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 .
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.
Examiner’s Note
Claim 15 is patent eligible applicant excludes “signal” from the definition of computer readable media. ( See spec [0042] FIG. 1 is a block diagram showing some of the components typically incorporated in at least some of the computer systems and other devices on which the facility operates. In various embodiments, these computer systems and other devices 100 can include server computer systems, cloud computing platforms or virtual machines in other configurations, …… ASIC; a computer memory 102—such as RAM, SDRAM, ROM, PROM, etc.—for storing programs and data while they are being used, including the facility and associated data, an operating system including a kernel, and device drivers; a persistent storage device 103, such as a hard drive or flash drive for persistently storing programs and data; a computer-readable media drive 104, such as a floppy, CD-ROM, or DVD drive, for reading programs and data stored on a computer-readable medium; and a network connection 105 for connecting the computer system to other computer systems to send and/or receive data, such as via the Internet …. None of the components shown in FIG. 1 and discussed above constitutes a data signal per se”)
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-3, 5-8, and 13-14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by MOON et al. , "Visualizing structure and transitions in high- dimensional biological data", NATURE BIOTECHNOLOGY, NATURE PUBLISHING GROUP US, NEW YORK, vol. 37, no. 12, 1 December 2019 (2019-12-01), pages 1482-1492, “Moon”).
Regarding claim 1, Moon teaches, A method in a computing system performed with respect to a sample of cells, (see abstract disclosing visualization method) the method comprising:
accessing analysis results indicating a detected expression level for each of a number of cellular constituents of each cell of the sample; (see fig 2, table 1, page 1487 left col, page 1488 left col, Methods section, disclosing accessing of a variety of data types)
accessing a cell type for each cell of the sample, where the cell type is among a plurality of cell types that is attributed to the cell based on each cell's cellular constituent expression levels; (see page 1488 left col "data exploration with PHATE')
for each of a plurality of pairs of cell types among the plurality of cell types, accessing a level of similarity between the cell types of each pair; (see "methods"//local affinities and the diffusion operator section disclosing transformation of global distances to local similarities using a Gaussian kernel quantifying the similarity between the two points (pairs of cell types) based on their Euclidean distance )
for each of the plurality of cell types, establishing a first representation of each cell type based on the accessed levels of similarity between each cell type and each of the other cell types of the plurality; { see "methods"//local affinities and the diffusion operator section disclosing that embedding local affinities directly results in a loss of global structure thus the proposed method constructs a diffusion geometry based on local similarities between data points (=first representation based on level of similarity))
accessing an emphasis weight specifying a degree to which cell type is to be emphasized relative to cell constituent expression levels in determining visualization coordinates for each cell of the sample; (“see "methods"// the á-decaying kernel and adaptive bandwidth section disclosing parameters for tuning the results (choice of kernel K (equation 3) and bandwidth E in the Propagating affinities via diffusion section disclosing raising the diffusion operator to its /-th power.”)
generating a cell matrix comprising a grid of values in which each row represents one of the cells of the sample, in which a first group of the columns correspond to constituent expression levels detected for the cell, and a second group of the columns correspond to the first representation established for the cell's cell type, the values in the first group of the columns being weighted against the values in the second group of the columns in accordance with the accessed emphasis weight; (see "methods"// the á-decaying kernel and adaptive bandwidth section. The emphasis weight in the context of the claim corresponds to the bandwidth chosen in Moon: "if the bandwidth is too small, then single-step transitions in the random walk using P₂ are largely confined to the nearest neighbors of each data point. In biological data, trajectories between major cell types may be relatively sparsely sampled. Thus if the bandwidth is too small, then the neighbors of points in the sparsely sampled regions may be excluded entirely and the trajectory structure in the probability matrix Pₑ, will not be encoded. Conversely if the bandwidth is too large, then the resulting probability matrix P₂ loses local information [...] which may result in an inability to resolve different trajectories.". The cell matrix is the P matrix. ) and
performing dimensionality reduction on the rows of the generated cell matrix to
obtain visualization coordinates for each cell of the sample. (see "methods"// embedding the potential distances in low dimensions section disclosing step (4) "capturing the data in low dimensions using MDS for visualization", thereby disclosing performance of a dimensionality reduction to obtain visualization coordinates for the low-dimensional plot.
Regarding claim 2, Moon teaches, constructing a visualization image containing, for each cell of the sample, a visual indication of the cell that appears in a spatial location specified by the visualization coordinates obtained for the cell. (see "methods: embedding the potential distances in low dimensions section disclosing step (4) "capturing the data in low dimensions using MDS for visualization", thereby disclosing performance of a dimensionality reduction to obtain visualization coordinates for the low-dimensional plot.)
Regarding claim 3, Moon teaches, causing the constructed visualization image to be presented. see "methods: embedding the potential distances in low dimensions section disclosing step (4) "capturing the data in low dimensions using MDS for visualization", thereby disclosing the constructed visualization image to be presented)
Regarding claim 5, Moon teaches, invoking an automatic analysis against the constructed visualization image. (See Page 1488, method: PHATE analysis of human ES cell differentiation data.)
Regarding claim 6, Moon teaches, wherein, in the constructed visualization image, each visual indication of a cell is shown in a color corresponding to the cell's cell type. ( See Fig. 1)
Regarding claim 7, Moon teaches, wherein, in the constructed visualization image, each visual indication of a cell is shown in a color corresponding to the expression level indicated for a distinguished cellular constituent in the cell. ( See Fig.1 Phate 1 display for a distinguished cellular constituent in the cell)
Regarding claim 8, Moon teaches, receiving input specifying the distinguished cellular constituent. ("Methods" invoking "EMD score analysis").
Regarding claim 13, Moon teaches, receiving input specifying the accessed emphasis weight. (figures 3, 6 and "Methods"// the alpha-decaying kernel and adaptive bandwidth section, in particular the passages pertaining to adaptive bandwidth.)
Regarding claim 14, Moon teaches, wherein the dimensionality reduction is performed using a process selected from among: t-distributed Stochastic Neighbor Embedding (t-SNE); and Uniform Manifold Approximation and Projection (UMAP). (Page 1487: “Table 3. We found that PHATE had the highest DEMaP score in 22 of 24 comparisons and was the top-performing method overall. Uniform manifold approximation and projection (UMAP) was the second best performing method overall but had the highest DEMaP score in only two of the comparisons, one of which is equal with PHATE. We ran further tests on cluster data using the adjusted Rand index26 and found that on average PHATE preserves local cluster structure as well as, or better than, t-SNE, UMAP and PCA (Supplementary Fig. 9)”)
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 4 is rejected under 35 U.S.C. 103 as being unpatentable over Moon in view of Moriya et al, ( US patent publication: 20100303330, “Moriya”)
Regarding claim 4, Moon doesn’t expressly teach, causing the constructed visualization image to be persistently stored.
Moriya teaches, a constructed visualization image to be persistently stored ( [0049] The system includes a radiographic image display apparatus 10 according to the presently disclosed subject matter, a photographing apparatus 40 installed at a medical facility, and the like, a console 42 which is used to perform an operation, and the like, of the photographing apparatus 40, an image database (image DB) 44 which stores a medical radiographic image, and the like, photographed by using the photographing apparatus 40, and a pathology database (pathology DB) 46 which manages information on a pathological examination, obtained as a result of the pathological examination of a tissue, cells, and the like, collected from a position of the pathological examination.”)
Moon and Moriya are analogous as they are from the field of medical image processing
Therefore it would have been obvious for an ordinary skilled person in the art before the effective filing date of the claimed invention to have modified Moon to have the constructed visualization image to be persistently stored as taught by Moriya.
The motivation to include the modification is to retrieve previously generated image when necessary.
Claim(s) 15 is rejected under 35 U.S.C. 103 as being unpatentable over Moon in view of Goldberg et al, ( US patent publication: 20240170096, “Goldberg”)
Claim 15 recites one or more instances of computer-readable media collectively having contents configured to cause a computing system to perform a method, the method of claim 1 which is taught by Moon as shown above.
Goldberg teaches computer implementation of methods of dimensionality reduction of cells. ([0425, “To perform any of the functionality described herein, the processor 1510 may execute one or more processor-executable instructions stored in one or more non-transitory computer-readable storage media (e.g., the memory 1520), which may serve as non-transitory computer-readable storage media storing processor-executable instructions for execution by the processor 1510.”).
Goldberg and Moon are from the field of dimensionality reduction of cells.
Therefore it would have been obvious for an ordinary skilled person in the art before the effective filing date of the claimed invention to have modified to have included one or more instances of computer-readable media collectively having contents configured to cause a computing system to perform the method of claim 1 (Moon’s teaching) as taught by Goldberg’s computer implementation of reduction of dimensions of cells.
The motivation for the modification is to achieve a different implementation of Moon’s method.
Allowable Subject Matter
Claim 16-20 are allowed.
The following is an examiner’s statement of reasons for allowance:
Independent claim 16 is allowable because applicant’s argument is persuasive that the prior art of record fails to teach the limitation of claim 16. Further search by examiner didn’t provide any applicable prior art to reject the limitation.
Dependent claims 17-20 are also allowable by virtue of dependency.
Claims 9-12 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim 9 is objected because applicant’s argument is persuasive that the prior art of record fails to teach the limitation of claim 9. Further search by examiner didn’t provide any applicable prior art to reject the limitation.
Claims 10-12 are also objected by virtue of dependency.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee. Such submissions should be clearly labeled “Comments on Statement of Reasons for Allowance.”
Response to Arguments
Applicant’s arguments, see remarks Pages 8-9, filed 08/20/2026, with respect to rejection of claim 1 under 35 USC 102(a)(1) have been fully considered and are not persuasive. The rejection has been maintained.
Applicant argues, see remarks Page Moon does not expressly or inherently disclose the feature, "accessing an emphasis weight specifying a degree to which cell type is to be emphasized relative to cell constituent expression levels in determining visualization coordinates for each cell of the sample" as recited in independent claim 1.
The cited portions of Moon describe a plurality of parameters-including an adaptive- bandwidth parameter, an α parameter of the α-decaying kernel, and a diffusion timescale parameter-that affect the extent to which local and global cell-to-cell relationships are encoded and represented in the resulting visualization. In Moon, the local structure corresponds to local affinities (similarities) between individual cells, while the global structure corresponds to relationships among individual cells captured by multi-step diffusion probabilities generated from those local affinities.
Although Moon describes parameters that affect the resulting visualization, the cited portions of Moon nowhere describe an emphasis weight used to specify a degree to which cell- type is to be emphasized relative to cell constituent expression levels in determining visualization coordinates for each cell of the sample. Instead, in Moon, the parameters affect the extent to which individual cell similarities (local structure) and diffusion-derived relationships among individual cells (global structure) are represented in the resulting visualization. However, claim 1 requires a single emphasis weight that specifies the relative contribution of cell-type information and cell constituent expression levels when determining visualization coordinates. At best, Moon's parameters specify the relative contribution of individual cell similarities and global cellular relationships of those individual cells when determining visualization coordinates. Thus, the cited portions of Moon do not disclose a parameter that controls the relative contribution of cell-type information and cell constituent expression levels as required by claim 1.”
Examiner replies, Moon teaches, Parameter kernel value or Parameter bandwidth are parameters that specify a degree to which cell type is to be emphasized relative to cell constituent expression levels in determining visualization coordinates for each cell of the sample. See equation 3 of section: The α-decaying kernel and adaptive bandwidth
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This equation indicates either K or bandwidth E can be changed to get visualization coordinates. The method describes In order to get preserve local information (cell constituent expression level) a set of values K and bandwidth can be used. See The α-decaying kernel and adaptive bandwidth : “…………..Our use of a locally adaptive bandwidth and the kernel Kk,α requires the choice of two tuning parameters: k and α. k should be sufficiently small to preserve local information, that is, to ensure that α ⋅ P[ ] k x , ( , ) is not a fully-supported uniform distribution. However, k should also be sufficiently large to ensure that the underlying graph represented by Pk,α is sufficiently connected, that is, the probability that we can walk from one point to another within the same trajectory in a finite number of steps is nonzero.” A [person has to use different value of K and bandwidth to get variable emphasis to cell constituent expression level Therefore the choice of value of parameter specify a degree to which cell type is to be emphasized relative to cell constituent expression levels in determining visualization coordinates. Therefore either K or bandwidth provides an emphasis weight used to specify a degree to which cell- type is to be emphasized relative to cell constituent expression levels in determining visualization coordinates for each cell of the sample. Applicant’s argument is not persuasive.
Applicant’s arguments, see remarks Pages 9-10, filed 08/20/2026, with respect to rejection of claim 9 under 35 USC 102(a)(1) have been fully considered and is persuasive. The rejection has been withdrawn.
Applicant’s arguments, see remarks Pages 10-11, filed 08/20/2026, with respect to rejection of claim 15 under 35 USC 103 have been fully considered and is not persuasive. The rejection has been maintained.
In response to applicant’s argument for claim 15, Examiner refers applicant to the reply given for independent claim 1 as the argued limitation is taught by Moon.
Applicant’s arguments, see remarks Pages 12-13, filed 08/20/2026, with respect to rejection of claim 16 under 35 USC 103 have been fully considered and is persuasive. The rejection has been withdrawn.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Tapas Mazumder whose telephone number is (571)270-7466. The examiner can normally be reached M-F 8:00 AM-5:00 PM PST.
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/TAPAS MAZUMDER/ Primary Examiner, Art Unit 2615
