DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office Action has been withdrawn pursuant to 37 CFR 1.114. Applicant’s submission filed on February 13, 2026 has been entered.
Status of Claims
Claims 1-3, 5-9, 11, 14, 17-20, and 23-27 are pending. Claim 27 is new.
Claims 4, 10, 12-13, 15-18, 21-22 are cancelled.
Response to Amendments
In light of Applicant’s amendments, the objections of record with respect to claims 25 and 26 are withdrawn.
Claim Objections
Claim 25 are objected to because of the following informalities:
Claim 25 recites “…each of which his associated with a cell region…” should be “…each of which is associated with a cell region…”
Appropriate corrections are required.
Response to Arguments
Applicant’s amendments of independent claim 1 which has altered the scope of the claims of the instant application, has necessitated the new ground(s) of rejection presented in this office action with respect to claims of the instant application. Accordingly, in response to Applicant’s arguments that are merely directed to the amended portion of the claims, new analyses, with respect to the supplementally amended claim set dated 02/13/2026, have been presented below, which make Applicant’s arguments moot.
Double Patenting
Non-statutory
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3, 5-9, 11, 14, 17-20, and 23-27 rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 12,608,963 B2 in view of Wong et al. (US 2020/0072730 A1), in further view of Breniman et al. (US 2012/0013727 A1).
This is a nonstatutory double patenting rejection because the patentably indistinct claims have in fact been patented.
For example, the following is a chart comparing claim 1 of the instant application to the claim 1 of U.S. Patent No. 12,608,963 B2:
Instant application: 18/258390
U.S. Patent No. 12,608,963 B2
Claim 1: A blood analyser, the blood analyser comprising a memory, an interface, and one or more processors, the blood analyser being configured to:
obtain image data of a prepared blood sample, the image data comprising data
of a stack of images, where each image of the stack of images is associated with an image plane, wherein each image plane is associated with a different height along a z-axis of the prepared blood sample;
select a first image associated with a first image plane of the prepared blood
sample from the image data;
select a second image associated with a second image plane of the prepared blood sample from the image data, wherein the second image is either a distal or a proximal image in relation to the first image;
characterize the first image, wherein the characterization of the first image comprises determining an initial candidate set of candidate cell regions each comprising a group of pixels in the first image and each representing one or more cells, one or more parts of one or more cells, or optical phenomena relating to one or more cells;
identify, between the initial candidate set of candidate cell regions, a first set of cell regions belonging to the first image plane, where each first cell region satisfies a first intensity contrast criterion, and wherein the first set of cell regions are indicative of one or more platelets;
identify, in the second image, one or more second image plane cell regions, each of which is associated with a cell region from the first set of cell regions, and each of which has a bright area;
determine a first blood parameter based on the first set of cell regions and the one or more second image plane cell regions
Claim 1: A blood analyser, the blood analyser comprising a memory, an interface, and one or more processors, the blood analyser being configured to:
obtain image data of a prepared blood sample, the image data comprising data of a stack of images where each image of the stack of images is associated with an image plane, wherein each image plane is associated with a different height along a z-axis of the prepared blood sample;
select a first image associated with a first image plane of the prepared blood sample from the image data;
Claim 1, 4th limitation: select a first distal image associated with a first distal image plane on a distal side of the first image plane, and
characterize the first image, wherein the characterization of the first image comprises determining a first set of cell regions belonging to the first image plane, wherein a cell region of the first set of cell regions is associated with a group of pixels in the first image representing one or more cells, a part of a cell, parts of cells, or an optical phenomena relating to one or more cells;
determine a first distal set of distal cell regions associated with the first set of cell regions, wherein a cell region of the first distal set of cell regions is associated with a group of pixels in the first distal image representing one or more cells, a part of a cell, parts of cells, or an optical phenomena relating to one or more cells, wherein the determination of the first distal set of distal cell regions comprises determining that the first set of cell regions do not belong to the first distal image plane; and
determine a first cell parameter for each cell region of the first set of cell regions based on the first distal set of distal cell regions.
Although U.S. Patent No. 12,608,963 B2 discloses a blood analyzer using image data of a first and second image captured at different image plane along the z-axis to determine a blood parameter using information from both the captured images. U.S. Patent No. 12,608,963 B2 does not disclose “identify, between the initial candidate set of candidate cell regions, a first set of cell regions belonging to the first image plane, where each first cell region satisfies a first intensity contrast criterion, and wherein the first set of cell regions are indicative of one or more platelets; identify, in the second image, one or more second image plane cell regions, each of which is associated with a cell region from the first set of cell regions, and each of which has a bright area;
However, Wong teaches “identify, between the initial candidate set of candidate cell regions, a first set of cell regions belonging to the first image plane, where each first cell region satisfies a first intensity contrast criterion (Wong paragraph [0028] "The background 204 may be segmented from the foreground 206 in the focused image using edge detection techniques, such as applying one or more thresholds to the focused image 202. The threshold may separate pixels based on their intensity value. For example, pixels that have an intensity value below the threshold may be classified as foreground 206 and pixels that have an intensity value above the threshold may be classified as background 204"), and wherein the first set of cell regions are indicative of one or more platelets (Wong paragraph [0114] "The particular range of wavelengths of light that the light filter 604 is configured to filter may depend upon, for example, the type(s) of cells being imaged"); (Wong paragraph [0051] "The imaging device 404 may be, for example, a monochrome imaging device, a red-green-blue (RGB) imaging device, a spectral imaging device, a fluorescence imaging device, and/or a multi-channel imaging device" - where when using fluorescence imaging device one with ordinary skill in the art knowns that bright or high fluorescence intensity indicates a cell and pixels that contain dark or baseline intensity are considered background)”.
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention of the instant application to combine a blood analyzer using multiple images captured at varied imaging planes to determine a blood parameter as taught by claim 1 of U.S. Patent No. 12,608,963 B2 to use an intensity criteria/brightness to identify objects within a cell, such as a platelet as taught by Wong.
The suggestion/motivation for doing so would have been that one of ordinary skill in the art would recognized a need for accurately counting cells within a blood sample “These techniques improved upon conventional cell counting techniques by providing a fast and accurate way to count cells ( e.g., cells in a cell culture), which reduces human error and promotes the completion of successful experiments” as disclosed by Wong in paragraph 19.
However, the combination of U.S. Patent No. 12,608,963 B2 and Wong is not relied on to teach “identify, in the second image, one or more second image plane cell regions, each of which is associated with a cell region from the first set of cell region”.
Breniman teaches “identify, in the second image, one or more second image plane cell regions (Breniman Figure 5 and paragraph [0024] "system 200 takes and stores a series of digital images at different focus locations"), each of which is associated with a cell region from the first set of cell regions (Breniman paragraph [0041] "FIG. SA shows a portion 801 of a digital image taken at the plane of best focus, and including two cells A and B. The image portion may be referred to as a "region", and for the purposes of classification of cell A, is centered on the location of cell A in the image taken at best focus. The size of the region is selected to be large enough to accommodate drift of cells within the region, but small enough for computational efficiency. In one example embodiment, region 801 may be between 60 and 150 pixels on a side. FIG. SB shows the same region extracted from a later image, in which objects 1 and 2 have been identified by the cell counting steps described above applied to the later image")”.
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention of the instant application to combine a blood analyzer using multiple images captured at varied imaging planes to identify cells using intensity/brightness criteria to determine a blood parameter as taught by claim 1 of U.S. Patent No. 12,608,963 B2 and Wong to use an additional image captured at a different imaging plane as taught by Breniman.
The suggestion/motivation for doing so would have been “No single image is accurate for both total cell counting and live cell characterization. Furthermore, no single image is found to correctly reveal the live or dead status of the cells. In accordance with embodiments of the invention, in order to improve the accuracy of classification of live and dead cells, other digital images in the stack of digital images are exploited to aid in the classification" as noted by the Breniman disclosure in paragraph 35-36.
Therefore, it would have been obvious to combine the claim set of U.S. Patent No. 12,608,963 B2 and Wong with the Breniman disclosure to obtain the invention as specified in the instant application claim 1 as there is reasonable expectation of success and/or because doing so merely combines prior art elements according to known method to yield predictable results. Claims 2-3, 5-9, 11, 14, 17-20, and 23-27 are similarly rejected under nonstatutory obvious-ness type double patenting as being unpatentable over U.S. Patent No. 12,608,963 B2 in view of Wong, and in further view of Breniman.
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 1-3, 5-9, 11, 14, 20 and 23-26 are rejected under 35 U.S.C. 103 as being unpatentable over Wong et al. (US 2020/0072730 A1) in view of Breniman et al. (US 2012/0013727 A1).
Regarding claim 1, Wong teaches “A blood analyser, the blood analyser comprising a memory, an interface (Wong paragraph [0112] "The controller 506 may display a resulting count for the number of cells in the vessel via a display 504 coupled to the controller 506. The display 504 may be implemented as, for example, a liquid crystal display (LCD), a plasma display, and/or an organic light emitting diode (OLED) display. It should be appreciated that the display 504 may be implemented as a touch screen display to allow the controller 506 to receive input commands from an operator"), and one or more processors (Wong paragraph [0022] "The system may comprise a controller that is coupled (e.g., communicatively coupled) to the imaging system. The controller may be implemented using, for example, a processor coupled to memory and/or non-volatile storage"), the blood analyser (Wong paragraph [0062] "cells (e.g., white blood cells) are isolated from blood") being configured to:
obtain image data of a prepared blood sample, the image data comprising data of a stack of images, where each image of the stack of images is associated with an image plane, wherein each image plane is associated with a different height along a z-axis of the prepared blood sample (Wong Fig. 2 and paragraph [0021] "send an instruction to the imaging system to trigger the imaging system to capture a plurality of images in different focal planes (or, equivalently, focal lengths). Such a plurality of images may be termed a "Z stack" as it may include two-dimensional (x-y) images at different focal lengths (different "z" coordinates) relative to an imaging device (e.g., a camera) in the imaging system");
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Wong Fig. 2
select a first image associated with a first image plane of the prepared blood sample from the image data (Wong Fig. 2 and paragraph [0032] "The process may be performed by a system comprising, for example, an imaging system that is configured to capture images of the cells in different focal planes and a controller that is coupled to the imaging system that is configured to analyze the captured images to analyze a focused image");
(Wong paragraph [0037] "the controller may determine that the best image in the plurality of images captured in act 304 is insufficient and repeat act 304 to capture a second plurality of images in a different set of focal planes (relative to the previous set of focal planes associated with the previous plurality of images)");
characterize the first image, wherein the characterization of the first image comprises determining an initial candidate set of candidate cell regions each comprising a group of pixels in the first image and each representing one or more cells, one or more parts of one or more cells, or optical phenomena relating to one or more cells (Wong Fig. 2 and paragraph [0025] "a focused image 202 may be selected from the plurality of images 201 and a foreground 206 of the focused image 202 may be separated from a background 204 of the focused image 204-with a goal of the foreground 206 including the parts of the image that contain cells and the background 204 include the parts of the image that do not contain cells");
identify, between the initial candidate set of candidate cell regions, a first set of cell regions belonging to the first image plane, where each first cell region satisfies a first intensity contrast criterion (Wong paragraph [0028] "The background 204 may be segmented from the foreground 206 in the focused image using edge detection techniques, such as applying one or more thresholds to the focused image 202. The threshold may separate pixels based on their intensity value. For example, pixels that have an intensity value below the threshold may be classified as foreground 206 and pixels that have an intensity value above the threshold may be classified as background 204"), and wherein the first set of cell regions are indicative of one or more platelets (Wong paragraph [0114] "The particular range of wavelengths of light that the light filter 604 is configured to filter may depend upon, for example, the type(s) of cells being imaged");
(Wong paragraph [0051] "The imaging device 404 may be, for example, a monochrome imaging device, a red-green-blue (RGB) imaging device, a spectral imaging device, a fluorescence imaging device, and/or a multi-channel imaging device" - where when using fluorescence imaging device one with ordinary skill in the art knowns that bright or high fluorescence intensity indicates a cell and pixels that contain dark or baseline intensity are considered background );
determine a first blood parameter based on the first set of cell regions (Wong paragraph [0025] "process 200 that may be performed to estimate a number of cells in a vessel. The process 200 may be performed by any of a variety of systems including, for example, a cell culture incubator ( e.g., cell culture incubator 400) or an automated cell counter ( e.g., automated cell counter 500")
However Wong is not relied on to teach “select a second image associated with a second image plane of the prepared blood sample from the image data”, “identify, in the second image, one or more second image plane cell regions, each of which is associated with a cell region from the first set of cell regions”, and determining a blood parameter based on “the one or more second image plane cell regions”.
Breniman teaches “select a second image associated with a second image plane of the prepared blood sample from the image data (Breniman [0037] "The cell is located in another of the digital images, and analyzed again to see if it can be classified as live based on the second digital image")”,
identify, in the second image, one or more second image plane cell regions (Breniman Figure 5 and paragraph [0024] "system 200 takes and stores a series of digital images at different focus locations"), each of which is associated with a cell region from the first set of cell regions (Breniman paragraph [0041] "FIG. SA shows a portion 801 of a digital image taken at the plane of best focus, and including two cells A and B. The image portion may be referred to as a "region", and for the purposes of classification of cell A, is centered on the location of cell A in the image taken at best focus. The size of the region is selected to be large enough to accommodate drift of cells within the region, but small enough for computational efficiency. In one example embodiment, region 801 may be between 60 and 150 pixels on a side. FIG. SB shows the same region extracted from a later image, in which objects 1 and 2 have been identified by the cell counting steps described above applied to the later image"), and each of which has a bright area (Wong paragraph [0051] "The imaging device 404 may be, for example, a monochrome imaging device, a red-green-blue (RGB) imaging device, a spectral imaging device, a fluorescence imaging device, and/or a multi-channel imaging device" - where when using fluorescence imaging device one with ordinary skill in the art knowns that bright or high fluorescence intensity indicates a cell and pixels that contain dark or baseline intensity are considered background )”, and
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Breniman Figure 5
determining a blood parameter using “the one or more second image plane cell regions (Breniman paragraph [0037] "The cell is located in another of the digital images, and analyzed again to see if it can be classified as live based on the second digital image. (Here "second" means the second image analyzed, which may not be the second image taken.) If so, the classification is made, and no further analysis is required in relation to that cell" and paragraph [0039] "This process may be performed for all of the cells in the list of identified cells, and the system may report statistics based on the analysis" and Breniman paragraph [0041] "FIG. SA shows a portion 801 of a digital image taken at the plane of best focus, and including two cells A and B. The image portion may be referred to as a "region", and for the purposes of classification of cell A, is centered on the location of cell A in the image taken at best focus. The size of the region is selected to be large enough to accommodate drift of cells within the region, but small enough for computational efficiency. In one example embodiment, region 801 may be between 60 and 150 pixels on a side. FIG. SB shows the same region extracted from a later image, in which objects 1 and 2 have been identified by the cell counting steps described above applied to the later image")”.
It would have been obvious to a person having ordinary skill in the art before effective filing date of the claimed invention of the instant application to combine a blood sample analyzer using the focus image captured at an image plane as taught by Wong to use an additional blood sample image captured at a different plane as taught by Breniman.
The suggestion/motivation for doing so would have been “No single image is accurate for both total cell counting and live cell characterization. Furthermore, no single image is found to correctly reveal the live or dead status of the cells. In accordance with embodiments of the invention, in order to improve the accuracy of classification of live and dead cells, other digital images in the stack of digital images are exploited to aid in the classification" as noted by the Breniman disclosure in paragraph 35-36.
Therefore, it would have been obvious to combine the disclosure of Wong with the Breniman disclosure to obtain the invention as specified in claim 1 as there is a reasonable expectation of success and/or because doing so merely combines prior art elements according to known methods to yield predictable results.
Regarding claim 2, the combination of Wong and Breniman teaches “The blood analyser according to claim 1, wherein the blood analyser is configured to select, from the image data, a first distal image (Wong paragraph [0037] "the controller may select one image from the plurality of images ( e.g., captured in act 304) as the focused image using the determined areas of the cell(s)”) associated with a first distal image plane on a distal side of the first image plane, and wherein the determining of the first set of cell regions is based on the first distal image (Wong paragraph [0034] "the controller may control the imaging system to capture a plurality of images of the cell(s) in a plurality of different focal planes (e.g., capture a Z stack) […] plurality of focal planes may be selected based on the particular type(s) of cells being counted. For example, focal planes that are above the top of the cells being imaged may be omitted from the plurality of focal planes. In other embodiments, the plurality of focal planes may be a fixed set of focal planes that is used regardless of the type of cell being counted).”
Regarding claim 3, the combination of Wong and Breniman teaches “The blood analyser according to claim 1, wherein the blood analyser is configured to select, from the image data, a first proximal image (Wong paragraph [0037] "the controller may select one image from the plurality of images ( e.g., captured in act 304) as the focused image using the determined areas of the cell(s)") associated with a first proximal image plane on a proximal side of the first image plane, and wherein the determining of the first set of cell regions is based on the first proximal image (Wong paragraph [0034] "the controller may control the imaging system to capture a plurality of images of the cell(s) in a plurality of different focal planes (e.g., capture a Z stack) […] plurality of focal planes may be selected based on the particular type(s) of cells being counted. For example, focal planes that are above the top of the cells being imaged may be omitted from the plurality of focal planes. In other embodiments, the plurality of focal planes may be a fixed set of focal planes that is used regardless of the type of cell being counted).”
Regarding claim 5, the combination of Wong and Breniman teaches “The blood analyser according to claim 4, wherein to determining the first initial candidate set of candidate cell regions comprises to determining a first background image of the first image, and wherein the first initial candidate set of candidate cell regions is based on the first background image (Wong paragraph [0025] "a focused image 202 may be selected from the plurality of images 201 and a foreground 206 of the focused image 202 may be separated from a background 204 of the focused image 204-with a goal of the foreground 206 including the parts of the image that contain cells and the background 204 include the parts of the image that do not contain cells").”
Regarding claim 6, the combination of Wong and Breniman teaches “The blood analyser according to claim 5, wherein to determining the first initial candidate set of candidate cell regions comprises to determining a first contrast image based on the first background image and the first image, and wherein the first initial candidate set of candidate cell regions is based on the first contrast image (Wong paragraph [0036] "a global threshold may be applied to the entire image to separate bright pixels (background) from dark pixels (foreground)").”
Regarding claim 7, the combination of Wong and Breniman teaches “The blood analyser according to claim 6, wherein to determining the first initial candidate set of candidate cell regions comprises to determining a first binary image based on the first contrast image, and wherein the first initial candidate set of candidate cell regions is based on the first binary image (Wong paragraph [0036] "Once the global threshold has been applied, a local threshold may be applied to bounded regions (e.g., bounded rectangles) in the image that include a continuous set of dark pixels to fine-tune the delineation between the foreground and the background. The local threshold may be identified by, for example, using the average intensity of pixel values in the selected region as the threshold. Once the local threshold has been applied, areas of the background that are completely ( or partially) surrounded by a continuous region of foreground pixels may be added to the foreground").”
Regarding claim 8, the combination of Wong and Breniman teaches “The blood analyser according to claim 7, wherein to determining the first initial candidate set of candidate cell regions comprises identifying connected regions in the first binary image, and wherein the first initial candidate set of candidate cell regions is based on the connected regions in the first binary image (Wong paragraph [0036] "The continuous regions in the resulting foreground may be identified as objects. The objects that have characteristics of a single cell (e.g., size, shape, and/or color) may be used in the calculation of the area of the cell(s)").”
Regarding claim 9, the combination of Wong and Breniman teaches “The blood analyser according to claim 8, wherein determining the first initial candidate set of candidate cell regions comprises determining whether each respective connected region satisfies an area criterion, and in accordance with the determination that the respective connected region satisfies the area criterion, including the respective connected region satisfying the area criterion as a candidate cell region in the first initial candidate set of candidate cell regions (Wong paragraph [0036] "The area of the identified single cells may be estimated by, for example, counting a number of pixels associated with the identified single cells and/or estimating a length of an axis of the identified single cells").”
Regarding claim 11, the combination of Wong and Breniman teaches “The blood analyser according to claim 4, wherein the characterization of the first image comprises determining whether each of the respective candidate cell regions of the first initial candidate set of candidate cell regions satisfies a first criterion (Wong paragraph [0030] "The object 208 may be identified in the focused image 206 by, for example, identifying continuous regions of pixels in the foreground 204 ( e.g., as indicated by the mask) as objects. Once the object 208 has been identified, the object 208 may be classified by, for example, identifying one or more features of the object 208 and providing the identified features of the object 208 as input to a classifier"), and in accordance with the determination that a respective candidate cell region of the first initial candidate set of candidate cell regions respectively satisfies the first criterion, including the respective candidate cell region in a first candidate set of cell regions, and wherein the first set of cell regions is based on the first candidate set of candidate cell regions (Wong paragraph [0030] "Once the features of the object 208 are identified, these features may be used as an input to a classifier that is configured ( e.g., trained) to distinguish between different classes of objects").”
Regarding claim 14, the combination of Wong and Breniman teaches “the blood analyser according to claim 1, wherein the first image plane is associated with a first height in the prepared blood sample (Wong Fig. 1B and paragraph [0035] "The plurality of focal planes may be evenly (or unevenly) spaced").”
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Wong Fig. 1B
Regarding claim 20, it recites a computer readable medium including computer executable instructions corresponding to the elements of the device recited in claim 1. Therefore, the recited instructions of the computer readable medium of claim 20 are mapped to the proposed combination in the same manner as the corresponding elements of the device in claim 1. Additionally, the rationale and motivation to combine Wong and Breniman presented in rejection of claim 1, apply to this claim.
Regarding claim 23, the combination of Wong and Breniman The blood analyser according to claim 1, wherein the blood analyser is configured to select, from the image data, a first distal image (Wong paragraph [0037] "the controller may select one image from the plurality of images ( e.g., captured in act 304) as the focused image using the determined areas of the cell(s)") associated with a first distal image plane on a distal side of the first image plane (Breniman paragraph [0037] "the system may search only the image taken at the plane of best focus and at most the three images taken at the next locations farther from the camera"), and wherein the determining of the first set of cell regions is based on the first distal image (Wong paragraph [0034] "the controller may control the imaging system to capture a plurality of images of the cell(s) in a plurality of different focal planes (e.g., capture a Z stack) […] plurality of focal planes may be selected based on the particular type(s) of cells being counted. For example, focal planes that are above the top of the cells being imaged may be omitted from the plurality of focal planes. In other embodiments, the plurality of focal planes may be a fixed set of focal planes that is used regardless of the type of cell being counted);
wherein the blood analyser is configured to select, from the image data, a first proximal image associated with a first proximal image plane on a proximal side of the first image plane (Wong paragraph [0037] "the controller may determine that the best image in the plurality of images captured in act 304 is insufficient and repeat act 304 to capture a second plurality of images in a different set of focal planes (relative to the previous set of focal planes associated with the previous plurality of images)"), and wherein the determining of the first set of cell regions is based on the first proximal image (Wong paragraph [0034] "the controller may control the imaging system to capture a plurality of images of the cell(s) in a plurality of different focal planes (e.g., capture a Z stack) […] plurality of focal planes may be selected based on the particular type(s) of cells being counted. For example, focal planes that are above the top of the cells being imaged may be omitted from the plurality of focal planes. In other embodiments, the plurality of focal planes may be a fixed set of focal planes that is used regardless of the type of cell being counted);
wherein the first image plane is associated with a first height in the prepared blood sample (Wong paragraph [0035] "plurality of focal planes may be selected based on the particular type(s) of cells being counted. For example, focal planes that are above the top of the cells being imaged may be omitted from the plurality of focal planes. In other embodiments, the plurality of focal planes may be a fixed set of focal planes that is used regardless of the type of cell being counted"); and
wherein the first distal image plane is associated with a first distal height in the prepared blood sample, the first distal height being different from the first height, and wherein the first proximal image plane is associated with a first proximal height in the prepared blood sample, the first proximal height being different from the first height (Wong paragraph [0035] "the controller may control the imaging system to capture a plurality of images of the cell(s) in a plurality of different focal planes (e.g., capture a Z stack) […] The plurality of focal planes may be evenly (or unevenly) spaced").”
Regarding claim 24, the combination of Wong and Breniman teaches “The blood analyser according to claim 1, wherein the blood analyser is configured to select, from the image data, a first distal image (Wong paragraph [0037] "the controller may select one image from the plurality of images ( e.g., captured in act 304) as the focused image using the determined areas of the cell(s).") associated with a first distal image plane on a distal side of the first image plane, and wherein the determining of the first set of cell regions is based on the first distal image (Wong paragraph [0034] "the controller may control the imaging system to capture a plurality of images of the cell(s) in a plurality of different focal planes (e.g., capture a Z stack) […] plurality of focal planes may be selected based on the particular type(s) of cells being counted. For example, focal planes that are above the top of the cells being imaged may be omitted from the plurality of focal planes. In other embodiments, the plurality of focal planes may be a fixed set of focal planes that is used regardless of the type of cell being counted);
wherein the blood analyser is configured to select, from the image data, a first proximal image (Wong paragraph [0037] "the controller may select one image from the plurality of images ( e.g., captured in act 304) as the focused image using the determined areas of the cell(s).") associated with a first proximal image plane on a proximal side of the first image plane, and wherein the determining of the first set of cell regions is based on the first proximal image (Wong paragraph [0034] "the controller may control the imaging system to capture a plurality of images of the cell(s) in a plurality of different focal planes (e.g., capture a Z stack) […] plurality of focal planes may be selected based on the particular type(s) of cells being counted. For example, focal planes that are above the top of the cells being imaged may be omitted from the plurality of focal planes. In other embodiments, the plurality of focal planes may be a fixed set of focal planes that is used regardless of the type of cell being counted); and
wherein a first distal distance between the first image plane and the first distal image plane, and a first proximal distance between the first image plane and the first proximal image plane are equal (Wong paragraph [0035] "The plurality of focal planes may be evenly (or unevenly) spaced").”
Regarding claim 25, the combination of Wong and Breniman teaches “A blood analyser, the blood analyser comprising a memory, an interface (Wong paragraph [0112] "The controller 506 may display a resulting count for the number of cells in the vessel via a display 504 coupled to the controller 506. The display 504 may be implemented as, for example, a liquid crystal display (LCD), a plasma display, and/or an organic light emitting diode (OLED) display. It should be appreciated that the display 504 may be implemented as a touch screen display to allow the controller 506 to receive input commands from an operator"), and one or more processors (Wong paragraph [0022] "The system may comprise a controller that is coupled (e.g., communicatively coupled) to the imaging system. The controller may be implemented using, for example, a processor coupled to memory and/or non-volatile storage"), the blood analyser being configured to: obtain image data of a prepared blood sample, the image data comprising data of a stack of images, where each image of the stack of images is associated with an image plane, wherein each image plane is associated with a different height along a z-axis of the prepared blood sample (Wong Fig. 2 and paragraph [0021] "send an instruction to the imaging system to trigger the imaging system to capture a plurality of images in different focal planes (or, equivalently, focal lengths). Such a plurality of images may be termed a "Z stack" as it may include two-dimensional (x-y) images at different focal lengths (different "z" coordinates) relative to an imaging device (e.g., a camera) in the imaging system");
select a first image associated with a first image plane of the prepared blood sample from the image data (Wong paragraph [0037] "the controller may select one image from the plurality of images ( e.g., captured in act 304) as the focused image using the determined areas of the cell(s)") ;
select, from the image data (Wong paragraph [0026] “The plurality of images 201 may be captured in a plurality of different focal planes (e.g., the plurality of images 201 may be a Z stack). The focal planes may be spaced evenly ( e.g., each focal plane is separated by two microns) or unevenly (e.g., some focal planes are separated by one micron while others are separated by three microns)”), a first distal image associated with a first distal image plane on a distal side of the first image plane (Breniman Figure 5 and paragraph [0037] "the system may search only the image taken at the plane of best focus and at most the three images taken at the next locations farther from the camera");
characterize the first image, wherein the characterization of the first image comprises determining a first set of an initial candidate set of candidate cell regions each comprising a group of pixels in the first image and each representing one or more cells, one or more parts of one or more cells, or optical phenomena relating to one or more cells (Wong Fig. 2 and paragraph [0025] "a focused image 202 may be selected from the plurality of images 201 and a foreground 206 of the focused image 202 may be separated from a background 204 of the focused image 204-with a goal of the foreground 206 including the parts of the image that contain cells and the background 204 include the parts of the image that do not contain cells");
identify, between the initial candidate set of candidate cell regions, a first set of cell regions belonging to the first image plane, where each first cell region satisfies a first intensity contrast criterion (Wong paragraph [0028] "The background 204 may be segmented from the foreground 206 in the focused image using edge detection techniques, such as applying one or more thresholds to the focused image 202. The threshold may separate pixels based on their intensity value. For example, pixels that have an intensity value below the threshold may be classified as foreground 206 and pixels that have an intensity value above the threshold may be classified as background 204"), and wherein the first set of cell regions are indicative of one or more platelets (Wong paragraph [0114] "The particular range of wavelengths of light that the light filter 604 is configured to filter may depend upon, for example, the type(s) of cells being imaged");
identify, in the first distal image (Breniman Figure 5 and paragraph [0037] "the system may search only the image taken at the plane of best focus and at most the three images taken at the next locations farther from the camera"), one or more first distal image plane cell regions, each of which his associated with a cell region from the first set of cell regions (Breniman paragraph [0041] "FIG. SA shows a portion 801 of a digital image taken at the plane of best focus, and including two cells A and B. The image portion may be referred to as a "region", and for the purposes of classification of cell A, is centered on the location of cell A in the image taken at best focus. The size of the region is selected to be large enough to accommodate drift of cells within the region, but small enough for computational efficiency. In one example embodiment, region 801 may be between 60 and 150 pixels on a side. FIG. SB shows the same region extracted from a later image, in which objects 1 and 2 have been identified by the cell counting steps described above applied to the later image"), and each of which has a bright area (Wong paragraph [0051] "The imaging device 404 may be, for example, a monochrome imaging device, a red-green-blue (RGB) imaging device, a spectral imaging device, a fluorescence imaging device, and/or a multi-channel imaging device" - where when using fluorescence imaging device one with ordinary skill in the art knowns that bright or high fluorescence intensity indicates a cell and pixels that contain dark or baseline intensity are considered background ); and
determine a first blood parameter based on the first set of cell regions (Wong paragraph [0025] "process 200 that may be performed to estimate a number of cells in a vessel. The process 200 may be performed by any of a variety of systems including, for example, a cell culture incubator ( e.g., cell culture incubator 400) or an automated cell counter ( e.g., automated cell counter 500" and Breniman paragraph [0034] "an example measurement showing how images taken at different focus positions, if analyzed individually, give different results for total cell count and the number of cells identified as being live") and the one or more first distal image plane (Breniman Figure 5 and paragraph [0037] "the system may search only the image taken at the plane of best focus and at most the three images taken at the next locations farther from the camera") cell regions (Breniman paragraph [0037] "The cell is located in another of the digital images, and analyzed again to see if it can be classified as live based on the second digital image. (Here "second" means the second image analyzed, which may not be the second image taken.) If so, the classification is made, and no further analysis is required in relation to that cell" and paragraph [0039] "This process may be performed for all of the cells in the list of identified cells, and the system may report statistics based on the analysis" and Breniman paragraph [0041] "FIG. SA shows a portion 801 of a digital image taken at the plane of best focus, and including two cells A and B. The image portion may be referred to as a "region", and for the purposes of classification of cell A, is centered on the location of cell A in the image taken at best focus. The size of the region is selected to be large enough to accommodate drift of cells within the region, but small enough for computational efficiency. In one example embodiment, region 801 may be between 60 and 150 pixels on a side. FIG. SB shows the same region extracted from a later image, in which objects 1 and 2 have been identified by the cell counting steps described above applied to the later image").
The proposed combination as well as the motivation for combining Wong and Breniman references presented in the rejection of claim 1, applies to claim 25. Finally the device recited in claim 25 is met by Wong and Breniman.
Regarding claim 26, the combination of Wong and Breniman teaches “A blood analyser, the blood analyser comprising a memory, an interface (Wong paragraph [0112] "The controller 506 may display a resulting count for the number of cells in the vessel via a display 504 coupled to the controller 506. The display 504 may be implemented as, for example, a liquid crystal display (LCD), a plasma display, and/or an organic light emitting diode (OLED) display. It should be appreciated that the display 504 may be implemented as a touch screen display to allow the controller 506 to receive input commands from an operator"), and one or more processors (Wong paragraph [0022] "The system may comprise a controller that is coupled (e.g., communicatively coupled) to the imaging system. The controller may be implemented using, for example, a processor coupled to memory and/or non-volatile storage"), the blood analyser being configured to: obtain image data of a prepared blood sample, the image data comprising data of a stack of images, where each image of the stack of images is associated with an image plane, wherein each image plane is associated with a different height along a z-axis of the prepared blood sample (Wong Fig. 2 and paragraph [0021] "send an instruction to the imaging system to trigger the imaging system to capture a plurality of images in different focal planes (or, equivalently, focal lengths). Such a plurality of images may be termed a "Z stack" as it may include two-dimensional (x-y) images at different focal lengths (different "z" coordinates) relative to an imaging device (e.g., a camera) in the imaging system");
select a first image associated with a first image plane of the prepared blood sample from the image data (Wong paragraph [0037] "the controller may select one image from the plurality of images ( e.g., captured in act 304) as the focused image using the determined areas of the cell(s)");
select, from the image data, a first proximal image (Breniman paragraph [0037] "The cell is located in another of the digital images, and analyzed again to see if it can be classified as live based on the second digital image. (Here "second" means the second image analyzed, which may not be the second image taken.)") associated with a first proximal image plane on a proximal side of the first image plane (Wong paragraph [0037] "the controller may determine that the best image in the plurality of images captured in act 304 is insufficient and repeat act 304 to capture a second plurality of images in a different set of focal planes (relative to the previous set of focal planes associated with the previous plurality of images)");
characterize the first image, wherein the characterization of the first image comprises determining a an initial candidate set of candidate cell regions each comprising a group of pixels in the first image and each representing one or more cells, one or more parts of one or more cells, or optical phenomena relating to one or more cells (Wong Fig. 2 and paragraph [0025] "a focused image 202 may be selected from the plurality of images 201 and a foreground 206 of the focused image 202 may be separated from a background 204 of the focused image 204-with a goal of the foreground 206 including the parts of the image that contain cells and the background 204 include the parts of the image that do not contain cells");
identify, between the initial candidate set of candidate cell regions, a first set of cell regions belonging to the first image plane, where each first cell region satisfies a first intensity contrast criterion (Wong paragraph [0028] "The background 204 may be segmented from the foreground 206 in the focused image using edge detection techniques, such as applying one or more thresholds to the focused image 202. The threshold may separate pixels based on their intensity value. For example, pixels that have an intensity value below the threshold may be classified as foreground 206 and pixels that have an intensity value above the threshold may be classified as background 204"), and wherein the first set of cell regions are indicative of one or more platelets (Wong paragraph [0114] "The particular range of wavelengths of light that the light filter 604 is configured to filter may depend upon, for example, the type(s) of cells being imaged");
identify, in the first proximal image (Wong paragraph [0037] "the controller may determine that the best image in the plurality of images captured in act 304 is insufficient and repeat act 304 to capture a second plurality of images in a different set of focal planes (relative to the previous set of focal planes associated with the previous plurality of images)"), one or more first proximal image plane cell regions, each of which is associated with a cell region from the first set of cell regions (Breniman paragraph [0041] "FIG. SA shows a portion 801 of a digital image taken at the plane of best focus, and including two cells A and B. The image portion may be referred to as a "region", and for the purposes of classification of cell A, is centered on the location of cell A in the image taken at best focus. The size of the region is selected to be large enough to accommodate drift of cells within the region, but small enough for computational efficiency. In one example embodiment, region 801 may be between 60 and 150 pixels on a side. FIG. SB shows the same region extracted from a later image, in which objects 1 and 2 have been identified by the cell counting steps described above applied to the later image"), and each of which has a bright area (Wong paragraph [0051] "The imaging device 404 may be, for example, a monochrome imaging device, a red-green-blue (RGB) imaging device, a spectral imaging device, a fluorescence imaging device, and/or a multi-channel imaging device" - where when using fluorescence imaging device one with ordinary skill in the art knowns that bright or high fluorescence intensity indicates a cell and pixels that contain dark or baseline intensity are considered background ); and
determine a first blood parameter based on the first set of cell regions (Wong paragraph [0025] "process 200 that may be performed to estimate a number of cells in a vessel. The process 200 may be performed by any of a variety of systems including, for example, a cell culture incubator ( e.g., cell culture incubator 400) or an automated cell counter ( e.g., automated cell counter 500" and Breniman paragraph [0034] "an example measurement showing how images taken at different focus positions, if analyzed individually, give different results for total cell count and the number of cells identified as being live") and the one or
more first proximal image plane ((Wong paragraph [0037] "the controller may determine that the best image in the plurality of images captured in act 304 is insufficient and repeat act 304 to capture a second plurality of images in a different set of focal planes (relative to the previous set of focal planes associated with the previous plurality of images)") cell regions (Breniman paragraph [0037] "The cell is located in another of the digital images, and analyzed again to see if it can be classified as live based on the second digital image. (Here "second" means the second image analyzed, which may not be the second image taken.) If so, the classification is made, and no further analysis is required in relation to that cell" and paragraph [0039] "This process may be performed for all of the cells in the list of identified cells, and the system may report statistics based on the analysis" and Breniman paragraph [0041] "FIG. SA shows a portion 801 of a digital image taken at the plane of best focus, and including two cells A and B. The image portion may be referred to as a "region", and for the purposes of classification of cell A, is centered on the location of cell A in the image taken at best focus. The size of the region is selected to be large enough to accommodate drift of cells within the region, but small enough for computational efficiency. In one example embodiment, region 801 may be between 60 and 150 pixels on a side. FIG. SB shows the same region extracted from a later image, in which objects 1 and 2 have been identified by the cell counting steps described above applied to the later image").
The proposed combination as well as the motivation for combining Wong and Breniman references presented in the rejection of claim 1, applies to claim 26. Finally the device recited in claim 26 is met by Wong and Breniman.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Wong and Breniman in view of Ruberto et al. (“Detection of Red and White Blood Cells from Microscopic Blood Images Using a Region Proposal Approach” – Publication year 2019).
Regarding claim 19, the combination of Wong and Breniman teaches the blood analyzer of claim 1. However, the combination of Wong and Breniman is not relied on to teach “a distance between two image planes of the image data is in the range of 1 μm to 10 μm.”
Ruberto teaches “a distance between two image planes of the image data is in the range of 1 μm to 10 μm (Ruberto page 2 left hand column paragraph 7 and 6 "RBCs (or erythrocytes) are also non-nucleated and have a 7–8 μm diameter with a uniform size […] WBCs (or leukocytes) have a diameter ranging from 10 to 20 μm).”
It would have been obvious to a person having ordinary skill in the art before
effective filing date of the claimed invention of the instant application to combine a
blood sample analyzer as taught by Wong and Breniman to include references to known cell properties for microscopic blood sample analysis as taught by Ruberto.
The suggestion/motivation for doing so would have been "blood smears are always performed to monitor patients under therapy, describing the appearance of the cells as well as any cell abnormalities. However, a manual blood smear analysis is lengthy and repetitive, and its results depend on the operator’s skills and opinion." as noted by the Ruberto disclosure in page 2 left hand column paragraph 3.
Therefore, it would have been obvious to combine the disclosure of Wong and Breniman with the Ruberto disclosure to obtain the invention as specified in claim 19 as there is a reasonable expectation of success and/or because doing so merely combines prior art elements according to known methods to yield predictable results.
Claim 27 is rejected under 35 U.S.C. 103 as being unpatentable over Wong and Breniman in view of Choi et al. (WO2022250460A1 - Translation from Espacenet).
Regarding claim 27, the combination of Wong and Breniman teaches “The blood analyser of claim 1, wherein: determining the first blood parameter based on the first set of cell regions and the one or more second image plane cell regions (Wong paragraph [0025] "process 200 that may be performed to estimate a number of cells in a vessel. The process 200 may be performed by any of a variety of systems including, for example, a cell culture incubator ( e.g., cell culture incubator 400) or an automated cell counter ( e.g., automated cell counter 500" and Breniman paragraph [0034] "an example measurement showing how images taken at different focus positions, if analyzed individually, give different results for total cell count and the number of cells identified as being live") comprises using a lens effect producing the bright areas in the one or more second image plane cell regions to distinguish platelet cell regions in the first set of cell regions from non-platelet cell regions in the first set of cell regions (Wong paragraph [0114] "The imaging device 608 may be configured to detect light that passes through the vessel 606 to capture an image of the cells in the vessel 606. The light source 602 may be configured to emit light in a broad spectrum (such as white light) to illuminate the vessel 606. The light source 602 may be implemented using light emitting diodes (LEDs), incandescent lamps, and/or halogen lamps. The light filter 604 may be configured to filter at least some of the light from the light source 602. For example, the light filter 604 may reduce an intensity of at least some light in a specified range of wavelengths. The particular range of wavelengths of light that the light filter 604 is configured to filter may depend upon, for example, the type(s) of cells being imaged")“
However, the combination of Wong and Breniman is not relied on to teach “the first blood parameter is a platelet count”.
Choi teaches “the first blood parameter is a platelet count (Choi paragraph [0014] "platelet counting step (S40) of counting individual platelets distributed in the single platelets and platelet aggregations")”.
It would have been obvious to a person having ordinary skill in the art before
effective filing date of the claimed invention of the instant application to combine a
blood sample analyzer as taught by Wong and Breniman to include counting platelets in a blood sample as taught by Choi.
The suggestion/motivation for doing so would have been " "corrective measures had problems such as deterioration of CBC samples or poor specimen quality, or excessive measurement of platelets, and ultimately had limitations in resolving the problem of inaccurate platelet counts" as noted by the Choi disclosure in paragraph 5.
Therefore, it would have been obvious to combine the disclosure of Wong and Breniman with the Choi disclosure to obtain the invention as specified in claim 27 as there is a reasonable expectation of success and/or because doing so merely combines prior art elements according to known methods to yield predictable results.
Reference Cited
The prior art made of record and not relied upon is considered pertinent to applicant’s disclosure.
US Publication 2017/0292905 A1 to Obrien et al. discloses a method for counting platelets and blood cells in a blood sample by adjusting focal lengths.
US Publication 2023/0003622 A1 to Yafin et al. discloses a system and method for detecting platelets using multiple microscopic images.
Conclusion
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/JASPREET KAUR/Examiner, Art Unit 2662
/AMANDEEP SAINI/Supervisory Patent Examiner, Art Unit 2662
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