computer) comprising:
a memory storing at least one program ([0047], memory); and
a processor ([0017 – 0018], computer processor) configured to perform at least one operation by executing the at least one program, wherein the processor is further configured to:
analyze a pathological slide image to classify at least one of cells and tissues included in the pathological slide image into at least one type ([0028], “applying one or more first machine learning algorithms to the one or more WSIs to identify at least one of a tissue region or cell of interest, wherein the at least one of the tissue region or cell of interest comprises one or more of cancer epithelium, cancer stroma, ductal carcinoma in situ, necrosis, cell membrane, or artifacts”);
segment the pathological slide image into subpatches based on a result of the classification ([0036], a first CNN is trained to segment the slide into regions, such as cancer epithelium, cancer stroma, necrosis, and artifact regions. A second CNN is trained to differentiate tumor morphology, e.g., invasive versus noninvasive);
generate, by using a machine learning model, subcell information including at least one of a first index and a second index for at least one of the components determined based on information regarding the subpatches and the components ([0036], “A third CNN is trained to identify regions (e.g., cancer cells, other cells, cell membrane) and patterns associated with the regions (e.g., HER2 membrane staining pattern (complete, partial, or unstained))”. [0037], “an intensity metric for each individual pixel corresponding to the cell membrane (e.g., a brownness metric) may be calculated. The metric is then aggregated across all membrane pixels corresponding to each cell to generate an intensity score (e.g., a brownness intensity score)”; [0038], “one or more trained ML models (e.g., one or more of the first, second, third, and fourth CNNs described above) may be applied to generate HER2 cell-level features for each slide that reflect the number of HER2 stained cells on a slide.”; Fig. 4, displays detailed information regarding cell staining intensity); and
control a display apparatus ([0038], display device) to display information regarding result of the at least one of cells and tissues (Fig. 4, [0039]).
However, Glass fails to explicitly disclose the processor further: calculate a third index corresponding to a cell membrane specificity of the at least one of cells and tissues included in the pathological slide image based on the second index, wherein the cell membrane specificity indicates how much of a targeted object is present in a cell membrane of the cell; and control a display apparatus to display information regarding the third index.
However, in a similar field of endeavor Spitzmueller discloses a method for predicting how a cancer patient will respond to an antibody drug conjugate (ADC) therapy involves computing a predictive response score by performing statistical operations on the staining of each cancer cell in a tissue sample (abstract). In addition, Spitzmueller discloses the method calculates a third index corresponding to a cell membrane specificity of the at least one of cells and tissues included in the pathological slide image based on the second index, wherein the cell membrane specificity indicates how much of a targeted object is present in a cell membrane of the cell ([0007 – 0008], calculates ADC (a third index corresponding to a cell membrane specificity) based on the staining intensities (the second index); The ADC includes an ADC payload and an ADC antibody that targets a protein on each cancer cell); and control a display apparatus to display information regarding the third index (Figs. 14 - 21).
There was some teaching, suggestion, or motivation, either in Glass and Spitzmueller or in the knowledge generally available to one of ordinary skill in the art, to modify Glass and Spitzmueller, or to combine reference teachings, and further, based on an indicator being located on an area corresponding to arrive at the claimed invention.
There was reasonable expectation of success to modify Glass according to Yoshikawa to arrive at the claimed invention (KSR scenario G).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Glass, and calculate a third index corresponding to a cell membrane specificity of the at least one of cells and tissues included in the pathological slide image based on the second index, wherein the cell membrane specificity indicates how much of a targeted object is present in a cell membrane of the cell; and control a display apparatus to display information regarding the third index. The motivation for doing this is that user can obtain more information that would be more useful for user for a treatment.
Regarding claim 4 (depend on claim 1), Glass discloses the first index further comprises at least one of a first class indicating that the cell membrane is negative or unstained, a second class indicating that the cell membrane is partially stained, or a third class indicating that the cell membrane is completely stained ([0028], “HER2 negative or unstained cells, HER2 partial positive, or HER2 complete positive cells”).
Regarding claims 11 and 14, they are corresponding to claims 1 and 4, respectively, thus, it is interpreted and rejected for a same reason set forth for claims 1 and 4.
Regarding claim 20, it is corresponding to claim 1, thus, it is interpreted and rejected for a same reason set forth for claim 1.
Regarding claim 21 (depend on claim 1), Spitzmueller discloses the apparatus wherein the processor is further configured to control the display apparatus to display an analysis result of an anti-cancer target or a prediction result of a treatment response based on the third index ([0007 – 0008], calculates ADC (a third index corresponding to a cell membrane specificity) based on the staining intensities (the second index); The ADC includes an ADC payload and an ADC antibody that targets a protein on each cancer cell).
Claim(s) 2, 5, 12 and 15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Glass in view of Spitzmueller and Japanese Inventors. (US 2021/0279866), hereinafter referred as JI.
Regarding claim 2 (depend on claim 1), Glass discloses the computing apparatus wherein the first index comprises a class corresponding to a level of staining of the cell membrane of the cell, and the second index comprises at least one of a first score corresponding to a staining intensity of the cell membrane of the cell ([0037 - 0038], staining pattern and intensity of the tumor cell),
However, Glass discloses fails to explicitly disclose further comprising a second score corresponding to a staining intensity of cytoplasm of the cell, and a third score corresponding to a staining intensity of a cell nucleus of the cell.
However, in a similar field of endeavor JI discloses a method for cell image processing (abstract). In addition, JI discloses a score corresponding to a staining intensity of cytoplasm of the cell, and a score corresponding to a staining intensity of a cell nucleus of the cell (page 3 last para to page 4 first para.).
There was some teaching, suggestion, or motivation, either in Glass and JI or in the knowledge generally available to one of ordinary skill in the art, to modify Glass and JI, or to combine reference teachings, and further comprising a second score corresponding to a staining intensity of cytoplasm of the cell, and a third score corresponding to a staining intensity of a cell nucleus of the cell.
There was reasonable expectation of success to modify Glass according to JI to arrive at the claimed invention (KSR scenario G).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Glass, and further comprising a second score corresponding to a staining intensity of cytoplasm of the cell, and a third score corresponding to a staining intensity of a cell nucleus of the cell. The motivation for doing this is that user can obtain more information that would be more useful for user.
Regarding claim 5 (depend on claim 1), Glass discloses the computing apparatus wherein the processor is further configured to: control the display apparatus ([0048]) to display at least one of a visualization result of a second index for at least one of components of each of cells included in the pathological slide image and a visualization result of the first index for any one of the components (Fig. 1, last row).
control the display apparatus to display a graph indicating a distribution of scores corresponding to a staining intensity of at least one of a membrane of each of the cells included in the pathological slide image (Fig. 1, last row; [0036 – 0038]).
However, Glass discloses fails to explicitly disclose further comprising a second score corresponding to a staining intensity of cytoplasm of the cell, and a third score corresponding to a staining intensity of a cell nucleus of the cell.
However, in a similar field of endeavor JI discloses a method for cell image processing (abstract). In addition, JI discloses a score corresponding to a staining intensity of cytoplasm of the cell, and a score corresponding to a staining intensity of a cell nucleus of the cell (page 3 last para to page 4 first para.).
There was some teaching, suggestion, or motivation, either in Glass and JI or in the knowledge generally available to one of ordinary skill in the art, to modify Glass and JI, or to combine reference teachings, and further comprising a second score corresponding to a staining intensity of cytoplasm of the cell, and a third score corresponding to a staining intensity of a cell nucleus of the cell.
There was reasonable expectation of success to modify Glass according to JI to arrive at the claimed invention (KSR scenario G).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Glass, and further comprising a second score corresponding to a staining intensity of cytoplasm of the cell, and a third score corresponding to a staining intensity of a cell nucleus of the cell. The motivation for doing this is that user can obtain more information that would be more useful for user.
Regarding claims 12 and 15, they are corresponding to claims 2 and 5, respectively, thus, it is interpreted and rejected for a same reason set forth for claims 2 and 5.
Claim(s) 3, 6, 13 and 16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Glass in view of Spitzmueller and Svekolkin et al. (US 2021/0279866), hereinafter referred as Svekolkin.
Regarding claim 3 (depend on claim 2), Glass fails to explicitly disclose the computing apparatus wherein the processor is further configured to: convert a format of the subpatches; calculate a histogram of each of color channels for the cell membrane, the cytoplasm, and the cell nucleus included in the converted subpatches; and calculate, by using the machine learning model, at least one of the first score, the second score, and the third score based on a combination of the histograms of the color channels.
However, in a similar field of endeavor Svekolkin a system for medical image processing (abstract). In addition, Svekolkin discloses the processor is further configured to: convert a format of the subpatch; calculate a histogram of each of color channels (Fig. 38, [0252]); Svekolkin discloses the cell membrane, the cytoplasm, and the cell nucleus included in the converted subpatches; and calculate, by using the machine learning model, at least one of the first score, the second score, and the third score ([0089], stain intensity, [0119], neural network, confident, [0122], nuclei, membrane, [0129], cytoplasm). Svekolkin discloses contains a “base” component upon which the claimed invention can be seen as an “improvement”.
Svekolkin discloses a combination of multi channels ([0148]). Glass and Svekolkin contains a “comparable component that has been improved in the same way as the claimed invention.
One of ordinary skill in the art could have applied the known “improvement” technique in the same way to the Glass and Svekolkin’s combination process to convert a format of the subpatch; calculate a histogram of each of color channels for the cell membrane, the cytoplasm, and the cell nucleus included in the converted subpatches; and calculate, by using the machine learning model, at least one of the first score, the second score, and the third score based on a combination of the histograms of the color channels, and the result would have been predictable to one of ordinary skill in the art (KSR scenario C).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Glass, and convert a format of the subpatches; calculate a histogram of each of color channels for the cell membrane, the cytoplasm, and the cell nucleus included in the converted subpatches; and calculate, by using the machine learning model, at least one of the first score, the second score, and the third score based on a combination of the histograms of the color channels. The motivation for doing this is that the combination histogram would explain a straightforward result to user.
Regarding claim 6 (depend on claim 5), Glass fails to explicitly disclose the computing apparatus wherein the processor is further configured to control the display apparatus to overlay and display a heatmap generated based on a score corresponding to the second index, on a screen on which at least a portion of the pathological slide image is output.
However, in a similar field of endeavor Svekolkin a system for medical image processing (abstract). In addition, Svekolkin discloses the processor is further configured to: control the display apparatus to overlay and display a heatmap generated based on a score corresponding to the second index, on a screen on which at least a portion of the pathological slide image is output (Fig. 38A, [0252]. “FIGS. 38A-B are diagrams of percentage heatmaps and distribution densities of histological features”).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Glass, and control the display apparatus to overlay and display a heatmap generated based on a score corresponding to the second index, on a screen on which at least a portion of the pathological slide image is output. The motivation for doing this is that display other information that would be convenient for user.
Regarding claims 13 and 16, they are corresponding to claims 3 and 6, respectively, thus, it is interpreted and rejected for a same reason set forth for claims 3 and 6.
Claim(s) 7 and 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Glass in view of Spitzmueller in further view of JI, Gallop et al. (US 10,818,101), hereinafter referred as Gallop, and Xia et al. (China Patent Application Publication CN 114235539), hereinafter referred as Xia.
Regarding claim 7 (depend on claim 5), Glass discloses the computing apparatus wherein the processor is further configured to control the display apparatus to display an object setting a threshold value ([0037], threshold) determining, based on the score corresponding to the second index, whether or not at least one of the components of the cell is stained ([0037]), and to display the visualization result of the second index based on a user input setting the threshold value through the object ([0048], Fig. 1), and to update the visualization result of the second index, and statistics according to types of the cells included in the pathological slide image as the threshold value is set ([0037, 0048], update by training and feedback).
However, Glass fails to explicitly disclose the processor wherein adjusting the threshold value; to update and display the visualization result based on a user input adjusting the threshold value through the object, the processor is further configured to control the display apparatus to update and display at least one of a tumor proportion score (TPS) and a combined positive score (CPS) corresponding to the pathological slide image.
However, in a similar field of endeavor Gallop discloses a system for medical image processing (abstract). In addition, Gallop discloses the system wherein adjusting the threshold value; to update and display the visualization result based on a user input adjusting the threshold value through the object (claim 1).
In a similar field of endeavor Xia discloses a system for medical image processing (abstract). In addition, Xia discloses the system is further configured to control the display apparatus to update and display at least one of a tumor proportion score (TPS) and a combined positive score (CPS) corresponding to the pathological slide image (page 7 para. 6).
One of ordinary skill in the art could have combined the elements as claimed by known method, and that in combination, each element merely performs the same function as it does separately.
One of ordinary skill in the art would have recognized that the result of the combination would have been predictable (KSR scenario A).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Glass, and adjusting the threshold value; to update and display the visualization result based on a user input adjusting the threshold value through the object, the processor is further configured to control the display apparatus to update and display at least one of a tumor proportion score (TPS) and a combined positive score (CPS) corresponding to the pathological slide image. The motivation for doing this is that the results with different threshold would be clear to user.
Regarding claim 17, it is corresponding to claim 7, thus, it is interpreted and rejected for a same reason set forth for claim 7.
Claim(s) 8 and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Glass in view of Spitzmueller, in further view of JI and PowerPoint (function) (version 2021).
Regarding claim 8 (depend on claim 5), Glass fails to explicitly disclose the computing apparatus wherein the processor is further configured to control the display apparatus to replace the heatmap generated based on the score corresponding to the second index with visualization results of components of each of the cells and display the visualization result, in a case where an enlargement magnification set according to a user input is a preset magnification or more.
However, in a similar field of endeavor PowerPoint discloses a method to control the display (see screenshot). In addition, PowerPoint discloses, in a case where a user drag panel bar from left to right to enlarge right panel, the left panel can be replaced and display only right panel (see screenshot 1 to 2).
There was some teaching, suggestion, or motivation, either in Glass and PowerPoint or in the knowledge generally available to one of ordinary skill in the art, to modify Glass and PowerPoint, or to combine reference teachings, and control the display apparatus to replace the heatmap generated based on the score corresponding to the second index with visualization results of components of each of the cells and display the visualization result, in a case where an enlargement magnification set according to a user input is a preset magnification or more.
There was reasonable expectation of success to modify Glass according to PowerPoint to arrive at the claimed invention (KSR scenario G).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Glass, and control the display apparatus to replace the heatmap generated based on the score corresponding to the second index with visualization results of components of each of the cells and display the visualization result, in a case where an enlargement magnification set according to a user input is a preset magnification or more. The motivation for doing this is that one important feature of the image can be emphasized.
Regarding claim 18, it is corresponding to claim 8, thus, it is interpreted and rejected for a same reason set forth for claim 8.
Allowable Subject Matter
Claims 9 – 10 and 19 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to QIAN YANG whose telephone number is (571)270-7239. The examiner can normally be reached on Monday-Thursday 8am-6pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew Bee can be reached on 571-270-5183. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/QIAN YANG/
Primary Examiner, Art Unit 2677