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 .
Status of the Claims
Claims 1-22 are examined; claims 23-70 are cancelled.
Priority
This application US 17/650,067 (02/04/2022) claims benefit of US Application 63/228,093 (07/31/2021) and US Application 63/146,541 (02/05/2021) as reflected in the filing receipt mailed on 03/04/2022. The claims to the benefit of priority are acknowledged and the effective filing date of claims 1-22 is 02/05/2021.
Information Disclosure Statement
No Information Disclosure Statement has been filed herein.
Drawings
In the instant drawings, Fig. 2A, Fig. 2B, Fig. 3, Fig. 4A, Fig. 4B and Fig. 5A are executed in color. Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee. Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2). According to the recorded decision on 04/29/2022, the decision about color drawings was granted.
Claim Rejections - 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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph: The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 3 and 7-8 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 3 recites “the multiplicity of infection (MOI)” which lacks antecedent basis.
Claim 7 recites “the range” which lacks antecedent basis.
Dependent claim 8 are similarly rejected because they are dependent on claim 7 and do not resolve the lack of clarity introduced
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.
Claims 1-22 are rejected under 35 USC § 101 because the claimed inventions are directed to an abstract idea without significantly more. "Claims directed to nothing more than abstract ideas (such as a mathematical formula or equation), natural phenomena, and laws of nature are not eligible for patent protection" (MPEP 2106.04 § I). Abstract ideas include mathematical concepts, and procedures for evaluating, analyzing or organizing information, which are a type of mental process (MPEP 2106.04(a)(2)).
MPEP 2106 organizes JE analysis into Steps 1, 2A (Prong One & Prong Two), and 2B as analyzed below.
Step 1: Are the claims directed to a process, machine, manufacture, or composition of matter (MPEP 2106.03)?
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 (MPEP 2106.04(a-c))?
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
Step 1: Are the claims directed to a 101 process, machine, manufacture, or composition of matter (MPEP 2106.03)?
The instant claims are directed to a system (claims 1-22), which falls within one of the categories of statutory subject matter. [Step 1: Yes].
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 (MPEP 2106.04(a-c))?
With respect to Step 2A, Prong One, the claims recite judicial exceptions in the form of abstract ideas. MPEP § 2106.04(a)(2) further explains that abstract ideas are defined as:
• mathematical concepts (mathematical formulas or equations, mathematical relationships
and mathematical calculations) (MPEP 2106.04(a)(2)(I));
• certain methods of organizing human activity (fundamental economic principles or practices, managing personal behavior or relationships or interactions between people) (MPEP 2106.04(a)(2)(II)); and/or
• mental processes (concepts practically performed in the human mind, including observations, evaluations, judgments, and opinions) (MPEP 2106.04(a)(2)(III)).
Mathematical concepts recited in instant claims 1-3, 7 and 13 include the terms “determine a ratio” (claims 1 and 13); “a ratio” (claim 2); “multiplicity of infection” (claim 3); “pixels numbering” (claim 7), which are mathematical concepts. The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one having ordinary skill in the art. Thus, the recited terms corresponds to verbal equivalents of mathematical concepts because they constitute actions executed by a group of mathematical steps in a form of a mathematical algorithm; thus mathematical concepts (MPEP 2106.04(a)(2)). This instant specification [0103] states that the claimed machine learning algorithm involves training “a pipeline of feature normalization, scoring, selection and classification algorithms from scikit-learn” with automatic optimization of parameters. Therefore, the recited “imaging Al models to be trained to analyze one or more known viruses” (claim 1), “provide one or more trained Al models for one or more known viruses” (claim 13); and “use the trained Al model to further provides the functionality of analyzing the captured images” (claim 13) correspond to verbal equivalents of mathematical concepts. A mathematical concept need not be expressed in mathematical symbols, because "words used in a claim operating on data to solve a problem can serve the same purpose as a formula." In re Grams, 888 F.2d 835, 837 and n.1, 12 USPQ2d 1824, 1826 and n.1 (Fed. Cir. 1989).
Mental processes, defined as concepts or steps practically performed in the human mind such as steps of observations, evaluations, judgments, analysis, opinions or organizing information include “detect morphological differences” (claim 1). Under the BRI, the recited limitations are mental processes because a human mind is sufficiently capable of detecting difference in captured images as claimed
Hence, the claims explicitly recite numerous elements that, individually and in combination, constitute abstract ideas. The instant claims must therefore be examined further to determine whether they integrate that abstract idea into a practical application (MPEP 2106.04(d)). [Step 2A Prong One: Yes]
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Instant claims 1 and 12-13 recite additional elements that are not abstract ideas: “computer system” (claims 1 and 13); “storing one or more captured images” (claims 1 and 13); “storage device” (claims 1 and 12-13); “read and process the one or more captured images (claim 1); and “storing metadata associated with the one or more captured images” (claim 12). The recited limitations in these claims are interpreted to require the use of a computer.
Dependent claims 2-11 and 14-22 recite further details about the computer system; dependent claims 5, 14-15 and 22 recite further details about “plate with wells containing cells”; dependent claims 4, 6-9 and 16 recite further details about “captured images”; dependent claims 2, 10-11 and 17-18 recite further details about “virus stock” and dependent claims 19-21 recite further details about the “imager”. The recited claims read on data gathering activities or the type of data being gathered such as capturing images from a plate with wells containing cells that may be infected virus; not amounting to a practical application.
Claims 1 and 12-13 relate to computers or further aspects of the information being analyzed by computers, and do not describe any specific computational steps by which the computer performs or carries out the abstract idea, nor do they provide any details of how specific structures of the computer are used to implement these functions.
Claims reciting “read or process the one or more captured images” read on receiving or transmitting data over a network, e.g., using the Internet to gather data, Symantec, 838 F.3d at 1321. Claims reciting “storing” data merely reads on data storage/collection, and therefore insignificant extra-solution activity.
There are no additional limitations to indicate that the claimed computer, processor, or computer readable medium require anything other than generic computer components in order to carry out the recited abstract idea in the claims. Claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible. Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. See also 573 U.S. at 224, 110 USPQ2d at 1984.
Hence, these are mere instructions to apply the abstract idea using a computer and insignificant extra-solution activity; and therefore the claim does not integrate that abstract idea into a practical application (see MPEP 2106.04(d) § I; 2106.05(f); and 2106.05(g)). None of the dependent claims recite any additional non-abstract elements; they are all directed to further aspects of the information being analyzed, the manner in which that analysis is performed, or the mathematical operations performed on the information. [Step 2A Prong Two: No]
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself. Step 2B of the 35 USC § 101 analysis determines whether the claims contain additional elements that amount to an inventive concept, and an inventive concept cannot be furnished by an abstract idea itself (MPEP 2106.05).
Claims 1 and 12-13 recite a computer or computer functions, interpreted as instructions to apply the abstract idea using a computer, where the computer does not impose meaningful limitations on the judicial exceptions; which can be performed without the use of a computer (MPEP 2106.04(d) § I; and MPEP 2106.05(f)).
Claims directed to “reading” data read on performing a standard computer task, which the courts have identified as a conventional computer function in Symantec, 838 F.3d at 1321, 120 USPQ2d at 1362; OIP Techs., Inc., v. Amazon.com, Inc., 788 F.3d 1359, 1363, 115 USPQ2d 1090, 1093 (Fed. Cir. 2015); and buySAFE, Inc. v. Google, Inc., 765 F.3d 1350, 1355, 112 USPQ2d 1093, 1096 (Fed. Cir. 2014).
It is known in the art that the use of computer systems involving detection of morphological differences in captures cells is well-understood, routine and conventional (Ying et. al. “Electron microscopy: essentials for viral structure, morphogenesis and rapid diagnosis” Sci. China Life Sci. 56(5):421-430 (2013) - pg. 422 col. 1 para. 1f or subcellular level image detection; pg. 426 col. 1 para. 2 for microcopy identification of morphological differences).
When the claims are considered as a whole, they do not integrate the abstract idea into a practical application; they do not confine the use of the abstract idea to a particular technology; they do not solve a problem rooted in or arising from the use of a particular technology; they do not improve a technology by allowing the technology to perform a function that it previously was not capable of performing; and they do not provide any limitations beyond generally linking the use of the abstract idea to a broad technological environment. See MPEP 2106.05(a) and 2106.05(h). [Step 2B: No]
Conclusion: Instant claims are directed to non-statutory subject matter
For these reasons, the claims in this instant application, when the limitations are considered individually and as a whole, are directed to an abstract idea and lack an inventive concept. Hence, the claimed invention does not constitute significantly more than the abstract idea, so instant claims 1-22 are rejected under 35 USC § 101 as being directed to non-statutory subject matter.
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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. The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 1-2, 4-6 and 12-16 are rejected under 35 U.S.C. 103(a) as being unpatentable over Wang et. al. "Differentiation of Cytopathic Effects (CPE) induced by influenza virus infection using deep Convolutional Neural Networks (CNN)." PLoS Computational Biology 16(5):e1007883 (2020) – referred to in the action as Wang – in view of Kensert et. al. "Transfer learning with deep convolutional neural networks for classifying cellular morphological changes." SLAS Discovery: Advancing Life Sciences R&D 24(4):466-475 (2019) – referred to in the action as Kensert – in view of Buckingham et. al. “Autophagic flux without a block differentiates varicella-zoster virus infection from herpes simplex virus infection” PNAS 112(1):256-261 (2015) – referred to in the action as Buckingham.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Independent claim 1 recites “a system for training one or more Al models for viral infectivity assays using machine learning, the system comprising; a first storage device storing one or more captured images … each captured image capturing a plurality of stain free cells infected with a known virus stock of a plurality of virus stocks, wherein the plurality of stain free cells include both stain free infected cells and stain free uninfected cells… and one or more imaging artificial intelligence (Al) models stored in the second storage device for use by the processor, the one or more imaging Al models to be trained to analyze one or more known viruses, the one or more imaging Al models used with instructions executed by the processor to process the captured images of stain free cells to detect morphological differences between the stain free infected cells and the stain free uninfected cells in the one or more captured images”. Independent claim 13 recites “a system for analyzing viral infectivity assays using machine learning, the system comprising; a plate with one or more wells with a plurality of stain free infected cells and a plurality of stain free uninfected cells in each of the one or more wells; an imager to capture images … of the plate with a plurality of stain free cells infected with a virus stock; a computer system coupled in communication with the imager …, wherein the processor executes further instructions to use the trained Al model to further provides the functionality of analyzing the captured images”.
Wang teaches the use of images collected with the Olympus IX71 microscope (i.e. reading on first device/system for storage of captured images) (pg. 14 para. 2) of influenza-infected cells and mock-infected cells using only a minimum essential medium and trypsin addition (i.e. reading on each captured image capturing a plurality of stain free cells infected with a known virus stock of a plurality of virus stocks, wherein the plurality of stain free cells include both stain free infected cells and stain free uninfected cells) (pg. 14 para. 3) to training of a deep convolutional neural network to recognize the morphological changes induced by virus infection (pg. 11 para. 2-3) with a global learning rate of 0.0001 (i.e. reading on a system for training one or more Al models for viral infectivity assays using machine learning)(pg. 15 para. 1); reading on the recited limitations in claims 1 and 13.
Independent claim 1 recites “a computer system in communication with the first storage device, the computer system including a processor and a second storage device storing instructions for execution by the processor, the processor to execute instructions stored in the second storage device to read and process the one or more captured images stored in the first storage device”. Dependent claim 12 recites “further comprises a database storing metadata associated with the one or more captured images, and wherein the processor further executes instructions stored in the second storage device to read the stored metadata and to further process the one or more captured images stored in the first storage device based on the stored metadata”. Independent claim 13 recites “the computer system including a processor and a storage device storing instructions for execution by the processor, wherein the processor when executing the stored instructions in the storage device to provide one or more trained Al models for one or more known viruses”.
Wang teaches that the model training, model validation, and influenza experiment datasets classified photos into two categories (i.e. database storing metadata) with uninfected MDCK cells labeled as negative samples and cells with cytopathic effects marked as positive samples (pg. 14 para. 2); reading on the recited limitations in claims 1, 12 and 13.
Dependent claim 2 recites “wherein the known virus stock of stain free cells has a known titer of concentration and known ratio of stain free infected cells to stain free uninfected cells”. Dependent claim 4 recites “wherein the captured images are captured by an imager to produce images selected from the group of brightfield images, darkfield images, phase contrast images, and differential interference contrast (DIC) images”. Dependent claim 5 recites “further comprising, a plate with one or more wells containing the plurality of stain free cells infected with the known virus stock”. Dependent claim 6 recites “ “wherein the one or more captured images are raw images taken of the plate and the one or more wells”. Dependent claim 14 recites “wherein the plate has a plurality of wells”. Dependent claim 15 recites “ wherein the plate has a range of one to three wells per sample to increase throughput”. Dependent claim 16 recites “ wherein the captured images captured by the imager as one selected from the group of brightfield images, darkfield images, phase contrast images, and differential interference contrast (DIC) images”.
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Regarding claims 1 and 13; Wang does not teach “captured at a subcellular resolution”. However, Kensert teaches the application of trained deep convolutional neural networks for the quantification and identification of cellular phenotypes from high-content microscopy images and distinguish between different cell morphologies using cell profiling datasets from the Broad Bioimage Benchmark Collection (i.e. reading on first device/system for storage of captured images) (pg. 466 para. 1); wherein the prediction of mechanisms of action was performed at subcellular resolution (pg. 468 Fig. 1) showing cytoplasm to nucleus translocation (pg. 2 para. 3); reading on the recited limitations in claims 1 and 13.
Regarding claims 1 and 13; Wang does not explicitly teach “determine a ratio of stain free infected cells to stain free uninfected cells indicating a predicted viral infectivity based on the one or more captured images”. However, Buckingham teaches the study of a viral infection where infected human skin was imaged using brightfield microscopy (pg. 257 col. 1 para. 1); wherein cells were infected at 1:8 infected:uninfected ratio (pg. 261 col. 1 para. 3); reading on the recited limitation in claims 1 and 13.
Regarding claims 2, 4-6 and 14-16; Wang does not teach the recited limitations above. However, Buckingham teaches the study of a viral infection where infected human skin was imaged using brightfield microscopy (pg. 257 col. 1 para. 1); wherein fibroblasts were infected with a titer of 400 pfu per 10cm2 (pg. 258 col. para. 1); and cell monolayers were infected at 1:8 infected:uninfected ratio (i.e. reading on infected with the known virus stock) (pg. 261 col. 1 para. 3); wherein generation of uninfected cells was done on 24 wells on six-well plates (pg. 261 col. 1 para. 3); wherein infected cells measurements were replicated (i.e. reading on wherein the plate has a range of one to three wells per sample to increase throughput) (pg. 257 col. 1 para. 1); reading on the recited limitation in claims 2, 4-6 and 14-16.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Regarding claims 1 and 12-13; it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the teachings by Kensert and Buckingham to the use of images collected with a microscope software of influenza-infected cells and mock-infected cells using only a minimum essential medium and trypsin addition to training of a deep convolutional neural network to recognize the morphological changes induced by virus infection as taught by Wang to capture images at subcellular resolution wherein the morphological differences between the stain free infected cells and the stain free uninfected cells in the one or more captured images are undeterminable by human eyesight at the subcellular resolution and to determine a ratio of stain free infected cells to stain free uninfected cells indicating a predicted viral infectivity based on the one or more captured images and to incorporate known virus stock of stain free cells has a known titer of concentration and known ratio of stain free infected cells to stain free uninfected cells; wherein the captured images are captured by an imager to produce images selected from the group of brightfield images, darkfield images, phase contrast images, and differential interference contrast (DIC) images; further comprising, a plate with one or more wells containing the plurality of stain free cells infected with the known virus stock; wherein the one or more captured images are raw images taken of the plate and the one or more wells. One of ordinary skill in the art would be motivated to apply the teachings by Kensert and Buckingham to the method by Wang to produce highly accurate classification of subcellular mechanisms of action (pg. 473 col. 1 para. 2 Kensert) and to examine conditions of viral infections (pg. 256 col. 1 para. 1 Buckingham). One of ordinary skill in the art would be able to motivated to combine the teachings in these references with a reasonable expectation of success since the described teachings pertain to methods for identifying an viral presence in biological cells.
Claims 3, 9 and 19-22 are rejected under 35 U.S.C. 103(a) as being unpatentable over Wang, Kensert and Buckingham as applied to claims 1, 4-6 and 13 above further in view of Panchal et. al. “Development of High-Content Imaging Assays for Lethal Viral Pathogens” J. Biomol. Screening 15(7):755-765 (2010) – referred to in the action as Panchal – as evidence by Shabram et. al. “Multiplicity of Infection/Multiplicity of Confusion” MOLECULAR THERAPY 2(5) (2000) - referred to in the action as Shabram.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Dependent claim 3 recites “wherein the multiplicity of infection (MOI) for the stain free infected cells is greater than 0.999 and the multiplicity of infection (MOI) for the stain free uninfected cells is zero”. Dependent claim 9 recites “wherein the one or more captured images are analyzed by the Al model on a cell to cell basis or a tile to tile basis”. Dependent claim 19 recites “wherein the imager is a plate imager”. Dependent claim 20 recites “wherein the imager is a microscope”. Dependent claim 21 recites “wherein the imager is an imaging robot that performs robotic microscopy”. Dependent claim 22 recites “further comprising fluid handling robots to process the plates for imaging”.
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Regarding claims 3, 9 and 19-22; neither Wang nor Kensert nor Buckingham teach the recited limitation above. However, Panchal teaches the use of imaging assays for identification of virus pathogens (pg. 755 para. 1); and sta-tistical analysis of single-cell images (i.e. analysis of cell to cell basis) from a minimum of 592 cells (pg. 764 col. 1para. 3); wherein cells analyzed were either uninfected or infected with 5 MOI (i.e. multiplicity of infection for infected cells is greater than 0.999) (pg. 759 col. 1 para. 1); wherein uninfected cells have a multiplicity of infection of zero (pg. 420 col. 1 para. 3) since multiplicity of infection is commonly defined as the ratio of infectious virions to cells in a culture as evidenced by Shabram (pg. 420 col. 1 para. 2 Shabram); wherein automated confocal imagery of a 96-well plate is done with a confocal microscopy (pg. 760 Fig. 3) for image-based screens to moni-tor viral infection with large liquid handling and robotic workstations used to manage viral identification in large well formats (pg. 762 col. 2 para. 3); reading on the recited limitation in claims 3, 9 and 19-22.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Regarding claims 3, 9 and 19-22; it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the teachings by Panchal to the use of images on a cell to cell basis collected with a microscope software of influenza-infected cells and mock-infected cells using only a minimum essential medium and trypsin addition to training of a deep convolutional neural network to recognize the morphological changes induced by virus infection as taught by Wang, Kensert and Buckingham to incorporate multiplicity of infection (MOI) for the stain free infected cells greater than 0.999 and the multiplicity of infection (MOI) for the stain free uninfected cells zero; wherein the imager is a plate imager; wherein the imager is a microscope and wherein the imager is an imaging robot that performs robotic microscopy. One of ordinary skill in the art would be motivated to apply the teachings by Panchal to the method by Wang, Kensert and Buckingham to incorporate analyses of single-cell data to account for heterogeneity in the subcellular localization (pg. 755 para. 1 Panchal). One of ordinary skill in the art would be able to motivated to combine the teachings in these references with a reasonable expectation of success since the described teachings pertain to methods for identifying an viral presence in biological cells.
Claim 7 is rejected under 35 U.S.C. 103(a) as being unpatentable over Wang, Kensert and Buckingham as applied to claims 1 and 4-6 above further in view of Huang et. al. “Coherent Brightfield Microscopy Provides the Spatiotemporal Resolution To Study Early Stage Viral Infection in Live Cells” ACS Nano 11:2575−2585 (2017) – referred to in the action as Huang.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Dependent claim 7 recites “wherein the one or more captured images are divided up into non-overlapping rectangular tiles with each tile having M pixels by N pixels numbering in the range inclusively between thirty- two pixels by thirty-two pixels and a pixel width by a pixel height of the one or more captured images”.
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Regarding claim 7; neither Wang nor Kensert nor Buckingham teach the recited limitation above. However, Huang teaches coherent brightfield imagery of a virus particle fitted to 9X9 pixels (pg. 2582 col. 1 para. 4); wherein imaging are 48 × 48 nm2 and 96 × 96 nm2 per pixel (i.e. a pixel width by a pixel height of the one or more captured images) (pg. 2582 col. 1 para. 2); reading on the recited limitation in claim 7.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Regarding claim 7; it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the teachings by Huang to the use of images collected with a microscope software of influenza-infected cells and mock-infected cells using only a minimum essential medium and trypsin addition to training of a deep convolutional neural network to recognize the morphological changes induced by virus infection as taught by Wang, Kensert and Buckingham to incorporate captured images divided up into non-overlapping rectangular tiles with each tile having M pixels by N pixels numbering in the range inclusively between thirty- two pixels by thirty-two pixels and a pixel width by a pixel height of the one or more captured images. One of ordinary skill in the art would be motivated to apply the teachings by Huang to the method by Wang, Kensert and Buckingham to unveil interactions between virus particles and biological cells (pg. 2575 para. 1 Huang). One of ordinary skill in the art would be able to motivated to combine the teachings in these references with a reasonable expectation of success since the described teachings pertain to methods for identifying an viral presence in biological cells.
Claims 8 is rejected under 35 U.S.C. 103(a) as being unpatentable over Wang, Kensert, Buckingham and Huang as applied to claims 1 and 4-7 above further in view of Panchal as evidenced by Shabram.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Dependent claim 8 recites “wherein the tiles are prefiltered to reject tiles that are substantially empty of cells; and the cells are not individually isolated”.
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Regarding claim 8; neither Wang nor Kensert nor Buckingham nor Huang teach the recited limitation above. However, Panchal teaches sta-tistical analysis of single-cell images (i.e. analysis of cell to cell basis) from a minimum of 592 cells (i.e. reading on filtering out images of no-cells or not isolated cells) (pg. 764 col. 1para. 3); reading on the recited limitation in claim 8.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Regarding claim 8; it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the teachings by Panchal to the use of images collected with a microscope software of influenza-infected cells and mock-infected cells using only a minimum essential medium and trypsin addition to training of a deep convolutional neural network to recognize the morphological changes induced by virus infection as taught by Wang, Kensert, Buckingham and Huang to incorporate tiles prefiltered to reject tiles that are substantially empty of cells; and with cells not individually isolated. One of ordinary skill in the art would be motivated to apply the teachings by Panchal to the method by Wang, Kensert, Buckingham and Huang to incorporate analyses of single-cell data to account for heterogeneity in the subcellular localization (pg. 755 para. 1 Panchal). One of ordinary skill in the art would be able to motivated to combine the teachings in these references with a reasonable expectation of success since the described teachings pertain to methods for identifying an viral presence in biological cells.
Claims 10-11 and 17-18 are rejected under 35 U.S.C. 103(a) as being unpatentable over Wang, Kensert and Buckingham as applied to claims 1 and 13 above further in view of Shokr et. al. “Mobile Health (mHealth) Viral Diagnostics Enabled with Adaptive Adversarial Learning” ACS Nano 15:665−673 (2021) – Published 11/23/2020 – referred to in action as Shokr.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Dependent claim 10 recites “wherein the known virus stock belongs to the family of coronavirus”. Dependent claim 11 recites “wherein the known virus stock is the SARS-CoV-2 virus. Dependent claim 17 recites “wherein the virus stock contains virus of the group of coated or uncoated DNA and coated or uncoated RNA”. Dependent claim 18 recites “wherein the virus is SARS CoV-2, an RNA coated virus which is the causative agent of COVID-19”.
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Regarding claims 10-11 and 17-18; neither Wang nor Kensert nor Buckingham teach the recited limitations above. However, Shokr teaches a system of adversarial neural networks with conditioning to develop an easily reconfigurable virus diagnostic platform via real image dataset (pg. 665 para. 1) wherein viral stocks were obtained from Nasopharyngeal swab samples from COVID-19 patients (i.e. infected by SARS-CoV-2 virus which is an RNA coated virus) (pg. 670 col.1 para. 3); wherein the training protocol allowed for detection of HBV, HCV, HIV and SARS-CoV-2 viruses (i.e. SARS-CoV-2 being from the coronavirus family and an RNA coated virus) (pg. 670 col. 1 para. 2); wherein the use of specific guide RNA to the nucleic acid target of choice in CRISPR/dCas9 recognition system (pg. 668 col. 2 para. 1) for detection of HBV, HCV, HIV and SARS-CoV-2 viruses (pg. 670 col. 1 para. 2); reading on the recited limitation in claims 10-11 and 17-18.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
Regarding claims 10-11 and 17-18; it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the teachings by to the use of images collected with a microscope software of influenza-infected cells and mock-infected cells using only a minimum essential medium and trypsin addition to training of a deep convolutional neural network to recognize the morphological changes induced by virus infection as taught by Wang, Kensert and Buckingham to incorporate a known virus stock from the family of coronavirus; wherein the known virus stock is the SARS-CoV-2 virus; wherein the virus stock contains virus of the group of coated or uncoated DNA and coated or uncoated RNA; wherein the virus is SARS CoV-2, an RNA coated virus which is the causative agent of COVID-19. One of ordinary skill in the art would be motivated to apply the teachings by Shokr the method by Wang, Kensert and Buckingham to provide a providing a platform based diagnostics that can be adapted to a given emerging viral agent (pg. 665 para. 1 Shokr). One of ordinary skill in the art would be able to motivated to combine the teachings in these references with a reasonable expectation of success since the described teachings pertain to methods for identifying an viral presence in biological cells.
Conclusion
No claims are allowed.
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/F.F.L./Examiner, Art Unit 1685
/OLIVIA M. WISE/Supervisory Patent Examiner, Art Unit 1685