DETAILED ACTION
Claim Status
Claims 1-20 are rejected.
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 .
Priority
This application is a CON of PCT/US2021/061878, filed 12/03/2021. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
This application claims Domestic Benefit to application # 63121477 , filed 12/04/2020. Domestic Benefit is acknowledged. Therefore, the effective filing date of claims 1-20 is 12/04/2020.
Information Disclosure Statement
The Information Disclosure Statements filed on 09/15/2023 and 10/08/2024 are in
compliance with the provisions of 37 CFR 1.97 and have been considered in full. A signed copy of list of
references cited from each IDS is included with this Office Action.
Drawings
No drawings were filed with this application.
Claim Rejections - 35 USC § 112
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 6-9 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 6 recites the limitation "the texture associated feature" in line 1. There is insufficient antecedent basis for this limitation in the claim. Claims 7-9 inherit the indefiniteness of this claim without resolving it, and are thus additionally rejected.
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 1-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
In accordance with MPEP § 2106, claims found to recite statutory subject matter ( Step 1 : YES) are then analyzed to determine if the claims recite any concepts that equate to an abstract idea, law of nature or natural phenomenon (Step 2A, Prong 1). In the instant application, the claims recite the following limitations that equate to an abstract idea:
1. determining multiparametric signatures of the first plurality of primary cells and the second plurality of primary cells, based at least in part on the detected expression patterns of the plurality of epigenetic marks;
1. computer processing the multiparametric signatures of the first plurality of primary cells and the multiparametric signatures of the second plurality of primary cells, wherein the computer processing comprises plotting against the first chronological age and the second chronological age
1. and determining the biological age of the primary cell, based at least in part on the computer processing.
4. The method of claim 1, wherein the multiparametric signatures comprise a texture-associated feature.
5. The method of claim 4, wherein the texture-associated feature comprises Haralick texture features, threshold adjacency statistics, Gabor related features, radial features, or a combination thereof.
6. The method of claim 1, further comprising computer processing the texture-associated feature using a subcellular feature analysis, a machine learning feature extraction algorithm, a machine learning algorithm, or a combination thereof.
7. The method of claim 6, wherein the machine learning algorithm comprises a member selected from the group consisting of a support vector machine, a support vector regression, a linear regression, a quadratic discriminant analysis, a neural network, and a combination thereof.
8. The method of claim 7, wherein the machine learning algorithm comprises the quadratic discriminant analysis, and wherein the method further comprises using the multiparametric signature of the first plurality of primary cells to distinguish a cell population of the first plurality of primary cells from multiple cell populations.
9. The method of claim 7, wherein the machine learning algorithm comprises the support vector machine, and wherein the method further comprises using the multiparametric signature of the first plurality of primary cells to identify a character of the first plurality of primary cells in a single-cell population.
10. The method of claim 1, wherein the computer processing further comprises determining a first centroid of a first element of the multiparametric signature of the first plurality of primary cells, and a second centroid of the first element of the multiparametric signature of the second plurality of primary cells.
11. The method of claim 10, further comprising calculating a first multivariant centroid of the first plurality of primary cells and a second multivariant centroid of the second plurality of primary cells.
12. The method of claim 1, further comprising performing a data dimensionality reduction algorithm on the detected expression patterns.
13. The method of claim 12, wherein the detected expression pattern comprises 3-dimensional topological distribution, and wherein the data dimensionality reduction algorithm further comprises interpreting the 3-dimensional topological distribution as a two-dimensional projection using a multidimensional scaling.
19. determining a multiparametric signature of the treated primary cell and the untreated primary cell, based at least in part on the detected expression patterns of the plurality of epigenetic marks;
19. comparing the multiparametric signature of the treated primary cell to the multiparametric signature of the untreated primary cell; and determining the effect of the treatment on the primary cell, based at least in part on the comparing.
20. A method of determining an aging, a residual lifespan, or a maximum lifespan of a biological entity, comprising: determining multiparametric signatures of the plurality of primary cells, based at least in part on the detected expression patterns of the plurality of epigenetic marks; determining an average value of coefficient of variance of the multiparametric signatures of the plurality of primary cells; and determining the aging, the residual lifespan, or the maximum lifespan of the biological entity based at least in part on the determined average value of the coefficient of variance of the multiparametric signatures.
The steps for “determining,” “processing,” and “performing” recite manipulations of data that could be performed by a human being with a pen and paper. Therefore, these limitations fall under the “Mental process” and “Mathematical concepts” groupings of abstract ideas. While claim 1 recites performing some aspects of the analysis with a “computer,” there are no additional limitations that indicate that this analysis engine requires anything other than carrying out the recited mental process or mathematical concept in a generic computer environment. Merely reciting that a mental process is being performed in a generic computer environment does not preclude the steps from being performed practically in the human mind or with pen and paper as claimed. If a claim limitation, under its broadest reasonable interpretation, covers performance of the limitation in the mind but for the recitation of generic computer components, then if falls within the “Mental processes” grouping of abstract ideas. As such, claims 1-20 recite an abstract idea ( Step 2A, Prong 1 : YES).
Claims found to recite a judicial exception under Step 2A, Prong 1 are then further analyzed to determine if the claims as a whole integrate the recited judicial exception into a practical application or not (Step 2A, Prong 2). This judicial exception is not integrated into a practical application because the claims do not recite an additional element that reflects an improvement to technology or applies or uses the recited judicial exception to effect a particular treatment for a condition. Rather, the instant claims recite additional elements that amount to mere instructions to implement the abstract idea in a generic computing environment or mere instructions to apply the recited judicial exception via a generic treatment. Specifically, the claims recite the following additional elements:
1. assaying a first plurality of primary cells and a second plurality of primary cells to detect expression patterns of a plurality of epigenetic marks, wherein the first plurality of primary cells are associated with a first chronological age, and wherein the second plurality of primary cells are associated with a second chronological age;
2. The method of claim 1, wherein detecting the expression patterns of the plurality of epigenetic marks in the first plurality of primary cells and the second plurality of primary cells further comprises detecting expression patterns of a plurality of epigenetic marks in a first nucleus of a first cell in the first plurality of primary cells and in a second nucleus of a second cell in the second plurality of primary cells.
3. The method of claim 1, wherein the assaying further comprises detecting a chromatin shape, detecting a deoxyribonucleic acid (DNA) modification, detecting a nuclear staining pattern, detecting a histone modification, detecting one or more genetically encoded epigenetic probes, or a combination thereof.
14. The method of claim 1, wherein the first plurality of primary cells and the second plurality of primary cells comprise a same cell type.
15. The method of claim 1, wherein the first plurality of primary cells and the second plurality of primary cells comprise a different cell type.
16. The method of claim 1, wherein the first plurality of primary cells or the second plurality of primary cells comprises a hepatocyte, a fibroblast, a peripheral blood mononuclear cell, or an immune cell.
17. The method of claim 1, wherein the assaying further comprises capturing a series of images of the first plurality of primary cells and the second plurality of primary cells over a period of time.
18. The method of claim 17, wherein capturing the series of images further comprises capturing at least one image of the first plurality of primary cells and the second plurality of primary cells before, during, and after mitosis.
19. detecting expression patterns of a plurality of epigenetic marks in the treated primary cell and an untreated primary cell;
19. applying the treatment to the primary cell, to obtain a treated primary cell;
20. detecting expression patterns of a plurality of epigenetic marks in a plurality of primary cells of a biological entity;
The steps for the assay and detection are a form of performing clinical tests on individuals to obtain input for an equation, In re Grams, 888 F.2d 835, 839-40; 12 USPQ2d 1824, 1827-28 (Fed. Cir. 1989). There are no limitations that indicate that the claimed analysis engine or the formats of the provided data require anything other than generic computing systems. As such, these limitations equate to mere instructions to implement the abstract idea on a generic computer that the courts have stated does not render an abstract idea eligible in Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. See also 573 U.S. at 224, 110 USPQ2d at 1984. The step for applying the treatment to the primary cell in order to obtain data for the analysis is a “mere data gathering” step, similar to determining the level of a biomarker in blood, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968. As such, claims 1-20 are directed to an abstract idea ( Step 2A, Prong 2 : NO).
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). The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite additional elements that equate to mere instructions to apply the recited exception in a generic way or in a generic computing environment. The instant claims recite additional elements listed above, in the section on step 2A.
Xu and Liu (FEBS J. 2019 Aug;286(16):3095-3109) provide evidence that the steps for assaying and detection are well understood, routine and conventional. A series of images can be taken over time (pg 9 ¶ 1), DNA modifications are imaged (fig. 2), and different populations can be imaged at once (pg 5 ¶ 2). As discussed above, there are no additional limitations to indicate that the claimed computer requires 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.Xiu and Liu discuss a number of methods in their review article where cells are differentially treated and others are left untreated, for example with protein tags, and then analyzed for epigenetic expression, which provides evidence that the step for applying the treatment is well understood, routine and conventional (pg 8 ¶ 1-2). . The additional elements do not comprise an inventive concept when considered individually or as an ordered combination that transforms the claimed judicial exception into a patent-eligible application of the judicial exception. Therefore, the claims do not amount to significantly more than the judicial exception itself ( Step 2B : No). As such, claims 1-20 are not patent eligible.
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)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-20 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Bjarki et al. (WO2021231978A1, IDS reference).
Bjarki ¶ 5 states that one embodiment of their invention is “A drug screening assay that can screen for the effects of small molecule modifiers on cellular aging.”
Regarding claim 1, this earlier application discloses a method using a biological age predictor (¶ 4, 76, 79, 84, 88, 106, 151, 159, Fig. 9, Fig.12). Bjarki discloses a system that predicts cellular age by analyzing features of cells from high content imaging data (¶133, 136). This system integrates molecular markers (e.g. epigenetic markers) and cellular phenotypes to identify age-related characteristics (¶ 84) which can be used to screen drugs that modulate aging (e.g. ¶ 4, 5, 41, 112, 118, 146). Furthermore, Bjarki outlines a method of perturbing cells, capturing images before and after treatment, and comparing predicted cellular ages (¶ 108, 147, 149, 151) to assess the effect of substances, including drugs, on aging phenotypes.
Regarding claim 2, Bjarki outlines a method of perturbing cells, capturing images before and after treatment, and comparing predicted cellular ages (¶ 108, 147, 149, 151).
Regarding claim 3, this system integrates molecular markers (e.g. epigenetic markers) and cellular phenotypes to identify age-related characteristics (¶ 84).
Regarding claims 4 and 5, Bjarki also mentions texture features of the cells as extracted features (¶ 54, 86, 141). The method is searching to detect DNA modifications (¶ 5).
Regarding claim 6, Bjarki discloses a system that employs machine learning algorithms, such as deep learning, to predict cellular age by analyzing features of cells from high content imaging data (¶133, 136).
Regarding claim 9, the model can be a support vector machine (¶ 71), and is trained to classify cells into young, middle aged, and old based on multiple parameters (¶ 71-75).
Regarding claims 12-13, the detected expression patterns are projected into two dimensions from a three-dimensional space with dimensionality reduction (¶ 154).
Regarding claim 7, Bjarki states “In various embodiments, the predictive model is one of a neural network, random forest, or regression model.” (¶ 7)
Bjarki is silent as to a quadratic discriminant analysis in claim 8. Evidentiary reference scikit-learn (https://scikit-learn.org/stable/modules/lda_qda.html, 2026) shows that QDA is a variant of a predictive model that would be included in possible embodiments of Bjarki.
Regarding claim 10-11, Bjarki’s method includes determining the centroids of two pluralities of cells using multiple variables (¶ 139).
Regarding claims 14-16, Bjarki analyzed progeria fibroblasts at different time points and additionally analyzed progeria fibroblasts in relation to healthy fibroblasts at different time points (¶ 139).
Regarding claim 17, a series of images are taken over time of the cell types to be compared in Bjarki (¶ 139).
Regarding claim 18, 49 images of cells are taken over an hour in Bjarki (¶ 139-141). Mitosis occurs several times within an hour. The 49 images, taken at regular intervals, would capture all stages of mitosis.
Regarding claim 19, Bjarki describes a drug screening pipeline with the same series of steps in fig. 12, described in (¶ 154-157).
Regarding claim 20, Bjarki has an aging analysis pipeline for determining an aging (¶ 134, fig. 7a). An average of multiparametric signatures of variance built from expression patterns is used (¶ 138).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GRACELYN M HILL whose telephone number is (571)272-9871. The examiner can normally be reached Monday-Friday 8:30-5pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Olivia M Wise can be reached at 571-272-2249. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/G.M.H./ Examiner, Art Unit 1685
/OLIVIA M. WISE/ Supervisory Patent Examiner, Art Unit 1685
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