DETAILED ACTION
Applicant’s response, filed 03/30/2026, has been fully considered. Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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 .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claim Status
Claims 1-6 and 9-20 are pending.
Claims 7-8 and 21-68 are canceled.
Claims 1-6 and 9-20 are rejected.
Priority
Applicant's claim for the benefit of a prior-filed application, PCT/IL2020/051178, filed 11/15/2020, which claims benefit domestic benefit to US provisional application 62/705,501, filed 6/30/2020, and claims benefit domestic benefit to US provisional application 62/935,843, filed 11/15/2019, is acknowledged.
Information Disclosure Statement
The information disclosure statements (IDS) filed on 10/29/2024, 11/22/2023, 07/13/2022 and 11/09/2023 are in compliance with the provisions of 37 CFR 1.97 and have therefore been considered. Signed copies of the IDS documents are included with this Office Action.
Drawings
The Drawings submitted 04/27/2022 are accepted.
Claim Rejections- 35 USC § 112
The outstanding rejections to the claims are withdrawn in view of the amendments submitted herein.
35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 1-6 and 9-20 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention. The instant rejection is newly stated and is necessitated by claim amendment.
Claim 1 limitation, recites “the relevant cells”. There is insufficient antecedent basis for these limitation in the claim as there is no previous recitation of “relevant cells”. The rejection may be overcome by amending the claim to “relevant cells”. Claim(s) 2-20 is/are rejected for the same reason because they depend from claim 1 and does not resolve the indefiniteness issue in those claims.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
For the following rejections, underlined text indicates newly recited portions necessitated by claim amendment.
Claims 1-6 and 9-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to one or more judicial exceptions without significantly more. Any newly recited portions are necessitated by claim amendment.
MPEP 2106 organizes judicial exception analysis into Steps 1, 2A (Prongs One and Two) and 2B as follows below. MPEP 2106 and the following USPTO website provide further explanation and case law citations: uspto.gov/patent/laws-and-regulations/examination-policy/examination-guidance-and-training-materials.
Framework with which to Evaluate Subject Matter Eligibility:
Step 1: Are the claims directed to a process, machine, manufacture, or composition of matter;
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e. a law of nature, a natural phenomenon, or an abstract idea;
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application (Prong Two); and
Step 2B: If the claims do not integrate the judicial exception, do the claims provide an inventive concept.
Framework Analysis as Pertains to the Instant Claims:
Step 1
With respect to Step 1: yes, the claims are directed to system, i.e., a process, machine, or manufacture within the above 101 categories [Step 1: YES; See MPEP § 2106.03].
Step 2A, Prong One
With respect to Step 2A, Prong One, the claims recite judicial exceptions in the form of abstract ideas. The MPEP at 2106.04(a)(2) further explains that abstract ideas are defined as:
mathematical concepts (mathematical formulas or equations, mathematical relationships and mathematical calculations);
certain methods of organizing human activity (fundamental economic practices or principles, managing personal behavior or relationships or interactions between people); and/or
mental processes (procedures for observing, evaluating, analyzing/ judging and organizing information).
With respect to the instant claims, under the Step 2A, Prong One evaluation, the claims are found to recite abstract ideas that fall into the grouping of mental processes (in particular procedures for observing, analyzing and organizing information) and mathematical concepts (in particular mathematical relationships and formulas) are as follows:
Independent claim 1:
classify the detected cells into a plurality of cell types
select from the detected cells a subset of cells to store in the cell data, wherein the relevant cells are selected based on a representative distribution of cell types from the detected cells
Dependent claim 5:
detect particles in the BMA sample and detect cells in the BMA sample separate from the detected particles.
Dependent claim 5:
identifying a cell lineage linking cells of different cell types and presenting the cell data further comprises presenting the cell lineage.
Dependent claim 12:
analyzing a preview image corresponding to the BMA sample to locate particles, wherein the preview image has a lower resolution than the scan data; and
determining, based on the analysis, a recommended scan area for the BMA sample.
Dependent claim 13:
determined based on a user input.
Dependent claim 14:
adjusting the recommended scan area to include or exclude a user-defined area.
Dependent claims 3-4, 6, 9-11, 15-20 recite further steps that limit the judicial exceptions in independent claim 1 and, as such, also are directed to those abstract ideas. For example, claim 3 further limits the particles of claim 1, claim 4 further limits the detected cells, claim 6 further limits the cell lineage of claim 5, claim 9 further limits the relevant cells of claim 7, claim 10 further limits scan time of claim 1, claim 11 further limits the scan data of claim 1, claims 15 and 16 further limit the instructions of claim 1, claim 17 further limits use input of claim 16, claim 18 further limits the notification of claim 17, claim 19 further limits the scan data of claim 1, and claim 20 further limits the image data of claim 19.
The abstract ideas recited in the claims are evaluated under the Broadest Reasonable Interpretation (BRI) and determined to each cover performance either in the mind and/or by mathematical operation because the method only requires a user to manually classify, detect, identify, select, determine, analyze, and adjust. Without further detail as to the methodology involved in “classify the detected cells”, “ detect particles “, “identifying a cell lineage linking cells “,”select from the detected cells “, “analyzing a preview image“, “determining, based on the analysis, a recommended scan area“, “determined based on a user input “, and “adjusting the recommended scan area “,under the BRI, one may simply, for example, use pen and paper to visualization of bone marrow cell populations.
Therefore, claim 1 and those claims dependent therefrom recite an abstract idea [Step 2A, Prong 1: YES; See MPEP § 2106.04].
Step 2A, Prong Two
Because the claims do recite judicial exceptions, direction under Step 2A, Prong Two, provides that the claims must be examined further to determine whether they integrate the judicial exceptions into a practical application (MPEP 2106.04(d)). A claim can be said to integrate a judicial exception into a practical application when it applies, relies on, or uses the judicial exception in a manner that imposes a meaningful limit on the judicial exception. This is performed by analyzing the additional elements of the claim to determine if the judicial exceptions are integrated into a practical application (MPEP 2106.04(d).I.; MPEP 2106.05(a-h)). If the claim contains no additional elements beyond the judicial exceptions, the claim is said to fail to integrate the judicial exceptions into a practical application (MPEP 2106.04(d).III).
Additional elements, Step 2A, Prong Two
With respect to the instant recitations, the claims recite the following additional elements:
Independent claim 1:
obtain, using the scanning apparatus, scan data of the BMA sample
detect cells in the BMA sample from the scan data
store, in the memory, cell data of the classified cells; and
a display configured to present the cell data
a scanning apparatus
Dependent claim 4:
image capture device
The claims also include non-abstract computing elements. For example, independent claim 1 includes a system, a processor, and a memory.
Considerations under Step 2A, Prong Two
With respect to Step 2A, Prong Two, the additional elements of the claims do not integrate the judicial exceptions into a practical application for the following reasons. Those steps directed to data gathering, such as “detect” and to data outputting, such as “store” and “display”, perform functions of collecting the data needed to carry out the judicial exceptions. Data gathering and outputting do not impose any meaningful limitation on the judicial exceptions, or on how the judicial exceptions are performed. Data gathering and outputting steps are not sufficient to integrate judicial exceptions into a practical application (MPEP 2106.05(g)).
Further steps directed to additional non-abstract elements of “a system, a processor, and a memory” do not describe any specific computational steps by which the “computer parts” perform or carry out the judicial exceptions, nor do they provide any details of how specific structures of the computer, such as the computer-readable recording media, are used to implement these functions. The claims state nothing more than a generic computer which performs the functions that constitute the judicial exceptions. Hence, these are mere instructions to apply the judicial exceptions using a computer, and therefore the claim does not integrate that judicial exceptions into a practical application. The courts have weighed in and consistently maintained that when, for example, a memory, display, processor, machine, etc.… are recited so generically (i.e., no details are provided) that they represent no more than mere instructions to apply the judicial exception on a computer, and these limitations may be viewed as nothing more than generally linking the use of the judicial exception to the technological environment of a computer (MPEP 2106.05(f)).
With respect to claims 1 and those claims dependent therefrom, the additional element of a scanning apparatus performs functions of collecting the data needed to carry out the judicial exceptions. Data gathering and outputting do not impose any meaningful limitation on the judicial exceptions, or on how the judicial exceptions are performed. Data gathering and outputting steps are not sufficient to integrate judicial exceptions into a practical application (MPEP 2106.05(g)).
With respect to claims 4 and those claims dependent therefrom, image capture device performs functions of collecting the data needed to carry out the judicial exceptions. Data gathering and outputting do not impose any meaningful limitation on the judicial exceptions, or on how the judicial exceptions are performed. Data gathering and outputting steps are not sufficient to integrate judicial exceptions into a practical application (MPEP 2106.05(g)).
Thus, none of the claims recite additional elements which would integrate a judicial exception into a practical application, and the claims are directed to one or more judicial exceptions [Step 2A, Prong 2: NO; See MPEP § 2106.04(d)].
Step 2B (MPEP 2106.05.A i-vi)
According to analysis so far, the additional elements described above do not provide significantly more than the judicial exception. A determination of whether additional elements provide significantly more also rests on whether the additional elements or a combination of elements represents other than what is well-understood, routine, and conventional. Conventionality is a question of fact and may be evidenced as: a citation to an express statement in the specification or to a statement made by an applicant during prosecution that demonstrates a well-understood, routine or conventional nature of the additional element(s); a citation to one or more of the court decisions as discussed in MPEP 2106(d)(II) as noting the well-understood, routine, conventional nature of the additional element(s); a citation to a publication that demonstrates the well-understood, routine, conventional nature of the additional element(s); and/or a statement that the examiner is taking official notice with respect to the well-understood, routine, conventional nature of the additional element(s).
With respect to the instant claims, the courts have found that receiving and outputting data are well-understood, routine, and conventional functions of a computer when claimed in a merely generic manner or as insignificant extra-solution activity (see Symantec, 838 F.3d at 1321, 120 USPQ2d at 1362 (utilizing an intermediary computer to forward information), buySAFE, Inc. v. Google, Inc., 765 F.3d 1350, 1355, 112 USPQ2d 1093, 1096 (Fed. Cir. 2014) (computer receives and sends information over a network), Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015), and OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93, as discussed in MPEP 2106.05(d)(II)(i)).
As such, the claims simply append well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception (MPEP2106.05(d)). The data gathering steps as recited in the instant claims constitute a general link to a technological environment which is insufficient to constitute an inventive concept which would render the claims significantly more than the judicial exception (MPEP2106.05(g)&(h)).
With respect to claims 1 and those claims dependent therefrom, the computer-related elements or the general purpose computer do not rise to the level of significantly more than the judicial exception. The claims state nothing more than a generic computer which performs the functions that constitute the judicial exceptions. Hence, these are mere instructions to apply the judicial exceptions using a computer, which the courts have found to not provide significantly more when recited in a claim with a judicial exception (see MPEP 2106.06(A)). The specification also notes that computer processors and systems, as example, are commercially available or widely used at [0031-0033]. The additional elements are set forth at such a high level of generality that they can be met by a general purpose computer. Therefore, the computer components constitute no more than a general link to a technological environment, which is insufficient to constitute an inventive concept that would render the claims significantly more than the judicial exceptions (see MPEP 2106.05(b)I-III).
With respect to claims 1 and those claims dependent therefrom, a scanning apparatus does not rise to the level of significantly more than the judicial exception. The claims state nothing more than a generic scanning apparatus which performs the functions that constitute the judicial exceptions. Hence, these are mere data gathering steps using a scanning apparatus, which the courts have found to not provide significantly more when recited in a claim with a judicial exception (see MPEP 2106.06(A)).
With respect to claims 4 and those claims dependent therefrom, image capture device does not rise to the level of significantly more than the judicial exception. The claims state nothing more than a generic image capture device which performs the functions that constitute the judicial exceptions. The specification discloses that an image capture device generally refers to a device that records the optical signals entering a lens as an image or a sequence of images. The optical signals may be in the near-infrared, infrared, visible, and ultraviolet spectrums. Examples of an image capture device comprise a CCD camera, a CMOS camera, a color camera, a photo sensor array, a video camera, a mobile phone equipped with a camera, a webcam, a preview camera, a microscope objective and detector, etc. [0029]. Hence, these are mere instructions to apply the judicial exceptions using a computer, which the courts have found to not provide significantly more when recited in a claim with a judicial exception (see MPEP 2106.06(A)).
Taken alone, the additional elements do not amount to significantly more than the above-identified judicial exception(s). Even when viewed as a combination, the additional elements fail to transform the exception into a patent-eligible application of that exception. Thus, the claims as a whole do not amount to significantly more than the exception itself [Step 2B: NO; See MPEP § 2106.05].
Therefore, the instant claims are not drawn to eligible subject matter as they are directed to one or more judicial exceptions without significantly more. For additional guidance, applicant is directed generally to the MPEP § 2106.
Response to Applicant Arguments
Applicant submits that the claims, as amended, do not recite a judication exception and accordingly, are patent eligible under Step 2A Prong One [p. 6, par. 1].
It is respectfully found not persuasive. It is important to keep in mind that an improvement in the abstract idea itself (e.g. a recited fundamental economic concept) is not an improvement in technology. Furthermore, it is important to note, the judicial exception alone cannot provide the improvement. The improvement can be provided by one or more additional elements or by the additional element(s) in combination with the recited judicial exception. See MPEP 2106.05(a). The additional elements recited in the claim 1 are data gathering steps, data outputting, scanning apparatus and general computer system. Those additional elements do not integrate the judicial exception into a practical application.
Applicant submits the claims are eligible at least because the claims improve computer, technology, or a technical field at least by improving the computer processing of microscopy image data, improving microscopy imaging, and by providing a novel way to select relevant cells based on a representative distribution of cell types from the detected cells [p. 6, par. 2].
It is respectfully found not persuasive. The improvement shown in the claims are to an improved analysis of bone marrow aspirate samples, not a technology. It is important to keep in mind that an improvement in the abstract idea itself is not an improvement in technology.
Claim Rejections - 35 USC § 102
The previous 102 rejection has been withdrawn in view of the amendments. Chandradevan is silent on select from the detected cells a subset of cells to store in the cell data, wherein the relevant cells are selected based on a representative distribution of cell types from the detected cells.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
For the following rejections, instantly claimed elements which are considered to be equivalent to the prior art teachings are described in bold for all claims, and underlined text indicates newly recited portions necessitated by claim amendment.
A. Claim(s)1-3 and 5-6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chandradevan, as applied to claim 1 as above in view of Cesano et al. (US 2016/0223554 A1, published 04/16/2016, cited on IDS dated 07/13/2022).
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Claim 1 is directed to a system for scanning a bone marrow aspirate (BMA) sample, the system comprising: a scanning apparatus for scanning the BMA sample; a processor coupled to the scanning apparatus and a memory and configured to execute instructions which cause the system to: obtain, using the scanning apparatus, scan data of the BMA sample; detect cells in the BMA sample from the scan data; classify the detected cells into a plurality of cell types; and store, in the memory, cell data of the classified cells; select from the detected cells a subset of cells to store in the cell data, wherein the relevant cells are selected based on a representative distribution of cell types from the detected cells; and a display configured to present the cell data.
Chandradevan discloses machine-based detection and classification for bone marrow aspirate differential counts: initial development focusing on nonneoplastic cells [title]. Chandradevan further discloses wright-stained BMA smears, made for routine patient care from 17 patients, were deidentified and scanned at 0.25 μm/pixel (×40 objective) using an Aperio AT2 scanner™ to generate whole-slide images [p. 99, col. 2, par. 3]. Chandradevan also discloses smears were selected at random from a set of cases, previously studied in manual DCC analyses ,provided they included cellular particles with at least 500 bone marrow hematopoietic cells, displayed reference range DCCs, minimal cellular degeneration, and a paucity of smearing artifacts [p. 99. Col. 2, par. 3 -pg. 100, col. 1, par. 1]. Chandradevan further discloses a cell detection algorithm is based on the Faster Region-Based Convolutional Network which combines bounding box regression for predicting bounding box locations, region pooling, and a residual convolutional network for extracting feature maps from the input images [p. 100, col. 2, par 2]. Chandradevan also discloses cell classes were predicted using the VGG16 convolutional network [p. 100, col. 2, par. 3]. Chandradevan further discloses the annotation system and protocols presented here establish a template to generate similar training and validation data, and results [p. 108, col. 2, par. 1]. Chandradevan is silent on selecting from the detected cells a subset of cells to store in the cell data, wherein the relevant cells are selected based on a representative distribution of cell types from the detected cells.
However, Cesano discloses the number of cells that have a specific activation level (e.g. specific amount of an activatable element) might be different between normal individuals and patients with a condition [0188]. Cesano further discloses a cell can be classified according to its location within a given region in the contour or density plot [0188]. Cesano also discloses the basis for classifying cells may use a series of population clusters whose centers, centroids, boundaries, relative positions describe the state of a cell, the diagnosis or prognosis of a patient, selection of treatment, or predicting response to treatment or to a combination of treatments, or long term outcome [0188]. Cesano further discloses the methods described herein provide a valuable method of determining the presence of cellular subsets within cellular populations [0337-0338].
Claim 2 is directed to the system of claim 1, wherein the processor is configured to detect particles in the BMA sample and detect cells in the BMA sample separate from the detected particles.
Chandradevan discloses creating and employing such datasets to develop a machine learning algorithm to detect and classify BMA cells [abstract] but is silent on detect particles in the BMA sample and detect cells in the BMA sample separate from the detected particles.
However, Cesano discloses activatable elements can be detected and/or quantified by any method that detects and/or quantitates the presence of the activatable element of interest [0321]. Cesano further discloses methods may include flow cytometry, mass cytometry, radioimmunoassay (RIA) or enzyme linked immunoabsorbance assay (ELISA), immunohistochemistry, immunofluorescent histochemistry with or without confocal microscopy, reversed phase assays, homogeneous enzyme immunoassays, and related non-enzymatic techniques, Western, Northern, and Southern blots, PCR, nucleic acid sequencing, whole cell staining, immunoelectron microscopy, nucleic acid amplification, gene array, protein array, mass spectrometry, patch clamp, 2-dimensional gel electrophoresis, differential display gel electrophoresis, microsphere-based multiplex protein assays, label-free cellular assays and flow cytometry, etc. [0321]. Cesan0 also discloses cell readouts for proteins and other cell determinants can be obtained using fluorescent or otherwise tagged reporter molecules [0321] which reads on detecting particles separate from cells.
Claim 3 is directed to the system of claim 2, wherein the particles comprise one or more of fat, or clusters of hematopoietic cells.
Chandradevan discloses bone marrow aspirate (BMA) differential cell counts (DCCs) are critical for the classification of hematologic disorders [abstract].
Cesano discloses the invention provides methods of diagnosing, prognosing, determining progression, predicting a response to a treatment or choosing a treatment for AML in an individual, the method comprising: (1) classifying one or more hematopoietic cells associated with AML in said individual by a method comprising: a) subjecting a cell population comprising said one or more hematopoietic cells from said individual to modulator conditions [0432].
Claim 5 is directed to the system of claim 1, wherein classifying the detected cells further comprises identifying a cell lineage linking cells of different cell types and presenting the cell data further comprises presenting the cell lineage.
Chandradevan discloses this procedure entails quantification of cells of different lineages to determine the proportions of each, the findings of which aid in the classification of numerous benign and malignant hematologic disorders [p. 98, par. 1].
Claim 6 is directed to the system of claim 5, wherein the cell lineage comprises a lineage of the cells from one or more of a myeloid lineage, a lymphoid lineage, or an erythroid lineage.
Chandradevan discloses classifying using cell class including erythroid [p. 101, table 1].
In regards to claim(s) 1-3, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine Chandradevan with Cesano as they both disclose machine-based detection and classification for bone marrow aspirate. The motivation would have been to combine the cell selection of Chandradevan with Cesano’s detection cells a subset of cells to data also suggest accuracy of stratification can be improved by first identifying distinct sub-populations of AML blasts as disclosed by Cesano [0703]. One could have therefore combined the elements as claimed by the known methods of Chandradevan and Cesano, and that in combination, a finding that one of ordinary skill in the art would have recognized that the results of the combination were predictable.
B. Claim(s) 4, 9, 10, 16-18, and 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chandradevan in view of Cesano, as applied to claims 1-3 as above in further view of Hunter et al. (US2013/0004053 A1, published 01/03/2013, cited on IDS dated 07/13/2022).
Claim 4 is directed to the system of claim 1, further comprising an image capture device comprising an effective numerical aperture (NA) of at least 0.8; wherein the detected cells comprise at least 100 cells; and wherein the instructions further comprise instructions for scanning an area of at least 0.5 square cm.
Cesano discloses useful detectors include a microscope( s) with multiple channels of fluorescence; plate readers to provide fluorescent, ultraviolet and visible spectrophotometric detection with single and dual wavelength endpoint and kinetics capability, fluorescence resonance energy transfer (FRET), luminescence, quenching, two-photon excitation, and intensity redistribution; CCD cameras to capture and transform data and images into quantifiable formats; and a computer workstation [0362], but is silent on device comprising an effective numerical aperture (NA) of at least 0.8; wherein the detected cells comprise at least 100 cells; and wherein the instructions further comprise instructions for scanning an area of at least 0.5 square cm.
However, Hunter discloses a system, a method, and a programmed device for measurement of translocational activity among cellular compartments process magnified images of cellular material exposed to an agent by segmenting and compartmentalizing the images and then measuring fractional localized intensity of two or more compartments in the segmented, compartmentalized image [abstract]. Hunter further discloses that resolving sparse cytoplasmic compartments requires the use of a high numerical aperture objective to obtain high resolution imaging [0046]. Hunter also discloses autofocus is critical for scanning large areas due to the variations in slide and coverslip surfaces and mechanical focus instability of the microscope [0049]. Hunter further discloses this can have a dramatic effect on the ability to locate cells. And by using a Nikon Fluor 0.75 NA 20x objective, for example, the mean fluorescence intensity has been shown to drop by about 35% at ±10 μm from focus [0049]. As the numerical aperture (NA) of Hunter is .75 and the instant claims are .80, adjusting the NA within a known range to balance a resolution, depth of field, or light collection is a routine optimization that any one skilled in the art would perform. Additionally there both systems function according to the same optical principles and the only difference reflects routine design optimization. Hunter also discloses full population analysis for the same number of cells n=100 [0097]. Hunter further discloses data from larger 10x15 mm2 scans [0055]. It would have been obvious to one of ordinary skill in the art to have modified the system of Nodality by including wherein an image capture device comprising an effective numerical aperture (NA) of at least 0.8; and wherein the instructions further comprise instructions for scanning an area of at least 0.5 square cm as taught by Hunter because it can more efficiently improve clinical efficacy as disclosed by Hunter [0044].
Claim 9 is directed to the system of claim 7, wherein a number of the relevant cells is between 100-500 cells, 500-1000 cells, 1000-2000 cells, or more than 2000 cells.
Chandradevan and Cesano are silent wherein a number of the relevant cells is between 100-500 cells, 500-1000 cells, 1000-2000 cells, or more than 2000 cells.
However, Hunter discloses full population analysis for the same number of cells n=100 [0097]. It would have been obvious to one of ordinary skill in the art to have modified the system of Chandradevan by including wherein a number of the relevant cells is between 100-500 cells, 500-1000 cells, 1000-2000 cells, or more than 2000 cells as taught by Hunter because it can more efficiently improve clinical efficacy as disclosed by Hunter [0044].
Claim 10 is directed to the system of claim 1, wherein a scan time for obtaining the scan data is faster than 20 minutes per square cm, 15 minutes per square cm, 10 minutes per square cm, 5 minutes per square cm, or 2 minutes per square cm.
Chandradevan and Cesano are silent on wherein a scan time for obtaining the scan data is faster than 20 minutes per square cm, 15 minutes per square cm, 10 minutes per square cm, 5 minutes per square cm, or 2 minutes per square cm.
However, Hunter discloses screening parameters are entered using a GUI tool... user enters a desired time per plate (typically in minutes) [0111]. It would have been obvious to one of ordinary skill in the art to have modified the system of Chandradevan by including wherein a scan time for obtaining the scan data is faster than 20 minutes per square cm, 15 minutes per square cm, 10 minutes per square cm, 5 minutes per square cm, or 2 minutes per square cm as taught by Hunter because it can more efficiently improve clinical efficacy as disclosed by Hunter [0044].
Claim 16 is directed to the system of claim 1, wherein the instructions further comprise instructions for receiving a user input to modify the cell data.
Chandradevan and Cesano are silent wherein the instructions further comprise instructions for receiving a user input to modify the cell data.
However, Hunter discloses GUI screens ... represent functionality for identifying to a user parameter ... and for enabling the user to input values for those parameters" [0019]; user-executed steps carried out... in order to initialize parameters that control the screen [0110]. It would have been obvious to one of ordinary skill in the art to have modified the system of Chandradevan by including wherein the instructions further comprise instructions for receiving a user input to modify the cell data as taught by Hunter because it can more efficiently improve clinical efficacy as disclosed by Hunter [0044].
Claim 17 is directed to the system of claim 16, wherein the user input includes at least one of marking a cell, adding a cell, deleting a cell, reclassifying a cell, or adding a notification to a cell.
Chandradevan and Cesano are silent wherein the instructions further comprise instructions for receiving a user input to modify the cell data.
However, Hunter discloses inputs included cell survival, growth, differentiation [0815]. Hunter further discloses adaptive object recognition algorithms incorporated into the assay system of the invention, including image segmentation and tessellation, allow a user to interactively define what constitutes an object of interest in an assay (i.e. the nucleus of a given cell type) [0012]. It would have been obvious to one of ordinary skill in the art to have modified the system of Chandradevan by including wherein the instructions further comprise instructions for receiving a user input to modify the cell data as taught by Hunter because it can more efficiently improve clinical efficacy as disclosed by Hunter [0044].
Claim 18 is directed to the system of claim 17, wherein the notification indicates at least one of toxic or abnormal.
Chandradevan and Cesano are silent wherein the notification indicates at least one of toxic or abnormal.
However, Hunter discloses more parameters may be measured in the same cell ... toxicity may be a more important limitation [0047].
Claim 20 is directed to the system of claim 19, wherein the high-resolution image data includes image data of the BMA sample scanned with an effective numerical aperture (NA) of at least 0.8.
Chandradevan discloses wherein a BMA sample bone marrow aspirate is obtained [abstract], but is silent on wherein the high-resolution image data includes image data of the sample scanned with an effective numerical aperture (NA) of at least 0.8.
However, Hunter discloses wherein the high-resolution image data includes image data of the sample scanned with an effective numerical aperture (NA) of at least 0.8 [0046].
C. Claims 12-15 are rejected under 35 U.S.C. 103 as being unpatentable over Chandradevan in view of Cesano, as applied to claim 1 as above in view of Nie et al. (US2012/0123205 A1, published 05/17/2012, cited on IDS dated 07/13/2022), and in further view of Hunter.
Claim 12 is directed to the system of claim 1, wherein the instructions further comprise instructions for: analyzing a preview image corresponding to the BMA sample to locate particles, wherein the preview image has a lower resolution than the scan data; and determining, based on the analysis, a recommended scan area for the BMA sample.
Chandradevan discloses bone marrow aspirate is obtained [abstract]. Chandradevan is silent on wherein the instructions further comprise instructions for: analyzing a preview image corresponding to the sample to locate particles, wherein the preview image has a lower resolution than the scan data; and determining, based on the analysis, a recommended scan area for the sample.
However, Nie discloses system and method incorporate an optical probe is integral to an endoscopic device or a therapeutic laser system, optically coupled to a light source; a display for displaying at least one visual representation of data; and a controller programmed to generate at least one real-time integrated visual representation of an area of interest and to display the real-time visual representation on the display for guidance during the diagnostic or therapeutic procedure [abstract]. Nie further discloses additional magnification is activated when the speed of scanning and the size of the area in which scanning occurs are both in a predefined range, and requires no explicit user trigger ... There can be multiple "layers" of zoom, so that... the system can increase magnification further [0107].
Hunter discloses designed to facilitate efficient AOI recall based on viewport overlay geometry. Efficient caching algorithms move disk-resident AOI data into RAM as needed. This allows for user browsing or sequential access [0064].
Claim 13 is directed to the system of claim 12, wherein the recommended scan area is further determined based on a user input.
Chandradevan, Cesano, and Nie are silent on wherein the recommended scan area is further determined based on a user input.
However, Hunter discloses efficient access to AOIs in these data is required by both front-end users through the graphical interface [0064].
Claim 14 is directed to the system of claim 13, wherein the user input includes adjusting the recommended scan area to include or exclude a user-defined area.
Chandradevan and Cesano are silent on wherein the user input includes adjusting the recommended scan area to include or exclude a user-defined area.
However, Nie discloses afford a user the ability to select and set parameters [0109].
Claim 15 is directed to the system of claim 12, wherein the instructions for obtaining the scan data further comprise instructions for scanning, using the scanning apparatus, the recommended scan area.
Chandradevan, Cesano, and Nie are silent to wherein the instructions for obtaining the scan data further comprise instructions for scanning, using the scanning apparatus, the recommended scan area.
However, Hunter discloses user-executed steps carried out ... in order to initialize parameters that control the screen [0110].
In regards to claim(s) 12-15, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine Chandradevan and Cesano with Nie and Hunter as they disclose machine-based detection and classification for bone marrow aspirate. It would have been obvious to one of ordinary skill in the art to have modified the system of Chandradevan and Cesano by including wherein the instructions further comprise instructions for: analyzing a preview image corresponding to the sample to locate particles, wherein the preview image has a lower resolution than the scan data as taught by Nie because it is more efficient in that it requires no explicit user trigger as disclosed by Nie [0107] and wherein determining, based on the analysis, a recommended scan area for the sample as taught by Hunter it can more efficiently improve clinical efficacy as disclosed by Hunter [0044].
D. Claim(s) 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chandradevan in view of Cesano, as applied to claim 1 as above in further view of Singh et al. et al. (Singh, Amol, and Robert S. Ohgami. "Super-resolution digital pathology image processing of bone marrow aspirate and cytology smears and tissue sections." Journal of pathology informatics 9.1 (2018), newly cited).
Claim 19 is directed to the system of claim 1, wherein the scan data includes high-resolution image data of the BMA sample, the high-resolution image data comprising at least 5 megapixels.
Cesano discloses useful detectors include a microscope( s) with multiple channels of fluorescence; plate readers to provide fluorescent, ultraviolet and visible spectrophotometric detection with single and dual wavelength endpoint and kinetics capability, fluorescence resonance energy transfer (FRET), luminescence, quenching, two-photon excitation, and intensity redistribution; CCD cameras to capture and transform data and images into quantifiable formats; and a computer workstation [0362]. Cesano further discloses assaying cells at this level of resolution allows the identification of rare cell populations [0776], but is silent on high-resolution image data.
However, Singh discloses super-resolution digital pathology image processing of bone marrow aspirate and cytology smears and tissue sections [title]. Singh further discloses using a SPOT Insight camera (SPOT Imaging, Sterling Heights, MI, USA), 4.0 megapixel, mounted to an Olympus BX41 (Olympus, Waltham, MA, 02453) microscope using SPOT Basic (SPOT Imaging) image capture software [p. 2, col. 2, par. 2]. While the sensor itself has a physical, native resolution of (2048 x 2048) pixels (which is 4.0 megapixels), the software allows for higher resolution capture over 5 megapixels. Singh also discloses that there was a clear increase in resolution and clarity of images after SR processing by MULTI-Z [p. 6, col. 1, par. 5] which reads on an increase from the resolution of 4 megapixels in the images. Given how the analysis was performed, a skilled artisan would perform the analysis and would understand that the higher the resolution the higher the increase in relevant data.
In regards to claim(s) 19, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine Chandradevan and Cesano with Singh as they disclose image processing for bone marrow aspirate. It would have been obvious to one of ordinary skill in the art to have modified the system of Chandradevan and Cesano by including the methods of super-high resolution imaging into the classification methods of Chandradevan and Cesano by applying the algorithm to bone marrow aspirate and cytology smears and tissue sections allows for a significant improvement in information entropy and image sharpness [p. 5, col. 2, par. 2]. A finding that one of ordinary skill in the art could have substituted one known element for another, and the results of the substitution would have been predictable.
Conclusion
No claims are allowed.
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.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Dawn Bickham whose telephone number (703)756-1817. The examiner can normally be reached on Monday - Friday 8-4.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Olivia Wise can be reached on (571)272-2249. 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 https://ppair-my.uspto.gov/pair/PrivatePair. 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.
/D.M.B./Examiner, Art Unit 1685 /Soren Harward/Primary Examiner, TC 1600
Prosecution Insights