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 Claims
Claims 1-21 are pending.
Claims 1-21 are rejected.
Claims 1 and 17 are objected to.
Priority
Applicant’s claim for the benefit of a prior-filed application, PCT/EP2022/064502 filed 27 May 2022 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Acknowledgment is made of applicant’s claim for foreign priority to GB2107576.7 filed 27 May 2021under 35 U.S.C. 119 (a)-(d). Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Accordingly, the effective filing date of the claimed invention is 27 May 2021.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 27 Nov. 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the list of cited references was considered in full by the examiner.
Drawings
The drawings filed 27 Nov. 2023 are objected to for the following reasons:
The drawings fail to comply with 37 CFR 1.84(p)(5) because they include the following reference character(s) not mentioned in the description: #22 in FIG. 1;
The drawings fail to comply with 37 CFR 1.84(u)(1), which states view numbers must be preceded by the abbreviation "FIG.". The view numbers for the drawing must each be preceded by “FIG.”
FIG. 25-30, 34, and 39-40 fail to comply with 37 CFR 1.84(u)(1), which states partial views intended to form one complete view, on one or several sheets, must be identified by the same number followed by a capital letter. Accordingly, each FIG. should be relabeled as FIG. 25A, FIG. 25B, etc.
Corrected drawing sheets in compliance with 37 CFR 1.121(d), or amendment to the specification to add the reference character(s) in the description in compliance with 37 CFR 1.121(b) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
References to Applicant’s specification are made with respect to the published version.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code at para. [0283]. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract of the disclosure is objected to because:
the abstract is over 150 words in length.
A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Objections
Claims 1 and 17 are objected to because of the following informalities:
Claims 1 and 17 use the indicators “a.”, “b.”, “c.”, etc. MPEP 608.01(m) states each claim begins with a capital letter and ends with a period. Periods may not be used elsewhere in the claims except for abbreviations. Claim 1 should be amended to recite “(a)”, “(b)”, “(c)”, etc., or a similar amendment that does not use periods.
Claim 17 recites “The method of claim 1, further comprising…a. using the causal network graphs; or b. assessing…”. Given these are different steps than in claim 1, claim 17 should use different letters other than “a.” and “b.”, which are already used in claim 1.
Appropriate correction is required.
Claim Interpretation
Claim 1 recites “h. classifying the perturbation as promoting a transition…when the dot product of the perturbation vector and the dimensionality-reduced STV is positive or inhibiting said transition when said dot product is negative. The classification of the perturbation as promoting or inhibiting the transition is a contingent limitation that depends on the dot product being positive or negative respectively. The broadest reasonable interpretation of a method (or process) claim having contingent limitations requires only those steps that must be performed and does not include steps that are not required to be performed because the condition(s) precedent are not met. If the claimed invention may be practiced without either the first or second condition happening, then neither step A or B is required by the broadest reasonable interpretation of the claim. See MPEP 2111.04 I. In the instant case, because a dot product may be 0 (i.e. neither positive or negative), under the broadest reasonable interpretation of the claims, the classification is not required.
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.
Claims 1-21 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.
Claim 1, and claims dependent therefrom, are indefinite for recitation of “the molecular mechanisms through which a perturbation…” in the preamble. There is insufficient antecedent basis for this limitation in the claim because claim 1 does not previously recite any molecular mechanisms, and as a result, it is not clear what molecular mechanisms through which perturbation promotes or inhibits a cellular transition are being referenced.
Claim 1, and claims dependent therefrom are indefinite for recitation of “a. processing…the cells that define said cell states”. There is insufficient antecedent basis for this limitation in the claim, because claim does not previously recite cells that define the cell states. Claim 1 recites cells “associated with said first and second states”, but does not require the cells define the states. Clarification is requested whether these are the same set of cells or different cells.
Claim 1, and claims dependent therefrom, are indefinite for recitation of “a. processing….(ii) identifying clusters of cells in said representation”. There is insufficient antecedent basis for this limitation in the claim because claim 1 does not previously recite a representation. As a result, it is not clear if “the representation” is intended to refer to the mapped cells in the multi-dimensional space, or some other representation. Steps “c.” and “d.” also recite “said representation”. For purpose of examination, claim 1 is interpreted to mean clusters of cells are identified in the multi-dimensional space, and references to the representation are interpreted to refer to the multi-dimensional space.
Claim 1, and claims dependent therefrom, are indefinite for recitation of “e. identifying…the components of a core biochemical network comprising the top ranked components, or the components regulating the top ranked components…”. Claim 11 is also indefinite for recitation of “wherein identifying within said ranked list the components of a core biochemical network…”. There is insufficient antecedent basis for the “the components of a core biochemical network”, “the top ranked components”, and “the components regulating the top ranked components” because claim 1 does not previously recite components of a core biochemical network, ranked components, or components regulating the top ranked components. Instead, claim 1 only recites an “SVT component” for each molecular feature, and provides a “ranked list of said molecular features” (i.e. ranked molecular features). Therefore it is not clear what components are being referenced. Clarification is requested via claim amendment.
Claim 1, and claims dependent therefrom, are indefinite for recitation of “e. identifying…of a core biochemical network…”. Claim 11 is also indefinite for recitation of “a core biochemical network”. The term “core ” is a relative term which renders the claim indefinite. The term “core” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. As a result, it is not clear what “biochemical networks” would be considered “core” biochemical networks versus a biochemical network.
Claim 1, and claims dependent therefrom, are indefinite for recitation of “g. determining the effect of a perturbation…”. There is insufficient antecedent basis for this limitation in the claim because claim 1 does not previously recite an effect of a perturbation. As a result, it is not clear what effect, “the effect” is referring to, particularly given a perturbation of cells may result in multiple effects. For purpose of examination, the limitation is interpreted to mean “determining an effect of…”.
Claim 1, and claims dependent therefrom, are indefinite for recitation of “g. determining...the perturbation was applied to cells” “classifying the perturbation….”, and “i. defining…the perturbation moves…”. Claims 5-6 and 9-10 also indefinite for recitation of “the perturbation”. Claim 1 previously recites “A molecular evaluation method for predicting the molecular mechanisms through which a perturbation promotes…”, “g. determining the effect of a perturbation…” and “i. defining…in response to a perturbation…”. Accordingly, it is not clear if “the perturbation” in g. is referring to the perturbation of the preamble or the perturbation recited earlier in g. Similarly, it is not clear if “the perturbation” in i. of claim 1 and claims 5-6 and 9-10 is referring to the perturbation in the preamble, the perturbation in g., or the perturbation earlier recited in i.. Alternatively, it is not clear if these are all intended to be the same perturbation. If Applicant intends for these to be different perturbations, the claims should be amended to refer to “a first perturbation”, “a second perturbation”, etc. For purpose of examination, the various perturbations are interpreted to be either the same or different.
Claim 1, and claims dependent therefrom, are indefinite for recitation of “j. calculating…the core components”. Claims 2 and 5 are also indefinite for recitation of “the core components”. There is insufficient antecedent basis for this limitation in the claim because claim 1 does not previously recite core components. As a result, it is not clear what components, “the core components” are referring.
Claim 1, and claims dependent therefrom, are indefinite for recitation of “j. calculating….whereby each of said graphs quantifies the effects of the core components on the DPD…”. There is insufficient antecedent basis for this limitation in the claim because claim 1 does not previously recite effects of core components on the DPD. As a result, it is not clear what effects, “the effects” is referring to, particularly given there may be any number of effects of core components on the DPD.
Claim 2 is indefinite for recitation of a respective causal network connection matrix specifying the strength of connection…”. There is insufficient antecedent basis for “the strength of connection” because claim 1 does not previously recite a strength of connection. As a result, it is not clear what strength, “the strength” is referring to. For example, it is not clear if “the strength” of connection between each of the core components and between each core component and the DPD is potentially referring to weights in the weighted edges of the graph, the quantifications of the effects of the core components on the DPD, or some other strength. Clarification is requested. For purpose of examination, claim 2 is interpreted to mean “specifying a strength of connection”.
Claim 5 and claims dependent therefrom, are indefinite for recitation of “experimentally perturbing the cell states, observing the effect of the perturbation on the cell states…”. As discussed above, it is not clear if “the perturbation” is referring to a perturbation in claim 1 or the perturbation in claim 5. Furthermore, it is not clear if the observed effect in claim 5 is referring to the determined effect of a perturbation in g. of claim 1, or if this is a separate observed effect of perturbation. If Applicant intends the latter, then there is insufficient antecedent basis for “the effect of the perturbation” because claim 5 does not previously recite an effect of the perturbation, and there may be multiple effects of the perturbation.
Claim 5, and claims dependent therefrom, are indefinite for recitation of “inferring from the observed effects the strength of connection between each of the core components…”. First, as discussed above for claim 2, there is insufficient antecedent basis for “the strength of connection” because claim 1 does not previously recite a strength of connection. As a result, it is not clear what strength, “the strength” is referring to. Furthermore, there is insufficient antecedent basis for “the observed effects” because claim 5 only previously recite “observing the effect”, but not multiple effects.
Claim 8, and claims dependent therefrom, are indefinite for recitation of “wherein a perturbation comprises exposing cells to a chemical compound, exposing cells to a biological compound…., and exposing cells to an interaction…”. Given claim 8 recites “a perturbation” (singular), it is unclear if Applicant intends for the perturbation to comprise exposing cells to a chemical compound, exposing cells to a biological compound…., or exposing cells to an interaction, or if Applicant intends for there to be multiple perturbations. For example, claim 9 which depends from claim 8, recites “The method of claim 8, wherein (i) the perturbation comprises exposing cells to a chemical compound, the chemical compound comprising a….; or (iv) the perturbation comprises exposing cells to a pathogen comprising…”, suggesting the perturbation is only intended to be one of the elements. Clarification is requested via claim amendment. For purpose of examination, the perturbation is interpreted to be one of the recited elements.
Claim 10 is indefinite for recitation of “the or each perturbation”. As discussed above, it is not clear which perturbation “the perturbation” is referring to. Similarly, if Applicant intends for each of the perturbations to be the same, it is unclear which perturbations “each perturbation” is referring to.
Claim 11, and claims dependent therefrom, are indefinite for recitation of “which maximises the number of components which can be mapped onto existing biochemical pathways while minimising the total number of ranked components used according to an optimisation function”. First, the metes and bounds of the number of components “which can be mapped onto existing biochemical pathways” are not clear because the metes and bounds of what components could or could not be mapped to potentially every existing biochemical pathway are not clear, and furthermore it is not clear what makes a “component” able to be mapped onto a pathway or not given the breadth of the term component. Furthermore, it is noted that claim 12 recites this step comprises “determining from one or more databases whether each component can be mapped to pathway…”, which suggests Applicant does not intend to determine the number if components which can be generally mapped onto existing biochemical pathways (i.e. all pathways). Furthermore, it is unclear what number is intended to be minimized because it is not clear what “the total number of ranked components used” are intended to be used for. As a result, it is not clear what is being minimized. For purpose of examination, claim 11 is interpreted to mean the number of molecular features which can be mapped to existing pathways in one or more databases is maximized and the total number of ranked components (or molecular features) identified are minimized.
Claim 17 is indefinite for recitation of “will move a said cell state along..”. Claims 1 and 17 previously recite “first and second cell states”, and therefore it is not clear which cell state, “said cell state” is referring to. The claim will be interpreted to mean “will move a cell state…”.
Claims 18-19 are indefinite for recitation of “the effect of the interventions”. There is insufficient antecedent basis for the effect of the interventions because claims 1 and 17, from which claim 18 depends, does not recite an effect of the interventions. As a result, it is not clear which effect is being referenced because interventions may have more than one effect.
Claim 20 is indefinite for recitation of “the distance from the first cell state data points”. First, there is insufficient antecedent basis for the effect of the interventions because claims 1 and 17 do not previously recite first cell state data points, and therefore it is not clear what data points are being referenced. If Applicant intends for the first cell state data points to refer to clusters of cells associated with the first state, the claim should be amended accordingly. Furthermore, given there are multiple data points, it is not clear what distance is being referenced. For example, it is not clear if “the distance” from multiple data points to a hyperplane is a single distance measured from a centroid of a cluster, or if the distance is the average distance of the data points to the hyperplane, etc. For purpose of examination, the limitation is interpreted to mean “a distance from…”.
Claim 21 is indefinite because the recited equations of the computational model are not legible. As a result, one of ordinary cannot ascertain the metes and bounds of computational models read on the claims.
Claim 21 is indefinite for recitation of “the restoring driving force”, “the signaling driving force”, “the outputs of signaling modules”, “the corresponding, BMRA-inferred connection coefficients to…”, and “the initial steady-state values…”. There is insufficient antecedent basis for these limitations in the claim because claims 1 and 17 do not previously recite any of these limitations.
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 1-21 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
The Supreme Court has established a two-step framework for this analysis, wherein a claim does not satisfy § 101 if (1) it is “directed to” a patent-ineligible concept, i.e., a law of nature, natural phenomenon, or abstract idea, and (2), if so, the particular elements of the claim, considered “both individually and as an ordered combination,” do not add enough to “transform the nature of the claim into a patent-eligible application.” Elec. Power Grp., LLC v. Alstom S.A., 830 F.3d 1350, 1353 (Fed. Cir. 2016) (quoting Alice, 134 S. Ct. at 2355). Applicant is also directed to MPEP 2106.
Step 1: The instantly claimed invention (claim 1 being representative) is directed to a method for predicting molecular mechanisms. Therefore, the instantly claimed invention falls into one of the four statutory categories. [Step 1: YES]
Step 2A: First it is determined in Prong One whether a claim recites a judicial exception, and if so, then it is determined in in Prong Two if the recited judicial exception is integrated into a practical application of that exception.
Step 2A, Prong 1: Under the MPEP § 2106.04, the Step 2A (Prong 1) analysis requires determining whether a claim recites an abstract idea, law of nature, or natural phenomenon.
Claim 1 recites the following steps which fall under the mathematical concepts and/or mental processes groupings of abstract ideas:
(a) processing data for a population of cells to identify cells associated with said first and second states respectively, wherein said processing comprises (i) mapping said cells in a multi-dimensional space whose dimensions correspond to distinct molecular features of the cells that define said cell states, the molecular features being selected from RNA expression, protein expression and posttranslational protein modification, and (ii) identifying clusters of cells in said representation associated with said first and second states;
(b) constructing a hypersurface in said representation that separates said first and second states;
(c) generating a state transition vector (STV) of unit length that determines the direction from the first state to the second state in said representation;
(d) generating a ranked list of said molecular features, wherein each molecular feature is ranked by determining the magnitude of the STV component in a dimension associated with the molecular feature;
(e) identifying within said ranked list the components of a core biochemical network comprising the top ranked components, or the components regulating the top ranked components, above a cut-off in the ranking;
(f) calculating, in a reduced multi-dimensional space whose dimensions correspond to those molecular features not identified as components of the core biochemical network, a dimensionality-reduced representation of said hypersurface and a dimensionality-reduced STV;
(g) determining the effect of a perturbation by generating a perturbation vector in the reduced multi-dimensional space, the perturbation vector connecting the centroids of point clouds associated with cell states before and after the perturbation was applied to cells;
(h) classifying the perturbation as promoting a transition between said first and second cell states when the dot product of the perturbation vector and the dimensionality-reduced STV is positive or inhibiting said transition when said dot product is negative;
(i) defining a Dynamic Phenotype Descriptor (DPD) that quantifies cell phenotypic changes in response to a perturbation by measuring whether the perturbation moves the cell states towards or away from the dimensionality-reduced hypersurface, wherein the DPD comprises the molecular features in the ranked list which are not components of the core biochemical network; and
(j) calculating a respective causal network graph for each of the first and second cell states, wherein each causal network graph is a directed, weighted network graph having the same nodes, the nodes of each graph comprising each of the core components together with the DPD represented as a node, and each causal network graph having directed and weighted edges that are specific to the associated first or second cell state, whereby each of said graphs quantifies the effects of the core components on the DPD in the first or second cell state respectively and thereby describes the molecular mechanisms that characterise the first and second cell states.
The identified claim limitations falls into one of the groups of abstract ideas of mathematical concepts and/or mental processes for the following reasons. First, the limitations of processing data of cells to identify cells associated with two states by mapping cells into a multi-dimensional space and identifying clusters, constructing a hypersurface in said representation that separates said first and second states, generating a state transition vector of unit length (STV), calculating, in a reduced multi-dimensional space, a dimensionality reduced representation of said hypersurface and a dimensionality-reduced STV, generating a perturbation vector connecting centroids of point clouds, defining a DPD that quantifies cell phenotypic changes by measuring whether the perturbation moves the cell states towards or away the dimensionality-reduced hyperspace, and calculating a respective network graph for each of the first and second cell states each recite a mathematical concept. MPEP 2106.04(a)(2) I. C. explains a claim that recites a mathematical calculation, when the claim is given its broadest reasonable interpretation in light of the specification, will be considered as falling within the "mathematical concepts" grouping. A mathematical calculation is a mathematical operation (such as multiplication) or an act of calculating using mathematical methods to determine a variable or number, e.g., performing an arithmetic operation such as exponentiation. The above limitations amount to textual equivalents of performing mathematical calculations. For example, mapping cells to a multi-dimensional space to identify clusters requires mathematically calculating coordinates for the cells in a multi-dimensional space and then calculating distances between points to identify clusters. Generating a state transition vector of unit length requires calculating a vector between the centroid of the first state and centroid of the second state, and then normalizing the vector to have a magnitude of 1. Calculating a dimensionality reduction representation of said hypersurface and a dimensionality-reduced STV encompasses performing a principal component analysis on the data and calculating another STV vector from the dimensionality-reduced space. Generating a perturbation vector in the reduced multi-dimensional space connecting centroids amounts to a textual equivalent to calculating a distance between the centroids (i.e. to obtain the magnitude of the vector) as well as directionality. Defining a DPD by measuring whether a perturbation moves the cell states towards or away from the hypersurface similarly amounts to a textual equivalent to calculating a distance between a cell state and hypersurface before and after perturbation. Furthermore, the construction of a hypersurface in a multi-dimensional space represents a mathematical relationship or equation between the first and second states in the multi-dimensional space. Similarly, calculating respective causal network graphs with directed and weighted edges recites a mathematical relationship, analogous to organizing information and manipulating information through mathematical correlations, Digitech Image Techs., LLC v. Electronics for Imaging, Inc., 758 F.3d 1344, 1350, 111 USPQ2d 1717, 1721 (Fed. Cir. 2014).
The limitations of (a), (c), (d), (e), (h), and (i) recite a mental process. In this case, processing data of cells to identify cells associated with two states by mapping cells into a multi-dimensional space and identifying clusters can be practically performed in the mind by calculating distances between molecular features of the cells, plotting the distances in a 2-D space, and identify groups of cells in the 2-D space. Generating a state transition vector can be practically performed in the mind by solving the Pythagorean theorem in a multi-dimensional space to identify the magnitude and direction of the vector. Ranking molecular features can be practically performed in the mind by performing data comparisons of magnitudes of the STV component in a dimensional for the feature. Identifying molecular features of a biochemical network from the ranked list can be practically performed in the mind by taking the top N ranked features. Classifying a perturbation as claimed can be practically performed in the mind by determining if a dot product is positive or negative. Last, defining a DPD can be practically performed in the mind by calculating a distance of points to a hypersurface before and after perturbation (e.g. performing subtraction). Therefore, these limitations recite a mental process.
Dependent claims 2-5, 7, 10-21 further recite an abstract idea and/or are part of the abstract idea of claim 1 above. Dependent claims 2-4 further limit the mathematical concept of calculating a respective causal network graph to calculate a connection matrix and infer topology and strengths of connections using a Bayesian modular response analysis, and therefore are part of the mathematical relationship of claim 1. Dependent claim 5 further recites the mental process of inferring strengths of connection between components and each core component and the DPD. Dependent claim 7 further recites the mental process of observing the effect of the perturbation on cell states. Dependent claim 10 further recites the mental process and mathematical concept of mapping said cells in the reduced multi-dimensional space and identifying clusters of cells. Dependent claim 11 further recites the mental process and mathematical concept of determining a cut-off in the ranking using an optimization function. Dependent claim 12 further limits the mental process of mathematical concept of claim 12 to involve determining components that can map to biochemical pathways in one or more databases. Dependent claim 13 further limits the first and second cell states to be from a set of three cell states, and further limits the mental process of processing data to identify cells associated with three cell states. Dependent claim 14 further limits the abstract idea of claim 1 by limiting the hypersurface to be a hyperplane. Dependent claims 15-16 further limit the molecular features of claim 1, and thus are part of the abstract idea of claim 1. Dependent claim 17 further recites the mental process of identifying an intervention using the causal graphs or the mental process and mathematical concept of assessing by kinetic computational models whether an intervention will move a cell state along the STV. Dependent claims 18-19 further limit the intervention being identified in claim 17, and therefore are part of the abstract idea of claim 17. Dependent claim 20 further recites the mental process and mathematical concept of determining whether a distance from the first cell state data points to the hypersurface decreases after intervention. Dependent claim 21 further limits the mathematical concept of claim 20 to be performed according to the recited equation.
Therefore, claims 1-21 recite an abstract idea. [Step 2A, Prong 1: YES]
Step 2A: Prong 2: Under the MPEP § 2106.04, the Step 2A, Prong 2 analysis requires identifying whether there are any additional elements recited in the claim beyond the judicial exception(s), and evaluating those additional elements to determine whether they integrate the exception into a practical application of the exception. This judicial exception is not integrated into a practical application for the following reasons.
Claims 1-4 and 10-21 do not recite any elements in addition to the judicial exception.
The additional elements of claims 5-9 include:
experimentally perturbing the cell states, observing the effect of the perturbation on the cell states (claim 5);
measuring one or more molecular responses to the experimental perturbation (claim 6);
applying a plurality of perturbations and observing the effect of the perturbations on the cell states (claim 7);
wherein a perturbation comprises exposing cells to a chemical compound, exposing cells to a biological compound, inducing an epigenetic or genetic change in cells, exposing cells to pathogens, exposing cells to an interaction with other cells, and exposing cells to an interaction with a biological or artificial surface (claim 8); and
wherein (i) the perturbation comprises exposing cells to a chemical compound, the chemical compound comprising a pharmaceutical drug, a toxin, or an environmental chemical; (ii) the perturbation comprises exposing cells to a biological compound, the biological compound comprising a growth factor, a hormone, a cytokine, a toxin, an antibody, a cellular receptor, an siRNA, an shRNA, or a ligand; (iii) the perturbation comprises exposing cells to an epigenetic or genetic change comprising an epigenetic modification, a gene mutation, a heterozygote gene knockout, a gene copy number aberration, a gene structural variant, or CRISPR/Cas9-mediated genetic modification; or (iv) the perturbation comprises exposing cells to a pathogen comprising a virus or a bacterium (claim 9).
The above additional elements of claims 5-9 of perturbing cells by exposing cells a chemical compound comprising a pharmaceutical drug, a toxin, or an environmental chemical or a biological compound comprising a growth factor, a hormone, a cytokine, a toxin, an antibody, etc. and observing effects of the perturbations by measuring molecular responses only serve to collect data for use by the abstract idea, which amounts to insignificant extra-solution activity that does not integrate the recited judicial exception into a practical application. See MPEP 2106.05(g).
Therefore, the additionally recited elements amount to insignificant extra-solution activity and, as such, the claims as a whole do not integrate the abstract idea into practical application. Thus, claims 1-21 are directed to an abstract idea. [Step 2A, Prong 2: NO]
Step 2B: In the second step it is determined whether the claimed subject matter includes additional elements that amount to significantly more than the judicial exception. See MPEP § 2106.05.
The claims do not include any additional steps appended to the judicial exception that are sufficient to amount to significantly more than the judicial exception.
Claims 1-4 and 10-21 do not recite any elements in addition to the judicial exception.
The additional elements of claims 5-9 include:
experimentally perturbing the cell states, observing the effect of the perturbation on the cell states (claim 5);
measuring one or more molecular responses to the experimental perturbation (claim 6);
applying a plurality of perturbations and observing the effect of the perturbations on the cell states (claim 7);
wherein a perturbation comprises exposing cells to a chemical compound, exposing cells to a biological compound, inducing an epigenetic or genetic change in cells, exposing cells to pathogens, exposing cells to an interaction with other cells, and exposing cells to an interaction with a biological or artificial surface (claim 8); and
wherein (i) the perturbation comprises exposing cells to a chemical compound, the chemical compound comprising a pharmaceutical drug, a toxin, or an environmental chemical; (ii) the perturbation comprises exposing cells to a biological compound, the biological compound comprising a growth factor, a hormone, a cytokine, a toxin, an antibody, a cellular receptor, an siRNA, an shRNA, or a ligand; (iii) the perturbation comprises exposing cells to an epigenetic or genetic change comprising an epigenetic modification, a gene mutation, a heterozygote gene knockout, a gene copy number aberration, a gene structural variant, or CRISPR/Cas9-mediated genetic modification; or (iv) the perturbation comprises exposing cells to a pathogen comprising a virus or a bacterium (claim 9).
The above additional elements of claims 5-9 of perturbing cells by exposing cells a chemical compound comprising a pharmaceutical drug, a toxin, or an environmental chemical or a biological compound comprising a growth factor, a hormone, a cytokine, a toxin, an antibody, etc. and observing effects of the perturbations by measuring molecular responses are well-understood, routine, and conventional. This position is supported by Heath et al. (Single-cell analysis tools for drug discovery, 2016, Nature Reviews, 15, pg. 204-216). Heath reviews single-cell analysis tools for drug discovery (Abstract), and discloses an emerging frontier is the use of microfluidics that permit highly customizable assays designed to correlate weak perturbations to cells with changes in the transcriptome or proteome (i.e. molecular responses), citing several studies that correlate how cells respond to drugs or molecular stimulations (pg. 210, col. 1, para. 5 to col. 2, para. 1; Box 1).
Therefore, 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]
Therefore, the instantly rejected claims are not drawn to eligible subject matter as they are directed to an abstract idea without significantly more. For additional guidance, applicant is directed generally to the MPEP § 2106.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Altschuler et al., US 2008/0195322 A1; cited in IDS filed 27 Nov. 2023.
Conclusion
No claims are allowed.
Claims 1-21 are free of the prior art.
The closest prior art of record, Altschuler, discloses a method for quantifying the effects of perturbations on biological samples (Abstract). Altschuler discloses producing biological sample feature distributions in a multidimensional feature space, and separating the control biological feature distribution (i.e. first cell state) and the perturbed biological sample (i.e. second cell state) feature distributions (i.e. clusters) using a multivariate classification ([0012]), wherein the biological samples are cells ([0001]; [0013]). Altschuler discloses separating feature distributions comprises constructing a hyperplane between the features using a support vector machine ([0013]; FIG. 2). Altschuler discloses generating a unit normal vector indicating the direction of maximum separation of the two distributions from the hyperplane (i.e. a state transition vector) ([0038]). Altschuler further discloses the coefficients of the unit normal vector indicate the relative importance of feature in deciding whether a cell belongs to the treated or control class ([0038]; FIG. 2), demonstrating the coefficients of the unit normal vector may serve as a ranking of feature importance.
However, Altschulder does not disclose identifying the top ranked STV components of a core biochemical network, calculate a dimensionality-reduced representation of the hypersurface and a dimensionality-reduced STV in a reduced multi-dimensional space whose dimensions correspond to those molecular features not identified as components of the core biochemical network, perform the perturbation analysis to ultimately calculate a dynamic phenotypic descriptor (DPD) using the reduced-multi-dimensional space with dimensions for molecular features that were not identified in (e), as recited in steps (g)-(i), and then construct causal network graphs quantifying the effects of the core components from (f) on the DPD determined in step (i), as recited in independent claim 1 and claims dependent therefrom.
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/KAITLYN L MINCHELLA/Primary Examiner, Art Unit 1685
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