DETAILED ACTION
Applicant's response, filed 03/11/2026, has been fully considered. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
CLAIM STATUS
Claims 1-18 are pending and under examination herein.
Claims 1-18 are rejected.
Priority
The instant application claims benefit to U.S. provisional application No. 63/210,678 filed on 06/15/2021. Domestic benefit is acknowledged. As such, the effective filing date of claims 1-18 is 06/15/2021.
Drawings
The amendments to the drawings were not entered because no replacement drawings were attached.
Fig. 13 is 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).
Claim Objections
Due to the amendments made, the objections to claims 2-3, 5-7, 11-12, and 14-16 are rescinded.
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.
Due to the amendments made to the claims, the rejections to claims 10 and 14 made previously are withdrawn.
Claims 4-14 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. This rejection is newly recited and necessitated by claim amendment.
Claims 4 and 6 recite “the incidence matrix” but now there is “an incidence matrix” recited in claims 4, 6 and claim 1, making it indefinite whether it is referring to separate matrices or the same incidence matrix. Claims 5 and 7-9 are dependent from claims 4 and 6 and do not resolve the indefiniteness of claims 4 and 6, and are thus also rejected.
In claim 10,“the incidence matrix” in line 14 is indefinite because there are two previously recited incidence matrices, one from the first biological sample and the one from the second. It is suggested to amend to clarify that the incidence matrix in line 14 is the incidence matrix from the second read data. Claims 11-14 are dependent from claim 10 and do not resolve its indefiniteness, and are thus also 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 1-18 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. Any newly recited portions herein are necessitated by claim amendment.
In accordance with MPEP § 2106, claims found to recite statutory subject matter 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:
Claim 1 recites the construction of a hypergraph where each node in the hypergraph represents a locus and hyperedges in the hypergraph represent interactions between two or more loci and the hypergraph represents the entire human genome.
Claim 1 recites constructing an incidence matrix from the read data
Claim 1 recites representing the incidence matrix as a hypergraph
Claim 4 recites constructing an incidence matrix from the read data; constructing a Laplacian matrix for the incidence matrix; computing eigenvalues of the Laplacian matrix using eigendecomposition; normalizing the eigenvalues of the Laplacian matrix; and determining entropy of the hypergraph using the normalized eigenvalues.
Claim 5 recites that the eigenvalues of the Laplacian matrix are normalized and entropy is computed using Shannon entropy formula.
Claims 6 recites constructing an incidence matrix for the hypergraph; for each multi-way contact in the incidence matrix, add a given multi-way contact to a set of potential transcription clusters in case where each locus associated with the given multi-way contact is accessible and at least one locus associated with the given multi-way contact is a binding site and the binding site is an indicator of transcription; for each multi-way contact in the set of potential transcription clusters, add a particular multi-way contact to a set of transcription clusters in case where loci associated with the particular multi-way contact contains two or more expressed genes and have at least one common transcription factor; and reporting multi-way contacts in the set of transcription clusters.
Claim 7 & 16 recite determining whether locus are accessible from the chromatin accessibility data
Claims 8 & 17 recite determining whether a given locus is a binding site from the binding data, wherein the binding site Is an indicator of transcription
Claims 9 & 18 recite determining whether a given loci contains two or more expressed genes from the gene expression data
Claim 10 recites constructing an incidence matrix from the read data, representing the incidence matrix as a hypergraph, where each node in the first hypergraph represents a locus and hyperedges in the first hypergraph represent interactions between two or more loci; constructing a second hypergraph from the read data, where each node in the second hypergraph represents a locus and hyperedges in the second hypergraph represent interactions between two or more loci; constructing an incidence matrix from the second read data, representing the incidence matrix as a second hypergraph and comparing the first hypergraph to the second hypergraph by computing a distance between the first hypergraph and the second hypergraph.
Claim 13 recites constructing a first incidence matrix for the first hypergraph; constructing a first normalized Laplacian matrix for the first incidence matrix; computing a first set eigenvalues of the first normalized Laplacian matrix using eigendecomposition; constructing a second incidence matrix for the second hypergraph; constructing a second normalized Laplacian matrix for the second incidence matrix; computing a second set of eigenvalues of the second normalized Laplacian matrix using eigendecomposition; computing the distance between the first hypergraph and the second hypergraph using the first set of eigenvalues and the second set of eigenvalues.
Claim 14 recites the equations of two Laplacian matrices.
Claim 15 recites constructing a hypergraph, constructing an incidence matrix for the hypergraph; for each multi-way contact in the incidence matrix, add a given multi-way contact to a set of potential transcription clusters in case where each locus associated with the given multi-way contact is accessible and at least one locus associated with the given multi-way contact is a binding site and the binding site is an indicator of transcription; for each multi-way contact in the set of potential transcription clusters, add a particular multi-way contact to a set of transcription clusters in case where loci associated with the particular multi-way contact contains two or more expressed genes and have at least one common transcription factor; and reporting multi-way contacts in the set of transcription clusters.
The limitations for performing the claimed interaction analysis (claims 1, 10, 15) require determining relationships between different loci and drawing out those representations in a graph. There is a limitation that the graph represents “the entire human genome,” but there are no limitations for how large or small the loci are or the amount or type of representative genomic data that make up the constructed loci, meaning that there are embodiments within the scope of the claim that would be simple to represent on paper. The human mind is capable of evaluating a relationship between at least two data points and drawing the graph with pen and paper. Therefore, this limitation equates to a mental process. Furthermore, the construction of a hypergraph involves organizing information by representing the mathematical relationships between the nodes, which equates to a mathematical process.
The limitations continue to stipulate (claims 4-6, 13-15) the construction of an incidence matrices and Laplacian matrices, eigendecomposition of the Laplacian matrices, and determination of the entropy of the hypergraphs, which are individually mathematical concepts because they involve organizing information by representing mathematical relationships and are verbal equivalents for mathematical calculations performed in the claim, and, when considered together, constitute a mental process because the human mind is capable of performing it.
The formulae for normalization of eigenvalues, the construction of normalized Laplacian matrices, and computation of entropy are claimed as steps of the process (claims 4-6, 13-15), which are mathematical concepts because they involve organizing information by representing mathematical relationships and are verbal equivalents for mathematical calculations performed in the claims.
A set of conditions and determinations for the addition of certain lengths of read data to be added to different sets of read data termed “transcription clusters” are claimed (claims 6-9, 15-18), which the human mind is capable of performing, thus making it a mental process.
The notion of determining characteristics of a locus from aspects of the information are claimed (claims 7-9, 16-18), which the human mind is capable of performing, therefore making them mental processes.
Comparison of two hypergraphs is also a claimed method step (claims 10, 13), which is an equation of difference - a type of information organized by a representation of a mathematical relationship - and therefore a mathematical concept.
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 1-18 recite an abstract idea.
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. 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 in some other meaningful way. Rather, the instant claims recite additional elements that amount to mere instructions to implement the abstract idea in a generic computing environment or insignificant extra-solution activity. Specifically, the claims recite the following additional elements:
Claim 1 recites receiving a biological sample of a cell from a subject; extracting read data using long read sequencing from the biological sample, where the read data includes a set of reads and implementing the abstract idea with a computer processor.
Claim 2 recites read data of a length from 100 to 500 base pairs.
Claim 3 recites read data which has a length selected from one of 100,000 base pairs, one million base pairs or 25 million base pairs.
Claim 7-9 recites receiving chromatin accessibility data for the biological sample, receiving binding data for the biological sample, & receiving gene expression data for the biological sample.
Claim 10 recites receiving a first biological sample of a cell from a subject; extracting read data using long read sequencing from the first biological sample, where the read data includes a set of reads & receiving a second biological sample of a cell from the subject; extracting read data using long read sequencing from the second biological sample, where the read data includes a set of reads
Claim 11 recites the first biological sample is taken from a cell having a first cell type and the second biological sample is taken from a cell having a second cell type different from the first cell type
Claim 12 recites the first biological sample is taken from a cell having a given cell type at a given time and the second biological sample is taken from a cell of the subject having the same cell type but at a time different than the given time.
Claim 15 recites receiving a biological sample of a cell from a subject; extracting read data from the biological sample, where the read data includes a set of reads
Claims 16-18 recites receiving chromatin accessibility data for the biological sample, receiving binding data for the biological sample, & receiving gene expression data for the biological sample.
There are no limitations that indicate that the processor in claim 1 requires anything other than a generic computer processor. As such, this limitation equates 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 other additional elements of claims 1-3, 7-9, 10-12 & 15-18 do not add a meaningful limitation to the abstract idea because they amount to mere data gathering steps that would be required for the claimed mental processes. These limitations serve to gather data that is used as input for the abstract idea and there is no indication that the abstract idea has any impact on those data gathering steps. The courts have indicated that mere data gathering activity is insignificant extra-solution activity that does not provide a practical application (see MPEP 2106.05(g)).
Therefore, the claims do not recite any additional elements that integrate the abstract idea into a practical application. As such, claims 1-18 are directed to an abstract idea.
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 computing environment or well-understood, routine and conventional activities. The instant claims recite the following additional elements:
Claim 1 recites receiving a biological sample of a cell from a subject; extracting read data from the biological sample, where the read data includes a set of reads and implementing the abstract idea with a computer processor.
Claim 2 recites read data of a length from 100 to 500 base pairs.
Claim 3 recites read data which has a length selected from one of 100,000 base pairs, one million base pairs or 25 million base pairs.
Claim 7-9 recites receiving chromatin accessibility data for the biological sample and determining whether locus are accessible from the chromatin accessibility data, receiving binding data for the biological sample and determining whether a given locus is a binding site from the binding data, where the binding site is an indicator of transcription, receiving gene expression data for the biological sample and determining whether a given loci contains two or more expressed genes from the gene expression data.
Claim 10 recites receiving a first biological sample of a cell from a subject; extracting read data from the first biological sample, where the read data includes a set of reads & receiving a second biological sample of a cell from the subject; extracting read data from the second biological sample, where the read data includes a set of reads
Claim 11 recites the first biological sample is taken from a cell having a first cell type and the second biological sample is taken from a cell having a second cell type different from the first cell type
Claim 12 recites the first biological sample is taken from a cell having a given cell type at a given time and the second biological sample is taken from a cell of the subject having the same cell type but at a time different than the given time.
Claim 15 recites receiving a biological sample of a cell from a subject; extracting read data from the biological sample, where the read data includes a set of reads
Claims 16-18 recites receiving chromatin accessibility data for the biological sample, receiving binding data for the biological sample, receiving gene expression data for the biological sample
As discussed above, there are no limitations that indicate that the processor in claim 1 requires anything other than a generic computer processor. As such, this limitation equates 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 generically recited computer element of claim 1 does not add significantly more to the abstract idea because it amounts to simply implementing the abstract idea on a computer.
The other additional elements of claims 1-3, 7-9, 10-12 & 15-18 do not add significantly more to the abstract idea because they recite well-understood, routine and conventional activities in the art.
The extraction of read data is commonly accomplished via sequencing, which applicant admits varies in read length. (Specification para 37: “Read data is extracted at 12 from the biological sample, where the read data includes a set of reads. Sequencing technologies vary in the length of the reads produced. For example, read lengths are typically in the range of 100-500 base pairs”). Table 1 of Hu et al. (Human Immunology 82, 2021, 801–811, previously cited) (hereafter “Hu”) describes that lengths of read data extracted using typical methods can vary from 100 bp to 500 bp to 100,000 bp to 1 million bp to 25 million bp or more, making extraction of read data at these lengths a conventional laboratory technique. Long read sequencing at the provided length is also described as conventional by Hu (Hu pg 805 right col ¶ 3, table 2).
Performing clinical tests on individuals to obtain input for an equation has been identified as a “mere data gathering” step that amounts to insignificant extra-solution activity, In re Grams, 888 F.2d 835, 839-40; 12 USPQ2d 1824, 1827-28 (Fed. Cir. 1989). Detecting DNA or enzymes in a sample has been found to be a conventional laboratory technique that amounts to insignificant extra-solution activity, Sequenom, 788 F.3d at 1377-78, 115 USPQ2d at 1157); Cleveland Clinic Foundation 859 F.3d at 1362, 123 USPQ2d at 1088 (Fed. Cir. 2017). The other additional elements of claims 1, 10 and 15, which claim the receipt of a biological sample of a cell from a subject, would be an example of such a clinical test/DNA detection, and therefore “mere data gathering.”
The other additional elements of claims 1-3, 7-9, 10-12 & 15-18 place limitations upon the extraction of read data from the biological cell. Analyzing DNA to provide sequence information or detect allelic variants has been found to be a conventional laboratory technique that amounts to insignificant extra-solution activity, Genetic Techs. Ltd., 818 F.3d at 1377; 118 USPQ2d at 1546. (see MPEP 2106.05(g)). The sequence information (“read data”) is a required input for the claimed interaction analyses, so its extraction is a “mere data gathering” step.
The other additional elements of claims 7 & 16 place limitations pertaining to the receipt of chromatin accessibility data. The introduction of Sinha et al. (Genomics Proteomics Bioinformatics ,19, (2021), 172–190, previously cited) (page 173 starting left col) illustrates the centrality of chromatin accessibility data extraction and analysis to bioinformatics research and lists several current chromatin accessibility data extraction and analysis methods. A person of ordinary skill in the art would recognize chromatin accessibility data extraction and analysis as a conventional laboratory technique.
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. As such, claims 1-18 are not patent eligible.
Response to Arguments
Applicant's arguments filed 03/11/2026 have been fully considered but they are not persuasive.
Applicant states that the claimed step of “extracting read data from a biological sample” cannot be performed by the human mind, and argues that the claimed invention cannot be a mental process due to this limitation (Pg 9 ¶ 2 of Applicant’s Remarks). This argument is not persuasive.
The limitation “extracting read data from a biological sample” was classified as an additional element that modifies the abstract ideas the application is directed to, not as a mental process abstract idea itself. However, the instant claims recite other limitations that correspond to an abstract idea, as set forth above. The mere inclusion of additional elements does not negate the fact that the claims recite other limitations that correspond to an abstract idea. Therefore, the claims recite an abstract idea.
Next, the applicant argues that the invention provides a practical application by improving technology, namely by deriving a hypergraph that represents the entire genome directly from the read data, and makes arguments about the differences between 3C and Pore-C that are not in the claims (Pg 9 ¶ 3-4 of Applicant’s Remarks). This argument is not persuasive.
MPEP § 2145 subsection VI warns that limitations from the specification are not to be read into the claims. Because the limitations recited in the arguments do not occur in the claims, the invention does not provide a practical application.
Finally, applicant argues that the invention improves technology by allowing a person to derive a hypergraph (pg 10 ¶ 3 of Applicant’s Remarks). This argument is not persuasive. MPEP 2106.05(a) states: “It is important to note, the judicial exception alone cannot provide the improvement. The improvement can be provided by one or more additional elements.”
“Deriving a hypergraph” is a verbal equivalent to a mathematical calculation, and is thus a judicial exception. The improvement must be realized by the additional elements of the claim, either alone or in combination with the judicial exception. Therefore, the invention does not provide an improvement to technology.
Claim Rejections – 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
The previous rejections are withdrawn in light of the claim amendments.
Claims 1-3, 10 and 15-18 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. (Cell System, 2020, Vol. 10, pgs. 397-407; 10/24/2022 IDS Document; previously cited) in view of Hu et al. (Human Immunology 82, 2021, 801–811, previously cited) (hereafter “Hu”) and Chen et al. (IEEE Transactions on network science and engineering, IEEE, 16 June 2020, vol 7, no. 4, pgs. 2889-2900; 5/15/2025 IDS Document; “hereafter “Chen”, previously cited). This rejection is newly recited and necessitated by claim amendment.
With respect to claim 1, Zhang et al. teaches a method for analyzing interactions in a human genome (box 1), and constructing, by a computer processor, a hypergraph from the read data, where each node in the hypergraph represents a locus and hyperedges in the hypergraph represent interactions between two or more loci (figure 1, page 398 left col last para).
Regarding Claim 10, Zhang teaches a method for analyzing interactions in a human genome (box 1), constructing and comparing multiple hypergraphs (page 403 left col 1st para-end of page) where each node in the hypergraph represents a locus and hyperedges in the hypergraph represent interactions between two or more loci (figure 1, page 398 left col last para).
Zhang is silent as to the construction of an incidence matrix in claim 1 and 10. Chen teaches the construction of incidence matrices (algorithm 1, 2890 left col first para).
Zhang is silent as to receiving a biological sample of a cell from a subject and extracting read data from a set of reads using long read sequencing in claim 1 and 10. Zhang is silent as to the number of base pairs of the extracted read data in claims 2-3. However, these limitations were known in the art at the time of the effective filing date of the invention, as taught by Hu et al.
Regarding claim 1 and 10, receiving a biological sample of a cell from a subject and extracting read data from a set of reads is taught by Hu (table 1). Hu also teaches the use of long read sequencing (pg 805 right col ¶ 3).
Regarding claim 2, Hu et al. teaches the use of between 100 and 500 base pairs of read data to analyze genomic interactions (Hu, table 1). Hu teaches that these lengths are also achievable by long read sequencing (Hu table 2).
Regarding claim 3, Hu et al. teaches a read data length of between 100,000, 1 million, or 25 million base pairs (Hu, table 1). Hu teaches that these lengths are also achievable by long read sequencing (Hu table 2).
Regarding Claim 15, Zhang teaches a method for analyzing interactions in a human genome (box 1), constructing a hypergraph (page 403 left col 1st para-end of page) where each node in the hypergraph represents a locus and hyperedges in the hypergraph represent interactions between two or more loci (figure 1, page 398 left col last para), and adding a given multi-way contact to a set of potential transcription clusters (“spatial localizations” in Zhang) where each locus associated with a given multi-way contact is a binding site and the binding site is an indicator of transcription (figure 3, page 400 left col).
Regarding claims 16-18, Zhang teaches the identification of “transcription clusters” (“spatial localizations” in Zhang) (404 left col). Zhang teaches the use of binding data and chromatin accessibility data (box 1). Zhang also suggests using RNA sequencing in future applications of the research to increase detection accuracy (405 left col 1st full para).
Zhang is silent as to receiving a biological cell from a subject and extracting read data from the biological sample where the read data includes a set of reads in claim 15. Zhang is also silent as to the construction of an incidence matrix in claim 15.
Regarding claim 15, receiving a biological sample of a cell from a subject and extracting read data from a set of reads is taught by Hu (table 2). Hu also teaches the use of long read sequencing (pg 805 right col ¶ 3). Chen teaches the use of incidence matrices (algorithm 1, 2890 left col first para).
Under Rationale D of MPEP 2143, an invention is prima facie obvious if it is an application of a known technique to a known method ready for improvement to yield predictable results. The prior art contained a “base” method (the “MATCHA” of Zhang) upon which the claimed invention can be seen as an “improvement.” The prior art technique of long-read data extraction found in Hu is applicable to the base method of genomic interaction analysis based on read data. The technique of using an incidence matrix to construct the hypergraph from Chen is also applicable to the base method. A person of ordinary skill in the art would have recognized that applying the known technique of read data extraction would have provided predictable results and resulted in an improved system because the method is now experimentally predicting real-world genome interactions rather than using the predefined data sets found in the original text of Zhang. A person of ordinary skill in the art would also recognize that constructing a hypergraph from the incidence matrix would have provided predictable results and resulted in an improved system because it would allow the method to better consider the genome as a dynamic graph (Chen pg 2889 Introduction left col ¶ 1).
Regarding claim 15, Under Rationale D of MPEP 2143, an invention is prima facie obvious if it is an application of a known technique to a known method ready for improvement to yield predictable results. The prior art contained a “base” method (the “MATCHA” of Zhang) upon which the claimed invention can be seen as an “improvement.” The prior art technique of read data extraction found in Hu is applicable to the base method of genomic interaction analysis based on read data found in Zhang. A person of ordinary skill in the art would have recognized that applying the known technique of read data extraction would have provided predictable results and resulted in an improved system because the method is now experimentally predicting real-world genome interactions rather than using the predefined data sets found in the original text of Zhang. The prior art technique of the incidence matrix as taught in Chen et al. is applicable to the base method of genomic interaction analysis based on read data found in Zhang. A person of ordinary skill in the art would have recognized that applying the known technique of the incidence matrix would have provided predictable results and resulted in an improved system because it is a repeatable mathematical formula with predictable results and because of the statement of improved genomic interaction analysis that is found in the text of Chen (abstract).
Regarding claims 16-18, An invention would have been prima facie obvious to one of ordinary skill in the art at the time of the effective filing date of the invention if some suggestion in the prior art would have led that person to combine the prior art teachings to arrive at the claimed invention. There is a suggestion to use RNA sequencing in the text of Zhang (405 left col 1st full para). There would be a reasonable expectation of success for this combination to a person of ordinary skill in the art, as the suggested modification is explained in the text of Zhang. Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time to modify the method of Zhang by adding a step to the algorithm incorporating RNA sequencing data, in order to better characterize higher-order interactions among different components in the nucleus.
The invention is therefore prima facie obvious.
Claims 4-9 and 11-14 are rejected under 35 U.S.C. 103 as being unpatentable over Zhang et al. in view of Hu and Chen as applied to claim 1 above, and further in view of Battiston et al. (Cornell Univeristy Library, 2 June 2020; 5/15/2025 IDS Document; hereafter “Battison”, previously cited)
Regarding Claim 6, Zhang teaches adding a given multi-way contact to a set of potential transcription clusters (“spatial localizations” in Zhang) where each locus associated with a given multi-way contact is a binding site and the binding site is an indicator of transcription (figure 3, page 400 left col).
Regarding claims 7-9, Zhang teaches the identification of “transcription clusters” (“spatial localizations” in Zhang) (404 left col). Zhang teaches the use of binding data and chromatin accessibility data (box 1). Zhang also suggests using RNA sequencing in future applications of the research to increase detection accuracy (405 left col 1st full para).
Regarding claim 4, Zhang and Hu are silent as to constructing an incidence matrix from the read data, constructing a Laplacian matrix for the incidence matrix, computing the eigenvalues of the Laplacian matrix, and determining the entropy of the hypergraph using the normalized eigenvalues.
Regarding claim 5, Zhang and Hu are silent as to the equation of the normalization of the eigenvalues of the Laplacian matrix and the method of computation of its entropy.
Regarding claim 6, Zhang and Hu are silent as to constructing an incidence matrix for the hypergraph.
However, these limitations were known in the art at the time of the effective filing date of the invention, as taught by Chen and Battison.
Regarding claims 4-6, Chen teaches the use of incidence (algorithm 1, 2890 left col first para) matrices.
Regarding claims 4-5, Chen teaches the use of Laplacian (equation 9) matrices, their construction from incidence matrices, and the Shannon entropy (equation 1). Battison teaches the computation of the eigenvalues of a matrix (section 3.1) and their normalization with computation of Shannon entropy (section 3.4).
An invention would have been prima facie obvious to one of ordinary skill in the art at the time of the effective filing date of the invention if some teaching, suggestion or motivation in the prior art would have led that person to combine the prior art teachings to arrive at the claimed invention. Chen discloses that the mathematical formulae enumerated are in the service of better considering the genome as a dynamic graph (page 2889 introduction). Battison discloses a motivation to modify genomic interaction methods such as that of Zhang with the methods of Battison, to better characterize the complexity of biological systems from the richness of interactions among their units (abstract). Furthermore, a person of ordinary skill in the art could have predicted that the methods of Chen and Battison could be readily added to the method of Zhang with a reasonable expectation of success because the methods are mathematical formulae with repeatable and computable results.
Regarding claim 13, Zhang teaches the comparative analysis of interactome profiles (page 403 left col first full para onto p 404).
Regarding claims 11-13,Zhang is silent as to the comparison of two hypergraphs.
Regarding claim 13, Zhang is silent as to construction of a first incidence matrix, constructing a first normalized Laplacian matrix for the first incidence matrix, computing a first set eigenvalues of the first normalized Laplacian matrix using eigendecomposition, construction of a second incidence matrix, constructing a second normalized Laplacian matrix for the second incidence matrix, and computing a second set eigenvalues of the second normalized Laplacian matrix using eigendecomposition.
Regarding claim 14, Zhang is silent as to the equation for the construction of the Laplacian matrix.
Battison teaches the spectral based comparison of two hypergraphs (sections 3.1, 3.3, 9) and suggests multiple applications including different time points and sample types (section 9: “Recently, higher-order inference frameworks have also been extended to deal with dynamic correlations of abundance levels of genes, transcripts and metabolites changing over time. The results provide a better picture of the global dynamic correlation patterns of the investigated biological systems. Higher-order interactions have also revealed key insights when designing effective drug combinations to prevent or contrast diseases.”). Battison also teaches the construction of a Laplacian matrix (section 3.5.1) and incidence matrix, their equations, normalization methods, the computation of eigenvalues and eigendecomposition (section 3.1.1).
There is a suggestion to use RNA sequencing in the text of Zhang (405 left col 1st full para). There would be a reasonable expectation of success for this combination to a person of ordinary skill in the art, as the suggested modification is explained in the text of Zhang. Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time to modify the method of Zhang by adding a step to the algorithm incorporating RNA sequencing data, in order to better characterize higher-order interactions among different components in the nucleus.
An invention would have been prima facie obvious to one of ordinary skill in the art at the time of the effective filing date of the invention if some motivation in the prior art would have led that person to combine the prior art teachings to arrive at the claimed invention. There would be a reasonable expectation of success for this combination to a person of ordinary skill in the art, as the modifications are mathematical formulae with predictable results. Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time to modify the method of Zhang with the matrix constructions and comparison implementation suggestions of Battison.
The invention is therefore prima facie obvious.
Response to Arguments
Applicant’s arguments, see page 11 ¶ 1-4 of applicant’s remarks, filed 03/11/2026, with respect to the rejections of claims 1-3 and 10 under 35 U.S.C. § 103 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new grounds of rejection is made in view of Zhang, Chen, and Hu.
Contact
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
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/G.M.H./Examiner, Art Unit 1684
/OLIVIA M. WISE/Supervisory Patent Examiner, Art Unit 1685
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