DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Preliminary amendments have been made, claims 1-4, 7-11, 14-17, and 31 have been amended. Claim 18 is rejected. Claims 1-17 and 19-21 are pending.
Priority
This application is a national phase filing under35 U.S.C. 371 of International Application No. PCT/US2022/032207, filed June 3. 2022, which claims priority to and the benefit of U.S. Provisional Application 63/337,252 filed on May 2, 2022, and to U.S. Provisional Application 63/196,415 filed on June 3, 2021.
Information Disclosure Statement
The IDS filed 11/29/23 is considered.
Claim objection
Claim 4 recites “wherein the at least one processor is further configured to determine prioritization of the at least one well based at least in part on based at least in part on the at least one cell in each well”. This seems to be erroneous duplicate language, correction is recommended.
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, 4-5, 8-9, 11-12, 15-16, 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over APPLEDORN (US 20030040104 A1 Hereinafter “APPLEDORN”) in view of Koebler (US 20040128077 A1 Hereinafter “Koebler”).
Regarding claim 1, APPLEDORN teaches a system comprising:
an incubation chamber that receives a filled well array (Fig. 6, Abstract: “Systems and methods are provided for automatically imaging and analyzing cell samples in an incubator. An actuated microscope operates to generate images of samples within wells of a sample container across days, weeks, or months");
wherein the filled well array comprises a well array having a sample of cells (Fig. 1, [0066]: “FIG. 1 illustrates the contents 100 of an example sample container (e.g., contents of a well of a sample container that contains an array of such wells). The contents 100 include a first cell 110a and a second cell 110b (e.g., first and second neurons)”);
wherein the well array comprises at least one well (Fig. 1, [0066]: “FIG. 1 illustrates the contents 100 of an example sample container (e.g., contents of a well of a sample container that contains an array of such wells)”. Fig. 6 also shows the array of wells that contain the sample);
an imaging device in or near the incubation chamber to capture a series of images of the filled well array during incubation in the incubation chamber ([0059]: “The samples, within their sample container(s), and the automated imaging system could both be disposed within an incubator, avoiding the necessity of removing the samples from an incubator in order to image them”);
wherein the imaging device communicates the series of images to at least one processor ([0091]: “For example, a first device could be an embedded processor(s) that could operate an actuated gantry, imaging apparatus, or other elements to generate images of biological samples during a plurality of different scan periods”);
wherein the at least one processor is configured to:
detect at least one cell of the sample of cells in each well of each image of the series of images of the filled well array ([0066]: “The cells 110a, 110b include active areas that may be detected, using the methods described herein, as respective active objects”),
While it is presumed APPLEDORN does teach detection and localization of the wells, so as to place the camera in the best position to take the image, APPLEDORN does not expressly disclose detection and localization of wells, and tracking a relative location of each cell of the at least one cell in each well in each image of the series of images, and determine cell-to-cell contact based at least in part on the relative location.
However, Koebler teaches detection and localization of the wells ([0094]: “By having the field of view of the camera great enough so that many wells appear in the image, the grayness scale can be used to identify the center of the wells in the image. This occurs again by the contrast of the pixels at the edge of each well will be distinct from the grayness of the pixels in the plate about the edge. The pixels having a corresponding grayness are linked to define the edge of the given well, and an approximate center of the well can be determined by calculating half the distance from the two sets of opposing sides in regard to a rectangular shaped well, or counting the pixels to determine the length of a diameter of a circle in regard to a round shaped well, and calculating the center of the circle from the diameter, as is well known in the art”) and tracking a relative location of each cell of the at least one cell (Table 1: Table 1 represents parameters measured. It includes 50-52 which are Unique track index, track size, and track boundary. All 3 work to create a track for the cells over multiple images, this track is based off the cells relative location) in each well in each image of the series of images ([0094-100]: These paragraphs describe the locating of the wells and alignment of them in relativity to the camera to take a picture “In the first image taken of the well, a predetermined location for the focal point, such as the middle of the well, or a small distance above the bottom of the well, can be used. Once cells are identified in the well from images obtained of the well, then subsequent images can have the lens of the microscope at different depths in the well depending on the depth of a cell being studied” [0099]. This describes the process for a single well, this process would be performed on every well since this is the described process for imaging a single well and there is samples in every well that need analyzed, resulting in the tracking of at least one cell in each well in a series of images), and determine cell-to-cell contact based at least in part on the relative location (Table 1: Table 1 represents parameters measured. It includes 57-59 which are Proximity (cell to cell contact), Frequency of proximity, and Duration of proximity. All 3 use the relative position and track of the cell to determine 2 cells get close to each other and if they come in contact).
At the time the invention was made, it would have been obvious to one of ordinary skill in the art to modify APPLEDORN’s cell incubation and imaging system to include Koebler’s detection and localization of wells and tracking of cells for determination of cell-cell contact because such a modification is the result of applying a known technique to a known device ready for improvement to yield predictable results. More specifically, include Koebler’s detection and localization of wells and tracking of cells for determination of cell-cell contact permits a method of detecting and localizing the well for image capture and acquiring additional information about the cells (tracking and cell-cell contact), which leads to an improved understanding of them (such as cell motility and a cell’s ability to perform functions present in cell-cell interactions). This known benefit in Koebler is applicable to APPLEDORN’s cell incubation and imaging system as they both share characteristics and capabilities, namely, they are directed to evaluation of cell cultures using imaging modalities. Therefore, it would have been recognized that modifying APPLEDORN’s cell incubation and imaging system to include Koebler’s detection and localization of wells and tracking of cells for determination of cell-cell contact would have yielded predictable results because (i) the level of ordinary skill in the art demonstrated by the references applied shows the ability to incorporate Koebler’s detection and localization of wells and tracking of cells for determination of cell-cell contact in evaluation of cell cultures using imaging modalities and (ii) the benefits of such a combination would have been recognized by those of ordinary skill in the art.
Regarding claim 2, the combination of APPLEDORN and Koebler teaches the system of claim 1, in addition, Koebler further teaches wherein the at least one processor is further configured to determine number of cells in each well in each image of the series of images based at least in part on a prioritization of the at least one well ([0018]: “The apparatus 10 comprises an automated biochamber 12 having a plate 14 with at least a first well 16 in which cells are disposed in a controlled environment automatically maintained at desired conditions”. The well being designated as “first” details some prioritization of the well. Table 1 also describes 1, 2, and 3 which is colony count, object count, and proliferation count. All three describe a process of determining the number of cells in a well).
At the time the invention was made, it would have been obvious to one of ordinary skill in the art to modify APPLEDORN’s cell incubation and imaging system to include Koebler’s prioritization of wells and counting of cells because such a modification is the result of applying a known technique to a known device ready for improvement to yield predictable results. More specifically, include Koebler’s prioritization of wells and counting of cells permits prioritizing a well for imaging and acquiring additional information about the cells (cell count), which leads to an improved understanding of them. This known benefit in Koebler is applicable to APPLEDORN’s cell incubation and imaging system as they both share characteristics and capabilities, namely, they are directed to evaluation of cell cultures using imaging modalities. Therefore, it would have been recognized that modifying APPLEDORN’s cell incubation and imaging system to include Koebler’s prioritization of wells and counting of cells would have yielded predictable results because (i) the level of ordinary skill in the art demonstrated by the references applied shows the ability to incorporate Koebler’s prioritization of wells and counting of cells in evaluation of cell cultures using imaging modalities and (ii) the benefits of such a combination would have been recognized by those of ordinary skill in the art.
Regarding claim 4, the combination of APPLEDORN and Koebler teaches the system of claim 1, in addition, Koebler further teaches wherein the at least one processor is further configured to determine prioritization of the at least one well based at least in part on based at least in part on the at least one cell in each well ([0018]: “The apparatus 10 comprises an automated biochamber 12 having a plate 14 with at least a first well 16 in which cells are disposed in a controlled environment automatically maintained at desired conditions”. The well being designated as “first” details some prioritization of the well. It is based on the at least one cell in the well because the determination of imaging the well is made based on if there is a cell present in the well).
The rationale for this combination is the same rationale as the combination in the rejection of claim 2 due to similar methods of combination and benefits (regarding the prioritization).
Regarding claim 5, the combination of APPLEDORN and Koebler teaches the system of claim 1, in addition, Koebler further teaches comprising at least one applicator that dispenses at least one substance onto the sample of cells to prepare the sample of cells for imaging ([0090]: “For surface-marker phenotype analysis, single fluorescent images are acquired only after staining”. The cells that are stained must be stained with an applicator).
At the time the invention was effectively filed, it would have been obvious to one of ordinary skill in the art to modify APPLEDORN’s cell incubation and imaging system to include Koebler’s staining and applicator for staining cells because such a modification is taught, suggested, or motivated by the art. More specifically, the motivation to modify APPLEDORN to include Koebler is expressly provided by Koebler, stating that to perform phenotype analysis, the cells must be stained first. Phenotype analysis of the cells allows them to obtain more information about the cells leader to overall better analysis of the cells. Therefore, it would have been obvious to one of ordinary skill in the art at the time of the invention to modify APPLEDORN’s cell incubation and imaging system to include Koebler’s staining and applicator for staining cells with the motivation of overall improving analysis of the cells. The person of ordinary skill in the art would have recognized the benefit of improved analysis of the cells.
Regarding claim 8, the content of claim 8 is similar to the content of claim 1, therefore it is rejected for the same reasons of obviousness as claim 1.
Regarding claim 9, the content of claim 9 is similar to the content of claim 2, therefore it is rejected for the same reasons of obviousness as claim 2.
Regarding claim 11, the content of claim 11 is similar to the content of claim 4, therefore it is rejected for the same reasons of obviousness as claim 4.
Regarding claim 12, the content of claim 12 is similar to the content of claim 5, therefore it is rejected for the same reasons of obviousness as claim 5.
Regarding claim 15, the content of claim 15 is similar to the content of claim 1, with the additional teachings of a non-transitory computer readable medium. AUTHOR also discloses this information (Source). Therefore, claim 15 is rejected for the same reasons of obviousness as claim 1, along with the additional teachings above.
Regarding claim 16, the content of claim 16 is similar to the content of claim 2, therefore it is rejected for the same reasons of obviousness as claim 2.
Regarding claim 18, the content of claim 18 is similar to the content of claim 4, therefore it is rejected for the same reasons of obviousness as claim 4.
Regarding claim 19, the content of claim 19 is similar to the content of claim 5, therefore it is rejected for the same reasons of obviousness as claim 5.
Claims 3, 10, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over APPLEDORN (US 20030040104 A1 Hereinafter “APPLEDORN”) in view of Koebler (US 20040128077 A1 Hereinafter “Koebler”) in further view of SAKAMOTO (US 20210062136 A1 Hereinafter “SAKAMOTO”).
Regarding claim 3, the combination of APPLEDORN and Koebler teaches the system of claim 1, further comprising
While it is presumed that a loader is present in APPLEDORN to load the cells into the well plates that are incubated, the combination of APPLEDORN and Koebler does not expressly disclose at least one loader to receive the sample of cells and load the sample of cells into the well array to form a filled well array.
However, SAKAMOTO teaches at least one loader to receive the sample of cells and load the sample of cells into the well array to form a filled well array ([0041]: “The cell transfer device S of the present embodiment picks up the cell C satisfying a required condition from the dish 2 and transfers the picked up cell C to the well 41 of the microplate”).
At the time the invention was made, it would have been obvious to one of ordinary skill in the art to modify the combination of APPLEDORN and Koebler’s cell incubation and imaging system to include SAKAMOTO’s cell loading device for loading cells into a well because such a modification is the result of applying a known technique to a known device ready for improvement to yield predictable results. More specifically, include SAKAMOTO’s cell loading device for loading cells into a well permits a method of loading cells from a source into wells for imaging. While it is presumed that APPLEDORN uses a device for loading the cells into the wells that are imaged, using SAKAMOTO’s machine to perform the loading would only improve the invention by providing an effective method of loading the wells with samples. This known benefit in SAKAMOTO is applicable to the combination of APPLEDORN and Koebler’s cell incubation and imaging system as they both share characteristics and capabilities, namely, they are directed to using wells to culture cells. Therefore, it would have been recognized that modifying the combination of APPLEDORN and Koebler’s cell incubation and imaging system to include SAKAMOTO’s cell loading device for loading cells into a well would have yielded predictable results because (i) the level of ordinary skill in the art demonstrated by the references applied shows the ability to incorporate SAKAMOTO’s cell loading device for loading cells into a well in using wells to culture cells and (ii) the benefits of such a combination would have been recognized by those of ordinary skill in the art.
Regarding claim 10, the content of claim 10 is similar to the content of claim 3, therefore it is rejected for the same reasons of obviousness as claim 3.
Regarding claim 17, the content of claim 17 is similar to the content of claim 3, therefore it is rejected for the same reasons of obviousness as claim 3.
Claims 6, 13, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over APPLEDORN (US 20030040104 A1 Hereinafter “APPLEDORN”) in view of Koebler (US 20040128077 A1 Hereinafter “Koebler”) in further view of GEDDES et al. (US 20130156938 A1 Hereinafter GEDDES).
Regarding claim 6, the combination of APPLEDORN and Koebler teaches the system of claim 1, teaches further comprising :
The combination of APPLEDORN and Koebler does not expressly disclose at least one vacuum chamber that receives the well array comprising at least one well; and
at least one plasma oxidizer in the at least one vacuum chamber to clean the well array in a vacuum.
However, GEDDES teaches at least one vacuum chamber that receives the well array comprising at least one well ([0128]: “Fill in ice in the ice chamber attached to vacuum pump Place the 96 well-plate in to Plasma cleaner Turn on vacuum pump and leave it under vacuum for 10 minutes Turn on Plasmon cleaner on medium for another 10 minutes Covering with Silver Turn block heater on 42.degree”. The ice chamber attached to the vacuum pump acts as the vacuum chamber); and at least one plasma oxidizer in the at least one vacuum chamber to clean the well array in a vacuum. ([0128]: “Fill in ice in the ice chamber attached to vacuum pump Place the 96 well-plate in to Plasma cleaner Turn on vacuum pump and leave it under vacuum for 10 minutes Turn on Plasmon cleaner on medium for another 10 minutes Covering with Silver Turn block heater on 42.degree”. The plasma cleaner uses a plasma oxidizer to clean the well-plate).
At the time the invention was made, it would have been obvious to one of ordinary skill in the art to modify the combination of APPLEDORN and Koebler’s cell incubation and imaging system to include GEDDES’s vacuum chamber and plasma oxidizer for cleaning because such a modification is the result of applying a known technique to a known device ready for improvement to yield predictable results. More specifically, include GEDDES’s vacuum chamber and plasma oxidizer for cleaning permits a method of assuring the well is sterile before it’s used for culturing cells, which in necessary for accurate results. While it is presumed that APPLEDORN uses clean wells for house their cells, using a machine to sterilize them before plating them would only improve the invention by assuring the wells are sterile. This known benefit in GEDDES is applicable to the combination of APPLEDORN and Koebler’s cell incubation and imaging system as they both share characteristics and capabilities, namely, they are directed to using wells to culture cells. Therefore, it would have been recognized that modifying the combination of APPLEDORN and Koebler’s cell incubation and imaging system to include GEDDES’s vacuum chamber and plasma oxidizer for cleaning would have yielded predictable results because (i) the level of ordinary skill in the art demonstrated by the references applied shows the ability to incorporate GEDDES’s vacuum chamber and plasma oxidizer for cleaning in using wells to culture cells and (ii) the benefits of such a combination would have been recognized by those of ordinary skill in the art.
Regarding claim 13, the content of claim 13 is similar to the content of claim 6, therefore it is rejected for the same reasons of obviousness as claim 6.
Regarding claim 20, the content of claim 20 is similar to the content of claim 6, therefore it is rejected for the same reasons of obviousness as claim 6.
Claims 7, 14, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over APPLEDORN (US 20030040104 A1 Hereinafter “APPLEDORN”) in view of Koebler (US 20040128077 A1 Hereinafter “Koebler”) in further view of Blanchard (US 20200347339 A1 Hereinafter “Blanchard”).
Regarding claim 7 Regarding claim 5, the combination of APPLEDORN and Koebler teaches the system of claim 1, in addition, Koebler further teaches further comprising
Table 1 describes 1, 2, and 3 which is colony count, object count, and proliferation count. All three describe a process of determining the number of cells in a well. Table 1: Table 1 represents parameters measured. It includes 57-59 which are Proximity (cell to cell contact), Frequency of proximity, and Duration of proximity. All 3 use the relative position and track of the cell to determine 2 cells get close to each other and if they come in contact).
At the time the invention was made, it would have been obvious to one of ordinary skill in the art to modify APPLEDORN’s cell incubation and imaging system to include Koebler’s cell counting and tracking of cells for determination of cell-cell contact because such a modification is the result of applying a known technique to a known device ready for improvement to yield predictable results. More specifically, include Koebler’s cell counting and tracking of cells for determination of cell-cell contact permits a method acquiring additional information about the cells (cell count, tracking, and cell-cell contact), which leads to an improved understanding of them (such as the amount of cells, the cell motility, and a cell’s ability to perform functions present in cell-cell interactions). This known benefit in Koebler is applicable to APPLEDORN’s cell incubation and imaging system as they both share characteristics and capabilities, namely, they are directed to evaluation of cell cultures using imaging modalities. Therefore, it would have been recognized that modifying APPLEDORN’s cell incubation and imaging system to include Koebler’s cell counting and tracking of cells for determination of cell-cell contact would have yielded predictable results because (i) the level of ordinary skill in the art demonstrated by the references applied shows the ability to incorporate Koebler’s cell counting and tracking of cells for determination of cell-cell contact in evaluation of cell cultures using imaging modalities and (ii) the benefits of such a combination would have been recognized by those of ordinary skill in the art.
The combination of APPLEDORN and Koebler does not expressly disclose at least one cell picker that receives the filled well array from the incubation chamber after incubation; and wherein the at least one processor is configured to control the at least one cell picker to extract a set of cells from the filled well array based at least in part on a number of cells in each well in each image, relative location of each cell of the at least one cell in each well in each image, and the cell-to-cell contact.
However, Blanchard teaches at least one cell picker that receives the filled well array from the incubation chamber after incubation ([0061]: “A manipulator may include a cell picker. A manipulator for manipulating cells may operate by detecting desirable cells or groups thereof present at a first location based on a predetermined criterion and transferring the desired cells or groups thereof from the first location to a second location”. Blanchard also uses an incubator, and the picker can pick cells after they have been imaged, this would mean they are picked after they have been incubated “In some embodiments, information produced by an imager may be analyzed to detect desirable or undesirable cells”); and wherein the at least one processor is configured to control the at least one cell picker to extract a set of cells from the filled well array based at least in part on a number of cells in each well in each image, relative location of each cell of the at least one cell in each well in each image, ([0068]: “The cell picker, which may or may not be resident at the imaging location, may then transfer the desirable or undesirable cells, e.g., by contacting each desired cell or cells with a needle, capillary, pipette, or micromanipulator and effecting a movement of the cell or cells, from their first location to a second location in or on the cell culture vessel or elsewhere in the internal chamber”. Blanchard has a machine that can pick cells based on their desirability status, the combination of APPLEDORN and Koebler teaches processes for measuring traits of cells that can be used to determine desirability, which includes number of cells, location, and cell to cell contact. So the combination of APPLEDORN, Koebler, and Blanchard teaches the above limitation).
At the time the invention was made, it would have been obvious to one of ordinary skill in the art to modify the combination of APPLEDORN and Koebler’s cell incubation and imaging system to include Blanchard’s cell picker because such a modification is the result of applying a known technique to a known device ready for improvement to yield predictable results. More specifically, include Blanchard’s cell picker permits a method of collecting cells when they are of interest. This known benefit in Blanchard is applicable to the combination of APPLEDORN and Koebler’s cell incubation and imaging system as they both share characteristics and capabilities, namely, they are directed to using wells to culture and analyze cells. If some cells were more desirable or wanted to be isolated by a user, Blanchard provides a device that. Therefore, it would have been recognized that modifying the combination of APPLEDORN and Koebler’s cell incubation and imaging system to include Blanchard’s cell picker would have yielded predictable results because (i) the level of ordinary skill in the art demonstrated by the references applied shows the ability to incorporate Blanchard’s cell picker in using wells to culture and analyze cells and (ii) the benefits of such a combination would have been recognized by those of ordinary skill in the art.
Regarding claim 14, the content of claim 14 is similar to the content of claim 7, therefore it is rejected for the same reasons of obviousness as claim 7.
Regarding claim 21, the content of claim 21 is similar to the content of claim 7, therefore it is rejected for the same reasons of obviousness as claim 7.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Banes et al. (US 20070225597 A1) teaches a method of imaging well inside an incubator.
Wagner (US 20190257743 A1) teaches a device for loading and unloading cell samples.
Adalsteinsson et al. (US 20190005304 A1) teaches a method of cellular analysis.
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/STEFANO ANTHONY DARDANO/Examiner, Art Unit 2663
/GREGORY A MORSE/Supervisory Patent Examiner, Art Unit 2698